BGAL_HUMAN
ID BGAL_HUMAN Reviewed; 677 AA.
AC P16278; B2R7H8; B7Z6B0; P16279;
DT 01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=Beta-galactosidase;
DE EC=3.2.1.23 {ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:24737316, ECO:0000269|PubMed:2511208, ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:3143362, ECO:0000269|PubMed:8200356};
DE AltName: Full=Acid beta-galactosidase;
DE Short=Lactase;
DE AltName: Full=Elastin receptor 1;
DE Flags: Precursor;
GN Name=GLB1; Synonyms=ELNR1;
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 1), AND CATALYTIC ACTIVITY.
RC TISSUE=Placenta;
RX PubMed=3143362; DOI=10.1016/s0006-291x(88)80038-x;
RA Oshima A., Tsuji A., Nagao Y., Sakuraba H., Suzuki Y.;
RT "Cloning, sequencing, and expression of cDNA for human beta-
RT galactosidase.";
RL Biochem. Biophys. Res. Commun. 157:238-244(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), PROTEIN SEQUENCE OF 29-46;
RP 287-299; 372-376 AND 443-457, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND VARIANT LEU-10.
RC TISSUE=Testis;
RX PubMed=2511208; DOI=10.1016/s0021-9258(19)47114-7;
RA Morreau H., Galjart N.J., Gillemans N., Willemsen R., van der Horst G.T.J.,
RA D'Azzo A.;
RT "Alternative splicing of beta-galactosidase mRNA generates the classic
RT lysosomal enzyme and a beta-galactosidase-related protein.";
RL J. Biol. Chem. 264:20655-20663(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP VARIANT LEU-10.
RX PubMed=2111707; DOI=10.1089/dna.1990.9.119;
RA Yamamoto Y., Hake C.A., Martin B.M., Kretz K.A., Ahern-Rindell A.J.,
RA Naylor S.L., Mudd M., O'Brien J.S.;
RT "Isolation, characterization, and mapping of a human acid beta-
RT galactosidase cDNA.";
RL DNA Cell Biol. 9:119-127(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP LEU-10.
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-10.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT CYS-521.
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-10.
RC TISSUE=Colon;
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 [8]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=3084261;
RA Willemsen R., Hoogeveen A.T., Sips H.J., van Dongen J.M., Galjaard H.;
RT "Immunoelectron microscopical localization of lysosomal beta-galactosidase
RT and its precursor forms in normal and mutant human fibroblasts.";
RL Eur. J. Cell Biol. 40:9-15(1986).
RN [9]
RP DOMAIN ELASTIN/LAMININ BINDING, AND TISSUE SPECIFICITY.
RX PubMed=8383699; DOI=10.1172/jci116280;
RA Hinek A., Rabinovitch M., Keeley F., Okamura-Oho Y., Callahan J.;
RT "The 67-kD elastin/laminin-binding protein is related to an enzymatically
RT inactive, alternatively spliced form of beta-galactosidase.";
RL J. Clin. Invest. 91:1198-1205(1993).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8200356; DOI=10.1111/j.1432-1033.1994.tb18844.x;
RA Zschoche A., Fuerst W., Schwarzmann G., Sanhoff K.;
RT "Hydrolysis of lactosylceramide by human galactosylceramidase and GM1-beta-
RT galactosidase in a detergent-free system and its stimulation by
RT sphingolipid activator proteins, sap-B and sap-C. Activator proteins
RT stimulate lactosylceramide hydrolysis.";
RL Eur. J. Biochem. 222:83-90(1994).
RN [11]
RP FUNCTION (ISOFORM 2).
RX PubMed=8922281;
RA Hinek A.;
RT "Biological roles of the non-integrin elastin/laminin receptor.";
RL Biol. Chem. 377:471-480(1996).
RN [12]
RP IDENTITY OF BETA-GALACTOSIDASE-RELATED PROTEIN WITH EBP.
RX PubMed=9497360; DOI=10.1074/jbc.273.11.6319;
RA Privitera S., Prody C.A., Callahan J.W., Hinek A.;
RT "The 67-kDa enzymatically inactive alternatively spliced variant of beta-
RT galactosidase is identical to the elastin/laminin-binding protein.";
RL J. Biol. Chem. 273:6319-6326(1998).
RN [13]
RP REVIEW.
RX PubMed=10571006; DOI=10.1016/s0925-4439(99)00075-7;
RA Callahan J.W.;
RT "Molecular basis of GM1 gangliosidosis and Morquio disease, type B.
RT Structure-function studies of lysosomal beta-galactosidase and the non-
RT lysosomal beta-galactosidase-like protein.";
RL Biochim. Biophys. Acta 1455:85-103(1999).
RN [14]
RP ELASTIC-FIBER ASSEMBLY STUDIES, AND FUNCTION (ISOFORM 2).
RX PubMed=10841810; DOI=10.1086/302968;
RA Hinek A., Zhang S., Smith A.C., Callahan J.W.;
RT "Impaired elastic-fiber assembly by fibroblasts from patients with either
RT Morquio B disease or infantile GM1-gangliosidosis is linked to deficiency
RT in the 67-kD spliced variant of beta-galactosidase.";
RL Am. J. Hum. Genet. 67:23-36(2000).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-464.
RC TISSUE=Platelet;
RX PubMed=16263699; DOI=10.1074/mcp.m500324-mcp200;
RA Lewandrowski U., Moebius J., Walter U., Sickmann A.;
RT "Elucidation of N-glycosylation sites on human platelet proteins: a
RT glycoproteomic approach.";
RL Mol. Cell. Proteomics 5:226-233(2006).
RN [16]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-464 AND ASN-555.
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 [17]
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 [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [20] {ECO:0007744|PDB:3THC, ECO:0007744|PDB:3THD}
RP X-RAY CRYSTALLOGRAPHY (1.79 ANGSTROMS) OF 24-677 IN COMPLEX WITH GALACTOSE,
RP SUBUNIT, ACTIVE SITE, GLYCOSYLATION AT ASN-247; ASN-464; ASN-498 AND
RP ASN-555, AND DISULFIDE BONDS.
RX PubMed=22128166; DOI=10.1074/jbc.m111.293795;
RA Ohto U., Usui K., Ochi T., Yuki K., Satow Y., Shimizu T.;
RT "Crystal structure of human beta-galactosidase: structural basis of Gm1
RT gangliosidosis and morquio B diseases.";
RL J. Biol. Chem. 287:1801-1812(2012).
RN [21] {ECO:0007744|PDB:3WEZ, ECO:0007744|PDB:3WF0, ECO:0007744|PDB:3WF1, ECO:0007744|PDB:3WF2, ECO:0007744|PDB:3WF3, ECO:0007744|PDB:3WF4}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 24-677 IN COMPLEX WITH GALACTOSE,
RP CATALYTIC ACTIVITY, GLYCOSYLATION AT ASN-247; ASN-464; ASN-498 AND ASN-555,
RP DISULFIDE BONDS, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANT
RP GM1G3 THR-51, AND CHARACTERIZATION OF VARIANT GM1G1 AND GM1G2 CYS-201.
RX PubMed=24737316; DOI=10.1074/jbc.m113.529529;
RA Suzuki H., Ohto U., Higaki K., Mena-Barragan T., Aguilar-Moncayo M.,
RA Ortiz Mellet C., Nanba E., Garcia Fernandez J.M., Suzuki Y., Shimizu T.;
RT "Structural basis of pharmacological chaperoning for human beta-
RT galactosidase.";
RL J. Biol. Chem. 289:14560-14568(2014).
RN [22]
RP VARIANTS MPS4B LEU-273; HIS-482 AND CYS-509, AND VARIANT GM1G1 CYS-494.
RX PubMed=1928092;
RA Oshima A., Yoshida K., Shimmoto M., Fukuhara Y., Sakuraba H., Suzuki Y.;
RT "Human beta-galactosidase gene mutations in morquio B disease.";
RL Am. J. Hum. Genet. 49:1091-1093(1991).
RN [23]
RP VARIANT GM1G1 CYS-49, VARIANT GM1G3 THR-51, AND VARIANT GM1G2 CYS-201.
RX PubMed=1909089;
RA Nishimoto J., Nanba E., Inui K., Okada S., Suzuki K.;
RT "GM1-gangliosidosis (genetic beta-galactosidase deficiency): identification
RT of four mutations in different clinical phenotypes among Japanese
RT patients.";
RL Am. J. Hum. Genet. 49:566-574(1991).
RN [24]
RP VARIANTS GM1G3 THR-51 AND GLN-457, VARIANTS GM1G1 ARG-123 AND CYS-316, AND
RP VARIANT GM1G2 CYS-201.
RX PubMed=1907800;
RA Yoshida K., Oshima A., Shimmoto M., Fukuhara Y., Sakuraba H.,
RA Yanagisawa N., Suzuki Y.;
RT "Human beta-galactosidase gene mutations in GM1-gangliosidosis: a common
RT mutation among Japanese adult/chronic cases.";
RL Am. J. Hum. Genet. 49:435-442(1991).
