ID HEXB_HUMAN Reviewed; 556 AA.
AC P07686;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 4.
DT 27-MAR-2024, entry version 234.
DE RecName: Full=Beta-hexosaminidase subunit beta {ECO:0000305};
DE EC=3.2.1.52 {ECO:0000269|PubMed:11329289, ECO:0000269|PubMed:11707436, ECO:0000269|PubMed:8123671, ECO:0000269|PubMed:8672428, ECO:0000269|PubMed:9694901};
DE AltName: Full=Beta-N-acetylhexosaminidase subunit beta;
DE Short=Hexosaminidase subunit B;
DE AltName: Full=Cervical cancer proto-oncogene 7 protein;
DE Short=HCC-7;
DE AltName: Full=N-acetyl-beta-glucosaminidase subunit beta;
DE Contains:
DE RecName: Full=Beta-hexosaminidase subunit beta chain B;
DE Contains:
DE RecName: Full=Beta-hexosaminidase subunit beta chain A;
DE Flags: Precursor;
GN Name=HEXB {ECO:0000312|HGNC:HGNC:4879}; ORFNames=HCC7;
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], AND VARIANT SER-62.
RX PubMed=3013851; DOI=10.1016/s0021-9258(19)83927-3;
RA Korneluk R.G., Mahuran D.J., Neote K., Klavins M.H., O'Dowd B.F.,
RA Tropak M., Willard H.F., Anderson M.-J., Lowden J.A., Gravel R.A.;
RT "Isolation of cDNA clones coding for the alpha-subunit of human beta-
RT hexosaminidase. Extensive homology between the alpha- and beta-subunits and
RT studies on Tay-Sachs disease.";
RL J. Biol. Chem. 261:8407-8413(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-62.
RX PubMed=2977375; DOI=10.1016/0888-7543(88)90116-4;
RA Neote K., Bapat B., Dumbrille-Ross A., Troxel C., Schuster S.M.,
RA Mahuran D.J., Gravel R.A.;
RT "Characterization of the human HEXB gene encoding lysosomal beta-
RT hexosaminidase.";
RL Genomics 3:279-286(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-62.
RX PubMed=2964638; DOI=10.1073/pnas.85.6.1883;
RA Proia R.L.;
RT "Gene encoding the human beta-hexosaminidase beta chain: extensive homology
RT of intron placement in the alpha- and beta-chain genes.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:1883-1887(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-62.
RA Kim J.W.;
RT "Identification of a new proto-oncogene in human cancers.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-62.
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 (AUG-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-62.
RC TISSUE=Skin;
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 [MRNA] OF 1-67, AND VARIANT SER-62.
RX PubMed=2971039; DOI=10.1016/s0021-9258(18)37728-7;
RA Sonderfeld-Fresko S., Proia R.L.;
RT "Synthesis and assembly of a catalytically active lysosomal enzyme, beta-
RT hexosaminidase B, in a cell-free system.";
RL J. Biol. Chem. 263:13463-13469(1988).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-52.
RX PubMed=2147427; DOI=10.1016/s0021-9258(17)45286-0;
RA Neote K., Brown C.A., Mahuran D.J., Gravel R.A.;
RT "Translation initiation in the HEXB gene encoding the beta-subunit of human
RT beta-hexosaminidase.";
RL J. Biol. Chem. 265:20799-20806(1990).
RN [10]
RP PROTEIN SEQUENCE OF 43-57 AND 122-151.
RX PubMed=2966076; DOI=10.1016/0014-5793(88)80699-9;
RA Stirling J., Leung A., Gravel R.A., Mahuran D.;
RT "Localization of the pro-sequence within the total deduced primary
RT structure of human beta-hexosaminidase B.";
RL FEBS Lett. 231:47-50(1988).
RN [11]
RP PROTEIN SEQUENCE OF 45-54 AND 315-324.
RX PubMed=2139028; DOI=10.1016/s0021-9258(19)39219-1;
RA Mahuran D.J.;
RT "Characterization of human placental beta-hexosaminidase I2. Proteolytic
RT processing intermediates of hexosaminidase A.";
RL J. Biol. Chem. 265:6794-6799(1990).
RN [12]
RP PROTEIN SEQUENCE OF 50-59.
RX PubMed=2525487; DOI=10.1016/0014-5793(89)80649-0;
RA Hubbes M., Callahan J., Gravel R., Mahuran D.;
RT "The amino-terminal sequences in the pro-alpha and -beta polypeptides of
RT human lysosomal beta-hexosaminidase A and B are retained in the mature
RT isozymes.";
RL FEBS Lett. 249:316-320(1989).
RN [13]
RP PROTEIN SEQUENCE OF 122-151 AND 315-340.
RX PubMed=2965147; DOI=10.1016/s0021-9258(18)68826-x;
RA Mahuran D.J., Neote K., Klavins M.H., Leung A., Gravel R.A.;
RT "Proteolytic processing of pro-alpha and pro-beta precursors from human
RT beta-hexosaminidase. Generation of the mature alpha and beta a beta b
RT subunits.";
RL J. Biol. Chem. 263:4612-4618(1988).
RN [14]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 226-283.
