HEXA_HUMAN
ID HEXA_HUMAN Reviewed; 529 AA.
AC P06865; B4DKE7; E7ENH7; Q53HS8; Q6AI32;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Beta-hexosaminidase subunit alpha {ECO:0000305};
DE EC=3.2.1.52 {ECO:0000269|PubMed:11707436, ECO:0000269|PubMed:8123671, ECO:0000269|PubMed:8672428, ECO:0000269|PubMed:9694901};
DE AltName: Full=Beta-N-acetylhexosaminidase subunit alpha;
DE Short=Hexosaminidase subunit A;
DE AltName: Full=N-acetyl-beta-glucosaminidase subunit alpha;
DE Flags: Precursor;
GN Name=HEXA {ECO:0000312|HGNC:HGNC:4878};
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 VARIANT VAL-436.
RX PubMed=2933746; DOI=10.1073/pnas.82.23.7830;
RA Myerowitz R., Piekarz R., Neufeld E.F., Shows T.B., Suzuki K.;
RT "Human beta-hexosaminidase alpha chain: coding sequence and homology with
RT the beta chain.";
RL Proc. Natl. Acad. Sci. U.S.A. 82:7830-7834(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-436.
RX PubMed=2952641; DOI=10.1016/s0021-9258(18)45628-1;
RA Proia R.L., Soravia E.;
RT "Organization of the gene encoding the human beta-hexosaminidase alpha-
RT chain.";
RL J. Biol. Chem. 262:5677-5681(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-436.
RX PubMed=1833974;
RA Triggs-Raine B.L., Akerman B.R., Clarke J.T.R., Gravel R.A.;
RT "Sequence of DNA flanking the exons of the HEXA gene, and identification of
RT mutations in Tay-Sachs disease.";
RL Am. J. Hum. Genet. 49:1041-1054(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Thalamus;
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 VAL-436.
RC TISSUE=Adipose tissue;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP PSEUDODEFICIENCY TRP-249 AND VAL-436.
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-436.
RC TISSUE=Brain, and Eye;
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 [9]
RP PROTEIN SEQUENCE OF 23-32 AND 85-94, FUNCTION, CATALYTIC ACTIVITY,
RP GLYCOSYLATION AT ASN-115; ASN-157 AND ASN-295, DISULFIDE BOND, AND ACTIVITY
RP 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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 40-529 (ISOFORM 1), AND VARIANT VAL-436.
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 [11]
RP PROTEIN SEQUENCE OF 89-99.
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 [12]
RP PROTEIN SEQUENCE OF 96-105, AND 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 [13]
RP GLYCOSYLATION AT ASN-115; ASN-157 AND ASN-295, AND MUTAGENESIS OF ASN-115;
RP ASN-157 AND ASN-295.
RX PubMed=1533633; DOI=10.1016/s0021-9258(19)50196-x;
RA Weitz G., Proia R.L.;
RT "Analysis of the glycosylation and phosphorylation of the alpha-subunit of
RT the lysosomal enzyme, beta-hexosaminidase A, by site-directed
RT mutagenesis.";
RL J. Biol. Chem. 267:10039-10044(1992).
RN [14]
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 [15]
RP CATALYTIC ACTIVITY, FUNCTION, 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 [16]
RP ACTIVE SITES.
RX PubMed=8652542; DOI=10.1021/bi960246+;
RA Tse R., Vavougios G., Hou Y., Mahuran D.J.;
RT "Identification of an active acidic residue in the catalytic site of beta-
RT hexosaminidase.";
RL Biochemistry 35:7599-7607(1996).
RN [17]
RP CATALYTIC ACTIVITY, AND FUNCTION.
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).
RN [18]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157 AND ASN-295.
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 [19]
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 [20]
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 [21]
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 [22]
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 [23]
RP REVIEW ON VARIANTS.
RX PubMed=9090523;
RX DOI=10.1002/(sici)1098-1004(1997)9:3<195::aid-humu1>3.0.co;2-7;
RA Myerowitz R.;
RT "Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A
RT gene.";
RL Hum. Mutat. 9:195-208(1997).
RN [24]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 23-529 IN COMPLEX WITH HEXB,
RP GLYCOSYLATION AT ASN-115; ASN-157 AND ASN-295, DISULFIDE BONDS, AND
RP SUBUNIT.
RX PubMed=16698036; DOI=10.1016/j.jmb.2006.04.004;
RA Lemieux M.J., Mark B.L., Cherney M.M., Withers S.G., Mahuran D.J.,
RA James M.N.;
RT "Crystallographic structure of human beta-hexosaminidase A: interpretation
RT of Tay-Sachs mutations and loss of GM2 ganglioside hydrolysis.";
RL J. Mol. Biol. 359:913-929(2006).
RN [25]
RP VARIANT GM2G1 LYS-482.