RN [25]
RP VARIANT GM1G1 HIS-482.
RX PubMed=1487238; DOI=10.1007/bf00220071;
RA Mosna G., Fattore S., Tubiello G., Brocca S., Trubia M., Gianazza E.,
RA Gatti R., Danesino C., Minelli A., Piantanida M.;
RT "A homozygous missense arginine to histidine substitution at position 482
RT of the beta-galactosidase in an Italian infantile GM1-gangliosidosis
RT patient.";
RL Hum. Genet. 90:247-250(1992).
RN [26]
RP VARIANTS GM1G1 CYS-208 AND ARG-578, AND VARIANTS GM1G2 HIS-590 AND GLY-632.
RX PubMed=8213816;
RA Boustany R.-M.N., Qian W.-H., Suzuki K.;
RT "Mutations in acid beta-galactosidase cause GM1-gangliosidosis in American
RT patients.";
RL Am. J. Hum. Genet. 53:881-888(1993).
RN [27]
RP VARIANT GM1G3 MET-82.
RX PubMed=8198123;
RA Chakraborty S., Rafi M.A., Wenger D.A.;
RT "Mutations in the lysosomal beta-galactosidase gene that cause the adult
RT form of GM1 gangliosidosis.";
RL Am. J. Hum. Genet. 54:1004-1013(1994).
RN [28]
RP VARIANTS GM1G1 SER-148 AND ALA-216, VARIANT GM1G3 TYR-214, AND VARIANT
RP GLY-532.
RA Hilson W.L., Okamura-Oho Y., Zhang S., Clarke J.T.R., Mahuran D.,
RA Callahan J.W.;
RT "Novel missense mutations in beta-galactosidase that result in GM1-
RT gangliosidosis.";
RL Am. J. Hum. Genet. 55:A223-A223(1994).
RN [29]
RP VARIANTS MPS4B HIS-83 AND CYS-482.
RX PubMed=7586649; DOI=10.1111/j.1399-0004.1995.tb04065.x;
RA Ishii N., Oohira T., Oshima A., Sakuraba H., Endo F., Matsuda I.,
RA Sukegawa K., Orii T., Suzuki Y.;
RT "Clinical and molecular analysis of a Japanese boy with Morquio B
RT disease.";
RL Clin. Genet. 48:103-108(1995).
RN [30]
RP VARIANT GM1G3 SER-263.
RA Suzuki Y., Sakuraba H., Oshima A.;
RT "Beta-galactosidase deficiency (beta-galactosidosis): GM1 gangliosidosis
RT and Morquio B disease.";
RL (In) Scriver C.R., Beaudet A.L., Sly W.S., Valle D. (eds.);
RL The metabolic and molecular bases of inherited disease, pp.2787-2823,
RL McGraw-Hill Publishing Co., New York (1995).
RN [31]
RP VARIANTS GM1G1 HIS-59; ASN-591 AND CYS-591.
RA Morrone A., Bardelli T., Donati M.A., Giorgi M., Di Rocco R., Gatti R.,
RA Taddeucci G., Ricci R., D'Azzo A., Zammarchi E.;
RT "Identification of new mutations in six Italian patients affected by a
RT variant form of infantile GM1-gangliosidosis with severe cardiomyopathy.";
RL Am. J. Hum. Genet. 61:A258-A258(1997).
RN [32]
RP VARIANTS SLOWLY PROGRESSIVE GM1-GANGLIOSIDOSIS HIS-201; SER-266 AND
RP CYS-509.
RX PubMed=9203065; DOI=10.1177/088307389701200404;
RA Kaye E.M., Shalish C., Livermore J., Taylor H.A., Stevenson R.E.,
RA Breakefield X.O.;
RT "Beta-Galactosidase gene mutations in patients with slowly progressive GM1
RT gangliosidosis.";
RL J. Child Neurol. 12:242-247(1997).
RN [33]
RP VARIANTS MPS4B GLU-438; LYS-484 AND ALA-500.
RX PubMed=12393180; DOI=10.1016/s0925-4439(02)00172-2;
RA Bagshaw R.D., Zhang S., Hinek A., Skomorowski M.-A., Whelan D.,
RA Clarke J.T.R., Callahan J.W.;
RT "Novel mutations (Asn 484 Lys, Thr 500 Ala, Gly 438 Glu) in Morquio B
RT disease.";
RL Biochim. Biophys. Acta 1588:247-253(2002).
RN [34]
RP VARIANTS GM1G1 HIS-59; SER-121; CYS-208; MET-240 AND ASN-491, AND VARIANTS
RP LEU-10; CYS-521 AND GLY-532.
RX PubMed=10338095;
RX DOI=10.1002/(sici)1098-1004(1999)13:5<401::aid-humu9>3.0.co;2-n;
RA Silva C.M.D., Severini M.H., Sopelsa A., Coelho J.C., Zaha A., d'Azzo A.,
RA Giugliani R.;
RT "Six novel beta-galactosidase gene mutations in Brazilian patients with
RT GM1-gangliosidosis.";
RL Hum. Mutat. 13:401-409(1999).
RN [35]
RP VARIANTS GM1G1 SER-148 AND ASN-332, VARIANT GLY-532, AND CHARACTERIZATION
RP OF VARIANT GLY-532.
RX PubMed=10839995; DOI=10.1042/bj3480621;
RA Zhang S., Bagshaw R., Hilson W., Oho Y., Hinek A., Clarke J.T.R., Hinek A.,
RA Callahan J.W.;
RT "Characterization of beta-galactosidase mutations Asp332-->Asn and
RT Arg148-->Ser, and a polymorphism, Ser532-->Gly, in a case of GM1
RT gangliosidosis.";
RL Biochem. J. 348:621-632(2000).
RN [36]
RP VARIANTS GM1G1 HIS-59; HIS-482; ASN-591 AND CYS-591, AND VARIANTS GM1G2
RP HIS-201 AND ASP-579.
RX PubMed=10737981;
RX DOI=10.1002/(sici)1098-1004(200004)15:4<354::aid-humu8>3.0.co;2-l;
RA Morrone A., Bardelli T., Donati M.A., Giorgi M., Di Rocco M., Gatti R.,
RA Parini R., Ricci R., Taddeucci G., D'Azzo A., Zammarchi E.;
RT "Beta-galactosidase gene mutations affecting the lysosomal enzyme and the
RT elastin-binding protein in GM1-gangliosidosis patients with cardiac
RT involvement.";
RL Hum. Mutat. 15:354-366(2000).
RN [37]
RP VARIANTS MPS4B LEU-273; PRO-408 AND ALA-500, VARIANTS GM1G3 MET-82; ASP-270
RP AND TYR-281, AND VARIANT LEU-10.
RX PubMed=11511921; DOI=10.1007/s004390100570;
RA Paschke E., Milos I., Kreimer-Erlacher H., Hoefler G., Beck M.,
RA Hoeltzenbein M., Kleijer W., Levade T., Michelakakis H., Radeva B.;
RT "Mutation analyses in 17 patients with deficiency in acid beta-
RT galactosidase: three novel point mutations and high correlation of mutation
RT W273L with Morquio disease type B.";
RL Hum. Genet. 109:159-166(2001).
RN [38]
RP VARIANTS GM1G2 TRP-68 AND CYS-201, CHARACTERIZATION OF VARIANTS GM1G2
RP TRP-68 AND CYS-201, VARIANT PHE-436, AND MODULATING ACTION OF VARIANT
RP PHE-436.
RX PubMed=12644936; DOI=10.1007/s00439-003-0930-8;
RA Caciotti A., Bardelli T., Cunningham J., D'Azzo A., Zammarchi E.,
RA Morrone A.;
RT "Modulating action of the new polymorphism L436F detected in the GLB1 gene
RT of a type-II GM1 gangliosidosis patient.";
RL Hum. Genet. 113:44-50(2003).
RN [39]
RP VARIANT GM1G1 TYR-151, AND CHARACTERIZATION OF VARIANT GM1G1 TYR-151.
RX PubMed=15365997; DOI=10.1002/humu.9279;
RA Georgiou T., Drousiotou A., Campos Y., Caciotti A., Sztriha L., Gururaj A.,
RA Ozand P., Zammarchi E., Morrone A., D'Azzo A.;
RT "Four novel mutations in patients from the Middle East with the infantile
RT form of GM1-gangliosidosis.";
RL Hum. Mutat. 24:352-352(2004).
RN [40]
RP ERRATUM OF PUBMED:15365997.
RA Georgiou T., Drousiotou A., Campos Y., Caciotti A., Sztriha L., Gururaj A.,
RA Ozand P., Zammarchi E., Morrone A., D'Azzo A.;
RL Hum. Mutat. 24:536-537(2004).