RX PubMed=2579389; DOI=10.1073/pnas.82.4.1184;
RA O'Dowd B.F., Quan F., Willard H.F., Lamhonwah A.-M., Korneluk R.G.,
RA Lowden J.A., Gravel R.A., Mahuran D.J.;
RT "Isolation of cDNA clones coding for the beta subunit of human beta-
RT hexosaminidase.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:1184-1188(1985).
RN [15]
RP STRUCTURE OF CARBOHYDRATES.
RX PubMed=2971395; DOI=10.1021/bi00414a041;
RA O'Dowd B.F., Cumming D.A., Gravel R.A., Mahuran D.J.;
RT "Oligosaccharide structure and amino acid sequence of the major
RT glycopeptides of mature human beta-hexosaminidase.";
RL Biochemistry 27:5216-5226(1988).
RN [16]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=8123671; DOI=10.1016/0304-4165(94)90118-x;
RA Novak A., Callahan J.W., Lowden J.A.;
RT "Classification of disorders of GM2 ganglioside hydrolysis using 3H-GM2 as
RT substrate.";
RL Biochim. Biophys. Acta 1199:215-223(1994).
RN [17]
RP MUTAGENESIS OF ARG-211, FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT.
RX PubMed=8672428; DOI=10.1021/bi9524575;
RA Hou Y., Tse R., Mahuran D.J.;
RT "Direct determination of the substrate specificity of the alpha-active site
RT in heterodimeric beta-hexosaminidase A.";
RL Biochemistry 35:3963-3969(1996).
RN [18]
RP GLYCOSYLATION AT ASN-327.
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 [19]
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, AND
RP MUTAGENESIS OF ASP-241; ASP-354; GLU-355 AND GLU-491.
RX PubMed=11329289; DOI=10.1021/bi002018s;
RA Hou Y., Vocadlo D.J., Leung A., Withers S.G., Mahuran D.;
RT "Characterization of the Glu and Asp residues in the active site of human
RT beta-hexosaminidase B.";
RL Biochemistry 40:2201-2209(2001).
RN [20]
RP DISULFIDE BONDS, AND GLYCOSYLATION AT ASN-84; ASN-142; ASN-190 AND ASN-327.
RX PubMed=11447134; DOI=10.1093/glycob/11.7.549;
RA Schuette C.G., Weisgerber J., Sandhoff K.;
RT "Complete analysis of the glycosylation and disulfide bond pattern of human
RT beta-hexosaminidase B by MALDI-MS.";
RL Glycobiology 11:549-556(2001).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=11707436; DOI=10.1074/jbc.m105457200;
RA Hepbildikler S.T., Sandhoff R., Kolzer M., Proia R.L., Sandhoff K.;
RT "Physiological substrates for human lysosomal beta -hexosaminidase S.";
RL J. Biol. Chem. 277:2562-2572(2002).
RN [22]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-84 AND ASN-327.
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 [23]
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 [24]
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 [25]
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 [26]
RP 3D-STRUCTURE MODELING.
RX PubMed=8673609; DOI=10.1038/nsb0796-638;
RA Tews I., Perrakis A., Oppenheim A., Dauter Z., Wilson K.S., Vorgias C.E.;
RT "Bacterial chitobiase structure provides insight into catalytic mechanism
RT and the basis of Tay-Sachs disease.";
RL Nat. Struct. Biol. 3:638-648(1996).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 50-556, AND DISULFIDE BONDS.
RX PubMed=12662933; DOI=10.1016/s0022-2836(03)00216-x;
RA Mark B.L., Mahuran D.J., Cherney M.M., Zhao D., Knapp S., James M.N.;
RT "Crystal structure of human beta-hexosaminidase B: understanding the
RT molecular basis of Sandhoff and Tay-Sachs disease.";
RL J. Mol. Biol. 327:1093-1109(2003).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 42-556, AND DISULFIDE BONDS.
RX PubMed=12706724; DOI=10.1016/s0022-2836(03)00311-5;
RA Maier T., Strater N., Schuette C.G., Klingenstein R., Sandhoff K.,
RA Saenger W.;
RT "The X-ray crystal structure of human beta-hexosaminidase B provides new
RT insights into Sandhoff disease.";
RL J. Mol. Biol. 328:669-681(2003).
RN [29]
RP REVIEW ON VARIANTS.
RX PubMed=1825792; DOI=10.1016/0925-4439(91)90044-a;
RA Mahuran D.J.;
RT "The biochemistry of HEXA and HEXB gene mutations causing GM2
RT gangliosidosis.";
RL Biochim. Biophys. Acta 1096:87-94(1991).
RN [30]
RP VARIANT GM2G2 SER-456, AND VARIANT VAL-207.
RX PubMed=1720305; DOI=10.1016/s0006-291x(05)81388-9;
RA Banerjee P., Siciliano L., Oliveri D., McCabe N.R., Boyers M.J.,
RA Horwitz A.L., Li S.-C., Dawson G.;
RT "Molecular basis of an adult form of beta-hexosaminidase B deficiency with
RT motor neuron disease.";
RL Biochem. Biophys. Res. Commun. 181:108-115(1991).
RN [31]
RP VARIANT GM2G2 LEU-417.