RX PubMed=2970528; DOI=10.1111/j.1471-4159.1988.tb01836.x;
RA Nakano T., Muscillo M., Ohno K., Hoffman A.J., Suzuki K.;
RT "A point mutation in the coding sequence of the beta-hexosaminidase alpha
RT gene results in defective processing of the enzyme protein in an unusual
RT GM2-gangliosidosis variant.";
RL J. Neurochem. 51:984-987(1988).
RN [26]
RP VARIANT GM2G1 SER-269.
RX PubMed=2522679; DOI=10.1126/science.2522679;
RA Navon R., Proia R.L.;
RT "The mutations in Ashkenazi Jews with adult GM2 gangliosidosis, the adult
RT form of Tay-Sachs disease.";
RL Science 243:1471-1474(1989).
RN [27]
RP VARIANT GM2G1 CYS-420.
RX PubMed=2144098;
RA Tanaka A., Punnett H.H., Suzuki K.;
RT "A new point mutation in the beta-hexosaminidase alpha subunit gene
RT responsible for infantile Tay-Sachs disease in a non-Jewish Caucasian
RT patient (a Kpn mutant).";
RL Am. J. Hum. Genet. 47:568-574(1990).
RN [28]
RP VARIANT GM2G1 HIS-504, AND CHARACTERIZATION OF VARIANT GM2G1 HIS-504.
RX PubMed=2140574; DOI=10.1016/s0021-9258(19)38870-2;
RA Paw B.H., Moskowitz S.M., Uhrhammer N., Wright N., Kaback M.M.,
RA Neufeld E.F.;
RT "Juvenile GM2 gangliosidosis caused by substitution of histidine for
RT arginine at position 499 or 504 of the alpha-subunit of beta-
RT hexosaminidase.";
RL J. Biol. Chem. 265:9452-9457(1990).
RN [29]
RP VARIANTS GM2G1 PHE-210 AND CYS-504.
RX PubMed=1837283; DOI=10.1016/0888-7543(91)90109-r;
RA Akli S., Lacorte J.-M., Poenaru L., Khan A.;
RT "Seven novel Tay-Sachs mutations detected by chemical mismatch cleavage of
RT PCR-amplified cDNA fragments.";
RL Genomics 11:124-134(1991).
RN [30]
RP VARIANT GM2G1 GLY-320 DEL, AND VARIANTS ASP-399 AND VAL-436.
RX PubMed=1532289;
RA Mules E.H., Hayflick S., Miller C.S., Reynolds L.W., Thomas G.H.;
RT "Six novel deleterious and three neutral mutations in the gene encoding the
RT alpha-subunit of hexosaminidase A in non-Jewish individuals.";
RL Am. J. Hum. Genet. 50:834-841(1992).
RN [31]
RP VARIANT PSEUDODEFICIENCY TRP-247.
RX PubMed=1384323;
RA Triggs-Raine B.L., Mules E.H., Kaback M.M., Lim-Steele J.S.T.,
RA Dowling C.E., Akerman B.R., Natowicz M.R., Grebner E.E., Navon R.,
RA Welch J.P., Greenberg C.R., Thomas G.H., Gravel R.A.;
RT "A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers:
RT implications for carrier screening.";
RL Am. J. Hum. Genet. 51:793-801(1992).
RN [32]
RP VARIANTS GM2G1 TRP-170 AND HIS-258.
RX PubMed=1302612; DOI=10.1093/hmg/1.9.759;
RA Fernandes M., Kaplan F., Natowicz M., Prence E., Kolodny E., Kaback M.,
RA Hechtman P.;
RT "A new Tay-Sachs disease B1 allele in exon 7 in two compound heterozygotes
RT each with a second novel mutation.";
RL Hum. Mol. Genet. 1:759-761(1992).
RN [33]
RP VARIANT GM2G1 ASP-250.
RX PubMed=1301189; DOI=10.1002/humu.1380010106;
RA Trop I., Kaplan F., Brown C., Mahuran D., Hechtman P.;
RT "A glycine250--> aspartate substitution in the alpha-subunit of
RT hexosaminidase A causes juvenile-onset Tay-Sachs disease in a Lebanese-
RT Canadian family.";
RL Hum. Mutat. 1:35-39(1992).
RN [34]
RP VARIANT GM2G1 ARG-485.
RX PubMed=1301190; DOI=10.1002/humu.1380010107;
RA Akalin N., Shi H.-P., Vavougios G., Hechtman P., Lo W., Scriver C.R.,
RA Mahuran D., Kaplan F.;
RT "Novel Tay-Sachs disease mutations from China.";
RL Hum. Mutat. 1:40-46(1992).
RN [35]
RP VARIANT PSEUDODEFICIENCY TRP-249.