RN [41]
RP VARIANTS GM1G1 HIS-59; CYS-59; CYS-208; MET-239; TYR-281; HIS-482; ASP-579;
RP ASN-591 AND CYS-591, VARIANT GM1G2 HIS-201, VARIANT CYS-521,
RP CHARACTERIZATION OF VARIANTS GM1G1 HIS-59; CYS-59; CYS-208; MET-239;
RP TYR-281; HIS-482; ASP-579; ASN-591 AND CYS-591, CHARACTERIZATION OF VARIANT
RP GM1G2 HIS-201, CHARACTERIZATION OF VARIANT CYS-521, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=15714521; DOI=10.1002/humu.20147;
RA Caciotti A., Donati M.A., Boneh A., d'Azzo A., Federico A., Parini R.,
RA Antuzzi D., Bardelli T., Nosi D., Kimonis V., Zammarchi E., Morrone A.;
RT "Role of beta-galactosidase and elastin binding protein in lysosomal and
RT nonlysosomal complexes of patients with GM1-gangliosidosis.";
RL Hum. Mutat. 25:285-292(2005).
RN [42]
RP VARIANT GM1G1 TYR-151, AND VARIANT LEU-10.
RX PubMed=15791924; DOI=10.1177/08830738050200010901;
RA Gururaj A., Sztriha L., Hertecant J., Johansen J.G., Georgiou T.,
RA Campos Y., Drousiotou A., d'Azzo A.;
RT "Magnetic resonance imaging findings and novel mutations in GM1
RT gangliosidosis.";
RL J. Child Neurol. 20:57-60(2005).
RN [43]
RP VARIANTS GM1G3 HIS-49; GLU-73; CYS-148 AND GLU-438.
RX PubMed=15986423; DOI=10.1002/mds.20593;
RA Roze E., Paschke E., Lopez N., Eck T., Yoshida K., Maurel-Ollivier A.,
RA Doummar D., Caillaud C., Galanaud D., Billette de Villemeur T.,
RA Vidailhet M., Roubergue A.;
RT "Dystonia and parkinsonism in GM1 type 3 gangliosidosis.";
RL Mov. Disord. 20:1366-1369(2005).
RN [44]
RP VARIANTS GM1G1 CYS-59; HIS-59; SER-136; VAL-151; PRO-173; CYS-199; ASP-272;
RP ASN-346; CYS-347; PRO-420; ARG-422; ASN-441 AND CYS-590, VARIANT GM1G2
RP SER-264, VARIANTS GM1G3 HIS-201 AND LYS-420, VARIANTS MPS4B CYS-83;
RP CYS-444; SER-494 AND ALA-500, AND VARIANTS PHE-436; CYS-521 AND GLY-532.
RX PubMed=16941474; DOI=10.1002/humu.9451;
RA Santamaria R., Chabas A., Coll M.J., Miranda C.S., Vilageliu L.,
RA Grinberg D.;
RT "Twenty-one novel mutations in the GLB1 gene identified in a large group of
RT GM1-gangliosidosis and Morquio B patients: possible common origin for the
RT prevalent p.R59H mutation among Gypsies.";
RL Hum. Mutat. 27:1060-1060(2006).
RN [45]
RP VARIANTS MPS4B LEU-273; HIS-482 AND CYS-509, AND VARIANTS GM1G1 CYS-201;
RP HIS-201 AND HIS-318.
RX PubMed=16538002; DOI=10.2152/jmi.53.103;
RA Tatano Y., Takeuchi N., Kuwahara J., Sakuraba H., Takahashi T., Takada G.,
RA Itoh K.;
RT "Elastogenesis in cultured dermal fibroblasts from patients with lysosomal
RT beta-galactosidase, protective protein/cathepsin A and neuraminidase-1
RT deficiencies.";
RL J. Med. Invest. 53:103-112(2006).
RN [46]
RP VARIANTS GM1G1 CYS-59; HIS-59; VAL-134; LEU-147 DEL; SER-162; CYS-208;
RP ASP-272; 377-VAL--LYS-381 DEL; TYR-491; LEU-549 AND CYS-590, VARIANT GM1G2
RP HIS-201, VARIANT GM1G3 ARG-155, AND VARIANTS GM1-GANGLIOSIDOSIS LEU-434 AND
RP GLU-554.
RX PubMed=17309651; DOI=10.1111/j.1399-0004.2007.00767.x;
RA Santamaria R., Blanco M., Chabas A., Grinberg D., Vilageliu L.;
RT "Identification of 14 novel GLB1 mutations, including five deletions, in 19
RT patients with GM1 gangliosidosis from South America.";
RL Clin. Genet. 71:273-279(2007).
RN [47]
RP VARIANT TRP-595, AND CHARACTERIZATION OF VARIANT TRP-595.
RX PubMed=17661814; DOI=10.1111/j.1399-0004.2007.00843.x;
RA Gort L., Santamaria R., Grinberg D., Vilageliu L., Chabas A.;
RT "Identification of a novel pseudodeficiency allele in the GLB1 gene in a
RT carrier of GM1 gangliosidosis.";
RL Clin. Genet. 72:109-111(2007).
RN [48]
RP CHARACTERIZATION OF VARIANTS GM1G1 HIS-59; SER-162; PRO-173; HIS-201;
RP PRO-420; ASN-441; CYS-521 AND CYS-590, CHARACTERIZATION OF VARIANTS MPS4B
RP CYS-83; CYS-444 AND SER-494, CHARACTERIZATION OF VARIANT GM1G3 LYS-420, AND
RP CHARACTERIZATION OF VARIANT GLY-532.
RX PubMed=17664528; DOI=10.1194/jlr.m700308-jlr200;
RA Santamaria R., Chabas A., Callahan J.W., Grinberg D., Vilageliu L.;
RT "Expression and characterization of 14 GLB1 mutant alleles found in GM1-
RT gangliosidosis and Morquio B patients.";
RL J. Lipid Res. 48:2275-2282(2007).
RN [49]
RP VARIANTS GM1G1 HIS-59; THR-132; ARG-184; ASP-190; CYS-201; HIS-201;
RP MET-239; HIS-255; ILE-329; GLU-332; ASN-346; GLN-442 AND SER-597, VARIANTS
RP GM1G2 GLN-68; ARG-155 AND HIS-333, VARIANTS GM1G3 MET-82; ASP-270 AND
RP GLU-438, VARIANTS MPS4B PHE-149; TYR-198; LEU-273; ALA-397; PRO-408 AND
RP ALA-500, CHARACTERIZATION OF VARIANTS GM1G1 THR-132; ARG-184; ASP-190;
RP CYS-201; HIS-201; HIS-255; ILE-329; GLU-332 AND SER-597, CHARACTERIZATION
RP OF VARIANTS GM1G2 GLN-68; ARG-155 AND HIS-333, CHARACTERIZATION OF VARIANTS
RP GM1G3 ASP-270 AND GLU-438, CHARACTERIZATION OF VARIANTS MPS4B PHE-149;
RP TYR-198; LEU-273; ALA-397; PRO-408 AND ALA-500, CATALYTIC ACTIVITY, AND
RP FUNCTION.
RX PubMed=19472408; DOI=10.1002/humu.21031;
RA Hofer D., Paul K., Fantur K., Beck M., Buerger F., Caillaud C., Fumic K.,
RA Ledvinova J., Lugowska A., Michelakakis H., Radeva B., Ramaswami U.,
RA Plecko B., Paschke E.;
RT "GM1 gangliosidosis and Morquio B disease: expression analysis of missense
RT mutations affecting the catalytic site of acid beta-galactosidase.";
RL Hum. Mutat. 30:1214-1221(2009).
RN [50]
RP VARIANTS GM1G2 CYS-49; ARG-134; CYS-148; GLU-262; LEU-314; PRO-337;
RP VAL-414; ASN-493; LEU-597 AND ILE-600, CHARACTERIZATION OF VARIANTS GM1G2
RP CYS-49; GLU-262; LEU-314; PRO-337; VAL-414; ASN-493; LEU-597 AND ILE-600,
RP VARIANTS GM1G1 TRP-68; ARG-123; PRO-236; CYS-331; ASN-332; PRO-337; HIS-482
RP AND PRO-514, CHARACTERIZATION OF VARIANTS GM1G1 TRP-68; ARG-123; PRO-236;
RP ASN-332; PRO-337; HIS-482 AND PRO-514, VARIANT GM1G3 PHE-297,
RP CHARACTERIZATION OF VARIANT GM1G3 PHE-297, VARIANTS GLN-129 AND CYS-521,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=25936995; DOI=10.1016/j.gene.2015.04.078;
RA Bidchol A.M., Dalal A., Trivedi R., Shukla A., Nampoothiri S., Sankar V.H.,
RA Danda S., Gupta N., Kabra M., Hebbar S.A., Bhat R.Y., Matta D.,
RA Ekbote A.V., Puri R.D., Phadke S.R., Gowrishankar K., Aggarwal S.,
RA Ranganath P., Sharda S., Kamate M., Datar C.A., Bhat K., Kamath N.,
RA Shah H., Krishna S., Gopinath P.M., Verma I.C., Nagarajaram H.A.,
RA Satyamoorthy K., Girisha K.M.;
RT "Recurrent and novel GLB1 mutations in India.";
RL Gene 567:173-181(2015).
