GLCM_HUMAN
ID GLCM_HUMAN Reviewed; 536 AA.
AC P04062; A8K796; B7Z5G2; B7Z6S1; J3KQG4; J3KQK9; Q16545; Q4VX22; Q6I9R6;
AC Q9UMJ8;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
DT 09-NOV-2004, sequence version 3.
DT 03-AUG-2022, entry version 257.
DE RecName: Full=Lysosomal acid glucosylceramidase {ECO:0000305};
DE Short=Lysosomal acid GCase {ECO:0000303|PubMed:24211208};
DE EC=3.2.1.45 {ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:32144204, ECO:0000269|PubMed:9201993};
DE AltName: Full=Acid beta-glucosidase;
DE AltName: Full=Alglucerase;
DE AltName: Full=Beta-glucocerebrosidase;
DE Short=Beta-GC;
DE AltName: Full=Cholesterol glucosyltransferase {ECO:0000305|PubMed:24211208};
DE Short=SGTase {ECO:0000303|PubMed:24211208};
DE EC=2.4.1.- {ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:32144204};
DE AltName: Full=Cholesteryl-beta-glucosidase {ECO:0000305|PubMed:24211208};
DE EC=3.2.1.- {ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:32144204};
DE AltName: Full=D-glucosyl-N-acylsphingosine glucohydrolase;
DE AltName: Full=Imiglucerase;
DE AltName: Full=Lysosomal cholesterol glycosyltransferase {ECO:0000305};
DE AltName: Full=Lysosomal galactosylceramidase {ECO:0000305};
DE EC=3.2.1.46 {ECO:0000269|PubMed:32144204};
DE AltName: Full=Lysosomal glycosylceramidase {ECO:0000305};
DE Flags: Precursor;
GN Name=GBA {ECO:0000312|HGNC:HGNC:4177}; Synonyms=GC, GLUC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
RC TISSUE=Placenta;
RX PubMed=3864160; DOI=10.1073/pnas.82.21.7289;
RA Sorge J., West C., Westwood B., Beutler E.;
RT "Molecular cloning and nucleotide sequence of human glucocerebrosidase
RT cDNA.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:7289-7293(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND VARIANT LEU-298.
RC TISSUE=Hepatoma;
RX PubMed=3001061; DOI=10.1016/s0021-9258(17)42428-8;
RA Tsuji S., Choudary P.V., Martin B.M., Winfield S., Barranger J.A.,
RA Ginns E.I.;
RT "Nucleotide sequence of cDNA containing the complete coding sequence for
RT human lysosomal glucocerebrosidase.";
RL J. Biol. Chem. 261:50-53(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=2914709; DOI=10.1016/0888-7543(89)90319-4;
RA Horowitz M., Wilder S., Horowitz Z., Reiner O., Gelbart T., Beutler E.;
RT "The human glucocerebrosidase gene and pseudogene: structure and
RT evolution.";
RL Genomics 4:87-96(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=1572652; DOI=10.1016/0888-7543(92)90311-f;
RA Beutler E., West C., Gelbart T.;
RT "Polymorphisms in the human glucocerebrosidase gene.";
RL Genomics 12:795-800(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND 3), VARIANTS GD ARG-223;
RP GLY-230; PRO-235; ARG-241; ILE-252 AND ARG-364, AND VARIANTS GLY-310 AND
RP HIS-368.
RX PubMed=8294033; DOI=10.1016/0378-1119(93)90497-q;
RA Imai K., Nakamura M., Yamada M., Asano A., Yokoyama S., Tsuji S.,
RA Ginns E.I.;
RT "A novel transcript from a pseudogene for human glucocerebrosidase in non-
RT Gaucher disease cells.";
RL Gene 136:365-368(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9331372; DOI=10.1101/gr.7.10.1020;
RA Winfield S.L., Tayebi N., Martin B.M., Ginns E.I., Sidransky E.;
RT "Identification of three additional genes contiguous to the
RT glucocerebrosidase locus on chromosome 1q21: implications for Gaucher
RT disease.";
RL Genome Res. 7:1020-1026(1997).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG; 4 AND 5), AND
RP VARIANT MET-408.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC TISSUE=Placenta;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-11.
RX PubMed=3359914; DOI=10.1089/dna.1988.7.107;
RA Reiner O., Wigderson M., Horowitz M.;
RT "Structural analysis of the human glucocerebrosidase genes.";
RL DNA 7:107-116(1988).
RN [11]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45, AND ALTERNATIVE INITIATION.
RX PubMed=3687939;
RA Sorge J.A., West C., Kuhl W., Treger L., Beutler E.;
RT "The human glucocerebrosidase gene has two functional ATG initiator
RT codons.";
RL Am. J. Hum. Genet. 41:1016-1024(1987).
RN [12]
RP PROTEIN SEQUENCE OF 40-44, AND CLEAVAGE OF SIGNAL PEPTIDE AFTER GLY-39.
RC TISSUE=Placenta;
RA Martin B.M., Murray G.J., Coligan J.E., Raum M., Brady R.O.,
RA Barranger J.A.;
RT "Structural studies of human placental glucocerebrosidase.";
RL Fed. Proc. 43:1869-1869(1984).
RN [13]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 403-416.
RX PubMed=6091633; DOI=10.1016/0006-291x(84)90268-7;
RA Ginns E.I., Choudary P.V., Martin B.M., Winfield S., Stubblefield B.,
RA Mayor J., Merkle-Lehman D., Murray G.J., Bowers L.A., Barranger J.A.;
RT "Isolation of cDNA clones for human beta-glucocerebrosidase using the
RT lambda gt11 expression system.";
RL Biochem. Biophys. Res. Commun. 123:574-580(1984).
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 409-462, AND VARIANT GD1 SER-409.
RC TISSUE=Skin;
RA Tsuji S., Martin B.M., Barranger J.A., Stubblefield B.K., LaMarca M.E.,
RA Ginns E.I.;
RT "Genetic heterogeneity in type 1 Gaucher disease: multiple genotypes in
RT Ashkenazic and non-Ashkenazic individuals.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:2349-2352(1988).
RN [15]
RP PROTEIN SEQUENCE OF 469-520.
RC TISSUE=Placenta;
RX PubMed=3456607; DOI=10.1073/pnas.83.6.1660;
RA Dinur T., Osiecki K.M., Legler G., Gatt S., Desnick R.J., Grabowski G.A.;
RT "Human acid beta-glucosidase: isolation and amino acid sequence of a
RT peptide containing the catalytic site.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:1660-1664(1986).
RN [16]
RP TOPOLOGY.
RX PubMed=1848227; DOI=10.1016/s0021-9258(19)67728-8;
RA Rijnboutt S., Aerts H.M., Geuze H.J., Tager J.M., Strous G.J.;
RT "Mannose 6-phosphate-independent membrane association of cathepsin D,
RT glucocerebrosidase, and sphingolipid-activating protein in HepG2 cells.";
RL J. Biol. Chem. 266:4862-4868(1991).
RN [17]
RP MUTAGENESIS OF GLU-379, ACTIVE SITE, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=7908905; DOI=10.1016/s0021-9258(19)78077-6;
RA Miao S., McCarter J.D., Grace M.E., Grabowski G.A., Aebersold R.,
RA Withers S.G.;
RT "Identification of Glu340 as the active-site nucleophile in human
RT glucocerebrosidase by use of electrospray tandem mass spectrometry.";
RL J. Biol. Chem. 269:10975-10978(1994).
RN [18]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION.
RX PubMed=9201993; DOI=10.1074/jbc.272.27.16862;
RA Vaccaro A.M., Tatti M., Ciaffoni F., Salvioli R., Barca A., Scerch C.;
RT "Effect of saposins A and C on the enzymatic hydrolysis of liposomal
RT glucosylceramide.";
RL J. Biol. Chem. 272:16862-16867(1997).
RN [19]
RP INTERACTION WITH SAPOSIN-C, ACTIVITY REGULATION, AND TOPOLOGY.
RX PubMed=10781797; DOI=10.1016/s0014-5793(00)01417-4;
RA Salvioli R., Tatti M., Ciaffoni F., Vaccaro A.M.;
RT "Further studies on the reconstitution of glucosylceramidase activity by
RT Sap C and anionic phospholipids.";
RL FEBS Lett. 472:17-21(2000).
RN [20]
RP GLYCOSYLATION AT ASN-98; ASN-185 AND ASN-309.
RX PubMed=12754519; DOI=10.1038/nbt827;
RA Zhang H., Li X.-J., Martin D.B., Aebersold R.;
RT "Identification and quantification of N-linked glycoproteins using
RT hydrazide chemistry, stable isotope labeling and mass spectrometry.";
RL Nat. Biotechnol. 21:660-666(2003).
RN [21]
RP SUBCELLULAR LOCATION, TOPOLOGY, AND INTERACTION WITH SCARB2.
RX PubMed=18022370; DOI=10.1016/j.cell.2007.10.018;
RA Reczek D., Schwake M., Schroder J., Hughes H., Blanz J., Jin X.,
RA Brondyk W., Van Patten S., Edmunds T., Saftig P.;
RT "LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent
RT targeting of beta-glucocerebrosidase.";
RL Cell 131:770-783(2007).
RN [22]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RC TISSUE=Placenta;
RX PubMed=17897319; DOI=10.1111/j.1600-0854.2007.00643.x;
RA Schroeder B., Wrocklage C., Pan C., Jaeger R., Koesters B., Schaefer H.,
RA Elsaesser H.-P., Mann M., Hasilik A.;
RT "Integral and associated lysosomal membrane proteins.";
RL Traffic 8:1676-1686(2007).
RN [23]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=19279011; DOI=10.1074/jbc.m802790200;
RA Kitatani K., Sheldon K., Rajagopalan V., Anelli V., Jenkins R.W., Sun Y.,
RA Grabowski G.A., Obeid L.M., Hannun Y.A.;
RT "Involvement of acid beta-glucosidase 1 in the salvage pathway of ceramide
RT formation.";
RL J. Biol. Chem. 284:12972-12978(2009).
RN [24]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-98 AND ASN-309.
RC TISSUE=Liver;
RX PubMed=19159218; DOI=10.1021/pr8008012;
RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.;
RT "Glycoproteomics analysis of human liver tissue by combination of multiple
RT enzyme digestion and hydrazide chemistry.";
RL J. Proteome Res. 8:651-661(2009).
RN [25]
RP INTERACTION WITH TCP1, CHARACTERIZATION OF VARIANT GD1 SER-409, AND
RP CHARACTERIZATION OF VARIANT GD2 SER-409 AND PRO-483.
RX PubMed=21098288; DOI=10.1073/pnas.1014376107;
RA Lu J., Chiang J., Iyer R.R., Thompson E., Kaneski C.R., Xu D.S., Yang C.,
RA Chen M., Hodes R.J., Lonser R.R., Brady R.O., Zhuang Z.;
RT "Decreased glucocerebrosidase activity in Gaucher disease parallels
RT quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:21665-21670(2010).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [27]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY, SUBSTRATE
RP SPECIFICITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=24211208; DOI=10.1016/j.bbrc.2013.10.145;
RA Akiyama H., Kobayashi S., Hirabayashi Y., Murakami-Murofushi K.;
RT "Cholesterol glucosylation is catalyzed by transglucosylation reaction of
RT beta-glucosidase 1.";
RL Biochem. Biophys. Res. Commun. 441:838-843(2013).
RN [28]
RP INTERACTION WITH SNCA.
RX PubMed=23266198; DOI=10.1016/j.ymgme.2012.11.010;
RA Yap T.L., Velayati A., Sidransky E., Lee J.C.;
RT "Membrane-bound alpha-synuclein interacts with glucocerebrosidase and
RT inhibits enzyme activity.";
RL Mol. Genet. Metab. 108:56-64(2013).
RN [29]
RP INTERACTION WITH GRN.
RX PubMed=27789271; DOI=10.1016/j.ebiom.2016.10.010;
RA Jian J., Tian Q.Y., Hettinghouse A., Zhao S., Liu H., Wei J., Grunig G.,
RA Zhang W., Setchell K.D.R., Sun Y., Overkleeft H.S., Chan G.L., Liu C.J.;
RT "Progranulin Recruits HSP70 to beta-Glucocerebrosidase and Is Therapeutic
RT Against Gaucher Disease.";
RL EBioMedicine 13:212-224(2016).
RN [30]
RP FUNCTION.
RX PubMed=27378698; DOI=10.1093/hmg/ddw185;
RA Magalhaes J., Gegg M.E., Migdalska-Richards A., Doherty M.K.,
RA Whitfield P.D., Schapira A.H.;
RT "Autophagic lysosome reformation dysfunction in glucocerebrosidase
RT deficient cells: relevance to Parkinson disease.";
RL Hum. Mol. Genet. 25:3432-3445(2016).
RN [31]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND ACTIVITY REGULATION.
RX PubMed=26724485; DOI=10.1194/jlr.m064923;
RA Marques A.R., Mirzaian M., Akiyama H., Wisse P., Ferraz M.J., Gaspar P.,
RA Ghauharali-van der Vlugt K., Meijer R., Giraldo P., Alfonso P., Irun P.,
RA Dahl M., Karlsson S., Pavlova E.V., Cox T.M., Scheij S., Verhoek M.,
RA Ottenhoff R., van Roomen C.P., Pannu N.S., van Eijk M., Dekker N.,
RA Boot R.G., Overkleeft H.S., Blommaart E., Hirabayashi Y., Aerts J.M.;
RT "Glucosylated cholesterol in mammalian cells and tissues: formation and
RT degradation by multiple cellular beta-glucosidases.";
RL J. Lipid Res. 57:451-463(2016).
RN [32]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=32144204; DOI=10.1074/jbc.ra119.012502;
RA Akiyama H., Ide M., Nagatsuka Y., Sayano T., Nakanishi E., Uemura N.,
RA Yuyama K., Yamaguchi Y., Kamiguchi H., Takahashi R., Aerts J.M.F.G.,
RA Greimel P., Hirabayashi Y.;
RT "Glucocerebrosidases catalyze a transgalactosylation reaction that yields a
RT newly-identified brain sterol metabolite, galactosylated cholesterol.";
RL J. Biol. Chem. 295:5257-5277(2020).
RN [33]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=33361282; DOI=10.1194/jlr.ra120001043;
RA Boer D.E., Mirzaian M., Ferraz M.J., Zwiers K.C., Baks M.V., Hazeu M.D.,
RA Ottenhoff R., Marques A.R.A., Meijer R., Roos J.C.P., Cox T.M., Boot R.G.,
RA Pannu N., Overkleeft H.S., Artola M., Aerts J.M.;
RT "Human glucocerebrosidase mediates formation of xylosyl-cholesterol by
RT beta-xylosidase and transxylosidase reactions.";
RL J. Lipid Res. 62:100018-100018(2021).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 40-536, GLYCOSYLATION AT ASN-58,
RP AND DISULFIDE BONDS.
RX PubMed=12792654; DOI=10.1038/sj.embor.embor873;
RA Dvir H., Harel M., McCarthy A.A., Toker L., Silman I., Futerman A.H.,
RA Sussman J.L.;
RT "X-ray structure of human acid-beta-glucosidase, the defective enzyme in
RT Gaucher disease.";
RL EMBO Rep. 4:704-709(2003).
RN [35]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 40-536 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR, AND ACTIVE SITE.