RX PubMed=1531140; DOI=10.1016/s0021-9258(18)45894-2;
RA Wakamatsu N., Kobayashi H., Miyatake T., Tsuji S.;
RT "A novel exon mutation in the human beta-hexosaminidase beta subunit gene
RT affects 3' splice site selection.";
RL J. Biol. Chem. 267:2406-2413(1992).
RN [32]
RP VARIANT GM2G2 GLN-505.
RX PubMed=8357844; DOI=10.1016/0925-4439(93)90134-m;
RA Bolhuis P.A., Ponne N.J., Bikker H., Baas F., Vianney de Jong J.M.B.;
RT "Molecular basis of an adult form of Sandhoff disease: substitution of
RT glutamine for arginine at position 505 of the beta-chain of beta-
RT hexosaminidase results in a labile enzyme.";
RL Biochim. Biophys. Acta 1182:142-146(1993).
RN [33]
RP VARIANT GM2G2 TYR-534.
RX PubMed=7626071; DOI=10.1006/bbrc.1995.2007;
RA Kuroki Y., Itoh K., Nadaoka Y., Tanaka T., Sakuraba H.;
RT "A novel missense mutation (C522Y) is present in the beta-hexosaminidase
RT beta-subunit gene of a Japanese patient with infantile Sandhoff disease.";
RL Biochem. Biophys. Res. Commun. 212:564-571(1995).
RN [34]
RP VARIANTS GM2G2 TYR-309 AND LEU-417.
RX PubMed=7557963; DOI=10.1007/bf00191799;
RA Gomez-Lira M., Sangalli A., Mottes M., Perusi C., Pignatti P.F.,
RA Rizzuto N., Salviati A.;
RT "A common beta hexosaminidase gene mutation in adult Sandhoff disease
RT patients.";
RL Hum. Genet. 96:417-422(1995).
RN [35]
RP INVOLVEMENT IN GM2G2, AND VARIANT SER-62.
RX PubMed=7633435; DOI=10.1093/hmg/4.4.777;
RA Zhang Z.-X., Wakamatsu N., Akerman B.R., Mules E.H., Thomas G.H.,
RA Gravel R.A.;
RT "A second, large deletion in the HEXB gene in a patient with infantile
RT Sandhoff disease.";
RL Hum. Mol. Genet. 4:777-780(1995).
RN [36]
RP VARIANT GM2G2 GLN-505, AND VARIANT VAL-207.
RX PubMed=8950198; DOI=10.1016/s0925-4439(96)00044-0;
RA Redonnet-Vernhet I., Mahuran D.J., Salvayre R., Dubas F., Levade T.;
RT "Significance of two point mutations present in each HEXB allele of
RT patients with adult GM2 gangliosidosis (Sandhoff disease) homozygosity for
RT the Ile207-->Val substitution is not associated with a clinical or
RT biochemical phenotype.";
RL Biochim. Biophys. Acta 1317:127-133(1996).
RN [37]
RP VARIANT GM2G2 THR-543.
RX PubMed=9401004;
RX DOI=10.1002/(sici)1098-1004(1997)10:6<424::aid-humu2>3.0.co;2-d;
RA Narkis G., Adam A., Jaber L., Pennybacker M., Proia R.L., Navon R.;
RT "Molecular basis of heat labile hexosaminidase B among Jews and Arabs.";
RL Hum. Mutat. 10:424-429(1997).
RN [38]
RP VARIANT GM2G2 ARG-255.
RX PubMed=9856491; DOI=10.1007/s004390050851;
RA Fujimaru M., Tanaka A., Choeh K., Wakamatsu N., Sakuraba H., Isshiki G.;
RT "Two mutations remote from an exon/intron junction in the beta-
RT hexosaminidase beta-subunit gene affect 3'-splice site selection and cause
RT Sandhoff disease.";
RL Hum. Genet. 103:462-469(1998).
RN [39]
RP VARIANT GM2G2 SER-504, CATALYTIC ACTIVITY, FUNCTION, CHARACTERIZATION OF
RP VARIANT GM2G2 SER-504, AND SUBCELLULAR LOCATION.
RX PubMed=9694901; DOI=10.1074/jbc.273.33.21386;
RA Hou Y., McInnes B., Hinek A., Karpati G., Mahuran D.;
RT "A Pro504 --> Ser substitution in the beta-subunit of beta-hexosaminidase A
RT inhibits alpha-subunit hydrolysis of GM2 ganglioside, resulting in chronic
RT Sandhoff disease.";
RL J. Biol. Chem. 273:21386-21392(1998).
CC -!- FUNCTION: Hydrolyzes the non-reducing end N-acetyl-D-hexosamine and/or
CC sulfated N-acetyl-D-hexosamine of glycoconjugates, such as the
CC oligosaccharide moieties from proteins and neutral glycolipids, or from
CC certain mucopolysaccharides (PubMed:11707436, PubMed:9694901,
CC PubMed:8672428, PubMed:8123671). The isozyme B does not hydrolyze each
CC of these substrates, however hydrolyzes efficiently neutral
CC oligosaccharide (PubMed:11707436). Only the isozyme A is responsible
CC for the degradation of GM2 gangliosides in the presence of GM2A
CC (PubMed:9694901, PubMed:8672428, PubMed:8123671). During fertilization
CC is responsible, at least in part, for the zona block to polyspermy.