CC -!- FUNCTION: [Isoform 1]: Cleaves beta-linked terminal galactosyl residues
CC from gangliosides, glycoproteins, and glycosaminoglycans.
CC {ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:19472408,
CC ECO:0000269|PubMed:2511208, ECO:0000269|PubMed:25936995,
CC ECO:0000269|PubMed:8200356}.
CC -!- FUNCTION: [Isoform 2]: Has no beta-galactosidase catalytic activity,
CC but plays functional roles in the formation of extracellular elastic
CC fibers (elastogenesis) and in the development of connective tissue.
CC Seems to be identical to the elastin-binding protein (EBP), a major
CC component of the non-integrin cell surface receptor expressed on
CC fibroblasts, smooth muscle cells, chondroblasts, leukocytes, and
CC certain cancer cell types. In elastin producing cells, associates with
CC tropoelastin intracellularly and functions as a recycling molecular
CC chaperone which facilitates the secretions of tropoelastin and its
CC assembly into elastic fibers. {ECO:0000269|PubMed:10841810,
CC ECO:0000269|PubMed:8922281}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of terminal non-reducing beta-D-galactose residues
CC in beta-D-galactosides.; EC=3.2.1.23;
CC Evidence={ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:19472408,
CC ECO:0000269|PubMed:24737316, ECO:0000269|PubMed:2511208,
CC ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:3143362,
CC ECO:0000269|PubMed:8200356};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 4.5-5.5.;
CC -!- SUBUNIT: Homodimer (PubMed:22128166). May form higher multimers
CC (Probable). {ECO:0000269|PubMed:22128166, ECO:0000305|PubMed:3084261}.
CC -!- INTERACTION:
CC P16278; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-989638, EBI-712073;
CC P16278; Q3KNW5: SLC10A6; NbExp=3; IntAct=EBI-989638, EBI-18159983;
CC P16278; Q9BRI3: SLC30A2; NbExp=3; IntAct=EBI-989638, EBI-8644112;
CC P16278; P30825: SLC7A1; NbExp=3; IntAct=EBI-989638, EBI-4289564;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Lysosome
CC {ECO:0000269|PubMed:2511208, ECO:0000269|PubMed:3084261}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:2511208}. Note=Localized to the perinuclear area of
CC the cytoplasm but not to lysosomes. {ECO:0000269|PubMed:2511208}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P16278-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta-galactosidase-related protein
CC {ECO:0000303|PubMed:2511208}, Beta-galactosidase-like protein, S-Gal
CC {ECO:0000303|PubMed:8383699}, Elastin-binding protein, EBP
CC {ECO:0000303|PubMed:9497360};
CC IsoId=P16278-2, P16279-1;
CC Sequence=VSP_031241;
CC Name=3;
CC IsoId=P16278-3; Sequence=VSP_039974;
CC -!- TISSUE SPECIFICITY: Detected in placenta (at protein level)
CC (PubMed:8383699). Detected in fibroblasts and testis (PubMed:2511208).
CC {ECO:0000269|PubMed:2511208, ECO:0000269|PubMed:8383699}.
CC -!- DISEASE: GM1-gangliosidosis 1 (GM1G1) [MIM:230500]: An autosomal
CC recessive lysosomal storage disease marked by the accumulation of GM1
CC gangliosides, glycoproteins and keratan sulfate primarily in neurons of
CC the central nervous system. GM1-gangliosidosis type 1 is characterized
CC by onset within the first three months of life, central nervous system
CC degeneration, coarse facial features, hepatosplenomegaly, skeletal
CC dysmorphology reminiscent of Hurler syndrome, and rapidly progressive
CC psychomotor deterioration. Urinary oligosaccharide levels are high. It
CC leads to death usually between the first and second year of life.
CC {ECO:0000269|PubMed:10338095, ECO:0000269|PubMed:10737981,
CC ECO:0000269|PubMed:10839995, ECO:0000269|PubMed:1487238,
CC ECO:0000269|PubMed:15365997, ECO:0000269|PubMed:15714521,
CC ECO:0000269|PubMed:15791924, ECO:0000269|PubMed:16538002,
CC ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651,
CC ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:1907800,
CC ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:1928092,
CC ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:24737316,
CC ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:8213816,
CC ECO:0000269|Ref.28, ECO:0000269|Ref.31}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: GM1-gangliosidosis 2 (GM1G2) [MIM:230600]: A gangliosidosis
CC characterized by onset between ages 1 and 5. The main symptom is
CC locomotor ataxia, ultimately leading to a state of decerebration with
CC epileptic seizures. Patients do not display the skeletal changes
CC associated with the infantile form, but they nonetheless excrete
CC elevated amounts of beta-linked galactose-terminal oligosaccharides.
CC Inheritance is autosomal recessive. {ECO:0000269|PubMed:10737981,
CC ECO:0000269|PubMed:12644936, ECO:0000269|PubMed:15714521,
CC ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651,
CC ECO:0000269|PubMed:1907800, ECO:0000269|PubMed:1909089,
CC ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:24737316,
CC ECO:0000269|PubMed:25936995, ECO:0000269|PubMed:8213816}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: GM1-gangliosidosis 3 (GM1G3) [MIM:230650]: A gangliosidosis
CC with a variable phenotype. Patients show mild skeletal abnormalities,
CC dysarthria, gait disturbance, dystonia and visual impairment.
CC Visceromegaly is absent. Intellectual deficit can initially be mild or
CC absent but progresses over time. Inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:11511921, ECO:0000269|PubMed:15986423,
CC ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651,
CC ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:1907800,
CC ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:19472408,
CC ECO:0000269|PubMed:24737316, ECO:0000269|PubMed:25936995,
CC ECO:0000269|PubMed:8198123, ECO:0000269|Ref.28, ECO:0000269|Ref.30}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Mucopolysaccharidosis 4B (MPS4B) [MIM:253010]: A form of
CC mucopolysaccharidosis type 4, an autosomal recessive lysosomal storage
CC disease characterized by intracellular accumulation of keratan sulfate
CC and chondroitin-6-sulfate. Key clinical features include short stature,
CC skeletal dysplasia, dental anomalies, and corneal clouding.
CC Intelligence is normal and there is no direct central nervous system
CC involvement, although the skeletal changes may result in neurologic
CC complications. There is variable severity, but patients with the severe
CC phenotype usually do not survive past the second or third decade of
CC life. {ECO:0000269|PubMed:11511921, ECO:0000269|PubMed:12393180,
CC ECO:0000269|PubMed:16538002, ECO:0000269|PubMed:16941474,
CC ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:1928092,
CC ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:7586649}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 35 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Beta-galactosidase entry;
CC URL="https://en.wikipedia.org/wiki/Beta-galactosidase";
CC ---------------------------------------------------------------------------
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DR EMBL; M22590; AAA51822.1; -; mRNA.
DR EMBL; M27507; AAA51819.1; -; mRNA.
DR EMBL; M27508; AAA35599.1; -; mRNA.
DR EMBL; M34423; AAA51823.1; -; mRNA.
DR EMBL; AK300021; BAH13196.1; -; mRNA.
DR EMBL; AK312988; BAG35825.1; -; mRNA.
DR EMBL; BT007147; AAP35811.1; -; mRNA.
DR EMBL; AC112211; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007493; AAH07493.1; -; mRNA.
DR CCDS; CCDS43061.1; -. [P16278-1]
DR CCDS; CCDS43062.1; -. [P16278-3]
DR CCDS; CCDS46785.1; -. [P16278-2]
DR PIR; A32688; A32611.
DR PIR; B32688; B32688.
DR RefSeq; NP_000395.2; NM_000404.3.
DR RefSeq; NP_001073279.1; NM_001079811.2. [P16278-3]
DR RefSeq; NP_001129074.1; NM_001135602.2. [P16278-2]
DR RefSeq; NP_001303969.1; NM_001317040.1.
DR PDB; 3THC; X-ray; 1.80 A; A/B/C/D=24-677.
DR PDB; 3THD; X-ray; 1.79 A; A/B/C/D=24-677.
DR PDB; 3WEZ; X-ray; 2.11 A; A/B/C/D=24-677.
DR PDB; 3WF0; X-ray; 2.20 A; A/B/C/D=24-677.
DR PDB; 3WF1; X-ray; 2.00 A; A/B/C/D=24-677.
DR PDB; 3WF2; X-ray; 2.30 A; A/B/C/D=24-677.
DR PDB; 3WF3; X-ray; 2.15 A; A/B/C/D=24-677.