RX PubMed=15817452; DOI=10.1074/jbc.m502799200;
RA Premkumar L., Sawkar A.R., Boldin-Adamsky S., Toker L., Silman I.,
RA Kelly J.W., Futerman A.H., Sussman J.L.;
RT "X-ray structure of human acid-beta-glucosidase covalently bound to
RT conduritol-B-epoxide. Implications for Gaucher disease.";
RL J. Biol. Chem. 280:23815-23819(2005).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 40-536, CATALYTIC ACTIVITY,
RP PATHWAY, CHARACTERIZATION OF VARIANTS GD SER-55; GLN-87; ASN-118; LEU-161;
RP VAL-162; VAL-166; ASN-200; PHE-213; PHE-224; GLU-232; GLU-237; LEU-298;
RP ILE-303; CYS-343; ILE-362; LYS-365; GLY-381; LYS-388; TRP-392; CYS-402;
RP SER-409; VAL-410; HIS-419; LYS-421; ARG-429; LEU-433; SER-436; ASN-438;
RP HIS-448; VAL-455; PRO-483; PRO-500; CYS-502 AND PRO-502, CHARACTERIZATION
RP OF VARIANT GD2 GLN-159, AND MUTAGENESIS OF CYS-43; CYS-57 AND CYS-62.
RX PubMed=16293621; DOI=10.1074/jbc.m511110200;
RA Liou B., Kazimierczuk A., Zhang M., Scott C.R., Hegde R.S., Grabowski G.A.;
RT "Analyses of variant acid beta-glucosidases: effects of Gaucher disease
RT mutations.";
RL J. Biol. Chem. 281:4242-4253(2006).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 40-536, AND GLYCOSYLATION AT
RP ASN-58; ASN-98 AND ASN-185.
RX PubMed=17139081; DOI=10.1107/s0907444906038303;
RA Brumshtein B., Wormald M.R., Silman I., Futerman A.H., Sussman J.L.;
RT "Structural comparison of differently glycosylated forms of acid-beta-
RT glucosidase, the defective enzyme in Gaucher disease.";
RL Acta Crystallogr. D 62:1458-1465(2006).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 40-536 IN COMPLEXES WITH
RP ISOFAGOMINE, AND SUBCELLULAR LOCATION.
RX PubMed=17187079; DOI=10.1038/nchembio850;
RA Lieberman R.L., Wustman B.A., Huertas P., Powe A.C. Jr., Pine C.W.,
RA Khanna R., Schlossmacher M.G., Ringe D., Petsko G.A.;
RT "Structure of acid beta-glucosidase with pharmacological chaperone provides
RT insight into Gaucher disease.";
RL Nat. Chem. Biol. 3:101-107(2007).
RN [39]
RP REVIEW ON GD VARIANTS.
RX PubMed=8118460; DOI=10.1002/humu.1380030102;
RA Horowitz M., Zimran A.;
RT "Mutations causing Gaucher disease.";
RL Hum. Mutat. 3:1-11(1994).
RN [40]
RP REVIEW ON GD VARIANTS.
RX PubMed=8889578;
RX DOI=10.1002/(sici)1098-1004(1996)8:3<207::aid-humu2>3.0.co;2-6;
RA Beutler E., Gelbart T.;
RT "Glucocerebrosidase (Gaucher disease).";
RL Hum. Mutat. 8:207-213(1996).
RN [41]
RP REVIEW ON GD VARIANTS.
RX PubMed=10527671; DOI=10.1006/mgme.1999.2918;
RA Tayebi N., Stone D.L., Sidransky E.;
RT "Type 2 Gaucher disease: an expanding phenotype.";
RL Mol. Genet. Metab. 68:209-219(1999).
RN [42]
RP REVIEW ON GD VARIANTS.
RX PubMed=10649495;
RX DOI=10.1002/(sici)1098-1004(200002)15:2<181::aid-humu7>3.0.co;2-s;
RA Stone D.L., Tayebi N., Orvisky E., Stubblefield B., Madike V.,
RA Sidransky E.;
RT "Glucocerebrosidase gene mutations in patients with type 2 Gaucher
RT disease.";
RL Hum. Mutat. 15:181-188(2000).
RN [43]
RP VARIANT GD TYR-255.
RX PubMed=1974409; DOI=10.1111/j.1469-1809.1990.tb00371.x;
RA Beutler E., Gelbart T.;
RT "Gaucher disease associated with a unique KpnI restriction site:
RT identification of the amino-acid substitution.";
RL Ann. Hum. Genet. 54:149-153(1990).
RN [44]
RP VARIANT GD CYS-502, AND CHARACTERIZATION OF VARIANT GD CYS-502.
RX PubMed=1972019; DOI=10.1089/dna.1990.9.233;
RA Hong C.M., Ohashi T., Yu X.J., Weiler S., Barranger J.A.;
RT "Sequence of two alleles responsible for Gaucher disease.";
RL DNA Cell Biol. 9:233-241(1990).
RN [45]
RP VARIANTS GD HIS-179; GLN-196 AND LYS-365.
RX PubMed=1864608; DOI=10.1007/bf00200914;
RA Eyal N., Firon N., Wilder S., Kolodny E.H., Horowitz M.;
RT "Three unique base pair changes in a family with Gaucher disease.";
RL Hum. Genet. 87:328-332(1991).
RN [46]
RP VARIANTS GD.
RX PubMed=8432537; DOI=10.1006/geno.1993.1035;
RA Beutler E., Gelbart T., West C.;
RT "Identification of six new Gaucher disease mutations.";
RL Genomics 15:203-205(1993).
RN [47]
RP VARIANT GD HIS-535.
RX PubMed=7916532; DOI=10.1002/ajmg.1320510216;
RA Choy F.Y.M., Wei C., Applegarth D.A., McGillivray B.C.;
RT "DNA analysis of an uncommon missense mutation in a Gaucher disease patient
RT of Jewish-Polish-Russian descent.";
RL Am. J. Med. Genet. 51:156-160(1994).
RN [48]
RP VARIANT GD ASN-438.
RX PubMed=8112750; DOI=10.1007/bf00210614;
RA Beutler E., Gelbart T.;
RT "Two new Gaucher disease mutations.";
RL Hum. Genet. 93:209-210(1994).
RN [49]
RP VARIANTS GD SER-409 AND CYS-457.
RX PubMed=8076951; DOI=10.1007/bf00208292;
RA Tuteja R., Tuteja N., Lilliu F., Bembi B., Galanello R., Cao A.,
RA Baralle F.E.;
RT "Y418C: a novel mutation in exon 9 of the glucocerebrosidase gene of a
RT patient with Gaucher disease creates a new Bgl I site.";
RL Hum. Genet. 94:314-315(1994).
RN [50]
RP VARIANTS GD ASP-215; THR-221; ARG-241; GLN-296; CYS-324; GLY-417 AND
RP ASN-419.
RX PubMed=8790604; DOI=10.1007/bf03403534;
RA Beutler E., Demina A., Gelbart T.;
RT "Glucocerebrosidase mutations in Gaucher disease.";
RL Mol. Med. 1:82-92(1994).
RN [51]
RP VARIANTS GD SER-409; HIS-448; PRO-483 AND CYS-502.
RX PubMed=7627184; DOI=10.1002/humu.1380050406;
RA Cormand B., Vilageliu L., Burguera J.M., Balcells S., Gonzalez-Duarte R.,
RA Grinberg D., Chabas A.;
RT "Gaucher disease in Spanish patients: analysis of eight mutations.";
RL Hum. Mutat. 5:303-309(1995).
RN [52]
RP VARIANT GD2 SER-217.
RX PubMed=7627192; DOI=10.1002/humu.1380050414;
RA Choy F.Y.M., Wei C.;
RT "Identification of a new mutation (P178S) in an African-American patient
RT with type 2 Gaucher disease.";
RL Hum. Mutat. 5:345-347(1995).
RN [53]
RP VARIANT GD HIS-448.
RX PubMed=7475546; DOI=10.1016/s0140-6736(95)91688-1;
RA Abrahamov A., Elstein D., Gross-Tsur V., Farber B., Glaser Y.,
RA Hadas-Halpern I., Ronen S., Tafakjdi M., Horowitz M., Zimran A.;
RT "Gaucher's disease variant characterised by progressive calcification of
RT heart valves and unique genotype.";
RL Lancet 346:1000-1003(1995).
RN [54]
RP VARIANTS GD SER-409; LEU-426; LEU-433 AND PRO-483.
RX PubMed=8937765; DOI=10.1111/j.1399-0004.1996.tb02352.x;
RA Morar B., Lane A.B.;
RT "The molecular characterization of Gaucher disease in South Africa.";
RL Clin. Genet. 50:78-84(1996).
RN [55]
RP VARIANTS GD LEU-54; GLU-85 AND SER-227.
RX PubMed=8829654;
RX DOI=10.1002/(sici)1098-1004(1996)7:3<214::aid-humu5>3.0.co;2-a;
RA Kim J.-W., Liou B.B., Lai M.-Y., Ponce E., Grabowski G.A.;
RT "Gaucher disease: identification of three new mutations in the Korean and
RT Chinese (Taiwanese) populations.";
RL Hum. Mutat. 7:214-218(1996).
RN [56]
RP VARIANTS GD HIS-352 AND GLN-398.
RX PubMed=8829663;
RX DOI=10.1002/(sici)1098-1004(1996)7:3<272::aid-humu14>3.0.co;2-#;
RA Cormand B., Vilageliu L., Balcells S., Gonzalez-Duatre R., Chabas A.,
RA Grinberg D.;
RT "Two novel (1098insA and Y313H) and one rare (R359Q) mutations detected in
RT exon 8 of the beta-glucocerebrosidase gene in Gaucher's disease patients.";
RL Hum. Mutat. 7:272-274(1996).
RN [57]
RP VARIANT GD1 THR-435.
RX PubMed=8889591;
RX DOI=10.1002/(sici)1098-1004(1996)8:3<280::aid-humu15>3.0.co;2-z;
RA Amaral O., Pinto E., Fortuna M., Lacerda L., Sa Miranda M.C.;
RT "Type 1 Gaucher disease: identification of N396T and prevalence of
RT glucocerebrosidase mutations in the Portuguese.";
RL Hum. Mutat. 8:280-281(1996).
RN [58]
RP VARIANTS GD3 LEU-437 AND ILE-530.
RX PubMed=8780099; DOI=10.1212/wnl.46.4.1102;
RA Seeman P.J.V., Finckh U., Hoeppner J., Lakner V., Liebisch I., Grau G.,
RA Rolfs A.;
RT "Two new missense mutations in a non-Jewish Caucasian family with type 3
RT Gaucher disease.";
RL Neurology 46:1102-1107(1996).
RN [59]
RP VARIANTS GD LEU-414 AND THR-441.
RX PubMed=9182788;
RX DOI=10.1002/(sici)1096-8628(19970627)70:4<437::aid-ajmg19>3.0.co;2-i;
RA Cormand B., Grinberg D., Gort L., Fiumara A., Barone R., Vilageliu L.,
RA Chabas A.;
RT "Two new mild homozygous mutations in Gaucher disease patients: clinical
RT signs and biochemical analyses.";
RL Am. J. Med. Genet. 70:437-443(1997).
RN [60]
RP VARIANTS GD VAL-76; GLU-85; TRP-87; TRP-159; SER-227; ILE-252 AND PRO-483.
RX PubMed=9217217;
RX DOI=10.1002/(sici)1096-8628(19970808)71:2<172::aid-ajmg10>3.0.co;2-b;
RA Choy F.Y.M., Humphries M.L., Shi H.;
RT "Identification of two novel and four uncommon missense mutations among
RT Chinese Gaucher disease patients.";
RL Am. J. Med. Genet. 71:172-178(1997).
RN [61]
RP VARIANT GD2 LYS-501.
RX PubMed=9279145; DOI=10.1136/adc.77.1.17;
RA Hatton C.E., Cooper A., Whitehouse C., Wraith J.E.;
RT "Mutation analysis in 46 British and Irish patients with Gaucher's
RT disease.";
RL Arch. Dis. Child. 77:17-22(1997).
RN [62]
RP VARIANTS GD TRP-87; GLU-234; ARG-241; ILE-252; ASN-310; LEU-391 AND
RP SER-409.
RX PubMed=9153297; DOI=10.1172/jci119437;
RA Grace M.E., Desnick R.J., Pastores G.M.;
RT "Identification and expression of acid beta-glucosidase mutations causing
RT severe type 1 and neurologic type 2 Gaucher disease in non-Jewish
RT patients.";
RL J. Clin. Invest. 99:2530-2537(1997).
RN [63]
RP VARIANTS GD VAL-228; ILE-252; GLY-405; HIS-448; GLN-452; PRO-483 AND
RP CYS-535.
RX PubMed=9061570; DOI=10.1023/a:1005313724361;
RA Ida H., Rennert O.M., Kawame H., Maekawa K., Eto Y.;
RT "Mutation prevalence among 47 unrelated Japanese patients with Gaucher
RT disease: identification of four novel mutations.";
RL J. Inherit. Metab. Dis. 20:67-73(1997).
RN [64]
RP VARIANT GD3C HIS-448.
RX PubMed=9040001; DOI=10.1136/jmg.34.2.175;
RA Uyama E., Uchino M., Ida H., Eto Y., Owada M.;
RT "D409H/D409H genotype in Gaucher-like disease.";
RL J. Med. Genet. 34:175-175(1997).
RN [65]
RP VARIANTS GD LEU-198; THR-380; ASN-405 AND ARG-432, AND VARIANT GD2 LEU-146.
RX PubMed=9554454; DOI=10.1159/000040815;
RA Demina A., Beutler E.;
RT "Six new Gaucher disease mutations.";
RL Acta Haematol. 99:80-82(1998).
RN [66]
RP VARIANTS GD.
RX PubMed=9683600; DOI=10.1086/301969;
RA Germain D.P., Puech J.-P., Caillaud C., Kahn A., Poenaru L.;
RT "Exhaustive screening of the acid beta-glucosidase gene, by fluorescence-
RT assisted mismatch analysis using universal primers: mutation profile and
RT genotype/phenotype correlations in Gaucher disease.";
RL Am. J. Hum. Genet. 63:415-427(1998).
RN [67]
RP VARIANT GD2 TYR-513.
RX PubMed=9637431;
RX DOI=10.1002/(sici)1096-8628(19980616)78:1<92::aid-ajmg19>3.0.co;2-j;
RA Choy F.Y.M., Humphries M.L., Ben-Yoseph Y.;
RT "Gaucher type 2 disease: identification of a novel transversion mutation in
RT a French-Irish patient.";
RL Am. J. Med. Genet. 78:92-93(1998).
RN [68]
RP VARIANTS GD.
RX PubMed=9516376; DOI=10.1006/bcmd.1998.0165;
RA Beutler E., Gelbart T.;
RT "Hematologically important mutations: Gaucher disease.";
RL Blood Cells Mol. Dis. 24:2-8(1998).
RN [69]
RP VARIANTS GD2 LYS-80; CYS-170 AND PRO-483.
RX PubMed=9851895; DOI=10.1006/bcmd.1998.0210;
RA Sinclair G., Choy F.Y.M., Humphries L.;
RT "A novel complex allele and two new point mutations in type 2 (acute
RT neuronopathic) Gaucher disease.";
RL Blood Cells Mol. Dis. 24:420-427(1998).
RN [70]
RP VARIANT GD GLY-392.
