BGLR_HUMAN
ID BGLR_HUMAN Reviewed; 651 AA.
AC P08236; B4E1F6; E9PCV0; Q549U0; Q96CL9;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=Beta-glucuronidase;
DE EC=3.2.1.31 {ECO:0000305|PubMed:3355537};
DE AltName: Full=Beta-G1;
DE Flags: Precursor;
GN Name=GUSB;
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), VARIANT PRO-649, AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Placenta;
RX PubMed=3468507; DOI=10.1073/pnas.84.3.685;
RA Oshima A., Kyle J.W., Miller R.D., Hoffmann J.W., Powell P.P., Grubb J.H.,
RA Sly W.S., Tropak M., Guise K.S., Gravel R.A.;
RT "Cloning, sequencing, and expression of cDNA for human beta-
RT glucuronidase.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:685-689(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT PRO-649.
RC TISSUE=Lung;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-70.
RX PubMed=1916806; DOI=10.1016/0888-7543(91)90192-h;
RA Shipley J.M., Miller R.D., Wu B.M., Grubb J.H., Christensen S.G.,
RA Kyle J.W., Sly W.S.;
RT "Analysis of the 5' flanking region of the human beta-glucuronidase gene.";
RL Genomics 10:1009-1018(1991).
RN [9]
RP PROTEIN SEQUENCE OF 23-32 AND 160-175.
RC TISSUE=Placenta;
RX PubMed=1311180; DOI=10.1515/bchm3.1992.373.1.57;
RA Tanaka J., Gasa S., Sakurada K., Miyazaki T., Kasai M., Makita A.;
RT "Characterization of the subunits and sugar moiety of human placental and
RT leukemic beta-glucuronidase.";
RL Biol. Chem. Hoppe-Seyler 373:57-62(1992).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 520-585.
RC TISSUE=Fibroblast;
RX PubMed=3924735; DOI=10.1016/0378-1119(85)90300-2;
RA Guise K.S., Korneluk R.G., Waye J., Lamhonwah A.-M., Quan F., Palmer R.,
RA Ganschow R.E., Sly W.S., Gravel R.A.;
RT "Isolation and expression in Escherichia coli of a cDNA clone encoding
RT human beta-glucuronidase.";
RL Gene 34:105-110(1985).
RN [11]
RP INHIBITION BY L-ASPARTIC ACID.
RX PubMed=11568288; DOI=10.1203/00006450-200110000-00007;
RA Kreamer B.L., Siegel F.L., Gourley G.R.;
RT "A novel inhibitor of beta-glucuronidase: L-aspartic acid.";
RL Pediatr. Res. 50:460-466(2001).
RN [12]
RP CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=3355537; DOI=10.1042/bj2500547;
RA Powell P.P., Kyle J.W., Miller R.D., Pantano J., Grubb J.H., Sly W.S.;
RT "Rat liver beta-glucuronidase. cDNA cloning, sequence comparisons and
RT expression of a chimeric protein in COS cells.";
RL Biochem. J. 250:547-555(1988).
RN [13]
RP GLYCOSYLATION AT ASN-272.
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 [14]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-272.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [15]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-173; ASN-272 AND ASN-631.
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 [16]
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 [17]
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 [18]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS).
RX PubMed=8599764; DOI=10.1038/nsb0496-375;
RA Jain S., Drendel W.B., Chen Z.W., Mathews F.S., Sly W.S., Grubb J.H.;
RT "Structure of human beta-glucuronidase reveals candidate lysosomal
RT targeting and active-site motifs.";
RL Nat. Struct. Biol. 3:375-381(1996).
RN [19]
RP REVIEW ON VARIANTS.
RX PubMed=19224584; DOI=10.1002/humu.20828;
RA Tomatsu S., Montano A.M., Dung V.C., Grubb J.H., Sly W.S.;
RT "Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly
RT Syndrome).";
RL Hum. Mutat. 30:511-519(2009).
RN [20]
RP VARIANT MPS7 TRP-216.
RX PubMed=8111412; DOI=10.1002/humu.1380020604;
RA Vervoort R., Lissens W., Liebaers I.;
RT "Molecular analysis of a patient with hydrops fetalis caused by beta-
RT glucuronidase deficiency, and evidence for additional pseudogenes.";
RL Hum. Mutat. 2:443-445(1993).