DR PDB; 3WF4; X-ray; 2.30 A; A/B/C/D=24-677.
DR PDBsum; 3THC; -.
DR PDBsum; 3THD; -.
DR PDBsum; 3WEZ; -.
DR PDBsum; 3WF0; -.
DR PDBsum; 3WF1; -.
DR PDBsum; 3WF2; -.
DR PDBsum; 3WF3; -.
DR PDBsum; 3WF4; -.
DR AlphaFoldDB; P16278; -.
DR SMR; P16278; -.
DR BioGRID; 108984; 95.
DR CORUM; P16278; -.
DR IntAct; P16278; 47.
DR MINT; P16278; -.
DR STRING; 9606.ENSP00000306920; -.
DR BindingDB; P16278; -.
DR ChEMBL; CHEMBL2522; -.
DR DrugBank; DB04465; Lactose.
DR DrugCentral; P16278; -.
DR CAZy; GH35; Glycoside Hydrolase Family 35.
DR GlyConnect; 1036; 15 N-Linked glycans (3 sites).
DR GlyGen; P16278; 8 sites, 14 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P16278; -.
DR PhosphoSitePlus; P16278; -.
DR SwissPalm; P16278; -.
DR BioMuta; GLB1; -.
DR DMDM; 215273939; -.
DR EPD; P16278; -.
DR jPOST; P16278; -.
DR MassIVE; P16278; -.
DR MaxQB; P16278; -.
DR PaxDb; P16278; -.
DR PeptideAtlas; P16278; -.
DR PRIDE; P16278; -.
DR ProteomicsDB; 53332; -. [P16278-1]
DR ProteomicsDB; 53333; -. [P16278-2]
DR ProteomicsDB; 53334; -. [P16278-3]
DR Antibodypedia; 3647; 732 antibodies from 38 providers.
DR DNASU; 2720; -.
DR Ensembl; ENST00000307363.10; ENSP00000306920.4; ENSG00000170266.16.
DR Ensembl; ENST00000399402.7; ENSP00000382333.2; ENSG00000170266.16.
DR GeneID; 2720; -.
DR KEGG; hsa:2720; -.
DR UCSC; uc003cfh.2; human. [P16278-1]
DR CTD; 2720; -.
DR DisGeNET; 2720; -.
DR GeneCards; GLB1; -.
DR GeneReviews; GLB1; -.
DR HGNC; HGNC:4298; GLB1.
DR HPA; ENSG00000170266; Low tissue specificity.
DR MalaCards; GLB1; -.
DR MIM; 230500; phenotype.
DR MIM; 230600; phenotype.
DR MIM; 230650; phenotype.
DR MIM; 253010; phenotype.
DR MIM; 611458; gene.
DR neXtProt; NX_P16278; -.
DR Orphanet; 79255; GM1 gangliosidosis type 1.
DR Orphanet; 79256; GM1 gangliosidosis type 2.
DR Orphanet; 79257; GM1 gangliosidosis type 3.
DR Orphanet; 309310; Mucopolysaccharidosis type 4B.
DR PharmGKB; PA28709; -.
DR VEuPathDB; HostDB:ENSG00000170266; -.
DR eggNOG; KOG0496; Eukaryota.
DR HOGENOM; CLU_007853_7_2_1; -.
DR InParanoid; P16278; -.
DR OrthoDB; 179316at2759; -.
DR PhylomeDB; P16278; -.
DR TreeFam; TF314816; -.
DR PathwayCommons; P16278; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-HSA-2022857; Keratan sulfate degradation.
DR Reactome; R-HSA-2024096; HS-GAG degradation.
DR Reactome; R-HSA-2206308; MPS IV - Morquio syndrome B.
DR Reactome; R-HSA-4085001; Sialic acid metabolism.
DR Reactome; R-HSA-4341670; Defective NEU1 causes sialidosis.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SABIO-RK; P16278; -.
DR SignaLink; P16278; -.
DR BioGRID-ORCS; 2720; 11 hits in 1081 CRISPR screens.
DR ChiTaRS; GLB1; human.
DR GeneWiki; GLB1; -.
DR GenomeRNAi; 2720; -.
DR Pharos; P16278; Tchem.
DR PRO; PR:P16278; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P16278; protein.
DR Bgee; ENSG00000170266; Expressed in monocyte and 178 other tissues.
DR ExpressionAtlas; P16278; baseline and differential.
DR Genevisible; P16278; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005773; C:vacuole; IBA:GO_Central.
DR GO; GO:0004565; F:beta-galactosidase activity; IDA:UniProtKB.
DR GO; GO:0016936; F:galactoside binding; IEA:Ensembl.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0044262; P:cellular carbohydrate metabolic process; IDA:BHF-UCL.
DR GO; GO:0019388; P:galactose catabolic process; IEA:Ensembl.
DR GO; GO:0006027; P:glycosaminoglycan catabolic process; TAS:Reactome.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:0042340; P:keratan sulfate catabolic process; TAS:Reactome.
DR GO; GO:0051413; P:response to cortisone; IEA:Ensembl.
DR GO; GO:1904016; P:response to Thyroglobulin triiodothyronine; IEA:Ensembl.
DR DisProt; DP02785; -.
DR InterPro; IPR026283; B-gal_1-like.
DR InterPro; IPR025300; BetaGal_jelly_roll_dom.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR031330; Gly_Hdrlase_35_cat.
DR InterPro; IPR019801; Glyco_hydro_35_CS.
DR InterPro; IPR001944; Glycoside_Hdrlase_35.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR PANTHER; PTHR23421; PTHR23421; 1.
DR Pfam; PF13364; BetaGal_dom4_5; 1.
DR Pfam; PF01301; Glyco_hydro_35; 1.
DR PIRSF; PIRSF006336; B-gal; 1.
DR PRINTS; PR00742; GLHYDRLASE35.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
DR PROSITE; PS01182; GLYCOSYL_HYDROL_F35; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Disease variant; Disulfide bond; Gangliosidosis; Glycoprotein; Glycosidase;
KW Hydrolase; Lysosome; Mucopolysaccharidosis; Reference proteome; Signal;
KW Zymogen.
FT SIGNAL 1..23
FT PROPEP 24..28
FT /evidence="ECO:0000305|PubMed:2511208"
FT /id="PRO_0000012185"
FT CHAIN 29..677
FT /note="Beta-galactosidase"
FT /id="PRO_0000012186"
FT REGION 650..677
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 188
FT /note="Proton donor"
FT /evidence="ECO:0000305|PubMed:22128166"
FT ACT_SITE 268
FT /note="Nucleophile"
FT /evidence="ECO:0000305|PubMed:22128166"
FT BINDING 83
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3WF3"
FT BINDING 129
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3WF3"
FT BINDING 187
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3WF3"
FT BINDING 333
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3WF3"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3THD, ECO:0007744|PDB:3WEZ,
FT ECO:0007744|PDB:3WF0, ECO:0007744|PDB:3WF1,
FT ECO:0007744|PDB:3WF2, ECO:0007744|PDB:3WF3,
FT ECO:0007744|PDB:3WF4"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16263699,
FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3THD, ECO:0007744|PDB:3WEZ,
FT ECO:0007744|PDB:3WF0, ECO:0007744|PDB:3WF1,
FT ECO:0007744|PDB:3WF2, ECO:0007744|PDB:3WF3,
FT ECO:0007744|PDB:3WF4"
FT CARBOHYD 498
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3THD, ECO:0007744|PDB:3WEZ,
FT ECO:0007744|PDB:3WF0, ECO:0007744|PDB:3WF1,
FT ECO:0007744|PDB:3WF2, ECO:0007744|PDB:3WF3,
FT ECO:0007744|PDB:3WF4"
FT CARBOHYD 542
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 545
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 555
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218,
FT ECO:0000269|PubMed:22128166, ECO:0000269|PubMed:24737316,
FT ECO:0007744|PDB:3THC, ECO:0007744|PDB:3THD,
FT ECO:0007744|PDB:3WEZ, ECO:0007744|PDB:3WF0,
FT ECO:0007744|PDB:3WF1, ECO:0007744|PDB:3WF2,
FT ECO:0007744|PDB:3WF3, ECO:0007744|PDB:3WF4"
FT DISULFID 195..230
FT /evidence="ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3THD, ECO:0007744|PDB:3WEZ,
FT ECO:0007744|PDB:3WF0, ECO:0007744|PDB:3WF1,
FT ECO:0007744|PDB:3WF2, ECO:0007744|PDB:3WF3,
FT ECO:0007744|PDB:3WF4"
FT DISULFID 626..634
FT /evidence="ECO:0000269|PubMed:22128166,
FT ECO:0000269|PubMed:24737316, ECO:0007744|PDB:3THC,
FT ECO:0007744|PDB:3THD, ECO:0007744|PDB:3WEZ,
FT ECO:0007744|PDB:3WF0, ECO:0007744|PDB:3WF1,
FT ECO:0007744|PDB:3WF2, ECO:0007744|PDB:3WF3,
FT ECO:0007744|PDB:3WF4"
FT VAR_SEQ 1..30
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_039974"
FT VAR_SEQ 83..244
FT /note="YVPWNFHEPWPGQYQFSEDHDVEYFLRLAHELGLLVILRPGPYICAEWEMGG
FT LPAWLLEKESILLRSSDPDYLAAVDKWLGVLLPKMKPLLYQNGGPVITVQVENEYGSYF
FT ACDFDYLRFLQKRFRHHLGDDVVLFTTDGAHKTFLKCGALQGLYTTVDFGT -> LPGS
FT CGQVVGSPSAQDEASPLSEWRASYNSA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2511208"
FT /id="VSP_031241"
FT VARIANT 10
FT /note="P -> L (in dbSNP:rs7637099)"
FT /evidence="ECO:0000269|PubMed:10338095,
FT ECO:0000269|PubMed:11511921, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15791924,