RX PubMed=9650766; DOI=10.1111/j.1399-0004.1998.tb02697.x;
RA Parenti G., Filocamo M., Titomanlio L., Rizzolo G., Silvestro E.,
RA Perretti A., Gatti R., Andria G.;
RT "A novel mutation of the beta-glucocerebrosidase gene associated with
RT neurologic manifestations in three sibs.";
RL Clin. Genet. 53:281-285(1998).
RN [71]
RP VARIANTS GD GLU-152; PRO-173; GLU-428; LEU-430; ILE-431 AND HIS-451.
RX PubMed=9554746;
RX DOI=10.1002/(sici)1098-1004(1998)11:4<295::aid-humu7>3.0.co;2-6;
RA Cormand B., Grinberg D., Gort L., Chabas A., Vilageliu L.;
RT "Molecular analysis and clinical findings in the Spanish Gaucher disease
RT population: putative haplotype of the N370S ancestral chromosome.";
RL Hum. Mutat. 11:295-305(1998).
RN [72]
RP VARIANTS GD1 GLY-230 AND SER-409.
RX PubMed=10206680;
RX DOI=10.1002/(sici)1098-1004(1998)11:5<411::aid-humu13>3.0.co;2-x;
RA Choy F.Y.M., Humphries M.L., Ben-Yoseph Y.;
RT "A novel mutation (V191G) in a German-British type 1 Gaucher disease
RT patient.";
RL Hum. Mutat. 11:411-412(1998).
RN [73]
RP VARIANTS GD1 SER-409 AND LEU-440.
RX PubMed=10340647;
RX DOI=10.1002/(sici)1096-8628(19990604)84:4<334::aid-ajmg5>3.0.co;2-p;
RA Wasserstein M.P., Martignetti J.A., Zeitlin R., Lumerman H., Solomon M.,
RA Grace M.E., Desnick R.J.;
RT "Type 1 Gaucher disease presenting with extensive mandibular lytic lesions:
RT identification and expression of a novel acid beta-glucosidase mutation.";
RL Am. J. Med. Genet. 84:334-339(1999).
RN [74]
RP VARIANTS GD ARG-241; CYS-244; ILE-252; HIS-448 AND PRO-483.
RX PubMed=10360404;
RX DOI=10.1002/(sici)1096-8628(19990611)84:5<484::aid-ajmg14>3.0.co;2-w;
RA Choy F.Y.M., Wong K., Shi H.P.;
RT "Glucocerebrosidase mutations among Chinese neuronopathic and non-
RT neuronopathic Gaucher disease patients.";
RL Am. J. Med. Genet. 84:484-486(1999).
RN [75]
RP VARIANTS GD.
RX PubMed=10744424;
RA Hodanov K., Hrebicek M., Cervenkov M., Mrzov L., Veprekov L., Zemen J.;
RT "Analysis of the beta-glucocerebrosidase gene in Czech and Slovak Gaucher
RT patients: mutation profile and description of six novel mutant alleles.";
RL Blood Cells Mol. Dis. 25:287-298(1999).
RN [76]
RP VARIANTS GDPL ARG-350 AND PHE-437.
RX PubMed=10352942; DOI=10.1038/sj.ejhg.5200315;
RA Stone D.L., van Diggelen O.P., de Klerk J.B.C., Gaillard J.L.J.,
RA Niermeijer M.F., Willemsen R., Tayebi N., Sidransky E.;
RT "Is the perinatal lethal form of Gaucher disease more common than classic
RT type 2 Gaucher disease?";
RL Eur. J. Hum. Genet. 7:505-509(1999).
RN [77]
RP VARIANTS GD PRO-173; TRP-234; SER-409; SER-416; HIS-448 AND PRO-483.
RX PubMed=10447266;
RX DOI=10.1002/(sici)1098-1004(1999)14:1<88::aid-humu16>3.0.co;2-e;
RA Sarria A.J., Giraldo P., Perez-Calvo J.I., Pocovi M.;
RT "Detection of three rare (G377S, T134P and 1451delAC), and two novel
RT mutations (G195W and Rec[1263del55;1342G>C]] in Spanish Gaucher disease
RT patients.";
RL Hum. Mutat. 14:88-88(1999).
RN [78]
RP VARIANTS GD TRP-87; ASN-118; THR-129; ASP-156; GLN-159; TRP-159; LEU-170;
RP ILE-173; CYS-209; PRO-209; SER-227; THR-229; PRO-235; ARG-241; ILE-252;
RP GLN-296; CYS-324; THR-380; MET-408; SER-409; SER-416; LEU-433; TYR-438;
RP HIS-448; PRO-483 AND CYS-502, VARIANT LYS-365, AND VARIANT GD2 GLN-159.
RX PubMed=10796875; DOI=10.1086/302925;
RA Koprivica V., Stone D.L., Park J.K., Callahan M., Frisch A., Cohen I.J.,
RA Tayebi N., Sidransky E.;
RT "Analysis and classification of 304 mutant alleles in patients with type 1
RT and type 3 Gaucher disease.";
RL Am. J. Hum. Genet. 66:1777-1786(2000).
RN [79]
RP VARIANTS GD SER-55 AND HIS-448.
RX PubMed=11992489; DOI=10.1002/ajmg.10385;
RA Bodamer O.A.F., Church H.J., Cooper A., Wraith J.E., Scott C.R.,
RA Scaglia F.;
RT "Variant Gaucher disease characterized by dysmorphic features, absence of
RT cardiovascular involvement, laryngospasm, and compound heterozygosity for a
RT novel mutation (D409H/C16S).";
RL Am. J. Med. Genet. 109:328-331(2002).
RN [80]
RP VARIANTS GD GLU-175; PRO-201; GLU-237 AND PHE-441, AND VARIANT GDPL
RP LEU-290.
RX PubMed=11933202; DOI=10.1002/humu.9024;
RA Orvisky E., Park J.K., Parker A., Walker J.M., Martin B.M.,
RA Stubblefield B.K., Uyama E., Tayebi N., Sidransky E.;
RT "The identification of eight novel glucocerebrosidase (GBA) mutations in
RT patients with Gaucher disease.";
RL Hum. Mutat. 19:458-459(2002).
RN [81]
RP VARIANTS GD THR-198; ARG-241; ARG-270; ILE-400 AND ARG-490.
RX PubMed=12204005; DOI=10.1002/humu.9058;
RA Filocamo M., Mazzotti R., Stroppiano M., Seri M., Giona F., Parenti G.,
RA Regis S., Corsolini F., Zoboli S., Gatti R.;
RT "Analysis of the glucocerebrosidase gene and mutation profile in 144
RT Italian Gaucher patients.";
RL Hum. Mutat. 20:234-235(2002).
RN [82]
RP POSSIBLE INVOLVEMENT IN PARKINSON DISEASE.
RX PubMed=12847165; DOI=10.1212/01.wnl.0000072482.70963.d7;
RA Bembi B., Zambito Marsala S., Sidransky E., Ciana G., Carrozzi M.,
RA Zorzon M., Martini C., Gioulis M., Pittis M.G., Capus L.;
RT "Gaucher's disease with Parkinson's disease: clinical and pathological
RT aspects.";
RL Neurology 61:99-101(2003).
RN [83]
RP VARIANT GD SER-55.
RX PubMed=15292921; DOI=10.1038/sj.ejhg.5201251;
RA Church H.J., Cooper A., Stewart F., Thornton C.M., Wraith J.E.;
RT "Homozygous loss of a cysteine residue in the glucocerebrosidase gene
RT results in Gaucher's disease with a hydropic phenotype.";
RL Eur. J. Hum. Genet. 12:975-978(2004).
RN [84]
RP CHARACTERIZATION OF VARIANT GD SER-409.
RX PubMed=15826241; DOI=10.1042/bj20050325;
RA Salvioli R., Tatti M., Scarpa S., Moavero S.M., Ciaffoni F., Felicetti F.,
RA Kaneski C.R., Brady R.O., Vaccaro A.M.;
RT "The N370S (Asn370->Ser) mutation affects the capacity of
RT glucosylceramidase to interact with anionic phospholipid-containing
RT membranes and saposin C.";
RL Biochem. J. 390:95-103(2005).
RN [85]
RP CHARACTERIZATION OF VARIANTS GD HIS-179 AND GLN-196, CATALYTIC ACTIVITY,
RP AND FUNCTION.
RX PubMed=15916907; DOI=10.1016/j.bcmd.2005.03.006;
RA Ron I., Dagan A., Gatt S., Pasmanik-Chor M., Horowitz M.;
RT "Use of fluorescent substrates for characterization of Gaucher disease
RT mutations.";
RL Blood Cells Mol. Dis. 35:57-65(2005).
RN [86]
RP VARIANTS GD1 ASN-63; SER-158; TRP-159; CYS-170; LEU-221; GLU-230; ARG-241;
RP GLN-294; CYS-324; SER-409; ASN-438; LEU-440; HIS-448; CYS-457; ASP-460;
RP PRO-483 AND ARG-490, AND CHARACTERIZATION OF VARIANTS GD1 ASN-63; SER-158;
RP LEU-221; GLU-230 AND ASP-460.
RX PubMed=15605411; DOI=10.1002/humu.9301;
RA Miocic S., Filocamo M., Dominissini S., Montalvo A.L., Vlahovicek K.,
RA Deganuto M., Mazzotti R., Cariati R., Bembi B., Pittis M.G.;
RT "Identification and functional characterization of five novel mutant
RT alleles in 58 Italian patients with Gaucher disease type 1.";
RL Hum. Mutat. 25:100-100(2005).
RN [87]
RP POSSIBLE INVOLVEMENT IN PARKINSON DISEASE.
RX PubMed=16148263; DOI=10.1212/01.wnl.0000176987.47875.28;
RA Aharon-Peretz J., Badarny S., Rosenbaum H., Gershoni-Baruch R.;
RT "Mutations in the glucocerebrosidase gene and Parkinson disease: phenotype-
RT genotype correlation.";
RL Neurology 65:1460-1461(2005).
RN [88]
RP INVOLVEMENT OF VARIANT GD PRO-483 IN SUSCEPTIBILITY TO PARKINSON DISEASE.
RX PubMed=17620502; DOI=10.1001/archneur.64.7.1056;
RA Tan E.K., Tong J., Fook-Chong S., Yih Y., Wong M.C., Pavanni R., Zhao Y.;
RT "Glucocerebrosidase mutations and risk of Parkinson disease in Chinese
RT patients.";
RL Arch. Neurol. 64:1056-1058(2007).
RN [89]
RP INVOLVEMENT OF VARIANTS GD SER-409 AND PRO-483 IN SUSCEPTIBILITY TO
RP PARKINSON DISEASE.
RX PubMed=18332251; DOI=10.1001/archneurol.2007.68;
RA Mata I.F., Samii A., Schneer S.H., Roberts J.W., Griffith A., Leis B.C.,
RA Schellenberg G.D., Sidransky E., Bird T.D., Leverenz J.B., Tsuang D.,
RA Zabetian C.P.;
RT "Glucocerebrosidase gene mutations: a risk factor for Lewy body
RT disorders.";
RL Arch. Neurol. 65:379-382(2008).
RN [90]
RP INVOLVEMENT IN PARKINSON DISEASE, AND VARIANTS GLU-46; CYS-170; GLU-232;
RP GLN-296; SER-409; ALA-419; HIS-448; ASN-482; PRO-483; PRO-495; LEU-497 AND
RP CYS-502.
RX PubMed=19286695; DOI=10.1093/brain/awp044;
RA Neumann J., Bras J., Deas E., O'Sullivan S.S., Parkkinen L., Lachmann R.H.,
RA Li A., Holton J., Guerreiro R., Paudel R., Segarane B., Singleton A.,
RA Lees A., Hardy J., Houlden H., Revesz T., Wood N.W.;
RT "Glucocerebrosidase mutations in clinical and pathologically proven
RT Parkinson's disease.";
RL Brain 132:1783-1794(2009).
RN [91]
RP INVOLVEMENT OF VARIANTS GD SER-409 AND PRO-483 IN SUSCEPTIBILITY TO
RP PARKINSON DISEASE.
RX PubMed=19846850; DOI=10.1056/nejmoa0901281;
RA Sidransky E., Nalls M.A., Aasly J.O., Aharon-Peretz J., Annesi G.,
RA Barbosa E.R., Bar-Shira A., Berg D., Bras J., Brice A., Chen C.M.,
RA Clark L.N., Condroyer C., De Marco E.V., Durr A., Eblan M.J., Fahn S.,
RA Farrer M.J., Fung H.C., Gan-Or Z., Gasser T., Gershoni-Baruch R.,
RA Giladi N., Griffith A., Gurevich T., Januario C., Kropp P., Lang A.E.,
RA Lee-Chen G.J., Lesage S., Marder K., Mata I.F., Mirelman A., Mitsui J.,
RA Mizuta I., Nicoletti G., Oliveira C., Ottman R., Orr-Urtreger A.,
RA Pereira L.V., Quattrone A., Rogaeva E., Rolfs A., Rosenbaum H.,
RA Rozenberg R., Samii A., Samaddar T., Schulte C., Sharma M., Singleton A.,
RA Spitz M., Tan E.K., Tayebi N., Toda T., Troiano A.R., Tsuji S.,
RA Wittstock M., Wolfsberg T.G., Wu Y.R., Zabetian C.P., Zhao Y.,
RA Ziegler S.G.;
RT "Multicenter analysis of glucocerebrosidase mutations in Parkinson's
RT disease.";
RL N. Engl. J. Med. 361:1651-1661(2009).
RN [92]
RP VARIANTS GD1 VAL-289; GLY-301 AND GLU-486.
RX PubMed=22658918; DOI=10.1016/j.ymgme.2012.05.006;
RA Duran R., McNeill A., Mehta A., Hughes D., Cox T., Deegan P.,
RA Schapira A.H., Hardy J.;
RT "Novel pathogenic mutations in the glucocerebrosidase locus.";
RL Mol. Genet. Metab. 106:495-497(2012).
RN [93]
RP VARIANTS GD1 LEU-266 AND SER-347.
RX PubMed=24577513; DOI=10.1007/s00277-014-2036-x;
RA Machaczka M., Klimkowska M.;
RT "Novel heterozygous c.798C>G and c.1040T>G mutations in the GBA1 gene are
RT associated with a severe phenotype of Gaucher disease type 1.";
RL Ann. Hematol. 93:1787-1789(2014).
RN [94]
RP VARIANTS GD1 SER-198; THR-284; SER-351; LYS-365; ARG-405; ASN-419 AND
RP CYS-420, CHARACTERIZATION OF VARIANTS GD1 SER-198; THR-284; SER-351;
RP LYS-365; ARG-405; SER-409; ASN-419 AND CYS-420, VARIANTS GD2 ILE-227 AND
RP LYS-274, CHARACTERIZATION OF VARIANTS GD2 ILE-227 AND LYS-274, VARIANTS GD3
RP SER-227 AND ARG-304, AND CHARACTERIZATION OF VARIANTS GD3 SER-227 AND
RP ARG-304.
RX PubMed=24022302; DOI=10.1038/ejhg.2013.182;
RA Malini E., Grossi S., Deganuto M., Rosano C., Parini R., Dominisini S.,
RA Cariati R., Zampieri S., Bembi B., Filocamo M., Dardis A.;
RT "Functional analysis of 11 novel GBA alleles.";
RL Eur. J. Hum. Genet. 22:511-516(2014).