RN [21]
RP VARIANTS MPS7 VAL-354 AND TRP-611.
RX PubMed=8111413; DOI=10.1002/humu.1380020605;
RA Wu B.M., Sly W.S.;
RT "Mutational studies in a patient with the hydrops fetalis form of
RT mucopolysaccharidosis type VII.";
RL Hum. Mutat. 2:446-457(1993).
RN [22]
RP VARIANTS MPS7 CYS-382 AND VAL-619.
RX PubMed=1702266;
RA Tomatsu S., Fukuda S., Sukegawa K., Ikedo Y., Yamada S., Yamada Y.,
RA Sasaki T., Okamoto H., Kuwahara T., Yamaguchi S., Kiman T., Shintaku H.,
RA Isshiki G., Orii T.;
RT "Mucopolysaccharidosis type VII: characterization of mutations and
RT molecular heterogeneity.";
RL Am. J. Hum. Genet. 48:89-96(1991).
RN [23]
RP VARIANT MPS7 CYS-627.
RX PubMed=7680524;
RA Shipley J.M., Klinkenberg M., Wu B.M., Bachinsky D.R., Grubb J.H.,
RA Sly W.S.;
RT "Mutational analysis of a patient with mucopolysaccharidosis type VII, and
RT identification of pseudogenes.";
RL Am. J. Hum. Genet. 52:517-526(1993).
RN [24]
RP VARIANT MPS7 PHE-176, AND VARIANT PRO-649.
RX PubMed=8089138; DOI=10.1016/s0021-9258(17)31569-7;
RA Wu B.M., Tomatsu S., Fukuda S., Sukegawa K., Orii T., Sly W.S.;
RT "Overexpression rescues the mutant phenotype of L176F mutation causing
RT beta-glucuronidase deficiency mucopolysaccharidosis in two Mennonite
RT siblings.";
RL J. Biol. Chem. 269:23681-23688(1994).
RN [25]
RP VARIANT MPS7 PHE-176, VARIANT ASN-152, AND CHARACTERIZATION OF VARIANT
RP ASN-152.
RX PubMed=7573038;
RA Vervoort R., Islam M.R., Sly W., Chabas A., Wevers R., de Jong J.,
RA Liebaers I., Lissens W.;
RT "A pseudodeficiency allele (D152N) of the human beta-glucuronidase gene.";
RL Am. J. Hum. Genet. 57:798-804(1995).
RN [26]
RP VARIANTS MPS7 SER-148 AND CYS-495.
RX PubMed=7633414; DOI=10.1093/hmg/4.4.651;
RA Yamada S., Tomatsu S., Sly W.S., Islam R., Wenger D.A., Fukuda S.,
RA Sukegawa K., Orii T.;
RT "Four novel mutations in mucopolysaccharidosis type VII including a unique
RT base substitution in exon 10 of the beta-glucuronidase gene that creates a
RT novel 5'-splice site.";
RL Hum. Mol. Genet. 4:651-655(1995).
RN [27]
RP VARIANTS MPS7 ARG-136; LYS-150; PHE-176; TRP-216; CYS-320; SER-320;
RP TYR-351; CYS-374; CYS-382; HIS-382; PRO-435; TRP-477; CYS-508; ASP-572;
RP ASN-606 AND CYS-627.
RX PubMed=8644704;
RA Vervoort R., Islam M.R., Sly W.S., Zabot M.T., Kleijer W.J., Chabas A.,
RA Fensom A., Young E.P., Liebaers I., Lissens W.;
RT "Molecular analysis of patients with beta-glucuronidase deficiency
RT presenting as hydrops fetalis or as early mucopolysaccharidosis VII.";
RL Am. J. Hum. Genet. 58:457-471(1996).
RN [28]
RP VARIANTS MPS7 SER-408 AND LEU-415.
RX PubMed=8707294; DOI=10.1007/s004390050207;
RA Islam M.R., Vervoort R., Lissens W., Hoo J.J., Valentino L.A., Sly W.S.;
RT "beta-Glucuronidase P408S, P415L mutations: evidence that both mutations
RT combine to produce an MPS VII allele in certain Mexican patients.";
RL Hum. Genet. 98:281-284(1996).
RN [29]
RP VARIANT MPS7 PHE-52, AND CHARACTERIZATION OF VARIANT MPS7 PHE-52.