FT ECO:0000269|PubMed:2111707, ECO:0000269|PubMed:2511208,
FT ECO:0000269|Ref.5"
FT /id="VAR_008671"
FT VARIANT 49
FT /note="R -> C (in GM1G1 and GM1G2; decrease in
FT galactosidase activity; dbSNP:rs72555358)"
FT /evidence="ECO:0000269|PubMed:1909089,
FT ECO:0000269|PubMed:25936995"
FT /id="VAR_003329"
FT VARIANT 49
FT /note="R -> H (in GM1G3; dbSNP:rs780523881)"
FT /evidence="ECO:0000269|PubMed:15986423"
FT /id="VAR_062340"
FT VARIANT 51
FT /note="I -> T (in GM1G3; no effect on catalytic activity;
FT decreased protein stability; dbSNP:rs72555390)"
FT /evidence="ECO:0000269|PubMed:1907800,
FT ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:24737316"
FT /id="VAR_003330"
FT VARIANT 59
FT /note="R -> C (in GM1G1; loss of galactosidase activity;
FT severe mutation; dbSNP:rs756878418)"
FT /evidence="ECO:0000269|PubMed:15714521,
FT ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651"
FT /id="VAR_026129"
FT VARIANT 59
FT /note="R -> H (in GM1G1; with cardiac involvement in some
FT patients; loss of galactosidase activity; severe mutation;
FT dbSNP:rs72555392)"
FT /evidence="ECO:0000269|PubMed:10338095,
FT ECO:0000269|PubMed:10737981, ECO:0000269|PubMed:15714521,
FT ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651,
FT ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:19472408,
FT ECO:0000269|Ref.31"
FT /id="VAR_008672"
FT VARIANT 68
FT /note="R -> Q (in GM1G2; 7.4% of wild-type galactosidase
FT activity; dbSNP:rs572237881)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062341"
FT VARIANT 68
FT /note="R -> W (in GM1G2 and GM1G1; loss of galactosidase
FT activity; dbSNP:rs72555370)"
FT /evidence="ECO:0000269|PubMed:12644936,
FT ECO:0000269|PubMed:25936995"
FT /id="VAR_026130"
FT VARIANT 73
FT /note="K -> E (in GM1G3)"
FT /evidence="ECO:0000269|PubMed:15986423"
FT /id="VAR_062342"
FT VARIANT 82
FT /note="T -> M (in GM1G3; mild phenotype; dbSNP:rs72555393)"
FT /evidence="ECO:0000269|PubMed:11511921,
FT ECO:0000269|PubMed:19472408, ECO:0000269|PubMed:8198123"
FT /id="VAR_008673"
FT VARIANT 83
FT /note="Y -> C (in MPS4B; decrease in galactosidase
FT activity; dbSNP:rs1553612220)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17664528"
FT /id="VAR_062343"
FT VARIANT 83
FT /note="Y -> H (in MPS4B; 2-5% of wild-type galactosidase
FT activity; dbSNP:rs72555364)"
FT /evidence="ECO:0000269|PubMed:7586649"
FT /id="VAR_008674"
FT VARIANT 109
FT /note="R -> W (in dbSNP:rs35289681)"
FT /id="VAR_053875"
FT VARIANT 121
FT /note="R -> S (in GM1G1; dbSNP:rs879050821)"
FT /evidence="ECO:0000269|PubMed:10338095"
FT /id="VAR_008675"
FT VARIANT 123
FT /note="G -> R (in GM1G1; decrease in galactosidase
FT activity; dbSNP:rs28934274)"
FT /evidence="ECO:0000269|PubMed:1907800,
FT ECO:0000269|PubMed:25936995"
FT /id="VAR_003331"
FT VARIANT 129
FT /note="E -> Q (in dbSNP:rs886042079)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074054"
FT VARIANT 132
FT /note="M -> T (in GM1G1; 4.3% of wild-type galactosidase
FT activity; dbSNP:rs1553612189)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062344"
FT VARIANT 134
FT /note="G -> R (in GM1G2; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074055"
FT VARIANT 134
FT /note="G -> V (in GM1G1; dbSNP:rs773562141)"
FT /evidence="ECO:0000269|PubMed:17309651"
FT /id="VAR_037937"
FT VARIANT 136
FT /note="P -> S (in GM1G1; dbSNP:rs747305905)"
FT /evidence="ECO:0000269|PubMed:16941474"
FT /id="VAR_062345"
FT VARIANT 147
FT /note="Missing (in GM1G1)"
FT /evidence="ECO:0000269|PubMed:17309651"
FT /id="VAR_037938"
FT VARIANT 148
FT /note="R -> C (in GM1G3 and GM1G2; dbSNP:rs192732174)"
FT /evidence="ECO:0000269|PubMed:15986423,
FT ECO:0000269|PubMed:25936995"
FT /id="VAR_062346"
FT VARIANT 148
FT /note="R -> S (in GM1G1; dbSNP:rs192732174)"
FT /evidence="ECO:0000269|PubMed:10839995, ECO:0000269|Ref.28"
FT /id="VAR_013541"
FT VARIANT 149
FT /note="S -> F (in MPS4B; 2.0% of wild-type galactosidase
FT activity; dbSNP:rs778700089)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062347"
FT VARIANT 151
FT /note="D -> V (in GM1G1)"
FT /evidence="ECO:0000269|PubMed:16941474"
FT /id="VAR_062348"
FT VARIANT 151
FT /note="D -> Y (in GM1G1; complete lack of protein; loss of
FT galactosidase activity)"
FT /evidence="ECO:0000269|PubMed:15365997,
FT ECO:0000269|PubMed:15791924"
FT /id="VAR_026131"
FT VARIANT 155
FT /note="L -> R (in GM1G2 and GM1G3; 6.7% of wild-type
FT galactosidase activity; dbSNP:rs376710410)"
FT /evidence="ECO:0000269|PubMed:17309651,
FT ECO:0000269|PubMed:19472408"
FT /id="VAR_037939"
FT VARIANT 162
FT /note="L -> S (in GM1G1; loss of galactosidase activity)"
FT /evidence="ECO:0000269|PubMed:17309651,
FT ECO:0000269|PubMed:17664528"
FT /id="VAR_037940"
FT VARIANT 173
FT /note="L -> P (in GM1G1; loss of galactosidase activity;
FT dbSNP:rs397515617)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17664528"
FT /id="VAR_062349"
FT VARIANT 184
FT /note="Q -> R (in GM1G1; loss of galactosidase activity)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062350"
FT VARIANT 190
FT /note="G -> D (in GM1G1; 3.4% of wild-type galactosidase
FT activity; dbSNP:rs756575833)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062351"
FT VARIANT 198
FT /note="D -> Y (in MPS4B; 17.4% of wild-type galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062352"
FT VARIANT 199
FT /note="Y -> C (in GM1G1)"
FT /evidence="ECO:0000269|PubMed:16941474"
FT /id="VAR_062353"
FT VARIANT 201
FT /note="R -> C (in GM1G1 and GM1G2; no effect on intrinsic
FT catalytic activity; decreased protein stability; 8.4% of
FT wild-type galactosidase activity; activity severely reduced
FT in transfection with variant F-436; dbSNP:rs72555360)"
FT /evidence="ECO:0000269|PubMed:12644936,
FT ECO:0000269|PubMed:16538002, ECO:0000269|PubMed:1907800,
FT ECO:0000269|PubMed:1909089, ECO:0000269|PubMed:19472408,
FT ECO:0000269|PubMed:24737316"
FT /id="VAR_003332"
FT VARIANT 201
FT /note="R -> H (in GM1G1 and GM1G2; also in a patient with a
FT slowly progressive GM1-gangliosidosis form; 36.2% of wild-
FT type galactosidase activity; dbSNP:rs189115557)"
FT /evidence="ECO:0000269|PubMed:10737981,
FT ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:16538002,
FT ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17309651,
FT ECO:0000269|PubMed:17664528, ECO:0000269|PubMed:19472408,
FT ECO:0000269|PubMed:9203065"
FT /id="VAR_013542"
FT VARIANT 208
FT /note="R -> C (in GM1G1; dbSNP:rs72555366)"
FT /evidence="ECO:0000269|PubMed:10338095,
FT ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:17309651,
FT ECO:0000269|PubMed:8213816"
FT /id="VAR_008676"
FT VARIANT 214
FT /note="D -> Y (in GM1G3)"
FT /evidence="ECO:0000269|Ref.28"
FT /id="VAR_013543"
FT VARIANT 216
FT /note="V -> A (in GM1G1; dbSNP:rs886042815)"
FT /evidence="ECO:0000269|Ref.28"
FT /id="VAR_013544"
FT VARIANT 236
FT /note="L -> P (in GM1G1; decrease in galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074056"
FT VARIANT 239
FT /note="T -> M (in GM1G1; loss of galactosidase activity;
FT severe mutation; causes a rapid degradation of the protein
FT precursor; dbSNP:rs746766232)"
FT /evidence="ECO:0000269|PubMed:15714521,
FT ECO:0000269|PubMed:19472408"
FT /id="VAR_026132"
FT VARIANT 240
FT /note="V -> M (in GM1G1)"
FT /evidence="ECO:0000269|PubMed:10338095"
FT /id="VAR_008677"
FT VARIANT 255
FT /note="Q -> H (in GM1G1; 2.4% of wild-type galactosidase