RN [95]
RP VARIANT GD1 TRP-62.
RX PubMed=24434810; DOI=10.1016/j.gene.2014.01.015;
RA Jack A., Amato D., Morris G., Choy F.Y.;
RT "Two novel mutations in glucocerebrosidase, C23W and IVS7-1 G>A, identified
RT in Type 1 Gaucher patients heterozygous for N370S.";
RL Gene 538:84-87(2014).
RN [96]
RP VARIANT PRO-363.
RX PubMed=26528954; DOI=10.1002/ana.24553;
RG International Parkinsonism Genetics Network;
RA Olgiati S., Quadri M., Fang M., Rood J.P., Saute J.A., Chien H.F.,
RA Bouwkamp C.G., Graafland J., Minneboo M., Breedveld G.J., Zhang J.,
RA Verheijen F.W., Boon A.J., Kievit A.J., Jardim L.B., Mandemakers W.,
RA Barbosa E.R., Rieder C.R., Leenders K.L., Wang J., Bonifati V.;
RT "DNAJC6 mutations associated with early-onset Parkinson's disease.";
RL Ann. Neurol. 79:244-256(2016).
CC -!- FUNCTION: Glucosylceramidase that catalyzes, within the lysosomal
CC compartment, the hydrolysis of glucosylceramides/GlcCers (such as beta-
CC D-glucosyl-(1<->1')-N-acylsphing-4-enine) into free ceramides (such as
CC N-acylsphing-4-enine) and glucose (PubMed:9201993, PubMed:24211208,
CC PubMed:15916907, PubMed:32144204). Plays a central role in the
CC degradation of complex lipids and the turnover of cellular membranes
CC (PubMed:27378698). Through the production of ceramides, participates in
CC the PKC-activated salvage pathway of ceramide formation
CC (PubMed:19279011). Catalyzes the glucosylation of cholesterol, through
CC a transglucosylation reaction where glucose is transferred from GlcCer
CC to cholesterol (PubMed:24211208, PubMed:26724485, PubMed:32144204).
CC GlcCer containing mono-unsaturated fatty acids (such as beta-D-
CC glucosyl-N-(9Z-octadecenoyl)-sphing-4-enine) are preferred as glucose
CC donors for cholesterol glucosylation when compared with GlcCer
CC containing same chain length of saturated fatty acids (such as beta-D-
CC glucosyl-N-octadecanoyl-sphing-4-enine) (PubMed:24211208). Under
CC specific conditions, may alternatively catalyze the reverse reaction,
CC transferring glucose from cholesteryl 3-beta-D-glucoside to ceramide
CC (PubMed:26724485) (Probable). Can also hydrolyze cholesteryl 3-beta-D-
CC glucoside producing glucose and cholesterol (PubMed:24211208,
CC PubMed:26724485). Catalyzes the hydrolysis of
CC galactosylceramides/GalCers (such as beta-D-galactosyl-(1<->1')-N-
CC acylsphing-4-enine), as well as the transfer of galactose between
CC GalCers and cholesterol in vitro, but with lower activity than with
CC GlcCers (PubMed:32144204). Contrary to GlcCer and GalCer,
CC xylosylceramide/XylCer (such as beta-D-xyosyl-(1<->1')-N-acylsphing-4-
CC enine) is not a good substrate for hydrolysis, however it is a good
CC xylose donor for transxylosylation activity to form cholesteryl 3-beta-
CC D-xyloside (PubMed:33361282). {ECO:0000269|PubMed:15916907,
CC ECO:0000269|PubMed:19279011, ECO:0000269|PubMed:24211208,
CC ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:27378698,
CC ECO:0000269|PubMed:32144204, ECO:0000269|PubMed:33361282,
CC ECO:0000269|PubMed:9201993, ECO:0000305|PubMed:32144204}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine + H2O = an N-
CC acylsphing-4-enine + D-glucose; Xref=Rhea:RHEA:13269,
CC ChEBI:CHEBI:4167, ChEBI:CHEBI:15377, ChEBI:CHEBI:22801,
CC ChEBI:CHEBI:52639; EC=3.2.1.45;
CC Evidence={ECO:0000269|PubMed:15916907, ECO:0000269|PubMed:16293621,
CC ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:32144204,
CC ECO:0000269|PubMed:9201993};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13270;
CC Evidence={ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:32144204};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine + H2O = an
CC N-acylsphing-4-enine + D-galactose; Xref=Rhea:RHEA:14297,
CC ChEBI:CHEBI:4139, ChEBI:CHEBI:15377, ChEBI:CHEBI:18390,
CC ChEBI:CHEBI:52639; EC=3.2.1.46;
CC Evidence={ECO:0000269|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14298;
CC Evidence={ECO:0000305|PubMed:32144204};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesteryl 3-beta-D-glucoside + H2O = cholesterol + D-
CC glucose; Xref=Rhea:RHEA:11956, ChEBI:CHEBI:4167, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17495;
CC Evidence={ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:33361282};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11957;
CC Evidence={ECO:0000269|PubMed:33361282, ECO:0000305|PubMed:24211208};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-glucosyl-(1<->1')-N-acylsphing-4-enine + cholesterol
CC = an N-acylsphing-4-enine + cholesteryl 3-beta-D-glucoside;
CC Xref=Rhea:RHEA:58264, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:22801, ChEBI:CHEBI:52639;
CC Evidence={ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485,
CC ECO:0000269|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58265;
CC Evidence={ECO:0000269|PubMed:32144204, ECO:0000305|PubMed:24211208};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58266;
CC Evidence={ECO:0000305|PubMed:32144204};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-N-(9Z-octadecenoyl)-sphing-4E-enine +
CC cholesterol = cholesteryl 3-beta-D-glucoside + N-(9Z-octadecenoyl)-
CC sphing-4-enine; Xref=Rhea:RHEA:58324, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:17495, ChEBI:CHEBI:77996, ChEBI:CHEBI:139140;
CC Evidence={ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58325;
CC Evidence={ECO:0000269|PubMed:32144204, ECO:0000305|PubMed:24211208};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58326;
CC Evidence={ECO:0000305|PubMed:32144204};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1<->1')-N-hexadecanoylsphing-4-enine +
CC cholesterol = cholesteryl 3-beta-D-glucoside + N-hexadecanoylsphing-
CC 4-enine; Xref=Rhea:RHEA:58316, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:72959, ChEBI:CHEBI:84716;
CC Evidence={ECO:0000269|PubMed:24211208};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:58317;
CC Evidence={ECO:0000305|PubMed:24211208};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:58318;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-N-octanoylsphing-4E-enine + cholesterol =
CC cholesteryl 3-beta-D-glucoside + N-octanoylsphing-4-enine;
CC Xref=Rhea:RHEA:70303, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:45815, ChEBI:CHEBI:65222;
CC Evidence={ECO:0000269|PubMed:24211208};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70304;
CC Evidence={ECO:0000305|PubMed:24211208};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70305;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-N-dodecanoylsphing-4-enine + cholesterol =
CC cholesteryl 3-beta-D-glucoside + N-dodecanoylsphing-4-enine;
CC Xref=Rhea:RHEA:70307, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:72956, ChEBI:CHEBI:76297;
CC Evidence={ECO:0000269|PubMed:24211208};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70308;
CC Evidence={ECO:0000305|PubMed:24211208};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70309;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1<->1)-N-octadecanoylsphing-4-enine +
CC cholesterol = cholesteryl 3-beta-D-glucoside + N-octadecanoylsphing-
CC 4-enine; Xref=Rhea:RHEA:70311, ChEBI:CHEBI:16113, ChEBI:CHEBI:17495,
CC ChEBI:CHEBI:72961, ChEBI:CHEBI:84719;
CC Evidence={ECO:0000269|PubMed:24211208};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70312;
CC Evidence={ECO:0000305|PubMed:24211208};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70313;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-glucosyl-(1<->1')-N-(15Z-tetracosenoyl)-sphing-4-enine
CC + cholesterol = cholesteryl 3-beta-D-glucoside + N-(15Z-
CC tetracosenoyl)-sphing-4-enine; Xref=Rhea:RHEA:70315,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:17495, ChEBI:CHEBI:74450,
CC ChEBI:CHEBI:84746; Evidence={ECO:0000269|PubMed:24211208};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70316;
CC Evidence={ECO:0000305|PubMed:24211208};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70317;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1<->1')-N-acylsphing-4-enine +
CC cholesterol = an N-acylsphing-4-enine + cholesteryl 3-beta-D-
CC galactoside; Xref=Rhea:RHEA:70235, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:18390, ChEBI:CHEBI:52639, ChEBI:CHEBI:189066;
CC Evidence={ECO:0000269|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70236;
CC Evidence={ECO:0000269|PubMed:32144204};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70237;
CC Evidence={ECO:0000305|PubMed:32144204};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-(beta-D-galactosyl)-N-dodecanoylsphing-4-enine + cholesterol
CC = cholesteryl 3-beta-D-galactoside + N-dodecanoylsphing-4-enine;
CC Xref=Rhea:RHEA:70255, ChEBI:CHEBI:16113, ChEBI:CHEBI:72956,
CC ChEBI:CHEBI:73432, ChEBI:CHEBI:189066;
CC Evidence={ECO:0000269|PubMed:32144204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70256;
CC Evidence={ECO:0000269|PubMed:32144204};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:70257;
CC Evidence={ECO:0000305|PubMed:32144204};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-xylosyl-(1<->1')-N-acylsphing-4-enine + cholesterol =
CC an N-acylsphing-4-enine + cholesteryl 3-beta-D-xyloside;
CC Xref=Rhea:RHEA:70239, ChEBI:CHEBI:16113, ChEBI:CHEBI:52639,
CC ChEBI:CHEBI:189067, ChEBI:CHEBI:189068;
CC Evidence={ECO:0000269|PubMed:33361282};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70240;
CC Evidence={ECO:0000269|PubMed:33361282};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-xylosyl-(1<->1')-N-(9Z-octadecenoyl)-sphing-4-enine +
CC cholesterol = cholesteryl 3-beta-D-xyloside + N-(9Z-octadecenoyl)-
CC sphing-4-enine; Xref=Rhea:RHEA:70251, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:77996, ChEBI:CHEBI:189067, ChEBI:CHEBI:189081;
CC Evidence={ECO:0000269|PubMed:33361282};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70252;
CC Evidence={ECO:0000269|PubMed:33361282};
CC -!- ACTIVITY REGULATION: Synergistically activated by saposin-A and
CC saposin-C, two saposin peptides produced by proteolytic processing of
CC prosaposin/PSAP (PubMed:9201993). Saposin-C activates GBA through its
CC recruitment to membranes (PubMed:10781797, PubMed:9201993). The
CC membrane structure and composition in anionic phospholipids are also
CC important for the activation (PubMed:9201993, PubMed:10781797).
CC Activated by PKC in the salvage pathway of ceramide formation
CC (PubMed:19279011). Inhibited by conduritol B epoxide/CBE
CC (PubMed:24211208, PubMed:26724485). {ECO:0000269|PubMed:10781797,
CC ECO:0000269|PubMed:19279011, ECO:0000269|PubMed:24211208,
CC ECO:0000269|PubMed:26724485, ECO:0000269|PubMed:9201993}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5.3. {ECO:0000269|PubMed:24211208};
CC Temperature dependence:
CC Optimum temperature is 43 degrees Celsius.
CC {ECO:0000269|PubMed:24211208};
CC -!- PATHWAY: Steroid metabolism; cholesterol metabolism.
CC {ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485}.
CC -!- PATHWAY: Sphingolipid metabolism. {ECO:0000269|PubMed:16293621,
CC ECO:0000269|PubMed:24211208, ECO:0000269|PubMed:26724485,
CC ECO:0000269|PubMed:9201993}.
CC -!- SUBUNIT: Interacts with saposin-C (PubMed:10781797). Interacts with
CC SCARB2 (PubMed:18022370). Interacts with TCP1 (PubMed:21098288). May
CC interact with SNCA; may inhibit the glucosylceramidase activity
CC (PubMed:23266198). Interacts with GRN; this interaction prevents
CC aggregation of GBA-SCARB2 complex via interaction with HSPA1A upon
CC stress (PubMed:27789271). {ECO:0000269|PubMed:10781797,
CC ECO:0000269|PubMed:18022370, ECO:0000269|PubMed:21098288,
CC ECO:0000269|PubMed:23266198, ECO:0000269|PubMed:27789271}.
CC -!- INTERACTION:
CC P04062; P17987: TCP1; NbExp=2; IntAct=EBI-1564609, EBI-356553;
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:17187079,
CC ECO:0000269|PubMed:17897319, ECO:0000269|PubMed:18022370}; Peripheral
CC membrane protein {ECO:0000269|PubMed:10781797,
CC ECO:0000269|PubMed:18022370, ECO:0000269|PubMed:1848227}; Lumenal side
CC {ECO:0000269|PubMed:18022370}. Note=Interaction with saposin-C promotes
CC membrane association (PubMed:10781797). Targeting to lysosomes occurs
CC through an alternative MPR-independent mechanism via SCARB2
CC (PubMed:18022370). {ECO:0000269|PubMed:10781797,
CC ECO:0000269|PubMed:18022370}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=5;
CC Name=Long;
CC IsoId=P04062-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P04062-2; Sequence=VSP_018800;
CC Name=3;
CC IsoId=P04062-3; Sequence=VSP_025216, VSP_025217, VSP_025218;
CC Name=4;
CC IsoId=P04062-4; Sequence=VSP_054655;
CC Name=5;
CC IsoId=P04062-5; Sequence=VSP_054656;
CC -!- DISEASE: Gaucher disease (GD) [MIM:230800]: A lysosomal storage disease
CC due to deficient activity of beta-glucocerebrosidase and characterized
CC by accumulation of glucosylceramide in the reticulo-endothelial system.
CC Different clinical forms are recognized depending on the presence
CC (neuronopathic forms) or absence of central nervous system involvement,
CC severity and age of onset. {ECO:0000269|PubMed:10352942,
CC ECO:0000269|PubMed:10360404, ECO:0000269|PubMed:10447266,
CC ECO:0000269|PubMed:10744424, ECO:0000269|PubMed:10796875,
CC ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:11992489,
CC ECO:0000269|PubMed:12204005, ECO:0000269|PubMed:15292921,
CC ECO:0000269|PubMed:15826241, ECO:0000269|PubMed:15916907,
CC ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:17620502,
CC ECO:0000269|PubMed:18332251, ECO:0000269|PubMed:1864608,
CC ECO:0000269|PubMed:1972019, ECO:0000269|PubMed:1974409,
CC ECO:0000269|PubMed:19846850, ECO:0000269|PubMed:7475546,
CC ECO:0000269|PubMed:7627184, ECO:0000269|PubMed:7627192,
CC ECO:0000269|PubMed:7916532, ECO:0000269|PubMed:8076951,
CC ECO:0000269|PubMed:8112750, ECO:0000269|PubMed:8294033,
CC ECO:0000269|PubMed:8432537, ECO:0000269|PubMed:8790604,
CC ECO:0000269|PubMed:8829654, ECO:0000269|PubMed:8829663,
CC ECO:0000269|PubMed:8937765, ECO:0000269|PubMed:9061570,
CC ECO:0000269|PubMed:9153297, ECO:0000269|PubMed:9182788,
CC ECO:0000269|PubMed:9217217, ECO:0000269|PubMed:9516376,
CC ECO:0000269|PubMed:9554454, ECO:0000269|PubMed:9554746,
CC ECO:0000269|PubMed:9650766, ECO:0000269|PubMed:9683600}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Gaucher disease 1 (GD1) [MIM:230800]: A form of Gaucher
CC disease characterized by hepatosplenomegaly with consequent anemia and
CC thrombopenia, and bone involvement. The central nervous system is not
CC involved. {ECO:0000269|PubMed:10206680, ECO:0000269|PubMed:10340647,
CC ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:21098288,
CC ECO:0000269|PubMed:22658918, ECO:0000269|PubMed:24022302,
CC ECO:0000269|PubMed:24434810, ECO:0000269|PubMed:24577513,
CC ECO:0000269|PubMed:8889591, ECO:0000269|Ref.14}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Gaucher disease 2 (GD2) [MIM:230900]: The most severe form of
CC Gaucher disease. It manifests soon after birth, with death generally
CC occurring before patients reach two years of age.