RX PubMed=7902672;
RA Cao Z., Natowicz M.R., Kaback M.M., Lim-Steele J.S.T., Prence E.M.,
RA Brown D., Chabot T., Triggs-Raine B.L.;
RT "A second mutation associated with apparent beta-hexosaminidase A
RT pseudodeficiency: identification and frequency estimation.";
RL Am. J. Hum. Genet. 53:1198-1205(1993).
RN [36]
RP VARIANTS GM2G1.
RX PubMed=8490625; DOI=10.1093/hmg/2.1.61;
RA Akli S., Chomel J.-C., Lacorte J.-M., Bachner L., Poenaru A., Poenaru L.;
RT "Ten novel mutations in the HEXA gene in non-Jewish Tay-Sachs patients.";
RL Hum. Mol. Genet. 2:61-67(1993).
RN [37]
RP VARIANT GM2G1 SER-25.
RX PubMed=8445615; DOI=10.1136/jmg.30.2.123;
RA Harmon D.L., Gardner-Medwin D., Stirling J.L.;
RT "Two new mutations in a late infantile Tay-Sachs patient are both in exon 1
RT of the beta-hexosaminidase alpha subunit gene.";
RL J. Med. Genet. 30:123-128(1993).
RN [38]
RP VARIANTS GM2G1 PHE-335 AND 347-ASP--GLU-352 DEL.
RX PubMed=7951261; DOI=10.1002/humu.1380040112;
RA Tomczak J., Grebner E.E.;
RT "Three novel beta-hexosaminidase A mutations in obligate carriers of Tay-
RT Sachs disease.";
RL Hum. Mutat. 4:71-72(1994).
RN [39]
RP VARIANTS GM2G1 TYR-458 AND GLN-484.
RX PubMed=7837766; DOI=10.1007/bf00711597;
RA Tanaka A., Sakazaki H., Murakami H., Isshiki G., Suzuki K.;
RT "Molecular genetics of Tay-Sachs disease in Japan.";
RL J. Inherit. Metab. Dis. 17:593-600(1994).
RN [40]
RP VARIANTS GM2G1 SER-196 AND SER-250.
RX PubMed=7717398;
RA Triggs-Raine B.L., Richard M., Wasel N., Prence E.M., Natowicz M.R.;
RT "Mutational analyses of Tay-Sachs disease: studies on Tay-Sachs carriers of
RT French Canadian background living in New England.";
RL Am. J. Hum. Genet. 56:870-879(1995).
RN [41]
RP VARIANT GM2G1 GLY-166.
RX PubMed=8581357; DOI=10.1006/bmme.1995.1018;
RA Peleg L., Meltzer F., Karpati M., Goldman B.;
RT "GM2 gangliosidosis B1 variant: biochemical and molecular characterization
RT of hexosaminidase A.";
RL Biochem. Mol. Med. 54:126-132(1995).
RN [42]
RP VARIANT GM2G1 MET-391.
RX PubMed=7898712; DOI=10.1212/wnl.45.3.539;
RA Navon R., Khosravi R., Korczyn T., Masson M., Sonnino S., Fardeau M.,
RA Eymard B., Lefevre N., Turpin J.C., Rondot P.;
RT "A new mutation in the HEXA gene associated with a spinal muscular atrophy
RT phenotype.";
RL Neurology 45:539-543(1995).
RN [43]
RP VARIANT GM2G1 HIS-180.
RX PubMed=8757036; DOI=10.1212/wnl.47.2.547;
RA de Gasperi R., Gama Sosa M.A., Battistini S., Yeretsian J., Raghavan S.,
RA Zelnik N., Leshinsky E., Kolodny E.H.;
RT "Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5
RT mutation (Tyr180-->His) in the Hex A alpha-chain gene.";
RL Neurology 47:547-552(1996).
RN [44]
RP VARIANTS GM2G1 PHE-127; PHE-226; ASP-269 AND VAL-314.
RX PubMed=9150157;
RA Akerman B.R., Natowicz M.R., Kaback M.M., Loyer M., Campeau E.,
RA Gravel R.A.;
RT "Novel mutations and DNA-based screening in non-Jewish carriers of Tay-
RT Sachs disease.";
RL Am. J. Hum. Genet. 60:1099-1106(1997).
RN [45]
RP VARIANTS GM2G1 GLN-170; PHE-304 DEL AND LYS-482.
RX PubMed=9338583;
RX DOI=10.1002/(sici)1098-1004(1997)10:4<295::aid-humu5>3.0.co;2-g;
RA Kaufman M., Grinshpun-Cohen J., Karpati M., Peleg L., Goldman B.,
RA Akstein E., Adam A., Navon R.;
RT "Tay-Sachs disease and HEXA mutations among Moroccan Jews.";
RL Hum. Mutat. 10:295-300(1997).
RN [46]
RP VARIANT GM2G1 ARG-455.