RX PubMed=9099834; DOI=10.1007/s004390050389;
RA Vervoort R., Buist N.R., Kleijer W.J., Wevers R., Fryns J.P., Liebaers I.,
RA Lissens W.;
RT "Molecular analysis of the beta-glucuronidase gene: novel mutations in
RT mucopolysaccharidosis type VII and heterogeneity of the polyadenylation
RT region.";
RL Hum. Genet. 99:462-468(1997).
RN [30]
RP VARIANT ASN-152, AND VARIANTS MPS7 GLY-38 AND HIS-626.
RX PubMed=9490302; DOI=10.1007/s004390050656;
RA Vervoort R., Gitzelmann R., Bosshard N., Maire I., Liebaers I., Lissens W.;
RT "Low beta-glucuronidase enzyme activity and mutations in the human beta-
RT glucuronidase gene in mild mucopolysaccharidosis type VII, pseudodeficiency
RT and a heterozygote.";
RL Hum. Genet. 102:69-78(1998).
RN [31]
RP VARIANT MPS7 PHE-176.
RX PubMed=12859417; DOI=10.1034/j.1399-0004.2003.00119.x;
RA Schwartz I., Silva L.R., Leistner S., Todeschini L.A., Burin M.G.,
RA Pina-Neto J.M., Islam R.M., Shah G.N., Sly W.S., Giugliani R.;
RT "Mucopolysaccharidosis VII: clinical, biochemical and molecular
RT investigation of a Brazilian family.";
RL Clin. Genet. 64:172-175(2003).
RN [32]
RP VARIANTS MPS7 ASN-350 AND LEU-577, AND CHARACTERIZATION OF VARIANT MPS7
RP ASN-350 LEU-577.
RX PubMed=12522561; DOI=10.1007/s00439-002-0849-5;
RA Storch S., Wittenstein B., Islam R., Ullrich K., Sly W.S., Braulke T.;
RT "Mutational analysis in longest known survivor of mucopolysaccharidosis
RT type VII.";
RL Hum. Genet. 112:190-194(2003).
CC -!- FUNCTION: Plays an important role in the degradation of dermatan and
CC keratan sulfates.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-glucuronoside + H2O = an alcohol + D-glucuronate;
CC Xref=Rhea:RHEA:17633, ChEBI:CHEBI:15377, ChEBI:CHEBI:30879,
CC ChEBI:CHEBI:58720, ChEBI:CHEBI:83411; EC=3.2.1.31;
CC Evidence={ECO:0000305|PubMed:3355537};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17634;
CC Evidence={ECO:0000305|PubMed:3355537};
CC -!- ACTIVITY REGULATION: Inhibited by L-aspartic acid.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Long;
CC IsoId=P08236-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P08236-2; Sequence=VSP_001799;
CC Name=3;
CC IsoId=P08236-3; Sequence=VSP_054830;
CC -!- PTM: N-linked glycosylated with 3 to 4 oligosaccharide chains.
CC {ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:16335952,
CC ECO:0000269|PubMed:19159218}.
CC -!- DISEASE: Mucopolysaccharidosis 7 (MPS7) [MIM:253220]: A form of
CC mucopolysaccharidosis, a group of lysosomal storage diseases
CC characterized by defective degradation of glycosaminoglycans, resulting
CC in their excessive accumulation and secretion. The diseases are
CC progressive and often display a wide spectrum of clinical severity.
CC MPS7 is an autosomal recessive form with a highly variable phenotype,
CC ranging from severe lethal hydrops fetalis to mild forms with survival
CC into adulthood. Most patients with the intermediate phenotype show
CC hepatomegaly, skeletal anomalies, coarse facies, and variable degrees
CC of mental impairment. {ECO:0000269|PubMed:12522561,
CC ECO:0000269|PubMed:12859417, ECO:0000269|PubMed:1702266,
CC ECO:0000269|PubMed:7573038, ECO:0000269|PubMed:7633414,
CC ECO:0000269|PubMed:7680524, ECO:0000269|PubMed:8089138,
CC ECO:0000269|PubMed:8111412, ECO:0000269|PubMed:8111413,
CC ECO:0000269|PubMed:8644704, ECO:0000269|PubMed:8707294,
CC ECO:0000269|PubMed:9099834, ECO:0000269|PubMed:9490302}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 2 family. {ECO:0000305}.
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DR EMBL; M15182; AAA52561.1; -; mRNA.