CC Present in the cortical granules of non-activated oocytes, is
CC exocytosed during the cortical reaction in response to oocyte
CC activation and inactivates the sperm galactosyltransferase-binding
CC site, accounting for the block in sperm binding to the zona pellucida
CC (By similarity). {ECO:0000250|UniProtKB:P20060,
CC ECO:0000269|PubMed:11707436, ECO:0000269|PubMed:8123671,
CC ECO:0000269|PubMed:8672428, ECO:0000269|PubMed:9694901}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of terminal non-reducing N-acetyl-D-hexosamine
CC residues in N-acetyl-beta-D-hexosaminides.; EC=3.2.1.52;
CC Evidence={ECO:0000269|PubMed:11329289, ECO:0000269|PubMed:11707436,
CC ECO:0000269|PubMed:8123671, ECO:0000269|PubMed:8672428,
CC ECO:0000269|PubMed:9694901};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-3-
CC sulfogalactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide = a beta-D-
CC 3-sulfogalactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide + N-
CC acetyl-beta-D-galactosamine; Xref=Rhea:RHEA:48276, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28497, ChEBI:CHEBI:90163, ChEBI:CHEBI:90164;
CC Evidence={ECO:0000269|PubMed:11707436};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48277;
CC Evidence={ECO:0000305|PubMed:11707436};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ganglioside GM2 (d18:1(4E)) + H2O = a ganglioside GM3
CC (d18:1(4E)) + N-acetyl-beta-D-galactosamine; Xref=Rhea:RHEA:47940,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28497, ChEBI:CHEBI:60065,
CC ChEBI:CHEBI:71502; Evidence={ECO:0000269|PubMed:8123671,
CC ECO:0000269|PubMed:8672428, ECO:0000269|PubMed:9694901};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47941;
CC Evidence={ECO:0000305|PubMed:9694901};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a ganglioside GM2 + H2O = a ganglioside GM3 + N-acetyl-beta-D-
CC galactosamine; Xref=Rhea:RHEA:47968, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:28497, ChEBI:CHEBI:79210, ChEBI:CHEBI:79218;
CC Evidence={ECO:0000269|PubMed:8123671, ECO:0000269|PubMed:8672428,
CC ECO:0000269|PubMed:9694901};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47969;
CC Evidence={ECO:0000305|PubMed:9694901};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-GalNAc-(1->4)-alpha-L-IdoA-(1->3)-beta-D-GalNAc-4-
CC sulfate-(1->4)-alpha-L-IdoA-(1->3)-D-GalNAc-4-sulfate + H2O = alpha-
CC L-IdoA-(1->3)-beta-D-GalNAc-4-sulfate-(1->4)-alpha-L-IdoA-(1->3)-D-
CC GalNAc-4-sulfate + N-acetyl-D-galactosamine; Xref=Rhea:RHEA:64372,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:28037, ChEBI:CHEBI:152565,
CC ChEBI:CHEBI:152566; Evidence={ECO:0000269|PubMed:11707436};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64373;
CC Evidence={ECO:0000305|PubMed:11707436};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + N-acetyl-beta-D-6-sulfogalactosaminyl-(1->4)-alpha-L-
CC iduronyl-(1->3)-N-acetyl-D-6-sulfogalactosamine = alpha-L-iduronyl-
CC (1->3)-N-acetyl-D-6-sulfogalactosamine + N-acetyl-D-6-
CC sulfogalactosamine; Xref=Rhea:RHEA:64384, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:152567, ChEBI:CHEBI:152568, ChEBI:CHEBI:153064;
CC Evidence={ECO:0000269|PubMed:11707436};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64385;
CC Evidence={ECO:0000305|PubMed:11707436};
CC -!- ACTIVITY REGULATION: Addition of GM2A stimulates the hydrolysis of
CC sulfated glycosphingolipid SM2 and the ganglioside GM2.
CC {ECO:0000269|PubMed:11707436}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 4. {ECO:0000269|PubMed:11329289};
CC -!- SUBUNIT: There are 3 forms of beta-hexosaminidase: hexosaminidase A is
CC an heterodimer composed of one subunit alpha and one subunit beta
CC (chain A and B); hexosaminidase B is an homodimer of two beta subunits
CC (two chains A and B); hexosaminidase S is a homodimer of two alpha
CC subunits (By similarity). The composition of the dimer (isozyme A
CC versus isozyme S) has a significant effect on the substrate specificity
CC of the alpha subunit active site (PubMed:8672428).
CC {ECO:0000250|UniProtKB:P06865, ECO:0000269|PubMed:8672428}.