RX PubMed=9375850;
RX DOI=10.1002/(sici)1098-1004(1997)10:5<359::aid-humu4>3.0.co;2-a;
RA Ribeiro M.G., Pinto R.A., Suzuki K., Sa Miranda M.C.;
RT "Two novel (1334delC and 1363G to A, G455R) mutations in exon 12 of the
RT beta-hexosaminidase alpha-chain gene in two Portuguese patients.";
RL Hum. Mutat. 10:359-360(1997).
RN [47]
RP VARIANT GM2G1 PRO-279.
RX PubMed=9401008;
RX DOI=10.1002/(sici)1098-1004(1997)10:6<451::aid-humu6>3.0.co;2-g;
RA Drucker L., Hemli J.A., Navon R.;
RT "Two mutated HEXA alleles in a Druze patient with late-infantile Tay-Sachs
RT disease.";
RL Hum. Mutat. 10:451-457(1997).
RN [48]
RP VARIANT GM2G1 CYS-474.
RX PubMed=9603435;
RX DOI=10.1002/(sici)1098-1004(1998)11:6<432::aid-humu3>3.0.co;2-z;
RA Petroulakis E., Cao Z., Clarke J.T.R., Mahuran D.J., Lee G.,
RA Triggs-Raine B.;
RT "W474C amino acid substitution affects early processing of the alpha-
RT subunit of beta-hexosaminidase A and is associated with subacute G(M2)
RT gangliosidosis.";
RL Hum. Mutat. 11:432-442(1998).
RN [49]
RP VARIANTS GM2G1 LEU-252; SER-295; CYS-420; CYS-499 AND HIS-499.
RX PubMed=14566483; DOI=10.1007/s10038-003-0080-9;
RA Tanaka A., Hoang L.T., Nishi Y., Maniwa S., Oka M., Yamano T.;
RT "Different attenuated phenotypes of GM2 gangliosidosis variant B in
RT Japanese patients with HEXA mutations at codon 499, and five novel
RT mutations responsible for infantile acute form.";
RL J. Hum. Genet. 48:571-574(2003).
RN [50]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-436, AND IDENTIFICATION BY MASS
RP 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 [51]
RP VARIANTS GM2G1 LYS-114; TRP-170; ASN-322; TYR-322; PRO-393; VAL-462 AND
RP ARG-478.
RX PubMed=22723944; DOI=10.1371/journal.pone.0039122;
RA Mistri M., Tamhankar P.M., Sheth F., Sanghavi D., Kondurkar P., Patil S.,
RA Idicula-Thomas S., Gupta S., Sheth J.;
RT "Identification of novel mutations in HEXA gene in children affected with
RT Tay Sachs disease from India.";
RL PLoS ONE 7:E39122-E39122(2012).
RN [52]
RP CHARACTERIZATION OF VARIANTS GM2G1 SER-269 AND LYS-482.
RX PubMed=27682588; DOI=10.1091/mbc.e16-01-0012;
RA Dersh D., Iwamoto Y., Argon Y.;
RT "Tay Sachs disease mutations in HEXA target the alpha chain of
RT hexosaminidase A to ER-associated degradation.";
RL Mol. Biol. Cell 27:3813-3827(2016).
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 S is as active as the
CC isozyme A on the anionic bis-sulfated glycans, the chondroitin-6-
CC sulfate trisaccharide (C6S-3), and the dermatan sulfate
CC pentasaccharide, and the sulfated glycosphingolipid SM2
CC (PubMed:11707436). The isozyme B does not hydrolyze each of these
CC substrates, however hydrolyzes efficiently neutral oligosaccharide
CC (PubMed:11707436). Only the isozyme A is responsible for the
CC degradation of GM2 gangliosides in the presence of GM2A
CC (PubMed:9694901, PubMed:8672428, PubMed:8123671).
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:11707436, ECO:0000269|PubMed:8123671,
CC ECO:0000269|PubMed:8672428, 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=ganglioside GM2 (d18:1(4E)) + H2O = 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=ganglioside GM2 + H2O = 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 -!- SUBUNIT: There are 3 beta-hexosaminidase isozymes: isozyme A
CC (hexosaminidase A) is an heterodimer composed of one subunit alpha and
CC one subunit beta (chain A and B); isozyme B (hexosaminidase B) is an
CC homodimer of two beta subunits (two chains A and B); isozyme S
CC (hexosaminidase S) is a homodimer of two alpha subunits
CC (PubMed:16698036). The composition of the dimer (isozyme A versus
CC isozyme S) has a significant effect on the substrate specificity of the
CC alpha subunit active site (PubMed:8672428).
CC {ECO:0000269|PubMed:16698036, ECO:0000269|PubMed:8672428}.