CC {ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:16293621,
CC ECO:0000269|PubMed:21098288, ECO:0000269|PubMed:24022302,
CC ECO:0000269|PubMed:7627192, ECO:0000269|PubMed:9279145,
CC ECO:0000269|PubMed:9554454, ECO:0000269|PubMed:9637431,
CC ECO:0000269|PubMed:9851895}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Gaucher disease 3 (GD3) [MIM:231000]: A subacute form of
CC neuronopathic Gaucher disease. It has later onset and slower
CC progression compared to the acute form of neuronopathic Gaucher disease
CC 2. {ECO:0000269|PubMed:11933202, ECO:0000269|PubMed:24022302,
CC ECO:0000269|PubMed:8780099}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Gaucher disease 3C (GD3C) [MIM:231005]: A variant of subacute
CC neuronopathic Gaucher disease 3 associated with cardiovascular
CC calcifications. {ECO:0000269|PubMed:9040001}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Gaucher disease perinatal lethal (GDPL) [MIM:608013]: Distinct
CC form of Gaucher disease type 2, characterized by fetal onset. Hydrops
CC fetalis, in utero fetal death and neonatal distress are prominent
CC features. When hydrops is absent, neurologic involvement begins in the
CC first week and leads to death within 3 months. Hepatosplenomegaly is a
CC major sign, and is associated with ichthyosis, arthrogryposis, and
CC facial dysmorphism. {ECO:0000269|PubMed:10352942,
CC ECO:0000269|PubMed:11933202}. Note=The disease is caused by variants
CC affecting the gene represented in this entry. Perinatal lethal Gaucher
CC disease is associated with non-immune hydrops fetalis, a generalized
CC edema of the fetus with fluid accumulation in the body cavities due to
CC non-immune causes. Non-immune hydrops fetalis is not a diagnosis in
CC itself but a symptom, a feature of many genetic disorders, and the end-
CC stage of a wide variety of disorders. {ECO:0000269|PubMed:10352942}.
CC -!- DISEASE: Parkinson disease (PARK) [MIM:168600]: A complex
CC neurodegenerative disorder characterized by bradykinesia, resting
CC tremor, muscular rigidity and postural instability. Additional features
CC are characteristic postural abnormalities, dysautonomia, dystonic
CC cramps, and dementia. The pathology of Parkinson disease involves the
CC loss of dopaminergic neurons in the substantia nigra and the presence
CC of Lewy bodies (intraneuronal accumulations of aggregated proteins), in
CC surviving neurons in various areas of the brain. The disease is
CC progressive and usually manifests after the age of 50 years, although
CC early-onset cases (before 50 years) are known. The majority of the
CC cases are sporadic suggesting a multifactorial etiology based on
CC environmental and genetic factors. However, some patients present with
CC a positive family history for the disease. Familial forms of the
CC disease usually begin at earlier ages and are associated with atypical
CC clinical features. {ECO:0000269|PubMed:12847165,
CC ECO:0000269|PubMed:16148263, ECO:0000269|PubMed:17620502,
CC ECO:0000269|PubMed:18332251, ECO:0000269|PubMed:19286695,
CC ECO:0000269|PubMed:19846850}. Note=Disease susceptibility may be
CC associated with variants affecting the gene represented in this entry.
CC -!- PHARMACEUTICAL: Available under the names Ceredase and Cerezyme
CC (Genzyme). Used to treat Gaucher disease.
CC -!- MISCELLANEOUS: [Isoform Long]: Major isoform.
CC {ECO:0000269|PubMed:3687939}.
CC -!- MISCELLANEOUS: [Isoform Short]: Produced by alternative initiation from
CC a downstream AUG. Two to three times less protein is produced from this
CC downstream AUG. {ECO:0000269|PubMed:3687939}.
CC -!- MISCELLANEOUS: [Isoform 3]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 30 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Ceredase; Note=Clinical information on Ceredase;
CC URL="https://www.rxlist.com/ceredase-drug.htm";
CC -!- WEB RESOURCE: Name=Cerezyme; Note=Clinical information on Cerezyme;
CC URL="https://www.rxlist.com/cerezyme-drug.htm";
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DR EMBL; M16328; AAA35873.1; -; mRNA.
DR EMBL; K02920; AAA35877.1; -; mRNA.
DR EMBL; J03059; AAC63056.1; -; Genomic_DNA.
DR EMBL; D13286; BAA02545.1; -; mRNA.
DR EMBL; D13287; BAA02546.1; -; mRNA.
DR EMBL; AF023268; AAC51820.1; -; Genomic_DNA.
DR EMBL; AK291911; BAF84600.1; -; mRNA.
DR EMBL; AK298900; BAH12898.1; -; mRNA.
DR EMBL; AK300829; BAH13357.1; -; mRNA.
DR EMBL; AL713999; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC003356; AAH03356.1; -; mRNA.
DR EMBL; M19285; AAA35880.1; -; mRNA.
DR EMBL; M18916; AAA35878.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M18917; AAA35879.1; ALT_SEQ; Genomic_DNA.
DR EMBL; M20248; AAA35874.1; -; Genomic_DNA.
DR EMBL; M20282; AAA35876.1; -; Genomic_DNA.
DR CCDS; CCDS1102.1; -. [P04062-1]
DR CCDS; CCDS53373.1; -. [P04062-4]
DR CCDS; CCDS53374.1; -. [P04062-5]
DR PIR; A94068; EUHUGC.
DR PIR; I52980; I52980.
DR PIR; I67792; I67792.
DR RefSeq; NP_000148.2; NM_000157.3. [P04062-1]
DR RefSeq; NP_001005741.1; NM_001005741.2. [P04062-1]
DR RefSeq; NP_001005742.1; NM_001005742.2. [P04062-1]
DR RefSeq; NP_001165282.1; NM_001171811.1. [P04062-4]
DR RefSeq; NP_001165283.1; NM_001171812.1. [P04062-5]
DR PDB; 1OGS; X-ray; 2.00 A; A/B=40-536.
DR PDB; 1Y7V; X-ray; 2.40 A; A/B=40-536.
DR PDB; 2F61; X-ray; 2.50 A; A/B=40-536.
DR PDB; 2J25; X-ray; 2.90 A; A/B=40-536.
DR PDB; 2NSX; X-ray; 2.11 A; A/B/C/D=40-536.
DR PDB; 2NT0; X-ray; 1.79 A; A/B/C/D=40-536.
DR PDB; 2NT1; X-ray; 2.30 A; A/B/C/D=40-536.
DR PDB; 2V3D; X-ray; 1.96 A; A/B=40-536.
DR PDB; 2V3E; X-ray; 2.00 A; A/B=40-536.
DR PDB; 2V3F; X-ray; 1.95 A; A/B=40-536.
DR PDB; 2VT0; X-ray; 2.15 A; A/B=40-536.
DR PDB; 2WCG; X-ray; 2.30 A; A/B=40-536.
DR PDB; 2WKL; X-ray; 2.70 A; A/B=40-536.
DR PDB; 2XWD; X-ray; 2.66 A; A/B=40-536.
DR PDB; 2XWE; X-ray; 2.31 A; A/B=40-536.
DR PDB; 3GXD; X-ray; 2.50 A; A/B/C/D=40-536.
DR PDB; 3GXF; X-ray; 2.40 A; A/B/C/D=40-536.
DR PDB; 3GXI; X-ray; 1.84 A; A/B/C/D=40-536.
DR PDB; 3GXM; X-ray; 2.20 A; A/B/C/D=40-536.
DR PDB; 3KE0; X-ray; 2.70 A; A/B=40-536.
DR PDB; 3KEH; X-ray; 2.80 A; A/B=40-536.
DR PDB; 3RIK; X-ray; 2.48 A; A/B/C/D=40-536.
DR PDB; 3RIL; X-ray; 2.40 A; A/B/C/D=40-536.
DR PDB; 5LVX; X-ray; 2.20 A; A/B/C/D=40-536.
DR PDB; 6MOZ; X-ray; 2.10 A; A/B=40-536.
DR PDB; 6Q1N; X-ray; 2.53 A; A/B=40-536.
DR PDB; 6Q1P; X-ray; 2.80 A; A/B=40-536.
DR PDB; 6Q6K; X-ray; 1.92 A; A/B=40-536.
DR PDB; 6Q6L; X-ray; 1.81 A; A/B=40-536.
DR PDB; 6Q6N; X-ray; 1.63 A; A/B=40-536.
DR PDB; 6T13; X-ray; 1.85 A; A/B/C/D=1-536.
DR PDB; 6TJJ; X-ray; 1.59 A; AAA/BBB=40-536.
DR PDB; 6TJK; X-ray; 1.56 A; AAA/BBB=40-536.
DR PDB; 6TJQ; X-ray; 1.41 A; BBB=40-536.
DR PDB; 6TN1; X-ray; 0.98 A; AAA=40-536.
DR PDB; 6YTP; X-ray; 1.70 A; AAA/BBB=40-536.
DR PDB; 6YTR; X-ray; 1.70 A; AAA/BBB=40-536.
DR PDB; 6YUT; X-ray; 1.76 A; AAA/BBB=40-536.
DR PDB; 6YV3; X-ray; 1.80 A; AAA/BBB=40-536.
DR PDB; 6Z39; X-ray; 1.70 A; AAA/BBB=40-536.
DR PDB; 6Z3I; X-ray; 1.80 A; BBB=40-536.
DR PDB; 7NWV; X-ray; 1.86 A; AAA/BBB=40-536.
DR PDBsum; 1OGS; -.
DR PDBsum; 1Y7V; -.
DR PDBsum; 2F61; -.
DR PDBsum; 2J25; -.
DR PDBsum; 2NSX; -.
DR PDBsum; 2NT0; -.
DR PDBsum; 2NT1; -.
DR PDBsum; 2V3D; -.
DR PDBsum; 2V3E; -.
DR PDBsum; 2V3F; -.
DR PDBsum; 2VT0; -.
DR PDBsum; 2WCG; -.
DR PDBsum; 2WKL; -.
DR PDBsum; 2XWD; -.
DR PDBsum; 2XWE; -.
DR PDBsum; 3GXD; -.
DR PDBsum; 3GXF; -.
DR PDBsum; 3GXI; -.
DR PDBsum; 3GXM; -.
DR PDBsum; 3KE0; -.
DR PDBsum; 3KEH; -.
DR PDBsum; 3RIK; -.
DR PDBsum; 3RIL; -.
DR PDBsum; 5LVX; -.
DR PDBsum; 6MOZ; -.
DR PDBsum; 6Q1N; -.
DR PDBsum; 6Q1P; -.
DR PDBsum; 6Q6K; -.
DR PDBsum; 6Q6L; -.
DR PDBsum; 6Q6N; -.
DR PDBsum; 6T13; -.
DR PDBsum; 6TJJ; -.
DR PDBsum; 6TJK; -.
DR PDBsum; 6TJQ; -.
DR PDBsum; 6TN1; -.
DR PDBsum; 6YTP; -.
DR PDBsum; 6YTR; -.
DR PDBsum; 6YUT; -.
DR PDBsum; 6YV3; -.
DR PDBsum; 6Z39; -.
DR PDBsum; 6Z3I; -.
DR PDBsum; 7NWV; -.
DR AlphaFoldDB; P04062; -.
DR SMR; P04062; -.
DR BioGRID; 108899; 75.
DR DIP; DIP-38645N; -.
DR IntAct; P04062; 35.
DR MINT; P04062; -.
DR STRING; 9606.ENSP00000314508; -.
DR BindingDB; P04062; -.
DR ChEMBL; CHEMBL2179; -.
DR DrugBank; DB08283; (2R,3R,4R,5S)-2-(HYDROXYMETHYL)-1-NONYLPIPERIDINE-3,4,5-TRIOL.
DR DrugBank; DB03740; N-acetyl-alpha-D-glucosamine.
DR DrugBank; DB03106; scyllo-inositol.
DR DrugBank; DB06720; Velaglucerase alfa.
DR DrugCentral; P04062; -.
DR SwissLipids; SLP:000001387; -.
DR Allergome; 8244; Hom s Glucocerebrosidase.
DR CAZy; GH30; Glycoside Hydrolase Family 30.
DR GlyConnect; 1271; 26 N-Linked glycans (4 sites).
DR GlyGen; P04062; 7 sites, 26 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P04062; -.
DR MetOSite; P04062; -.
DR PhosphoSitePlus; P04062; -.
DR SwissPalm; P04062; -.
DR BioMuta; GBA; -.
DR DMDM; 55584151; -.
DR EPD; P04062; -.
DR jPOST; P04062; -.
DR MassIVE; P04062; -.
DR MaxQB; P04062; -.
DR PaxDb; P04062; -.
DR PeptideAtlas; P04062; -.
DR PRIDE; P04062; -.
DR ProteomicsDB; 51642; -. [P04062-1]
DR ProteomicsDB; 51643; -. [P04062-2]
DR ProteomicsDB; 51644; -. [P04062-3]
DR ABCD; P04062; 7 sequenced antibodies.
DR Antibodypedia; 1678; 494 antibodies from 34 providers.
DR DNASU; 2629; -.
DR Ensembl; ENST00000327247.9; ENSP00000314508.5; ENSG00000177628.16. [P04062-1]
DR Ensembl; ENST00000368373.8; ENSP00000357357.3; ENSG00000177628.16. [P04062-1]
DR Ensembl; ENST00000427500.7; ENSP00000402577.2; ENSG00000177628.16. [P04062-5]
DR Ensembl; ENST00000428024.3; ENSP00000397986.2; ENSG00000177628.16. [P04062-4]
DR GeneID; 2629; -.
DR KEGG; hsa:2629; -.
DR MANE-Select; ENST00000368373.8; ENSP00000357357.3; NM_000157.4; NP_000148.2.
DR UCSC; uc001fjh.4; human. [P04062-1]
DR CTD; 2629; -.
DR DisGeNET; 2629; -.
DR GeneCards; GBA; -.
DR GeneReviews; GBA; -.
DR HGNC; HGNC:4177; GBA.
DR HPA; ENSG00000177628; Low tissue specificity.
DR MalaCards; GBA; -.
DR MIM; 168600; phenotype.
DR MIM; 230800; phenotype.
DR MIM; 230900; phenotype.
DR MIM; 231000; phenotype.
DR MIM; 231005; phenotype.
DR MIM; 606463; gene.
DR MIM; 608013; phenotype.
DR neXtProt; NX_P04062; -.
DR OpenTargets; ENSG00000177628; -.