CC -!- INTERACTION:
CC P07686; Q9Y575-3: ASB3; NbExp=3; IntAct=EBI-7133736, EBI-14199987;
CC P07686; O75808: CAPN15; NbExp=3; IntAct=EBI-7133736, EBI-6149008;
CC P07686; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-7133736, EBI-350590;
CC P07686; Q96KR6: FAM210B; NbExp=3; IntAct=EBI-7133736, EBI-18938272;
CC P07686; P06865: HEXA; NbExp=3; IntAct=EBI-7133736, EBI-723519;
CC P07686; P49639: HOXA1; NbExp=3; IntAct=EBI-7133736, EBI-740785;
CC P07686; Q8N4N3: KLHL36; NbExp=3; IntAct=EBI-7133736, EBI-6426427;
CC P07686; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-7133736, EBI-739832;
CC P07686; Q13064: MKRN3; NbExp=3; IntAct=EBI-7133736, EBI-2340269;
CC P07686; Q13564: NAE1; NbExp=3; IntAct=EBI-7133736, EBI-718631;
CC P07686; Q8NFH3: NUP43; NbExp=3; IntAct=EBI-7133736, EBI-1059321;
CC P07686; Q9GZY0: NXF2; NbExp=3; IntAct=EBI-7133736, EBI-444173;
CC P07686; Q96FW1: OTUB1; NbExp=3; IntAct=EBI-7133736, EBI-1058491;
CC P07686; O75925: PIAS1; NbExp=3; IntAct=EBI-7133736, EBI-629434;
CC P07686; Q96PM5-4: RCHY1; NbExp=3; IntAct=EBI-7133736, EBI-21252376;
CC P07686; Q96D59: RNF183; NbExp=3; IntAct=EBI-7133736, EBI-743938;
CC P07686; Q6NW29: RWDD4; NbExp=3; IntAct=EBI-7133736, EBI-743971;
CC P07686; Q04724: TLE1; NbExp=3; IntAct=EBI-7133736, EBI-711424;
CC P07686; Q9NUH8: TMEM14B; NbExp=3; IntAct=EBI-7133736, EBI-8638294;
CC P07686; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-7133736, EBI-10180829;
CC P07686; O95164: UBL3; NbExp=3; IntAct=EBI-7133736, EBI-12876508;
CC P07686; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-7133736, EBI-947187;
CC P07686; Q9H347: UBQLN3; NbExp=3; IntAct=EBI-7133736, EBI-25832660;
CC P07686; Q8IYU4: UBQLNL; NbExp=3; IntAct=EBI-7133736, EBI-12295223;
CC P07686; Q8IWV7: UBR1; NbExp=3; IntAct=EBI-7133736, EBI-711736;
CC P07686; O00308: WWP2; NbExp=3; IntAct=EBI-7133736, EBI-743923;
CC P07686; P98170: XIAP; NbExp=3; IntAct=EBI-7133736, EBI-517127;
CC P07686; Q05516: ZBTB16; NbExp=3; IntAct=EBI-7133736, EBI-711925;
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:9694901}.
CC Cytoplasmic vesicle, secretory vesicle, Cortical granule
CC {ECO:0000250|UniProtKB:P20060}.
CC -!- PTM: N-linked glycans at Asn-142 and Asn-190 consist of Man(3)-
CC GlcNAc(2) and Man(5 to 7)-GlcNAc(2), respectively.
CC {ECO:0000269|PubMed:11447134, ECO:0000269|PubMed:12754519,
CC ECO:0000269|PubMed:19159218}.
CC -!- PTM: The beta-A and beta-B chains are produced by proteolytic
CC processing of the precursor beta chain.
CC -!- DISEASE: GM2-gangliosidosis 2 (GM2G2) [MIM:268800]: An autosomal
CC recessive lysosomal storage disease marked by the accumulation of GM2
CC gangliosides in the neuronal cells. Clinically indistinguishable from
CC GM2-gangliosidosis type 1, presenting startle reactions, early
CC blindness, progressive motor and mental deterioration, macrocephaly and
CC cherry-red spots on the macula. {ECO:0000269|PubMed:1531140,
CC ECO:0000269|PubMed:1720305, ECO:0000269|PubMed:7557963,
CC ECO:0000269|PubMed:7626071, ECO:0000269|PubMed:7633435,
CC ECO:0000269|PubMed:8357844, ECO:0000269|PubMed:8950198,
CC ECO:0000269|PubMed:9401004, ECO:0000269|PubMed:9694901,
CC ECO:0000269|PubMed:9856491}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 20 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA51828.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M13519; AAA51828.1; ALT_FRAME; mRNA.
DR EMBL; M23294; AAA52645.1; -; Genomic_DNA.
DR EMBL; M23282; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23283; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23284; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23285; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23286; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23287; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23288; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23290; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23291; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23292; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M23293; AAA52645.1; JOINED; Genomic_DNA.
DR EMBL; M19735; AAA68620.1; -; mRNA.
DR EMBL; AF378118; AAM46114.1; -; mRNA.
DR EMBL; BT009919; AAP88921.1; -; mRNA.
DR EMBL; AC026405; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093214; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017378; AAH17378.1; -; mRNA.
DR EMBL; M34906; AAA51829.1; -; mRNA.
DR CCDS; CCDS4022.1; -.
DR PIR; A31250; A31250.
DR RefSeq; NP_000512.1; NM_000521.3.
DR RefSeq; NP_001278933.1; NM_001292004.1.
DR PDB; 1NOU; X-ray; 2.40 A; A/B=50-556.
DR PDB; 1NOW; X-ray; 2.20 A; A/B=50-556.
DR PDB; 1NP0; X-ray; 2.50 A; A/B=50-556.
DR PDB; 1O7A; X-ray; 2.25 A; A/B/C/D/E/F=42-556.
DR PDB; 2GJX; X-ray; 2.80 A; B/C/F/G=50-556.
DR PDB; 2GK1; X-ray; 3.25 A; B/D/F/H=50-552.