CC -!- INTERACTION:
CC P06865; P07686: HEXB; NbExp=3; IntAct=EBI-723519, EBI-7133736;
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P06865-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P06865-2; Sequence=VSP_056657, VSP_056658, VSP_056659;
CC -!- PTM: N-linked glycan at Asn-115 consists of Man(3)-GlcNAc(2)
CC (PubMed:1533633, PubMed:16698036, PubMed:19159218) (Probable). N-linked
CC glycan at Asn-157 consists of either GlcNAc or GlcNAc(2)-Man(7-9). N-
CC linked glycan at Asn-295 consists of either GlcNAc, GlcNAc-Fuc, or
CC GlcNAc(2)-Man(4) (Probable). {ECO:0000269|PubMed:1533633,
CC ECO:0000269|PubMed:16698036, ECO:0000269|PubMed:19159218,
CC ECO:0000305|PubMed:11707436}.
CC -!- DISEASE: GM2-gangliosidosis 1 (GM2G1) [MIM:272800]: An autosomal
CC recessive lysosomal storage disease marked by the accumulation of GM2
CC gangliosides in the neuronal cells. It is characterized by GM2
CC gangliosides accumulation in the absence of HEXA activity, leading to
CC neurodegeneration and, in the infantile form, death in early childhood.
CC It exists in several forms: infantile (most common and most severe),
CC juvenile and adult (late-onset). {ECO:0000269|PubMed:1301189,
CC ECO:0000269|PubMed:1301190, ECO:0000269|PubMed:1302612,
CC ECO:0000269|PubMed:14566483, ECO:0000269|PubMed:1532289,
CC ECO:0000269|PubMed:1837283, ECO:0000269|PubMed:2140574,
CC ECO:0000269|PubMed:2144098, ECO:0000269|PubMed:22723944,
CC ECO:0000269|PubMed:2522679, ECO:0000269|PubMed:27682588,
CC ECO:0000269|PubMed:2970528, ECO:0000269|PubMed:7717398,
CC ECO:0000269|PubMed:7837766, ECO:0000269|PubMed:7898712,
CC ECO:0000269|PubMed:7951261, ECO:0000269|PubMed:8445615,
CC ECO:0000269|PubMed:8490625, ECO:0000269|PubMed:8581357,
CC ECO:0000269|PubMed:8757036, ECO:0000269|PubMed:9150157,
CC ECO:0000269|PubMed:9338583, ECO:0000269|PubMed:9375850,
CC ECO:0000269|PubMed:9401008, ECO:0000269|PubMed:9603435}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 20 family. {ECO:0000305}.
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DR EMBL; M16424; AAB00965.1; -; Genomic_DNA.
DR EMBL; M16411; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16412; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16413; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16414; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16415; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16416; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16417; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16418; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16419; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16420; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16421; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16422; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; M16423; AAB00965.1; JOINED; Genomic_DNA.
DR EMBL; S62076; AAD13932.1; -; Genomic_DNA.
DR EMBL; S62047; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62049; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62051; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62053; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62055; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62057; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62059; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62061; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62063; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62066; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62068; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62070; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; S62072; AAD13932.1; JOINED; Genomic_DNA.
DR EMBL; AK296528; BAG59159.1; -; mRNA.
DR EMBL; AK222502; BAD96222.1; -; mRNA.
DR EMBL; CR627386; CAH10482.1; -; mRNA.
DR EMBL; AC009690; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC018927; AAH18927.1; -; mRNA.
DR EMBL; BC084537; AAH84537.1; -; mRNA.
DR EMBL; M13520; AAA51827.1; -; mRNA.
DR CCDS; CCDS10243.1; -. [P06865-1]
DR PIR; A23561; AOHUBA.
DR RefSeq; NP_000511.2; NM_000520.5. [P06865-1]
DR RefSeq; NP_001305754.1; NM_001318825.1.
DR PDB; 2GJX; X-ray; 2.80 A; A/D/E/H=23-529.
DR PDB; 2GK1; X-ray; 3.25 A; A/C/E/G=23-529.
DR PDBsum; 2GJX; -.
DR PDBsum; 2GK1; -.
DR AlphaFoldDB; P06865; -.
DR SMR; P06865; -.
DR BioGRID; 109322; 63.
DR ComplexPortal; CPX-502; Beta-hexosaminidase A complex.
DR ComplexPortal; CPX-687; Beta-hexosaminidase S complex.
DR CORUM; P06865; -.
DR IntAct; P06865; 17.
DR STRING; 9606.ENSP00000268097; -.
DR BindingDB; P06865; -.
DR ChEMBL; CHEMBL1250415; -.
DR DrugCentral; P06865; -.
DR SwissLipids; SLP:000001416; -. [P06865-1]
DR CAZy; GH20; Glycoside Hydrolase Family 20.
DR GlyConnect; 1038; 8 N-Linked glycans (1 site).
DR GlyGen; P06865; 5 sites, 7 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P06865; -.
DR PhosphoSitePlus; P06865; -.
DR SwissPalm; P06865; -.