DR Orphanet; 85212; Fetal Gaucher disease.
DR Orphanet; 77259; Gaucher disease type 1.
DR Orphanet; 77260; Gaucher disease type 2.
DR Orphanet; 77261; Gaucher disease type 3.
DR Orphanet; 2072; Gaucher disease-ophthalmoplegia-cardiovascular calcification syndrome.
DR Orphanet; 411602; Hereditary late-onset Parkinson disease.
DR Orphanet; 1648; NON RARE IN EUROPE: Dementia with Lewy body.
DR Orphanet; 319705; NON RARE IN EUROPE: Parkinson disease.
DR PharmGKB; PA28591; -.
DR VEuPathDB; HostDB:ENSG00000177628; -.
DR eggNOG; KOG2566; Eukaryota.
DR GeneTree; ENSGT00390000009464; -.
DR HOGENOM; CLU_014379_1_2_1; -.
DR InParanoid; P04062; -.
DR OMA; FGGIAWH; -.
DR OrthoDB; 324863at2759; -.
DR PhylomeDB; P04062; -.
DR TreeFam; TF314254; -.
DR BRENDA; 3.2.1.45; 2681.
DR PathwayCommons; P04062; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-390471; Association of TriC/CCT with target proteins during biosynthesis.
DR SignaLink; P04062; -.
DR UniPathway; UPA00296; -.
DR BioGRID-ORCS; 2629; 9 hits in 1080 CRISPR screens.
DR ChiTaRS; GBA; human.
DR EvolutionaryTrace; P04062; -.
DR GeneWiki; Glucocerebrosidase; -.
DR GenomeRNAi; 2629; -.
DR Pharos; P04062; Tclin.
DR PRO; PR:P04062; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P04062; protein.
DR Bgee; ENSG00000177628; Expressed in stromal cell of endometrium and 100 other tissues.
DR ExpressionAtlas; P04062; baseline and differential.
DR Genevisible; P04062; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0019898; C:extrinsic component of membrane; NAS:ARUK-UCL.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0043202; C:lysosomal lumen; ISS:BHF-UCL.
DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB.
DR GO; GO:0005764; C:lysosome; IMP:ARUK-UCL.
DR GO; GO:0005802; C:trans-Golgi network; ISS:UniProtKB.
DR GO; GO:0004336; F:galactosylceramidase activity; IEA:RHEA.
DR GO; GO:0004348; F:glucosylceramidase activity; IDA:UniProtKB.
DR GO; GO:0046527; F:glucosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0005124; F:scavenger receptor binding; IPI:ARUK-UCL.
DR GO; GO:0005102; F:signaling receptor binding; ISS:BHF-UCL.
DR GO; GO:0050295; F:steryl-beta-glucosidase activity; IDA:UniProtKB.
DR GO; GO:0019882; P:antigen processing and presentation; IEA:Ensembl.
DR GO; GO:1905037; P:autophagosome organization; IEA:Ensembl.
DR GO; GO:0006914; P:autophagy; IMP:UniProtKB.
DR GO; GO:1901805; P:beta-glucoside catabolic process; IEA:Ensembl.
DR GO; GO:0048854; P:brain morphogenesis; IEA:Ensembl.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IMP:BHF-UCL.
DR GO; GO:0046513; P:ceramide biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0021694; P:cerebellar Purkinje cell layer formation; IEA:Ensembl.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0006680; P:glucosylceramide catabolic process; IDA:UniProtKB.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IEA:Ensembl.
DR GO; GO:0048872; P:homeostasis of number of cells; IEA:Ensembl.
DR GO; GO:0030259; P:lipid glycosylation; IDA:UniProtKB.
DR GO; GO:0019915; P:lipid storage; IEA:Ensembl.
DR GO; GO:0072676; P:lymphocyte migration; IEA:Ensembl.
DR GO; GO:0007040; P:lysosome organization; IMP:UniProtKB.
DR GO; GO:0014004; P:microglia differentiation; IEA:Ensembl.
DR GO; GO:0061518; P:microglial cell proliferation; IEA:Ensembl.
DR GO; GO:0061744; P:motor behavior; IEA:Ensembl.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IC:BHF-UCL.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:BHF-UCL.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:1901215; P:negative regulation of neuron death; IGI:ParkinsonsUK-UCL.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IDA:ParkinsonsUK-UCL.
DR GO; GO:0050905; P:neuromuscular process; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:1904925; P:positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization; IEA:Ensembl.
DR GO; GO:1904457; P:positive regulation of neuronal action potential; IMP:ParkinsonsUK-UCL.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; IMP:BHF-UCL.
DR GO; GO:1903061; P:positive regulation of protein lipidation; IGI:ParkinsonsUK-UCL.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IGI:ParkinsonsUK-UCL.
DR GO; GO:0043243; P:positive regulation of protein-containing complex disassembly; IDA:ParkinsonsUK-UCL.
DR GO; GO:1903052; P:positive regulation of proteolysis involved in protein catabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0021859; P:pyramidal neuron differentiation; IEA:Ensembl.
DR GO; GO:0032268; P:regulation of cellular protein metabolic process; IMP:ParkinsonsUK-UCL.
DR GO; GO:1905165; P:regulation of lysosomal protein catabolic process; TAS:ParkinsonsUK-UCL.
DR GO; GO:0016241; P:regulation of macroautophagy; TAS:ParkinsonsUK-UCL.
DR GO; GO:0032006; P:regulation of TOR signaling; IMP:UniProtKB.
DR GO; GO:0033561; P:regulation of water loss via skin; IEA:Ensembl.
DR GO; GO:0022904; P:respiratory electron transport chain; IEA:Ensembl.
DR GO; GO:0071548; P:response to dexamethasone; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0009268; P:response to pH; IEA:Ensembl.
DR GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR GO; GO:0097066; P:response to thyroid hormone; IEA:Ensembl.
DR GO; GO:0043589; P:skin morphogenesis; IEA:Ensembl.
DR GO; GO:0046512; P:sphingosine biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0023021; P:termination of signal transduction; IMP:BHF-UCL.
DR InterPro; IPR033452; GH30_C.
DR InterPro; IPR001139; Glyco_hydro_30.
DR InterPro; IPR033453; Glyco_hydro_30_TIM-barrel.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR11069; PTHR11069; 1.
DR Pfam; PF02055; Glyco_hydro_30; 1.
DR Pfam; PF17189; Glyco_hydro_30C; 1.
DR PRINTS; PR00843; GLHYDRLASE30.
DR SUPFAM; SSF51445; SSF51445; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Alternative splicing;
KW Cholesterol metabolism; Direct protein sequencing; Disease variant;
KW Disulfide bond; Gaucher disease; Glycoprotein; Glycosidase;
KW Glycosyltransferase; Hydrolase; Ichthyosis; Lipid metabolism; Lysosome;
KW Membrane; Neurodegeneration; Parkinson disease; Parkinsonism;
KW Pharmaceutical; Reference proteome; Signal; Sphingolipid metabolism;
KW Steroid metabolism; Sterol metabolism; Transferase.
FT SIGNAL 1..39
FT /evidence="ECO:0000269|Ref.12"
FT CHAIN 40..536
FT /note="Lysosomal acid glucosylceramidase"
FT /id="PRO_0000012177"
FT ACT_SITE 274
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:15817452"
FT ACT_SITE 379
FT /note="Nucleophile"
FT /evidence="ECO:0000269|PubMed:15817452"
FT CARBOHYD 58
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12792654,
FT ECO:0000269|PubMed:17139081"
FT CARBOHYD 98
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:17139081, ECO:0000269|PubMed:19159218"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:17139081"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 501
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 43..55
FT /evidence="ECO:0000269|PubMed:12792654"
FT DISULFID 57..62
FT /evidence="ECO:0000269|PubMed:12792654"
FT VAR_SEQ 1..161
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8294033"
FT /id="VSP_025216"
FT VAR_SEQ 1..87
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054655"
FT VAR_SEQ 1..20
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:3001061,
FT ECO:0000303|PubMed:3864160"
FT /id="VSP_018800"
FT VAR_SEQ 103..151
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054656"
FT VAR_SEQ 422..423
FT /note="LA -> PS (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8294033"
FT /id="VSP_025217"
FT VAR_SEQ 425..536
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:8294033"
FT /id="VSP_025218"
FT VARIANT 46
FT /note="K -> E (in a patient with Parkinson disease;
FT dbSNP:rs142761046)"
FT /evidence="ECO:0000269|PubMed:19286695"
FT /id="VAR_063066"
FT VARIANT 54
FT /note="V -> L (in GD; dbSNP:rs121908302)"
FT /evidence="ECO:0000269|PubMed:8829654"
FT /id="VAR_003255"
FT VARIANT 55
FT /note="C -> S (in GD; neuronopathic and perinatal lethal
FT forms; loss of glucosylceramidase activity;
FT dbSNP:rs773007510)"
FT /evidence="ECO:0000269|PubMed:11992489,
FT ECO:0000269|PubMed:15292921, ECO:0000269|PubMed:16293621"
FT /id="VAR_032394"
FT VARIANT 62
FT /note="C -> W (in GD1)"
FT /evidence="ECO:0000269|PubMed:24434810"
FT /id="VAR_081188"
FT VARIANT 63
FT /note="D -> N (in GD1; very low glucosylceramidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:15605411"
FT /id="VAR_032395"
FT VARIANT 76
FT /note="F -> V (in GD)"
FT /evidence="ECO:0000269|PubMed:9217217"
FT /id="VAR_003256"
FT VARIANT 80
FT /note="E -> K (in GD2)"
FT /evidence="ECO:0000269|PubMed:9851895"
FT /id="VAR_009033"
FT VARIANT 82
FT /note="T -> I (in GD; dbSNP:rs1141811)"
FT /id="VAR_003257"
FT VARIANT 85
FT /note="G -> E (in GD; dbSNP:rs77829017)"
FT /evidence="ECO:0000269|PubMed:8829654,
FT ECO:0000269|PubMed:9217217"
FT /id="VAR_003258"
FT VARIANT 87
FT /note="R -> Q (in GD; decreased glucosylceramidase
FT activity; 20% of normal activity; dbSNP:rs78769774)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032197"
FT VARIANT 87
FT /note="R -> W (in GD; mild; dbSNP:rs1141814)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:9153297, ECO:0000269|PubMed:9217217"
FT /id="VAR_003259"
FT VARIANT 92
FT /note="M -> T (in dbSNP:rs1141815)"
FT /id="VAR_032396"
FT VARIANT 118
FT /note="K -> N (in GD; mild; decreased glucosylceramidase
FT activity; 8% of normal activity; increases susceptibility
FT to proteolytic degradation; dbSNP:rs121908312)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:16293621"
FT /id="VAR_003260"
FT VARIANT 129
FT /note="A -> T (in GD)"
FT /evidence="ECO:0000269|PubMed:10796875"
FT /id="VAR_032397"
FT VARIANT 146
FT /note="S -> L (in GD2; dbSNP:rs758447515)"
FT /evidence="ECO:0000269|PubMed:9554454"
FT /id="VAR_009034"
FT VARIANT 152
FT /note="G -> E (in GD)"
FT /evidence="ECO:0000269|PubMed:9554746"
FT /id="VAR_003261"
FT VARIANT 156
FT /note="N -> D (in GD)"
FT /evidence="ECO:0000269|PubMed:10796875"
FT /id="VAR_032398"
FT VARIANT 158
FT /note="I -> S (in GD1; very low glucosylceramidase
FT activity; dbSNP:rs77834747)"
FT /evidence="ECO:0000269|PubMed:15605411"
FT /id="VAR_032399"
FT VARIANT 158
FT /note="I -> T (in GD; dbSNP:rs77834747)"
FT /id="VAR_003262"
FT VARIANT 159
FT /note="R -> Q (in GD2; decreased glucosylceramidase
FT activity; 13% of normal activity; dbSNP:rs79653797)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:16293621"
FT /id="VAR_003263"
FT VARIANT 159
FT /note="R -> W (in GD; severe; dbSNP:rs439898)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:9217217"
FT /id="VAR_003264"
FT VARIANT 161
FT /note="P -> L (in GD; decreased glucosylceramidase
FT activity; 16% of normal activity; dbSNP:rs79637617)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032198"
FT VARIANT 161
FT /note="P -> S (in GD; mild; dbSNP:rs121908299)"
FT /id="VAR_003265"
FT VARIANT 162
FT /note="M -> V (in GD; loss of glucosylceramidase activity;
FT increases susceptibility to proteolytic degradation;
FT dbSNP:rs377325220)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032199"
FT VARIANT 166
FT /note="D -> V (in GD; decreased glucosylceramidase
FT activity; 9% of normal activity; increases susceptibility
FT to proteolytic degradation; dbSNP:rs79796061)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032200"
FT VARIANT 170
FT /note="R -> C (in GD1 and GD2; also found in a patient with
FT Parkinson disease; dbSNP:rs398123530)"
FT /evidence="ECO:0000269|PubMed:15605411,
FT ECO:0000269|PubMed:19286695, ECO:0000269|PubMed:9851895"
FT /id="VAR_009035"
FT VARIANT 170
FT /note="R -> L (in GD; dbSNP:rs80356763)"
FT /evidence="ECO:0000269|PubMed:10796875"
FT /id="VAR_009036"
FT VARIANT 173
FT /note="T -> I (in GD; dbSNP:rs78657146)"
FT /evidence="ECO:0000269|PubMed:10796875"
FT /id="VAR_032400"
FT VARIANT 173
FT /note="T -> P (in GD; dbSNP:rs1441909908)"
FT /evidence="ECO:0000269|PubMed:10447266,
FT ECO:0000269|PubMed:9554746"
FT /id="VAR_003266"
FT VARIANT 175
FT /note="A -> E (in GD; dbSNP:rs79660787)"
FT /evidence="ECO:0000269|PubMed:11933202"
FT /id="VAR_032401"
FT VARIANT 179
FT /note="D -> H (in GD; decreased glucosylceramide catabolic
FT process; dbSNP:rs147138516)"
FT /evidence="ECO:0000269|PubMed:15916907,
FT ECO:0000269|PubMed:1864608"
FT /id="VAR_003267"
FT VARIANT 196
FT /note="K -> Q (in GD; severe; decreased protein abundance;
FT decreased glucosylceramide catabolic process;
FT dbSNP:rs121908297)"
FT /evidence="ECO:0000269|PubMed:15916907,
FT ECO:0000269|PubMed:1864608"
FT /id="VAR_003268"
FT VARIANT 198
FT /note="P -> L (in GD; dbSNP:rs80222298)"
FT /evidence="ECO:0000269|PubMed:9554454"
FT /id="VAR_009037"
FT VARIANT 198
FT /note="P -> S (in GD1; decreased glucosylceramide catabolic