DR PDB; 3LMY; X-ray; 2.80 A; A/B=1-556.
DR PDB; 5BRO; X-ray; 2.40 A; A=43-556.
DR PDBsum; 1NOU; -.
DR PDBsum; 1NOW; -.
DR PDBsum; 1NP0; -.
DR PDBsum; 1O7A; -.
DR PDBsum; 2GJX; -.
DR PDBsum; 2GK1; -.
DR PDBsum; 3LMY; -.
DR PDBsum; 5BRO; -.
DR AlphaFoldDB; P07686; -.
DR SMR; P07686; -.
DR BioGRID; 109323; 64.
DR ComplexPortal; CPX-502; Beta-hexosaminidase A complex.
DR ComplexPortal; CPX-686; Beta-hexosaminidase B complex.
DR CORUM; P07686; -.
DR ELM; P07686; -.
DR IntAct; P07686; 40.
DR MINT; P07686; -.
DR STRING; 9606.ENSP00000261416; -.
DR BindingDB; P07686; -.
DR ChEMBL; CHEMBL5877; -.
DR DrugBank; DB03861; (2R,3R,4S,5R)-2-acetamido-3,4-dihydroxy-5-hydroxymethyl-piperidine.
DR DrugBank; DB02813; 2-Acetamido-2-Deoxy-D-Glucono-1,5-Lactone.
DR DrugBank; DB09301; Chondroitin sulfate.
DR DrugBank; DB03747; N-Acetyl-glucosamine thiazoline.
DR DrugBank; DB00205; Pyrimethamine.
DR DrugCentral; P07686; -.
DR CAZy; GH20; Glycoside Hydrolase Family 20.
DR GlyConnect; 1039; 4 N-Linked glycans (3 sites).
DR GlyCosmos; P07686; 4 sites, 13 glycans.
DR GlyGen; P07686; 7 sites, 13 N-linked glycans (4 sites), 1 O-linked glycan (1 site).
DR iPTMnet; P07686; -.
DR MetOSite; P07686; -.
DR PhosphoSitePlus; P07686; -.
DR SwissPalm; P07686; -.
DR BioMuta; HEXB; -.
DR DMDM; 123081; -.
DR UCD-2DPAGE; P07686; -.
DR CPTAC; CPTAC-78; -.
DR CPTAC; CPTAC-79; -.
DR EPD; P07686; -.
DR jPOST; P07686; -.
DR MassIVE; P07686; -.
DR MaxQB; P07686; -.
DR PaxDb; 9606-ENSP00000261416; -.
DR PeptideAtlas; P07686; -.
DR ProteomicsDB; 52022; -.
DR Pumba; P07686; -.
DR TopDownProteomics; P07686; -.
DR Antibodypedia; 24338; 303 antibodies from 34 providers.
DR DNASU; 3074; -.
DR Ensembl; ENST00000261416.12; ENSP00000261416.7; ENSG00000049860.14.
DR GeneID; 3074; -.
DR KEGG; hsa:3074; -.
DR MANE-Select; ENST00000261416.12; ENSP00000261416.7; NM_000521.4; NP_000512.2.
DR UCSC; uc003kdf.4; human.
DR AGR; HGNC:4879; -.
DR CTD; 3074; -.
DR DisGeNET; 3074; -.
DR GeneCards; HEXB; -.
DR GeneReviews; HEXB; -.
DR HGNC; HGNC:4879; HEXB.
DR HPA; ENSG00000049860; Low tissue specificity.
DR MalaCards; HEXB; -.
DR MIM; 268800; phenotype.
DR MIM; 606873; gene.
DR neXtProt; NX_P07686; -.
DR OpenTargets; ENSG00000049860; -.
DR Orphanet; 309169; Sandhoff disease, adult form.
DR Orphanet; 309155; Sandhoff disease, infantile form.
DR Orphanet; 309162; Sandhoff disease, juvenile form.
DR PharmGKB; PA29257; -.
DR VEuPathDB; HostDB:ENSG00000049860; -.
DR eggNOG; KOG2499; Eukaryota.
DR GeneTree; ENSGT00390000008107; -.
DR HOGENOM; CLU_007082_0_3_1; -.
DR InParanoid; P07686; -.
DR OMA; GHDVVMC; -.
DR OrthoDB; 178991at2759; -.
DR PhylomeDB; P07686; -.
DR TreeFam; TF313036; -.
DR BioCyc; MetaCyc:HS00629-MONOMER; -.
DR BRENDA; 3.2.1.52; 2681.
DR PathwayCommons; P07686; -.
DR Reactome; R-HSA-2022857; Keratan sulfate degradation.
DR Reactome; R-HSA-2024101; CS/DS degradation.
DR Reactome; R-HSA-2160916; Hyaluronan uptake and degradation.
DR Reactome; R-HSA-3656248; Defective HEXB causes GM2G2.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-9840310; Glycosphingolipid catabolism.
DR SABIO-RK; P07686; -.
DR SignaLink; P07686; -.
DR BioGRID-ORCS; 3074; 16 hits in 1163 CRISPR screens.
DR ChiTaRS; HEXB; human.
DR EvolutionaryTrace; P07686; -.
DR GeneWiki; HEXB; -.
DR GenomeRNAi; 3074; -.