DR BioMuta; HEXA; -.
DR DMDM; 311033393; -.
DR EPD; P06865; -.
DR jPOST; P06865; -.
DR MassIVE; P06865; -.
DR MaxQB; P06865; -.
DR PaxDb; P06865; -.
DR PeptideAtlas; P06865; -.
DR PRIDE; P06865; -.
DR ProteomicsDB; 4455; -.
DR ProteomicsDB; 51937; -. [P06865-1]
DR Antibodypedia; 26658; 504 antibodies from 32 providers.
DR DNASU; 3073; -.
DR Ensembl; ENST00000268097.10; ENSP00000268097.6; ENSG00000213614.11. [P06865-1]
DR GeneID; 3073; -.
DR KEGG; hsa:3073; -.
DR MANE-Select; ENST00000268097.10; ENSP00000268097.6; NM_000520.6; NP_000511.2.
DR UCSC; uc002aun.5; human. [P06865-1]
DR CTD; 3073; -.
DR DisGeNET; 3073; -.
DR GeneCards; HEXA; -.
DR GeneReviews; HEXA; -.
DR HGNC; HGNC:4878; HEXA.
DR HPA; ENSG00000213614; Low tissue specificity.
DR MalaCards; HEXA; -.
DR MIM; 272800; phenotype.
DR MIM; 606869; gene.
DR neXtProt; NX_P06865; -.
DR OpenTargets; ENSG00000213614; -.
DR Orphanet; 309192; Tay-Sachs disease, B variant, adult form.
DR Orphanet; 309178; Tay-Sachs disease, B variant, infantile form.
DR Orphanet; 309185; Tay-Sachs disease, B variant, juvenile form.
DR Orphanet; 309239; Tay-Sachs disease, B1 variant.
DR PharmGKB; PA29256; -.
DR VEuPathDB; HostDB:ENSG00000213614; -.
DR eggNOG; KOG2499; Eukaryota.
DR GeneTree; ENSGT00390000008107; -.
DR InParanoid; P06865; -.
DR OMA; QYWVDHA; -.
DR OrthoDB; 545162at2759; -.
DR PhylomeDB; P06865; -.
DR TreeFam; TF313036; -.
DR BioCyc; MetaCyc:ENSG00000140495-MON; -.
DR BRENDA; 3.2.1.169; 2681.
DR PathwayCommons; P06865; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
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-3656234; Defective HEXA causes GM2G1.
DR SABIO-RK; P06865; -.
DR SignaLink; P06865; -.
DR BioGRID-ORCS; 3073; 11 hits in 1077 CRISPR screens.
DR ChiTaRS; HEXA; human.
DR EvolutionaryTrace; P06865; -.
DR GeneWiki; HEXA; -.
DR GenomeRNAi; 3073; -.
DR Pharos; P06865; Tchem.
DR PRO; PR:P06865; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; P06865; protein.
DR Bgee; ENSG00000213614; Expressed in type B pancreatic cell and 196 other tissues.
DR ExpressionAtlas; P06865; baseline and differential.
DR Genevisible; P06865; HS.
DR GO; GO:0042582; C:azurophil granule; IDA:UniProtKB.
DR GO; GO:1905379; C:beta-N-acetylhexosaminidase complex; IDA:ComplexPortal.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
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:0102148; F:N-acetyl-beta-D-galactosaminidase activity; IEA:UniProtKB-EC.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:MGI.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; IEA:Ensembl.
DR GO; GO:0006689; P:ganglioside catabolic process; IDA:UniProtKB.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IDA:UniProtKB.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; IDA:ComplexPortal.
DR GO; GO:0019915; P:lipid storage; 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:0042552; P:myelination; IEA:Ensembl.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0050884; P:neuromuscular process controlling posture; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0019953; P:sexual reproduction; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
DR Gene3D; 3.30.379.10; -; 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; PTHR22600; 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; SSF51445; 1.