FT process)"
FT /evidence="ECO:0000269|PubMed:24022302"
FT /id="VAR_081189"
FT VARIANT 198
FT /note="P -> T (in GD)"
FT /evidence="ECO:0000269|PubMed:12204005"
FT /id="VAR_032402"
FT VARIANT 200
FT /note="I -> N (in GD; decreased glucosylceramidase
FT activity; 5% of normal activity; dbSNP:rs77933015)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032201"
FT VARIANT 200
FT /note="I -> S (in GD; dbSNP:rs77933015)"
FT /id="VAR_010059"
FT VARIANT 201
FT /note="H -> P (in GD; dbSNP:rs76500263)"
FT /evidence="ECO:0000269|PubMed:11933202"
FT /id="VAR_032403"
FT VARIANT 209
FT /note="R -> C (in GD; dbSNP:rs398123532)"
FT /evidence="ECO:0000269|PubMed:10796875"
FT /id="VAR_032404"
FT VARIANT 209
FT /note="R -> P (in GD; dbSNP:rs749416070)"
FT /evidence="ECO:0000269|PubMed:10796875"
FT /id="VAR_003269"
FT VARIANT 213
FT /note="L -> F (in GD, decreased glucosylceramidase
FT activity; 12% of normal activity; dbSNP:rs374591570)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032202"
FT VARIANT 215
FT /note="A -> D (in GD)"
FT /evidence="ECO:0000269|PubMed:8790604"
FT /id="VAR_003270"
FT VARIANT 217
FT /note="P -> S (in GD2)"
FT /evidence="ECO:0000269|PubMed:7627192"
FT /id="VAR_003271"
FT VARIANT 221
FT /note="P -> L (in GD1; very low glucosylceramidase
FT activity; dbSNP:rs80205046)"
FT /evidence="ECO:0000269|PubMed:15605411"
FT /id="VAR_032405"
FT VARIANT 221
FT /note="P -> T (in GD; dbSNP:rs866075757)"
FT /evidence="ECO:0000269|PubMed:8790604"
FT /id="VAR_003272"
FT VARIANT 223
FT /note="W -> R (in GD; gene conversion; dbSNP:rs61748906)"
FT /evidence="ECO:0000269|PubMed:8294033"
FT /id="VAR_003273"
FT VARIANT 224
FT /note="L -> F (in GD; decreased glucosylceramidase
FT activity; 4% of normal activity; increases susceptibility
FT to proteolytic degradation)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032203"
FT VARIANT 227
FT /note="N -> I (in GD2; decreased glucosylceramide catabolic
FT process)"
FT /evidence="ECO:0000269|PubMed:24022302"
FT /id="VAR_081190"
FT VARIANT 227
FT /note="N -> K (in GD; gene conversion; dbSNP:rs381418)"
FT /id="VAR_003275"
FT VARIANT 227
FT /note="N -> S (in GD and GD3; decreased glucosylceramide
FT catabolic process; dbSNP:rs364897)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:24022302, ECO:0000269|PubMed:8829654,
FT ECO:0000269|PubMed:9217217"
FT /id="VAR_003274"
FT VARIANT 228
FT /note="G -> V (in GD; dbSNP:rs78911246)"
FT /evidence="ECO:0000269|PubMed:9061570"
FT /id="VAR_010060"
FT VARIANT 229
FT /note="A -> E (in GD2; dbSNP:rs75636769)"
FT /id="VAR_009038"
FT VARIANT 229
FT /note="A -> T (in GD)"
FT /evidence="ECO:0000269|PubMed:10796875"
FT /id="VAR_032406"
FT VARIANT 230
FT /note="V -> E (in GD1; very low glucosylceramidase
FT activity; dbSNP:rs381427)"
FT /evidence="ECO:0000269|PubMed:15605411"
FT /id="VAR_032407"
FT VARIANT 230
FT /note="V -> G (in GD1; gene conversion; dbSNP:rs381427)"
FT /evidence="ECO:0000269|PubMed:10206680,
FT ECO:0000269|PubMed:8294033"
FT /id="VAR_003276"
FT VARIANT 232
FT /note="G -> E (in GD; also found in a patient with
FT Parkinson disease; decreased glucosylceramidase activity;
FT 7% of normal activity; dbSNP:rs1376479747)"
FT /evidence="ECO:0000269|PubMed:16293621,
FT ECO:0000269|PubMed:19286695"
FT /id="VAR_032204"
FT VARIANT 234
FT /note="G -> E (in GD; severe; dbSNP:rs74462743)"
FT /evidence="ECO:0000269|PubMed:9153297"
FT /id="VAR_003277"
FT VARIANT 234
FT /note="G -> W (in GD)"
FT /evidence="ECO:0000269|PubMed:10447266"
FT /id="VAR_009039"
FT VARIANT 235
FT /note="S -> P (in GD2; gene conversion; dbSNP:rs1064644)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:8294033"
FT /id="VAR_003278"
FT VARIANT 237
FT /note="K -> E (in GD; severe; loss of glucosylceramidase
FT activity; increases susceptibility to proteolytic
FT degradation; dbSNP:rs773409311)"
FT /evidence="ECO:0000269|PubMed:11933202,
FT ECO:0000269|PubMed:16293621"
FT /id="VAR_032205"
FT VARIANT 241
FT /note="G -> E (in GD; dbSNP:rs77451368)"
FT /id="VAR_010061"
FT VARIANT 241
FT /note="G -> R (in GD1 and GD2; gene conversion;
FT dbSNP:rs409652)"
FT /evidence="ECO:0000269|PubMed:10360404,
FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:12204005,
FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:8294033,
FT ECO:0000269|PubMed:8790604, ECO:0000269|PubMed:9153297"
FT /id="VAR_003279"
FT VARIANT 244
FT /note="Y -> C (in GD; dbSNP:rs76026102)"
FT /evidence="ECO:0000269|PubMed:10360404"
FT /id="VAR_010062"
FT VARIANT 251
FT /note="Y -> H (in GD; dbSNP:rs121908300)"
FT /id="VAR_003280"
FT VARIANT 252
FT /note="F -> I (in GD2; gene conversion; dbSNP:rs381737)"
FT /evidence="ECO:0000269|PubMed:10360404,
FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:8294033,
FT ECO:0000269|PubMed:9061570, ECO:0000269|PubMed:9153297,
FT ECO:0000269|PubMed:9217217"
FT /id="VAR_003281"
FT VARIANT 255
FT /note="F -> Y (in GD; mild; dbSNP:rs74500255)"
FT /evidence="ECO:0000269|PubMed:1974409"
FT /id="VAR_003282"
FT VARIANT 266
FT /note="F -> L (in GD1)"
FT /evidence="ECO:0000269|PubMed:24577513"
FT /id="VAR_081191"
FT VARIANT 270
FT /note="T -> R (in GD; dbSNP:rs76725886)"
FT /evidence="ECO:0000269|PubMed:12204005"
FT /id="VAR_032408"
FT VARIANT 274
FT /note="E -> K (in GD2; loss of glucosylceramide catabolic
FT process)"
FT /evidence="ECO:0000269|PubMed:24022302"
FT /id="VAR_081192"
FT VARIANT 276
FT /note="S -> P (in GD)"
FT /id="VAR_003283"
FT VARIANT 284
FT /note="P -> T (in GD1; loss of glucosylceramide catabolic
FT process)"
FT /evidence="ECO:0000269|PubMed:24022302"
FT /id="VAR_081193"
FT VARIANT 289
FT /note="G -> V (in GD1; dbSNP:rs878853321)"
FT /evidence="ECO:0000269|PubMed:22658918"
FT /id="VAR_081194"
FT VARIANT 290
FT /note="F -> L (in GDPL; dbSNP:rs121908313)"
FT /evidence="ECO:0000269|PubMed:11933202"
FT /id="VAR_032409"
FT VARIANT 294
FT /note="H -> Q (in GD1 and GD2; dbSNP:rs367968666)"
FT /evidence="ECO:0000269|PubMed:15605411"
FT /id="VAR_009040"
FT VARIANT 296
FT /note="R -> Q (in GD2; also found in a patient with
FT Parkinson disease; dbSNP:rs78973108)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:19286695, ECO:0000269|PubMed:8790604"
FT /id="VAR_003284"
FT VARIANT 298
FT /note="F -> L (in GD2; decreased glucosylceramidase
FT activity; 4% of normal activity)"
FT /evidence="ECO:0000269|PubMed:16293621,
FT ECO:0000269|PubMed:3001061"
FT /id="VAR_009041"
FT VARIANT 301
FT /note="R -> G (in GD1)"
FT /evidence="ECO:0000269|PubMed:22658918"
FT /id="VAR_081195"
FT VARIANT 303
FT /note="L -> I (in GD; decreased glucosylceramidase
FT activity; 5% of normal activity; dbSNP:rs1296507371)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032206"
FT VARIANT 304
FT /note="G -> D (in GD; dbSNP:rs80116658)"
FT /id="VAR_010063"
FT VARIANT 304
FT /note="G -> R (in GD3; loss of glucosylceramide catabolic
FT process)"
FT /evidence="ECO:0000269|PubMed:24022302"
FT /id="VAR_081196"
FT VARIANT 305
FT /note="P -> R (in GD; mild; dbSNP:rs79215220)"
FT /id="VAR_003285"
FT VARIANT 310
FT /note="S -> G (in dbSNP:rs1057942)"
FT /evidence="ECO:0000269|PubMed:8294033"
FT /id="VAR_032410"
FT VARIANT 310
FT /note="S -> N (in GD; decreased glucosylceramidase
FT activity; less than 5% of normal activity;
FT dbSNP:rs74731340)"
FT /evidence="ECO:0000269|PubMed:9153297"
FT /id="VAR_010064"
FT VARIANT 324
FT /note="R -> C (in GD1; dbSNP:rs765633380)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:8790604"
FT /id="VAR_003286"
FT VARIANT 324
FT /note="R -> H (in GD2; dbSNP:rs79696831)"
FT /id="VAR_009042"
FT VARIANT 328
FT /note="P -> L (in GD; mild; dbSNP:rs121908298)"
FT /id="VAR_003287"
FT VARIANT 342
FT /note="K -> I (in GD; dbSNP:rs77714449)"
FT /id="VAR_003288"
FT VARIANT 343
FT /note="Y -> C (in GD2; decreased glucosylceramidase
FT activity; 16% of normal activity; increases susceptibility
FT to proteolytic degradation; dbSNP:rs77321207)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_009043"
FT VARIANT 347
FT /note="I -> S (in GD1)"
FT /evidence="ECO:0000269|PubMed:24577513"
FT /id="VAR_081197"
FT VARIANT 348
FT /note="A -> V (in GD; dbSNP:rs78396650)"
FT /id="VAR_003289"
FT VARIANT 350
FT /note="H -> R (in GDPL; dbSNP:rs78198234)"
FT /evidence="ECO:0000269|PubMed:10352942"
FT /id="VAR_009044"
FT VARIANT 351
FT /note="W -> C (in GD; mild; dbSNP:rs121908304)"
FT /id="VAR_003290"
FT VARIANT 351
FT /note="W -> S (in GD1; loss of glucosylceramide catabolic
FT process; dbSNP:rs1553217294)"
FT /evidence="ECO:0000269|PubMed:24022302"
FT /id="VAR_081198"
FT VARIANT 352
FT /note="Y -> H (in GD)"
FT /evidence="ECO:0000269|PubMed:8829663"
FT /id="VAR_003291"
FT VARIANT 354
FT /note="D -> H (in GD; dbSNP:rs398123526)"
FT /id="VAR_003292"
FT VARIANT 357
FT /note="A -> D (in GD; dbSNP:rs78188205)"
FT /id="VAR_003293"
FT VARIANT 362
FT /note="T -> I (in GD; decreased glucosylceramidase
FT activity; 6% of normal activity; dbSNP:rs76539814)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_003294"
FT VARIANT 363
FT /note="L -> P (in GD; unknown pathological significance;
FT dbSNP:rs1178732315)"
FT /evidence="ECO:0000269|PubMed:26528954"
FT /id="VAR_003295"
FT VARIANT 364
FT /note="G -> R (in GD2; dbSNP:rs121908305)"
FT /evidence="ECO:0000269|PubMed:8294033"
FT /id="VAR_003296"
FT VARIANT 365
FT /note="E -> K (in GD and GD1; mild; decreased
FT glucosylceramidase activity; 42% of normal activity;
FT dbSNP:rs2230288)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:1864608,
FT ECO:0000269|PubMed:24022302"
FT /id="VAR_003297"
FT VARIANT 368
FT /note="R -> H (in dbSNP:rs1064648)"
FT /evidence="ECO:0000269|PubMed:8294033"
FT /id="VAR_032411"
FT VARIANT 380
FT /note="A -> T (in GD; dbSNP:rs781306264)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:9554454"
FT /id="VAR_009045"
FT VARIANT 381
FT /note="C -> G (in GD2; loss of glucosylceramidase activity;
FT dbSNP:rs121908306)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_003298"
FT VARIANT 388
FT /note="E -> K (in GD; decreased glucosylceramidase
FT activity; 12% of normal activity; dbSNP:rs1161552095)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032207"
FT VARIANT 391
FT /note="V -> L (in GD; dbSNP:rs398123527)"
FT /evidence="ECO:0000269|PubMed:9153297"
FT /id="VAR_010065"
FT VARIANT 392
FT /note="R -> G (in GD; dbSNP:rs121908308)"
FT /evidence="ECO:0000269|PubMed:9650766"
FT /id="VAR_010066"
FT VARIANT 392
FT /note="R -> W (in GD; decreased glucosylceramidase
FT activity; 5% of normal activity; dbSNP:rs121908308)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032208"
FT VARIANT 398
FT /note="R -> Q (in GD; mild; dbSNP:rs74979486)"
FT /evidence="ECO:0000269|PubMed:8829663"
FT /id="VAR_003299"
FT VARIANT 400
FT /note="M -> I (in GD; dbSNP:rs149487315)"
FT /evidence="ECO:0000269|PubMed:12204005"
FT /id="VAR_032412"
FT VARIANT 402
FT /note="Y -> C (in GD; decreased glucosylceramidase
FT activity; 8% of normal activity; increases susceptibility
FT to proteolytic degradation; dbSNP:rs76228122)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032209"
FT VARIANT 403
FT /note="S -> T (in GD; mild; dbSNP:rs121908307)"
FT /id="VAR_003300"
FT VARIANT 405
FT /note="S -> G (in GD)"
FT /evidence="ECO:0000269|PubMed:9061570"
FT /id="VAR_010067"
FT VARIANT 405
FT /note="S -> N (in GD; dbSNP:rs1392291885)"
FT /evidence="ECO:0000269|PubMed:9554454"
FT /id="VAR_009046"
FT VARIANT 405
FT /note="S -> R (in GD1; loss of glucosylceramide catabolic
FT process; dbSNP:rs75528494)"
FT /evidence="ECO:0000269|PubMed:24022302"
FT /id="VAR_081199"
FT VARIANT 408
FT /note="T -> M (in GD; dbSNP:rs75548401)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:14702039"
FT /id="VAR_003301"
FT VARIANT 409
FT /note="N -> S (in GD1; mild; common mutation; associated
FT with susceptibility to Parkinson disease; increased
FT proteasomal degradation; decreased protein abundance;
FT decreased glucosylceramide catabolic process; no effect on
FT glucosylceramidase activity; alters interaction with
FT saposin-C; dbSNP:rs76763715)"
FT /evidence="ECO:0000269|PubMed:10206680,
FT ECO:0000269|PubMed:10340647, ECO:0000269|PubMed:10447266,
FT ECO:0000269|PubMed:10796875, ECO:0000269|PubMed:15605411,
FT ECO:0000269|PubMed:15826241, ECO:0000269|PubMed:16293621,
FT ECO:0000269|PubMed:18332251, ECO:0000269|PubMed:19286695,
FT ECO:0000269|PubMed:19846850, ECO:0000269|PubMed:21098288,
FT ECO:0000269|PubMed:24022302, ECO:0000269|PubMed:7627184,
FT ECO:0000269|PubMed:8076951, ECO:0000269|PubMed:8937765,
FT ECO:0000269|PubMed:9153297, ECO:0000269|Ref.14"
FT /id="VAR_003302"
FT VARIANT 410
FT /note="L -> V (in GD; decreased glucosylceramidase
FT activity; 15% of normal activity; increases susceptibility
FT to proteolytic degradation; dbSNP:rs121908314)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032210"
FT VARIANT 414