DR Pharos; P07686; Tchem.
DR PRO; PR:P07686; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P07686; Protein.
DR Bgee; ENSG00000049860; Expressed in placenta and 198 other cell types or tissues.
DR ExpressionAtlas; P07686; baseline and differential.
DR Genevisible; P07686; HS.
DR GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR GO; GO:0042582; C:azurophil granule; IDA:UniProtKB.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:1905379; C:beta-N-acetylhexosaminidase complex; IPI:ComplexPortal.
DR GO; GO:0060473; C:cortical granule; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0043202; C:lysosomal lumen; TAS:Reactome.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0004563; F:beta-N-acetylhexosaminidase activity; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0102148; F:N-acetyl-beta-D-galactosaminidase activity; IEA:UniProtKB-EC.
DR GO; GO:0043615; P:astrocyte cell migration; IEA:Ensembl.
DR GO; GO:0030207; P:chondroitin sulfate catabolic process; IEA:Ensembl.
DR GO; GO:0030209; P:dermatan sulfate catabolic process; IEA:Ensembl.
DR GO; GO:0006689; P:ganglioside catabolic process; IDA:UniProtKB.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; IDA:ComplexPortal.
DR GO; GO:0030214; P:hyaluronan catabolic process; IEA:Ensembl.
DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0019915; P:lipid storage; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0007040; P:lysosome organization; IEA:Ensembl.
DR GO; GO:0051651; P:maintenance of location in cell; IEA:Ensembl.
DR GO; GO:0008049; P:male courtship behavior; IEA:Ensembl.
DR GO; GO:0042552; P:myelination; IEA:Ensembl.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IEA:Ensembl.
DR GO; GO:0048477; P:oogenesis; IEA:Ensembl.
DR GO; GO:0007341; P:penetration of zona pellucida; IEA:Ensembl.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0008360; P:regulation of cell shape; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0007338; P:single fertilization; ISS:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR CDD; cd06562; GH20_HexA_HexB-like; 1.
DR Gene3D; 3.30.379.10; Chitobiase/beta-hexosaminidase domain 2-like; 1.
DR Gene3D; 3.20.20.80; Glycosidases; 1.
DR InterPro; IPR025705; Beta_hexosaminidase_sua/sub.
DR InterPro; IPR015883; Glyco_hydro_20_cat.
DR InterPro; IPR017853; Glycoside_hydrolase_SF.
DR InterPro; IPR029018; Hex-like_dom2.
DR InterPro; IPR029019; HEX_eukaryotic_N.
DR PANTHER; PTHR22600; BETA-HEXOSAMINIDASE; 1.
DR PANTHER; PTHR22600:SF38; BETA-HEXOSAMINIDASE SUBUNIT BETA; 1.
DR Pfam; PF00728; Glyco_hydro_20; 1.
DR Pfam; PF14845; Glycohydro_20b2; 1.
DR PIRSF; PIRSF001093; B-hxosamndse_ab_euk; 1.
DR PRINTS; PR00738; GLHYDRLASE20.
DR SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR SUPFAM; SSF55545; beta-N-acetylhexosaminidase-like domain; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasmic vesicle; Direct protein sequencing;
KW Disease variant; Disulfide bond; Gangliosidosis; Glycoprotein; Glycosidase;
KW Hydrolase; Lipid metabolism; Lysosome; Neurodegeneration;
KW Reference proteome; Signal; Zymogen.
FT SIGNAL 1..42
FT /evidence="ECO:0000255"
FT PROPEP 43..121
FT /evidence="ECO:0000269|PubMed:2965147,
FT ECO:0000269|PubMed:2966076"
FT /id="PRO_0000012002"
FT CHAIN 122..556
FT /note="Beta-hexosaminidase subunit beta"
FT /id="PRO_0000012003"
FT CHAIN 122..311
FT /note="Beta-hexosaminidase subunit beta chain B"
FT /id="PRO_0000012004"
FT CHAIN 315..556
FT /note="Beta-hexosaminidase subunit beta chain A"
FT /id="PRO_0000012005"
FT ACT_SITE 355
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:11329289"
FT SITE 497
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:11447134"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:11447134,
FT ECO:0000269|PubMed:19159218"
FT CARBOHYD 142
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:11447134"
FT CARBOHYD 190
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:11447134"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:11447134,
FT ECO:0000269|PubMed:12754519, ECO:0000269|PubMed:19159218"
FT DISULFID 91..137
FT DISULFID 309..360
FT DISULFID 534..551
FT VARIANT 62
FT /note="L -> S (in dbSNP:rs820878)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:2964638, ECO:0000269|PubMed:2971039,
FT ECO:0000269|PubMed:2977375, ECO:0000269|PubMed:3013851,
FT ECO:0000269|PubMed:7633435, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.5"
FT /id="VAR_003247"
FT VARIANT 121
FT /note="K -> R (in dbSNP:rs11556045)"
FT /id="VAR_003248"
FT VARIANT 207
FT /note="I -> V (in dbSNP:rs10805890)"
FT /evidence="ECO:0000269|PubMed:1720305,
FT ECO:0000269|PubMed:8950198"
FT /id="VAR_003249"
FT VARIANT 255
FT /note="S -> R (in GM2G2; dbSNP:rs1554035829)"
FT /evidence="ECO:0000269|PubMed:9856491"
FT /id="VAR_011704"
FT VARIANT 309