DR EMBL; AK303819; BAG64768.1; -; mRNA.
DR EMBL; AK223406; BAD97126.1; -; mRNA.
DR EMBL; AC073261; AAQ96851.1; -; Genomic_DNA.
DR EMBL; CH236961; EAL23740.1; -; Genomic_DNA.
DR EMBL; CH471140; EAX07951.1; -; Genomic_DNA.
DR EMBL; BC014142; AAH14142.1; -; mRNA.
DR EMBL; M65002; AAA52622.1; -; Genomic_DNA.
DR EMBL; M10618; AAA52621.1; -; mRNA.
DR EMBL; S72462; AAD14101.1; -; Genomic_DNA.
DR CCDS; CCDS5530.1; -. [P08236-1]
DR CCDS; CCDS64665.1; -. [P08236-3]
DR PIR; A26581; A26581.
DR RefSeq; NP_000172.2; NM_000181.3. [P08236-1]
DR RefSeq; NP_001271219.1; NM_001284290.1. [P08236-3]
DR RefSeq; NP_001280033.1; NM_001293104.1.
DR RefSeq; NP_001280034.1; NM_001293105.1.
DR RefSeq; XP_005250354.1; XM_005250297.3. [P08236-2]
DR PDB; 1BHG; X-ray; 2.53 A; A/B=21-633.
DR PDB; 3HN3; X-ray; 1.70 A; A/B/D/E=21-633.
DR PDBsum; 1BHG; -.
DR PDBsum; 3HN3; -.
DR AlphaFoldDB; P08236; -.
DR SMR; P08236; -.
DR BioGRID; 109245; 91.
DR DIP; DIP-29724N; -.
DR IntAct; P08236; 11.
DR MINT; P08236; -.
DR STRING; 9606.ENSP00000302728; -.
DR BindingDB; P08236; -.
DR ChEMBL; CHEMBL2728; -.
DR DrugBank; DB09301; Chondroitin sulfate.
DR DrugBank; DB11793; Niraparib.
DR DrugBank; DB09340; Tyropanoic acid.
DR CAZy; GH2; Glycoside Hydrolase Family 2.
DR GlyConnect; 1037; 11 N-Linked glycans (3 sites).
DR GlyGen; P08236; 6 sites, 11 N-linked glycans (3 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P08236; -.
DR PhosphoSitePlus; P08236; -.
DR BioMuta; GUSB; -.
DR DMDM; 146345377; -.
DR EPD; P08236; -.
DR jPOST; P08236; -.
DR MassIVE; P08236; -.
DR MaxQB; P08236; -.
DR PaxDb; P08236; -.
DR PeptideAtlas; P08236; -.
DR PRIDE; P08236; -.
DR ProteomicsDB; 19519; -.
DR ProteomicsDB; 52092; -. [P08236-1]
DR ProteomicsDB; 52093; -. [P08236-2]
DR Antibodypedia; 14064; 392 antibodies from 36 providers.
DR DNASU; 2990; -.
DR Ensembl; ENST00000304895.9; ENSP00000302728.4; ENSG00000169919.17. [P08236-1]
DR Ensembl; ENST00000421103.5; ENSP00000391390.1; ENSG00000169919.17. [P08236-3]
DR GeneID; 2990; -.
DR KEGG; hsa:2990; -.
DR MANE-Select; ENST00000304895.9; ENSP00000302728.4; NM_000181.4; NP_000172.2.
DR UCSC; uc003tun.4; human. [P08236-1]
DR CTD; 2990; -.
DR DisGeNET; 2990; -.
DR GeneCards; GUSB; -.
DR HGNC; HGNC:4696; GUSB.
DR HPA; ENSG00000169919; Low tissue specificity.
DR MalaCards; GUSB; -.
DR MIM; 253220; phenotype.
DR MIM; 611499; gene.
DR neXtProt; NX_P08236; -.
DR OpenTargets; ENSG00000169919; -.
DR Orphanet; 584; Mucopolysaccharidosis type 7.
DR PharmGKB; PA29075; -.
DR VEuPathDB; HostDB:ENSG00000169919; -.
DR eggNOG; KOG2024; Eukaryota.
DR GeneTree; ENSGT00390000001752; -.
DR HOGENOM; CLU_006501_6_1_1; -.
DR InParanoid; P08236; -.
DR OMA; IHDHVGW; -.