FT activity; dbSNP:rs1553610553)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062354"
FT VARIANT 262
FT /note="G -> E (in GM1G2; decrease in galactosidase
FT activity; dbSNP:rs377174858)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074057"
FT VARIANT 263
FT /note="P -> S (in GM1G3)"
FT /evidence="ECO:0000269|Ref.30"
FT /id="VAR_013545"
FT VARIANT 264
FT /note="L -> S (in GM1G2)"
FT /evidence="ECO:0000269|PubMed:16941474"
FT /id="VAR_062355"
FT VARIANT 266
FT /note="N -> S (in GM1G3; dbSNP:rs1214295886)"
FT /evidence="ECO:0000269|PubMed:9203065"
FT /id="VAR_013546"
FT VARIANT 270
FT /note="Y -> D (in GM1G3; originally classified as Morquio
FT syndrome; dbSNP:rs376663785)"
FT /evidence="ECO:0000269|PubMed:11511921,
FT ECO:0000269|PubMed:19472408"
FT /id="VAR_013547"
FT VARIANT 272
FT /note="G -> D (in GM1G1)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17309651"
FT /id="VAR_038346"
FT VARIANT 273
FT /note="W -> L (in MPS4B; decreased galactosidase activity;
FT dbSNP:rs72555362)"
FT /evidence="ECO:0000269|PubMed:11511921,
FT ECO:0000269|PubMed:16538002, ECO:0000269|PubMed:1928092,
FT ECO:0000269|PubMed:19472408"
FT /id="VAR_003333"
FT VARIANT 281
FT /note="H -> Y (in GM1G1 and GM1G3; dbSNP:rs745386663)"
FT /evidence="ECO:0000269|PubMed:11511921,
FT ECO:0000269|PubMed:15714521"
FT /id="VAR_013548"
FT VARIANT 297
FT /note="L -> F (in GM1G3; decrease in galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074058"
FT VARIANT 314
FT /note="F -> L (in GM1G2; decrease in galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074059"
FT VARIANT 316
FT /note="Y -> C (in GM1G1; dbSNP:rs72555361)"
FT /evidence="ECO:0000269|PubMed:1907800"
FT /id="VAR_003334"
FT VARIANT 318
FT /note="N -> H (in GM1G1; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:16538002"
FT /id="VAR_062356"
FT VARIANT 329
FT /note="T -> I (in GM1G1; 5.0% of wild-type galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062357"
FT VARIANT 331
FT /note="Y -> C (in GM1G1; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074060"
FT VARIANT 332
FT /note="D -> E (in GM1G1; 2.3% of wild-type galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062358"
FT VARIANT 332
FT /note="D -> N (in GM1G1; decrease in galactosidase
FT activity; dbSNP:rs781658798)"
FT /evidence="ECO:0000269|PubMed:10839995,
FT ECO:0000269|PubMed:25936995"
FT /id="VAR_013549"
FT VARIANT 333
FT /note="Y -> H (in GM1G2; 3.0% of wild-type galactosidase
FT activity; the mutant protein is localized in the lysosomal-
FT endosomal compartment)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062359"
FT VARIANT 337
FT /note="L -> P (in GM1G1 and GM1G2; loss of galactosidase
FT activity; dbSNP:rs752177002)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074061"
FT VARIANT 346
FT /note="K -> N (in GM1G1; dbSNP:rs749980306)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:19472408"
FT /id="VAR_062360"
FT VARIANT 347
FT /note="Y -> C (in GM1G1)"
FT /evidence="ECO:0000269|PubMed:16941474"
FT /id="VAR_062361"
FT VARIANT 377..381
FT /note="Missing (in GM1G1)"
FT /evidence="ECO:0000269|PubMed:17309651"
FT /id="VAR_037941"
FT VARIANT 397
FT /note="P -> A (in MPS4B; 24.0% of wild-type galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062362"
FT VARIANT 408
FT /note="Q -> P (in MPS4B; 1.1% of wild-type galactosidase
FT activity; dbSNP:rs72555369)"
FT /evidence="ECO:0000269|PubMed:11511921,
FT ECO:0000269|PubMed:19472408"
FT /id="VAR_013550"
FT VARIANT 414
FT /note="G -> V (in GM1G2; decrease in galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074062"
FT VARIANT 420
FT /note="T -> K (in GM1G3; decrease in galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17664528"
FT /id="VAR_062363"
FT VARIANT 420
FT /note="T -> P (in GM1G1; loss of galactosidase activity;
FT dbSNP:rs200181401)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17664528"
FT /id="VAR_062364"
FT VARIANT 422
FT /note="L -> R (in GM1G1; dbSNP:rs758203004)"
FT /evidence="ECO:0000269|PubMed:16941474"
FT /id="VAR_062365"
FT VARIANT 434
FT /note="S -> L (in GM1-gangliosidosis; unclassified clinical
FT type; dbSNP:rs267599773)"
FT /evidence="ECO:0000269|PubMed:17309651"
FT /id="VAR_037942"
FT VARIANT 436
FT /note="L -> F (seems to have a modulating action in the
FT expression of the severity of other mutations;
FT dbSNP:rs34421970)"
FT /evidence="ECO:0000269|PubMed:12644936,
FT ECO:0000269|PubMed:16941474"
FT /id="VAR_026133"
FT VARIANT 438
FT /note="G -> E (in GM1G3 and MPS4B; mild form; 5.7% of wild-
FT type galactosidase activity; dbSNP:rs72555367)"
FT /evidence="ECO:0000269|PubMed:12393180,
FT ECO:0000269|PubMed:15986423, ECO:0000269|PubMed:19472408"
FT /id="VAR_013551"
FT VARIANT 441
FT /note="D -> N (in GM1G1; loss of galactosidase activity;
FT dbSNP:rs780724173)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17664528"
FT /id="VAR_062366"
FT VARIANT 442
FT /note="R -> Q (in GM1G1; dbSNP:rs564428355)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062367"
FT VARIANT 444
FT /note="Y -> C (in MPS4B; loss of galactosidase activity)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17664528"
FT /id="VAR_062368"
FT VARIANT 457
FT /note="R -> Q (in GM1G3; dbSNP:rs28934886)"
FT /evidence="ECO:0000269|PubMed:1907800"
FT /id="VAR_003335"
FT VARIANT 482
FT /note="R -> C (in MPS4B; loss of galactosidase activity;
FT dbSNP:rs72555365)"
FT /evidence="ECO:0000269|PubMed:7586649"
FT /id="VAR_008678"
FT VARIANT 482
FT /note="R -> H (in MPS4B and GM1G1; severe decrease in
FT galactosidase activity; dbSNP:rs72555391)"
FT /evidence="ECO:0000269|PubMed:10737981,
FT ECO:0000269|PubMed:1487238, ECO:0000269|PubMed:15714521,
FT ECO:0000269|PubMed:16538002, ECO:0000269|PubMed:1928092,
FT ECO:0000269|PubMed:25936995"
FT /id="VAR_003336"
FT VARIANT 484
FT /note="N -> K (in MPS4B; mild form; fibroblasts from MPS4B
FT compound heterozygotes for K-484 and A-500 have 1.9% of
FT wild-type galactosidase activity; dbSNP:rs968221254)"
FT /evidence="ECO:0000269|PubMed:12393180"
FT /id="VAR_013552"
FT VARIANT 491
FT /note="D -> N (in GM1G1; dbSNP:rs780232995)"
FT /evidence="ECO:0000269|PubMed:10338095"
FT /id="VAR_008679"
FT VARIANT 491
FT /note="D -> Y (in GM1G1)"
FT /evidence="ECO:0000269|PubMed:17309651"
FT /id="VAR_037943"
FT VARIANT 493
FT /note="K -> N (in GM1G2; decrease in galactosidase
FT activity; dbSNP:rs1172435886)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074063"
FT VARIANT 494
FT /note="G -> C (in GM1G1; dbSNP:rs1312626201)"
FT /evidence="ECO:0000269|PubMed:1928092"
FT /id="VAR_013553"
FT VARIANT 494
FT /note="G -> S (in MPS4B; loss of galactosidase activity)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17664528"
FT /id="VAR_062369"
FT VARIANT 500
FT /note="T -> A (in MPS4B; mild form; 2.1% of wild-type
FT galactosidase activity; dbSNP:rs72555368)"
FT /evidence="ECO:0000269|PubMed:11511921,
FT ECO:0000269|PubMed:12393180, ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:19472408"
FT /id="VAR_013554"
FT VARIANT 509
FT /note="W -> C (in MPS4B; also in a patient with a slowly
FT progressive form of GM1-gangliosidosis; loss of
FT galactosidase activity; dbSNP:rs72555363)"
FT /evidence="ECO:0000269|PubMed:16538002,
FT ECO:0000269|PubMed:1928092, ECO:0000269|PubMed:9203065"
FT /id="VAR_003337"
FT VARIANT 514
FT /note="L -> P (in GM1G1; decrease in galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074064"