FT /note="C -> Y (in GM2G2; adult type; severe;
FT dbSNP:rs1554036641)"
FT /evidence="ECO:0000269|PubMed:7557963"
FT /id="VAR_003250"
FT VARIANT 417
FT /note="P -> L (in GM2G2; dbSNP:rs28942073)"
FT /evidence="ECO:0000269|PubMed:1531140,
FT ECO:0000269|PubMed:7557963"
FT /id="VAR_003251"
FT VARIANT 456
FT /note="Y -> S (in GM2G2; dbSNP:rs121907982)"
FT /evidence="ECO:0000269|PubMed:1720305"
FT /id="VAR_003252"
FT VARIANT 504
FT /note="P -> S (in GM2G2; decreases the isozyme A transport
FT out of the endoplasmic reticulum. Lowers its heat
FT stability. Affects the ability of isozyme A to hydrolyze
FT GM2 ganglioside; dbSNP:rs121907985)"
FT /evidence="ECO:0000269|PubMed:9694901"
FT /id="VAR_011705"
FT VARIANT 505
FT /note="R -> Q (in GM2G2; dbSNP:rs121907983)"
FT /evidence="ECO:0000269|PubMed:8357844,
FT ECO:0000269|PubMed:8950198"
FT /id="VAR_003253"
FT VARIANT 534
FT /note="C -> Y (in GM2G2; infantile type;
FT dbSNP:rs727503960)"
FT /evidence="ECO:0000269|PubMed:7626071"
FT /id="VAR_003254"
FT VARIANT 543
FT /note="A -> T (in GM2G2; dbSNP:rs121907984)"
FT /evidence="ECO:0000269|PubMed:9401004"
FT /id="VAR_011706"
FT MUTAGEN 211
FT /note="R->K: Does not affect the native conformation of the
FT isozyme A. Does not affect hydrolysis of GM2 ganglioside by
FT the isozyme A."
FT /evidence="ECO:0000269|PubMed:8672428"
FT MUTAGEN 241
FT /note="D->N: 2.7-fold reduction in substrate affinity. 39-
FT fold reduction in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11329289"
FT MUTAGEN 354
FT /note="D->N: No effect on substrate affinity. 1750-fold
FT reduction in catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11329289"
FT MUTAGEN 355
FT /note="E->Q: 1.5-fold increase in substrate affinity. 2300-
FT fold reduction in catalytic efficiency. Reduces optimal pH
FT to 3-3.5."
FT /evidence="ECO:0000269|PubMed:11329289"
FT MUTAGEN 491
FT /note="E->Q: No effect on substrate affinity and on
FT catalytic efficiency."
FT /evidence="ECO:0000269|PubMed:11329289"
FT STRAND 61..71
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 83..86
FT /evidence="ECO:0007829|PDB:1O7A"
FT HELIX 92..105
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 155..164
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 165..178
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 187..196
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 201..212
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 216..228
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 233..237
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 253..258
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 259..261
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 262..264
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 284..294
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 298..301
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 318..322
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 327..343
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 346..352
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 359..362
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 365..373
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 380..397
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 401..405
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 406..410
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 420..423
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 429..438
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:3LMY"
FT STRAND 450..453
FT /evidence="ECO:0007829|PDB:2GK1"
FT STRAND 455..457
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 460..465
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 475..479
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 481..488
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 490..492
FT /evidence="ECO:0007829|PDB:3LMY"
FT TURN 495..497
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 498..502
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 505..514
FT /evidence="ECO:0007829|PDB:1NOW"
FT HELIX 522..538
FT /evidence="ECO:0007829|PDB:1NOW"
FT STRAND 546..548
FT /evidence="ECO:0007829|PDB:1NOW"
SQ SEQUENCE 556 AA; 63137 MW; 2267BF1453EA50EF CRC64;
MELCGLGLPR PPMLLALLLA TLLAAMLALL TQVALVVQVA EAARAPSVSA KPGPALWPLP
LLVKMTPNLL HLAPENFYIS HSPNSTAGPS CTLLEEAFRR YHGYIFGFYK WHHEPAEFQA
KTQVQQLLVS ITLQSECDAF PNISSDESYT LLVKEPVAVL KANRVWGALR GLETFSQLVY
QDSYGTFTIN ESTIIDSPRF SHRGILIDTS RHYLPVKIIL KTLDAMAFNK FNVLHWHIVD
DQSFPYQSIT FPELSNKGSY SLSHVYTPND VRMVIEYARL RGIRVLPEFD TPGHTLSWGK
GQKDLLTPCY SRQNKLDSFG PINPTLNTTY SFLTTFFKEI SEVFPDQFIH LGGDEVEFKC
WESNPKIQDF MRQKGFGTDF KKLESFYIQK VLDIIATINK GSIVWQEVFD DKAKLAPGTI
VEVWKDSAYP EELSRVTASG FPVILSAPWY LDLISYGQDW RKYYKVEPLD FGGTQKQKQL
FIGGEACLWG EYVDATNLTP RLWPRASAVG ERLWSSKDVR DMDDAYDRLT RHRCRMVERG
IAAQPLYAGY CNHENM
//