DR OrthoDB; 653343at2759; -.
DR PhylomeDB; P08236; -.
DR TreeFam; TF300685; -.
DR BRENDA; 3.2.1.31; 2681.
DR PathwayCommons; P08236; -.
DR Reactome; R-HSA-2024096; HS-GAG degradation.
DR Reactome; R-HSA-2160916; Hyaluronan uptake and degradation.
DR Reactome; R-HSA-2206292; MPS VII - Sly syndrome.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P08236; -.
DR BioGRID-ORCS; 2990; 14 hits in 1081 CRISPR screens.
DR ChiTaRS; GUSB; human.
DR EvolutionaryTrace; P08236; -.
DR GeneWiki; GUSB; -.
DR GenomeRNAi; 2990; -.
DR Pharos; P08236; Tchem.
DR PRO; PR:P08236; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; P08236; protein.
DR Bgee; ENSG00000169919; Expressed in endometrium epithelium and 206 other tissues.
DR ExpressionAtlas; P08236; baseline and differential.
DR Genevisible; P08236; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0004566; F:beta-glucuronidase activity; IBA:GO_Central.
DR GO; GO:0030246; F:carbohydrate binding; IBA:GO_Central.
DR GO; GO:0019904; F:protein domain specific binding; IPI:AgBase.
DR GO; GO:0005102; F:signaling receptor binding; IPI:AgBase.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0019391; P:glucuronoside catabolic process; IBA:GO_Central.
DR GO; GO:0006027; P:glycosaminoglycan catabolic process; TAS:ProtInc.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR036156; Beta-gal/glucu_dom_sf.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR006101; Glyco_hydro_2.
DR InterPro; IPR023232; Glyco_hydro_2_AS.
DR InterPro; IPR006103; Glyco_hydro_2_cat.
DR InterPro; IPR023230; Glyco_hydro_2_CS.
DR InterPro; IPR006102; Glyco_hydro_2_Ig-like.
DR InterPro; IPR006104; Glyco_hydro_2_N.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR013783; Ig-like_fold.
DR Pfam; PF00703; Glyco_hydro_2; 1.
DR Pfam; PF02836; Glyco_hydro_2_C; 1.
DR Pfam; PF02837; Glyco_hydro_2_N; 1.
DR PRINTS; PR00132; GLHYDRLASE2.
DR SUPFAM; SSF49303; SSF49303; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF51445; SSF51445; 1.
DR PROSITE; PS00719; GLYCOSYL_HYDROL_F2_1; 1.
DR PROSITE; PS00608; GLYCOSYL_HYDROL_F2_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Direct protein sequencing;
KW Disease variant; Glycoprotein; Glycosidase; Hydrolase; Lysosome;
KW Mucopolysaccharidosis; Reference proteome; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:1311180"
FT CHAIN 23..651
FT /note="Beta-glucuronidase"
FT /id="PRO_0000012161"
FT ACT_SITE 451
FT /note="Proton donor"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:12754519,
FT ECO:0000269|PubMed:16335952, ECO:0000269|PubMed:19159218"
FT CARBOHYD 420
FT /note="N-linked (GlcNAc...) asparagine"
FT CARBOHYD 631
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:19159218"
FT VAR_SEQ 159..304
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054830"
FT VAR_SEQ 305..355
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_001799"
FT VARIANT 30
FT /note="P -> S (in MPS7; dbSNP:rs747792546)"
FT /id="VAR_058511"
FT VARIANT 38
FT /note="C -> G (in MPS7; very mild phenotype;
FT dbSNP:rs779499448)"
FT /evidence="ECO:0000269|PubMed:9490302"
FT /id="VAR_037914"
FT VARIANT 52
FT /note="S -> F (in MPS7; loss of activity;
FT dbSNP:rs1424546265)"
FT /evidence="ECO:0000269|PubMed:9099834"
FT /id="VAR_037915"
FT VARIANT 136
FT /note="G -> R (in MPS7; dbSNP:rs1417426295)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037916"
FT VARIANT 148
FT /note="P -> S (in MPS7; dbSNP:rs121918177)"
FT /evidence="ECO:0000269|PubMed:7633414"
FT /id="VAR_037917"
FT VARIANT 150
FT /note="E -> K (in MPS7)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037918"
FT VARIANT 152
FT /note="D -> G (in MPS7)"
FT /id="VAR_058512"
FT VARIANT 152
FT /note="D -> N (likely benign variant; associated with beta-
FT glucuronidase pseudodeficiency with no clinical