DR SUPFAM; SSF55545; SSF55545; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; 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..22
FT /evidence="ECO:0000269|PubMed:2952641,
FT ECO:0000305|PubMed:11707436"
FT PROPEP 23..88
FT /evidence="ECO:0000269|PubMed:2965147"
FT /id="PRO_0000011993"
FT CHAIN 89..529
FT /note="Beta-hexosaminidase subunit alpha"
FT /id="PRO_0000011994"
FT REGION 423..424
FT /note="Critical for hydrolysis GM2 gangliosides"
FT ACT_SITE 323
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT CARBOHYD 115
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1533633,
FT ECO:0000269|PubMed:16698036, ECO:0000305|PubMed:11707436"
FT CARBOHYD 157
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1533633,
FT ECO:0000269|PubMed:16698036, ECO:0000269|PubMed:19159218,
FT ECO:0000305|PubMed:11707436"
FT CARBOHYD 295
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:1533633,
FT ECO:0000269|PubMed:16698036, ECO:0000269|PubMed:19159218,
FT ECO:0000305|PubMed:11707436"
FT DISULFID 58..104
FT /evidence="ECO:0000269|PubMed:16698036,
FT ECO:0000305|PubMed:11707436"
FT DISULFID 277..328
FT /evidence="ECO:0000269|PubMed:16698036,
FT ECO:0000305|PubMed:11707436"
FT DISULFID 505..522
FT /evidence="ECO:0000269|PubMed:16698036,
FT ECO:0000305|PubMed:11707436"
FT VAR_SEQ 1..192
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056657"
FT VAR_SEQ 359..360
FT /note="LL -> YP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056658"
FT VAR_SEQ 361..529
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056659"
FT VARIANT 25
FT /note="P -> S (in GM2G1; late infantile)"
FT /evidence="ECO:0000269|PubMed:8445615"
FT /id="VAR_003202"
FT VARIANT 39
FT /note="L -> R (in GM2G1; infantile; dbSNP:rs121907979)"
FT /id="VAR_003203"
FT VARIANT 114
FT /note="E -> K (in GM2G1; unknown pathological significance;
FT dbSNP:rs748190164)"
FT /evidence="ECO:0000269|PubMed:22723944"
FT /id="VAR_077497"
FT VARIANT 127
FT /note="L -> F (in GM2G1)"
FT /evidence="ECO:0000269|PubMed:9150157"
FT /id="VAR_022439"
FT VARIANT 127
FT /note="L -> R (in GM2G1; infantile; dbSNP:rs121907975)"
FT /id="VAR_003204"
FT VARIANT 166
FT /note="R -> G (in GM2G1; late infantile)"
FT /evidence="ECO:0000269|PubMed:8581357"
FT /id="VAR_003205"
FT VARIANT 170
FT /note="R -> Q (in GM2G1; infantile; inactive or unstable
FT protein; dbSNP:rs121907957)"
FT /evidence="ECO:0000269|PubMed:9338583"
FT /id="VAR_003206"
FT VARIANT 170
FT /note="R -> W (in GM2G1; infantile; dbSNP:rs121907972)"
FT /evidence="ECO:0000269|PubMed:1302612,
FT ECO:0000269|PubMed:22723944"
FT /id="VAR_003207"
FT VARIANT 178
FT /note="R -> C (in GM2G1; infantile; inactive protein;
FT dbSNP:rs121907953)"
FT /id="VAR_003208"
FT VARIANT 178
FT /note="R -> H (in GM2G1; infantile; inactive protein;
FT dbSNP:rs28941770)"
FT /id="VAR_003209"
FT VARIANT 178
FT /note="R -> L (in GM2G1; infantile; dbSNP:rs28941770)"
FT /id="VAR_003210"
FT VARIANT 180
FT /note="Y -> H (in GM2G1; dbSNP:rs28941771)"
FT /evidence="ECO:0000269|PubMed:8757036"
FT /id="VAR_003211"
FT VARIANT 192
FT /note="V -> L (in GM2G1; infantile; dbSNP:rs387906310)"
FT /id="VAR_003212"
FT VARIANT 196
FT /note="N -> S (in GM2G1; dbSNP:rs753862880)"
FT /evidence="ECO:0000269|PubMed:7717398"
FT /id="VAR_003213"
FT VARIANT 197
FT /note="K -> T (in GM2G1; dbSNP:rs121907973)"
FT /id="VAR_003214"
FT VARIANT 200
FT /note="V -> M (in GM2G1; dbSNP:rs1800429)"
FT /id="VAR_003215"
FT VARIANT 204
FT /note="H -> R (in GM2G1; infantile; dbSNP:rs121907976)"
FT /id="VAR_003216"
FT VARIANT 210
FT /note="S -> F (in GM2G1; infantile; dbSNP:rs121907961)"
FT /evidence="ECO:0000269|PubMed:1837283"
FT /id="VAR_003217"
FT VARIANT 211
FT /note="F -> S (in GM2G1; infantile; dbSNP:rs121907974)"