FT VARIANT 521
FT /note="R -> C (in GM1G1; mild phenotype; unknown
FT pathological significance; reduction of galactosidase
FT activity; dbSNP:rs4302331)"
FT /evidence="ECO:0000269|PubMed:10338095,
FT ECO:0000269|PubMed:15714521, ECO:0000269|PubMed:16641997,
FT ECO:0000269|PubMed:16941474, ECO:0000269|PubMed:17664528,
FT ECO:0000269|PubMed:25936995"
FT /id="VAR_008680"
FT VARIANT 532
FT /note="S -> G (results in near-normal activity
FT corresponding to 60%-100% of the wild-type depending on the
FT expression system; dbSNP:rs73826339)"
FT /evidence="ECO:0000269|PubMed:10338095,
FT ECO:0000269|PubMed:10839995, ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17664528, ECO:0000269|Ref.28"
FT /id="VAR_008681"
FT VARIANT 549
FT /note="P -> L (in GM1G1; dbSNP:rs776327443)"
FT /evidence="ECO:0000269|PubMed:17309651"
FT /id="VAR_037944"
FT VARIANT 554
FT /note="G -> E (in GM1-gangliosidosis; unclassified clinical
FT type)"
FT /evidence="ECO:0000269|PubMed:17309651"
FT /id="VAR_037945"
FT VARIANT 578
FT /note="K -> R (in GM1G1; dbSNP:rs371582179)"
FT /evidence="ECO:0000269|PubMed:8213816"
FT /id="VAR_008682"
FT VARIANT 579
FT /note="G -> D (in GM1G1 and GM1G2; loss of galactosidase
FT activity; severe mutation; dbSNP:rs746350513)"
FT /evidence="ECO:0000269|PubMed:10737981,
FT ECO:0000269|PubMed:15714521"
FT /id="VAR_013555"
FT VARIANT 590
FT /note="R -> C (in GM1G1; loss of galactosidase activity;
FT dbSNP:rs794727165)"
FT /evidence="ECO:0000269|PubMed:16941474,
FT ECO:0000269|PubMed:17309651, ECO:0000269|PubMed:17664528"
FT /id="VAR_037946"
FT VARIANT 590
FT /note="R -> H (in GM1G2; dbSNP:rs398123351)"
FT /evidence="ECO:0000269|PubMed:8213816"
FT /id="VAR_008683"
FT VARIANT 591
FT /note="Y -> C (in GM1G1; with cardiac involvement in some
FT patients; loss of galactosidase activity; severe mutation;
FT causes a rapid degradation of the protein precursor;
FT dbSNP:rs72555371)"
FT /evidence="ECO:0000269|PubMed:10737981,
FT ECO:0000269|PubMed:15714521, ECO:0000269|Ref.31"
FT /id="VAR_008684"
FT VARIANT 591
FT /note="Y -> N (in GM1G1; with cardiac involvement in some
FT patients; loss of galactosidase activity; severe mutation;
FT causes a rapid degradation of the protein precursor;
FT dbSNP:rs72555373)"
FT /evidence="ECO:0000269|PubMed:10737981,
FT ECO:0000269|PubMed:15714521, ECO:0000269|Ref.31"
FT /id="VAR_008685"
FT VARIANT 595
FT /note="R -> W (reduction of galactosidase activity;
FT dbSNP:rs201807974)"
FT /evidence="ECO:0000269|PubMed:17661814"
FT /id="VAR_037947"
FT VARIANT 597
FT /note="P -> L (in GM1G2; decrease in galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074065"
FT VARIANT 597
FT /note="P -> S (in GM1G1; 2.1% of wild-type galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:19472408"
FT /id="VAR_062370"
FT VARIANT 600
FT /note="T -> I (in GM1G2; decrease in galactosidase
FT activity)"
FT /evidence="ECO:0000269|PubMed:25936995"
FT /id="VAR_074066"
FT VARIANT 632
FT /note="E -> G (in GM1G2)"
FT /evidence="ECO:0000269|PubMed:8213816"
FT /id="VAR_008686"
FT CONFLICT 89
FT /note="H -> Y (in Ref. 4; BAH13196)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="R -> A (in Ref. 1; AAA51822)"
FT /evidence="ECO:0000305"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:3THD"
FT TURN 36..39
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 51..54
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 57..59
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 65..74
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 86..89
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 104..113
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 117..121
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 131..134
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 137..141
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 152..169
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 170..172
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 174..176
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 178..184
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:3WF0"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 197..211
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 213..224
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 225..231
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 236..241
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 248..258
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 265..272
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 286..298
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 302..306
FT /evidence="ECO:0007829|PDB:3THD"
FT TURN 322..324
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 345..354
FT /evidence="ECO:0007829|PDB:3THD"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 375..378
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 380..384
FT /evidence="ECO:0007829|PDB:3THD"
FT TURN 385..388
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 389..392
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 398..402
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 407..409
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 413..421
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 426..433
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 439..447
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 450..456
FT /evidence="ECO:0007829|PDB:3THD"
FT TURN 457..459
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 462..467
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 472..478
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 487..489
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 509..513
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 516..521
FT /evidence="ECO:0007829|PDB:3THD"
FT TURN 522..527
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 550..556
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 568..572
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 578..583
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 586..591
FT /evidence="ECO:0007829|PDB:3THD"
FT TURN 593..595
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 601..603
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 605..607
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 610..612
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 614..622
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 627..629
FT /evidence="ECO:0007829|PDB:3THD"
FT HELIX 631..633
FT /evidence="ECO:0007829|PDB:3THD"
FT STRAND 634..641
FT /evidence="ECO:0007829|PDB:3THD"
SQ SEQUENCE 677 AA; 76075 MW; 74421586B1BCFECA CRC64;
MPGFLVRILP LLLVLLLLGP TRGLRNATQR MFEIDYSRDS FLKDGQPFRY ISGSIHYSRV
PRFYWKDRLL KMKMAGLNAI QTYVPWNFHE PWPGQYQFSE DHDVEYFLRL AHELGLLVIL
RPGPYICAEW EMGGLPAWLL EKESILLRSS DPDYLAAVDK WLGVLLPKMK PLLYQNGGPV
ITVQVENEYG SYFACDFDYL RFLQKRFRHH LGDDVVLFTT DGAHKTFLKC GALQGLYTTV
DFGTGSNITD AFLSQRKCEP KGPLINSEFY TGWLDHWGQP HSTIKTEAVA SSLYDILARG
ASVNLYMFIG GTNFAYWNGA NSPYAAQPTS YDYDAPLSEA GDLTEKYFAL RNIIQKFEKV
PEGPIPPSTP KFAYGKVTLE KLKTVGAALD ILCPSGPIKS LYPLTFIQVK QHYGFVLYRT
TLPQDCSNPA PLSSPLNGVH DRAYVAVDGI PQGVLERNNV ITLNITGKAG ATLDLLVENM
GRVNYGAYIN DFKGLVSNLT LSSNILTDWT IFPLDTEDAV RSHLGGWGHR DSGHHDEAWA
HNSSNYTLPA FYMGNFSIPS GIPDLPQDTF IQFPGWTKGQ VWINGFNLGR YWPARGPQLT
LFVPQHILMT SAPNTITVLE LEWAPCSSDD PELCAVTFVD RPVIGSSVTY DHPSKPVEKR
LMPPPPQKNK DSWLDHV