FT consequences; reduced activity levels; dbSNP:rs149606212)"
FT /evidence="ECO:0000269|PubMed:7573038,
FT ECO:0000269|PubMed:9490302"
FT /id="VAR_037919"
FT VARIANT 176
FT /note="L -> F (in MPS7; dbSNP:rs121918181)"
FT /evidence="ECO:0000269|PubMed:12859417,
FT ECO:0000269|PubMed:7573038, ECO:0000269|PubMed:8089138,
FT ECO:0000269|PubMed:8644704"
FT /id="VAR_037920"
FT VARIANT 216
FT /note="R -> W (in MPS7; dbSNP:rs121918174)"
FT /evidence="ECO:0000269|PubMed:8111412,
FT ECO:0000269|PubMed:8644704"
FT /id="VAR_003196"
FT VARIANT 243
FT /note="L -> P (in MPS7)"
FT /id="VAR_058513"
FT VARIANT 320
FT /note="Y -> C (in MPS7)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037921"
FT VARIANT 320
FT /note="Y -> S (in MPS7; dbSNP:rs886044680)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037922"
FT VARIANT 339
FT /note="N -> S (in MPS7)"
FT /id="VAR_058514"
FT VARIANT 350
FT /note="K -> N (in MPS7; dbSNP:rs121918182)"
FT /evidence="ECO:0000269|PubMed:12522561"
FT /id="VAR_037923"
FT VARIANT 351
FT /note="H -> Y (in MPS7; dbSNP:rs191153460)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037924"
FT VARIANT 354
FT /note="A -> V (in MPS7; dbSNP:rs121918175)"
FT /evidence="ECO:0000269|PubMed:8111413"
FT /id="VAR_003197"
FT VARIANT 361..369
FT /note="Missing (in MPS7)"
FT /id="VAR_058515"
FT VARIANT 362
FT /note="D -> N (in MPS7; dbSNP:rs398123234)"
FT /id="VAR_058516"
FT VARIANT 364
FT /note="P -> L (in MPS7; dbSNP:rs771629102)"
FT /id="VAR_058517"
FT VARIANT 374
FT /note="R -> C (in MPS7; dbSNP:rs747572640)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037925"
FT VARIANT 376
FT /note="L -> F (in dbSNP:rs11559283)"
FT /id="VAR_055884"
FT VARIANT 382
FT /note="R -> C (in MPS7; dbSNP:rs121918173)"
FT /evidence="ECO:0000269|PubMed:1702266,
FT ECO:0000269|PubMed:8644704"
FT /id="VAR_003198"
FT VARIANT 382
FT /note="R -> H (in MPS7; dbSNP:rs764018631)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037926"
FT VARIANT 408
FT /note="P -> S (in MPS7; dbSNP:rs779091113)"
FT /evidence="ECO:0000269|PubMed:8707294"
FT /id="VAR_037927"
FT VARIANT 415
FT /note="P -> L (in MPS7; dbSNP:rs751025746)"
FT /evidence="ECO:0000269|PubMed:8707294"
FT /id="VAR_037928"
FT VARIANT 435
FT /note="R -> P (in MPS7)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037929"
FT VARIANT 477
FT /note="R -> W (in MPS7; dbSNP:rs774393243)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037930"
FT VARIANT 495
FT /note="Y -> C (in MPS7; dbSNP:rs121918178)"
FT /evidence="ECO:0000269|PubMed:7633414"
FT /id="VAR_037931"
FT VARIANT 508
FT /note="Y -> C (in MPS7)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037932"
FT VARIANT 540
FT /note="E -> K (in MPS7)"
FT /id="VAR_058518"
FT VARIANT 572
FT /note="G -> D (in MPS7)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037933"
FT VARIANT 577
FT /note="R -> L (in MPS7; loss of activity;
FT dbSNP:rs121918183)"
FT /evidence="ECO:0000269|PubMed:12522561"
FT /id="VAR_037934"
FT VARIANT 606
FT /note="K -> N (in MPS7)"
FT /evidence="ECO:0000269|PubMed:8644704"
FT /id="VAR_037935"
FT VARIANT 607
FT /note="G -> A (in MPS7; dbSNP:rs1250112198)"
FT /id="VAR_058519"
FT VARIANT 611
FT /note="R -> W (in MPS7; dbSNP:rs121918176)"
FT /evidence="ECO:0000269|PubMed:8111413"
FT /id="VAR_003199"
FT VARIANT 619
FT /note="A -> V (in MPS7; dbSNP:rs121918172)"
FT /evidence="ECO:0000269|PubMed:1702266"
FT /id="VAR_003200"
FT VARIANT 626
FT /note="Y -> H (in MPS7; very mild phenotype;
FT dbSNP:rs777613366)"
FT /evidence="ECO:0000269|PubMed:9490302"
FT /id="VAR_037936"
FT VARIANT 627
FT /note="W -> C (in MPS7; dbSNP:rs121918184)"
FT /evidence="ECO:0000269|PubMed:7680524,
FT ECO:0000269|PubMed:8644704"
FT /id="VAR_003201"
FT VARIANT 649
FT /note="L -> P (in dbSNP:rs9530)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:3468507, ECO:0000269|PubMed:8089138"