FT /note="V -> L (in GD; mild; dbSNP:rs398123528)"
FT /evidence="ECO:0000269|PubMed:9182788"
FT /id="VAR_010068"
FT VARIANT 416
FT /note="G -> S (in GD; mild; dbSNP:rs121908311)"
FT /evidence="ECO:0000269|PubMed:10447266,
FT ECO:0000269|PubMed:10796875"
FT /id="VAR_003303"
FT VARIANT 417
FT /note="W -> G (in GD; dbSNP:rs1450426641)"
FT /evidence="ECO:0000269|PubMed:8790604"
FT /id="VAR_003304"
FT VARIANT 419
FT /note="D -> A (in GD2; also found in a patient with
FT Parkinson disease; dbSNP:rs77284004)"
FT /evidence="ECO:0000269|PubMed:19286695"
FT /id="VAR_003305"
FT VARIANT 419
FT /note="D -> H (in GD; decreased glucosylceramidase
FT activity; 4% of normal activity)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032211"
FT VARIANT 419
FT /note="D -> N (in GD and GD1; loss of glucosylceramide
FT catabolic process)"
FT /evidence="ECO:0000269|PubMed:24022302,
FT ECO:0000269|PubMed:8790604"
FT /id="VAR_003306"
FT VARIANT 420
FT /note="W -> C (in GD1; loss of glucosylceramide catabolic
FT process)"
FT /evidence="ECO:0000269|PubMed:24022302"
FT /id="VAR_081200"
FT VARIANT 421
FT /note="N -> K (in GD; decreased glucosylceramidase
FT activity; 22% of normal activity)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032212"
FT VARIANT 426
FT /note="P -> L (in GD; dbSNP:rs1057519357 and
FT dbSNP:rs994723035)"
FT /evidence="ECO:0000269|PubMed:8937765"
FT /id="VAR_010069"
FT VARIANT 428
FT /note="G -> E (in GD2)"
FT /evidence="ECO:0000269|PubMed:9554746"
FT /id="VAR_003307"
FT VARIANT 429
FT /note="G -> R (in GD; decreased glucosylceramidase
FT activity; 17% of normal activity)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032213"
FT VARIANT 430
FT /note="P -> L (in GD; dbSNP:rs76910485)"
FT /evidence="ECO:0000269|PubMed:9554746"
FT /id="VAR_003308"
FT VARIANT 431
FT /note="N -> I (in GD2; dbSNP:rs77738682)"
FT /evidence="ECO:0000269|PubMed:9554746"
FT /id="VAR_003309"
FT VARIANT 432
FT /note="W -> R (in GD)"
FT /evidence="ECO:0000269|PubMed:9554454"
FT /id="VAR_009047"
FT VARIANT 433
FT /note="V -> L (in GD; severe; decreased glucosylceramidase
FT activity; 12% of normal activity; dbSNP:rs80356769)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:8937765"
FT /id="VAR_003310"
FT VARIANT 435
FT /note="N -> T (in GD1; mild; dbSNP:rs75385858)"
FT /evidence="ECO:0000269|PubMed:8889591"
FT /id="VAR_003311"
FT VARIANT 436
FT /note="F -> S (in GD; decreased glucosylceramidase
FT activity; 6% of normal activity; alters protein stability
FT and increases susceptibility to proteolytic degradation;
FT dbSNP:rs75243000)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032214"
FT VARIANT 437
FT /note="V -> F (in GDPL; dbSNP:rs121908310)"
FT /evidence="ECO:0000269|PubMed:10352942"
FT /id="VAR_009048"
FT VARIANT 437
FT /note="V -> L (in GD3; dbSNP:rs121908310)"
FT /evidence="ECO:0000269|PubMed:8780099"
FT /id="VAR_010070"
FT VARIANT 438
FT /note="D -> N (in GD1 and GD2; decreased glucosylceramidase
FT activity; 14% of normal activity; increases susceptibility
FT to proteolytic degradation; dbSNP:rs1553217009)"
FT /evidence="ECO:0000269|PubMed:15605411,
FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:8112750"
FT /id="VAR_003312"
FT VARIANT 438
FT /note="D -> Y (in GD)"
FT /evidence="ECO:0000269|PubMed:10796875"
FT /id="VAR_032413"
FT VARIANT 440
FT /note="P -> L (in GD1; dbSNP:rs74598136)"
FT /evidence="ECO:0000269|PubMed:10340647,
FT ECO:0000269|PubMed:15605411"
FT /id="VAR_010071"
FT VARIANT 441
FT /note="I -> F (in GD3)"
FT /evidence="ECO:0000269|PubMed:11933202"
FT /id="VAR_032414"
FT VARIANT 441
FT /note="I -> T (in GD; mild; dbSNP:rs75564605)"
FT /evidence="ECO:0000269|PubMed:9182788"
FT /id="VAR_010072"
FT VARIANT 448
FT /note="D -> H (in GD1 and GD3C; at homozygosity it causes
FT GD3C; also found in a patient with Parkinson disease; gene
FT conversion; very low glucosylceramidase activity; alters
FT protein stability; dbSNP:rs1064651)"
FT /evidence="ECO:0000269|PubMed:10360404,
FT ECO:0000269|PubMed:10447266, ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:11992489, ECO:0000269|PubMed:15605411,
FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:19286695,
FT ECO:0000269|PubMed:7475546, ECO:0000269|PubMed:7627184,
FT ECO:0000269|PubMed:9040001, ECO:0000269|PubMed:9061570"
FT /id="VAR_003313"
FT VARIANT 448
FT /note="D -> V (in GD; severe; very low activity; alters
FT protein stability; dbSNP:rs77369218)"
FT /id="VAR_003314"
FT VARIANT 450
FT /note="F -> I (in GD; dbSNP:rs1553216985)"
FT /id="VAR_010073"
FT VARIANT 451
FT /note="Y -> H (in GD)"
FT /evidence="ECO:0000269|PubMed:9554746"
FT /id="VAR_003315"
FT VARIANT 452
FT /note="K -> Q (in GD)"
FT /evidence="ECO:0000269|PubMed:9061570"
FT /id="VAR_010074"
FT VARIANT 454
FT /note="P -> R (in GD2; dbSNP:rs121908295)"
FT /id="VAR_003316"
FT VARIANT 455
FT /note="M -> V (in GD; loss of glucosylceramidase activity;
FT increases susceptibility to proteolytic degradation)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032215"
FT VARIANT 456
FT /note="F -> V (in GD)"
FT /id="VAR_003317"
FT VARIANT 457
FT /note="Y -> C (in GD; dbSNP:rs74752878)"
FT /evidence="ECO:0000269|PubMed:15605411,
FT ECO:0000269|PubMed:8076951"
FT /id="VAR_003318"
FT VARIANT 460
FT /note="G -> D (in GD1; associated with R-490; loss of
FT glucosylceramidase activity)"
FT /evidence="ECO:0000269|PubMed:15605411"
FT /id="VAR_032415"
FT VARIANT 464
FT /note="K -> E (in GD; severe)"
FT /id="VAR_003319"
FT VARIANT 482
FT /note="D -> N (in a patient with Parkinson disease;
FT dbSNP:rs75671029)"
FT /evidence="ECO:0000269|PubMed:19286695"
FT /id="VAR_063067"
FT VARIANT 483
FT /note="L -> P (in GD1 and GD2; common mutation; associated
FT with susceptibility to Parkinson disease; gene conversion;
FT alters protein stability; increased proteasomal
FT degradation; decreased protein abundance; very low
FT glucosylceramide catabolic process; no effect on
FT glucosylceramidase activity; dbSNP:rs421016)"
FT /evidence="ECO:0000269|PubMed:10360404,
FT ECO:0000269|PubMed:10447266, ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:15605411, ECO:0000269|PubMed:16293621,
FT ECO:0000269|PubMed:19286695, ECO:0000269|PubMed:21098288,
FT ECO:0000269|PubMed:7627184, ECO:0000269|PubMed:8937765,
FT ECO:0000269|PubMed:9061570, ECO:0000269|PubMed:9217217,
FT ECO:0000269|PubMed:9851895"
FT /id="VAR_003321"
FT VARIANT 483
FT /note="L -> R (in GD; severe; dbSNP:rs421016)"
FT /id="VAR_003320"
FT VARIANT 485
FT /note="A -> P (in GD)"
FT /id="VAR_003322"
FT VARIANT 486
FT /note="V -> E (in GD1)"
FT /evidence="ECO:0000269|PubMed:22658918"
FT /id="VAR_081201"
FT VARIANT 490
FT /note="H -> R (in GD1; associated with D-460;
FT dbSNP:rs76071730)"
FT /evidence="ECO:0000269|PubMed:12204005,
FT ECO:0000269|PubMed:15605411"
FT /id="VAR_032416"
FT VARIANT 495
FT /note="A -> P (in GD; gene conversion; dbSNP:rs368060)"
FT /evidence="ECO:0000269|PubMed:19286695"
FT /id="VAR_003323"
FT VARIANT 497
FT /note="V -> L"
FT /evidence="ECO:0000269|PubMed:19286695"
FT /id="VAR_063068"
FT VARIANT 500
FT /note="L -> P (in GD; decreased glucosylceramidase
FT activity; 10% of normal activity; increases susceptibility
FT to proteolytic degradation; dbSNP:rs1362103320)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032216"
FT VARIANT 501
FT /note="N -> K (in GD2)"
FT /evidence="ECO:0000269|PubMed:9279145"
FT /id="VAR_009049"
FT VARIANT 502
FT /note="R -> C (in GD; also found in patients with Parkinson
FT disease; no effect on protein abundance; decreased
FT glucosylceramidase activity; 37% of normal activity;
FT dbSNP:rs80356771)"
FT /evidence="ECO:0000269|PubMed:10796875,
FT ECO:0000269|PubMed:16293621, ECO:0000269|PubMed:19286695,
FT ECO:0000269|PubMed:1972019, ECO:0000269|PubMed:7627184"
FT /id="VAR_003324"
FT VARIANT 502
FT /note="R -> P (in GD; loss of glucosylceramidase activity;
FT increases susceptibility to proteolytic degradation)"
FT /evidence="ECO:0000269|PubMed:16293621"
FT /id="VAR_032217"
FT VARIANT 509
FT /note="L -> P"
FT /id="VAR_003325"
FT VARIANT 513
FT /note="D -> Y (in GD2)"
FT /evidence="ECO:0000269|PubMed:9637431"
FT /id="VAR_009050"
FT VARIANT 517
FT /note="G -> S (in GD; dbSNP:rs121908301)"
FT /id="VAR_003326"
FT VARIANT 530
FT /note="T -> I (in GD3; dbSNP:rs78016673)"
FT /evidence="ECO:0000269|PubMed:8780099"
FT /id="VAR_010075"
FT VARIANT 535
FT /note="R -> C (in GD; mild; dbSNP:rs747506979)"
FT /evidence="ECO:0000269|PubMed:9061570"
FT /id="VAR_003327"
FT VARIANT 535
FT /note="R -> H (in GD; mild; dbSNP:rs75822236)"
FT /evidence="ECO:0000269|PubMed:7916532"
FT /id="VAR_003328"
FT MUTAGEN 43
FT /note="C->S: Loss of glucosylceramidase activity."
FT /evidence="ECO:0000269|PubMed:16293621"
FT MUTAGEN 57
FT /note="C->S: Loss of glucosylceramidase activity."
FT /evidence="ECO:0000269|PubMed:16293621"
FT MUTAGEN 62
FT /note="C->S: Loss of glucosylceramidase activity."
FT /evidence="ECO:0000269|PubMed:16293621"
FT MUTAGEN 379
FT /note="E->G: 1000-fold decreases of glucosylceramidase
FT activity."
FT /evidence="ECO:0000269|PubMed:7908905"
FT CONFLICT 176
FT /note="D -> G (in Ref. 7; BAH13357)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="N -> R (in Ref. 5; BAA02546)"
FT /evidence="ECO:0000305"
FT CONFLICT 470
FT /note="S -> I (in Ref. 15; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 534
FT /note="R -> H (in Ref. 1; AAA35873)"
FT /evidence="ECO:0000305"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:6Q1P"
FT STRAND 49..52
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 75..82
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 88..94
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 103..116
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 126..133
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 137..148
FT /evidence="ECO:0007829|PDB:6Q6N"
FT TURN 150..153
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 157..163
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:6Q6K"
FT HELIX 190..194
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 196..206
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 212..218
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 222..224
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 225..227
FT /evidence="ECO:0007829|PDB:6Q1N"
FT STRAND 228..233
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 243..261
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 267..271
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 275..279
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:3GXF"
FT HELIX 292..301
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 303..308
FT /evidence="ECO:0007829|PDB:6Q6N"
FT TURN 311..314
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 315..323
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 324..326
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 329..335
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 338..341
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 346..350
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 354..356
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 359..369
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 373..380
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 385..388
FT /evidence="ECO:0007829|PDB:6MOZ"
FT HELIX 396..411
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 414..422
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:3KEH"
FT STRAND 432..434
FT /evidence="ECO:0007829|PDB:6Q1N"
FT STRAND 440..444
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 449..452
FT /evidence="ECO:0007829|PDB:6Q6N"
FT HELIX 454..463
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 471..479
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 482..489
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 495..501
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 503..505
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 507..513
FT /evidence="ECO:0007829|PDB:6Q6N"
FT TURN 514..516
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 517..523
FT /evidence="ECO:0007829|PDB:6Q6N"
FT STRAND 527..533
FT /evidence="ECO:0007829|PDB:6Q6N"
SQ SEQUENCE 536 AA; 59716 MW; FA1E15684344A0E6 CRC64;
MEFSSPSREE CPKPLSRVSI MAGSLTGLLL LQAVSWASGA RPCIPKSFGY SSVVCVCNAT
YCDSFDPPTF PALGTFSRYE STRSGRRMEL SMGPIQANHT GTGLLLTLQP EQKFQKVKGF
GGAMTDAAAL NILALSPPAQ NLLLKSYFSE EGIGYNIIRV PMASCDFSIR TYTYADTPDD
FQLHNFSLPE EDTKLKIPLI HRALQLAQRP VSLLASPWTS PTWLKTNGAV NGKGSLKGQP
GDIYHQTWAR YFVKFLDAYA EHKLQFWAVT AENEPSAGLL SGYPFQCLGF TPEHQRDFIA
RDLGPTLANS THHNVRLLML DDQRLLLPHW AKVVLTDPEA AKYVHGIAVH WYLDFLAPAK
ATLGETHRLF PNTMLFASEA CVGSKFWEQS VRLGSWDRGM QYSHSIITNL LYHVVGWTDW
NLALNPEGGP NWVRNFVDSP IIVDITKDTF YKQPMFYHLG HFSKFIPEGS QRVGLVASQK
NDLDAVALMH PDGSAVVVVL NRSSKDVPLT IKDPAVGFLE TISPGYSIHT YLWRRQ