FT /id="VAR_016179"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:1BHG"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:1BHG"
FT HELIX 57..60
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 75..81
FT /evidence="ECO:0007829|PDB:3HN3"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 90..93
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 97..105
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 109..113
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 117..124
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 137..147
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 154..157
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 166..173
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 185..188
FT /evidence="ECO:0007829|PDB:3HN3"
FT TURN 192..194
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 200..203
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 218..238
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 241..252
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 256..263
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 265..267
FT /evidence="ECO:0007829|PDB:1BHG"
FT STRAND 269..282
FT /evidence="ECO:0007829|PDB:3HN3"
FT TURN 291..293
FT /evidence="ECO:0007829|PDB:1BHG"
FT STRAND 294..296
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 301..311
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 314..324
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 341..343
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 345..349
FT /evidence="ECO:0007829|PDB:3HN3"
FT TURN 355..357
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 363..376
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 380..382
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 390..399
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 402..406
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 415..417
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 420..437
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 443..451
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 457..473
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 479..483
FT /evidence="ECO:0007829|PDB:3HN3"
FT TURN 487..489
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 493..495
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 497..502
FT /evidence="ECO:0007829|PDB:3HN3"
FT TURN 505..507
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 508..510
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 514..516
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 517..532
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 536..540
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 559..574
FT /evidence="ECO:0007829|PDB:3HN3"
FT TURN 575..580
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 581..587
FT /evidence="ECO:0007829|PDB:3HN3"
FT STRAND 600..604
FT /evidence="ECO:0007829|PDB:3HN3"
FT HELIX 617..631
FT /evidence="ECO:0007829|PDB:3HN3"
SQ SEQUENCE 651 AA; 74732 MW; 6BA7B1D935C9ABBD CRC64;
MARGSAVAWA ALGPLLWGCA LGLQGGMLYP QESPSRECKE LDGLWSFRAD FSDNRRRGFE
EQWYRRPLWE SGPTVDMPVP SSFNDISQDW RLRHFVGWVW YEREVILPER WTQDLRTRVV
LRIGSAHSYA IVWVNGVDTL EHEGGYLPFE ADISNLVQVG PLPSRLRITI AINNTLTPTT
LPPGTIQYLT DTSKYPKGYF VQNTYFDFFN YAGLQRSVLL YTTPTTYIDD ITVTTSVEQD
SGLVNYQISV KGSNLFKLEV RLLDAENKVV ANGTGTQGQL KVPGVSLWWP YLMHERPAYL
YSLEVQLTAQ TSLGPVSDFY TLPVGIRTVA VTKSQFLING KPFYFHGVNK HEDADIRGKG
FDWPLLVKDF NLLRWLGANA FRTSHYPYAE EVMQMCDRYG IVVIDECPGV GLALPQFFNN
VSLHHHMQVM EEVVRRDKNH PAVVMWSVAN EPASHLESAG YYLKMVIAHT KSLDPSRPVT
FVSNSNYAAD KGAPYVDVIC LNSYYSWYHD YGHLELIQLQ LATQFENWYK KYQKPIIQSE
YGAETIAGFH QDPPLMFTEE YQKSLLEQYH LGLDQKRRKY VVGELIWNFA DFMTEQSPTR
VLGNKKGIFT RQRQPKSAAF LLRERYWKIA NETRYPHSVA KSQCLENSLF T