FT /id="VAR_003218"
FT VARIANT 226
FT /note="S -> F (in GM2G1; dbSNP:rs769866128)"
FT /evidence="ECO:0000269|PubMed:9150157"
FT /id="VAR_022440"
FT VARIANT 247
FT /note="R -> W (in HEXA pseudodeficiency;
FT dbSNP:rs121907970)"
FT /evidence="ECO:0000269|PubMed:1384323"
FT /id="VAR_003219"
FT VARIANT 249
FT /note="R -> W (in HEXA pseudodeficiency;
FT dbSNP:rs138058578)"
FT /evidence="ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:7902672"
FT /id="VAR_003220"
FT VARIANT 250
FT /note="G -> D (in GM2G1; juvenile; dbSNP:rs121907959)"
FT /evidence="ECO:0000269|PubMed:1301189"
FT /id="VAR_003221"
FT VARIANT 250
FT /note="G -> S (in GM2G1; dbSNP:rs1057521137)"
FT /evidence="ECO:0000269|PubMed:7717398"
FT /id="VAR_003222"
FT VARIANT 252
FT /note="R -> H (in GM2G1; dbSNP:rs762255098)"
FT /id="VAR_003223"
FT VARIANT 252
FT /note="R -> L (in GM2G1)"
FT /evidence="ECO:0000269|PubMed:14566483"
FT /id="VAR_017188"
FT VARIANT 258
FT /note="D -> H (in GM2G1; infantile; dbSNP:rs121907971)"
FT /evidence="ECO:0000269|PubMed:1302612"
FT /id="VAR_003224"
FT VARIANT 269
FT /note="G -> D (in GM2G1; dbSNP:rs121907980)"
FT /evidence="ECO:0000269|PubMed:9150157"
FT /id="VAR_022441"
FT VARIANT 269
FT /note="G -> S (in GM2G1; late onset; inhibited subunit
FT dissociation; loss of processing to a mature form;
FT increased degradation; dbSNP:rs121907954)"
FT /evidence="ECO:0000269|PubMed:2522679,
FT ECO:0000269|PubMed:27682588"
FT /id="VAR_003225"
FT VARIANT 279
FT /note="S -> P (in GM2G1; late infantile)"
FT /evidence="ECO:0000269|PubMed:9401008"
FT /id="VAR_003226"
FT VARIANT 293
FT /note="S -> I (in dbSNP:rs1054374)"
FT /id="VAR_058477"
FT VARIANT 295
FT /note="N -> S (in GM2G1; dbSNP:rs199578185)"
FT /evidence="ECO:0000269|PubMed:14566483"
FT /id="VAR_017189"
FT VARIANT 301
FT /note="M -> R (in GM2G1; infantile; dbSNP:rs121907977)"
FT /id="VAR_003227"
FT VARIANT 304
FT /note="Missing (in GM2G1; infantile; Moroccan Jewish;
FT dbSNP:rs121907960)"
FT /evidence="ECO:0000269|PubMed:9338583"
FT /id="VAR_003228"
FT VARIANT 314
FT /note="D -> V (in GM2G1; dbSNP:rs1555472696)"
FT /evidence="ECO:0000269|PubMed:9150157"
FT /id="VAR_022442"
FT VARIANT 320
FT /note="Missing (in GM2G1; late infantile;
FT dbSNP:rs797044434)"
FT /evidence="ECO:0000269|PubMed:1532289"
FT /id="VAR_003229"
FT VARIANT 322
FT /note="D -> N (in GM2G1; dbSNP:rs772180415)"
FT /evidence="ECO:0000269|PubMed:22723944"
FT /id="VAR_077498"
FT VARIANT 322
FT /note="D -> Y (in GM2G1; dbSNP:rs772180415)"
FT /evidence="ECO:0000269|PubMed:22723944"
FT /id="VAR_077499"
FT VARIANT 335
FT /note="I -> F (in GM2G1; dbSNP:rs1555472604)"
FT /evidence="ECO:0000269|PubMed:7951261"
FT /id="VAR_003230"
FT VARIANT 347..352
FT /note="Missing (in GM2G1)"
FT /evidence="ECO:0000269|PubMed:7951261"
FT /id="VAR_003231"
FT VARIANT 391
FT /note="V -> M (in GM2G1; mild; associated with spinal
FT muscular atrophy)"
FT /evidence="ECO:0000269|PubMed:7898712"
FT /id="VAR_003232"
FT VARIANT 393
FT /note="R -> P (in GM2G1; dbSNP:rs370266293)"
FT /evidence="ECO:0000269|PubMed:22723944"
FT /id="VAR_077500"
FT VARIANT 399
FT /note="N -> D (in dbSNP:rs1800430)"
FT /evidence="ECO:0000269|PubMed:1532289"
FT /id="VAR_003233"
FT VARIANT 420
FT /note="W -> C (in GM2G1; infantile; inactive protein;
FT dbSNP:rs121907958)"
FT /evidence="ECO:0000269|PubMed:14566483,
FT ECO:0000269|PubMed:2144098"
FT /id="VAR_003234"
FT VARIANT 436
FT /note="I -> V (in dbSNP:rs1800431)"
FT /evidence="ECO:0000269|PubMed:1532289,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:1833974, ECO:0000269|PubMed:2933746,
FT ECO:0000269|PubMed:2952641, ECO:0000269|PubMed:3013851,
FT ECO:0000269|Ref.5, ECO:0007744|PubMed:21269460"
FT /id="VAR_003235"
FT VARIANT 454
FT /note="G -> S (in GM2G1; infantile; dbSNP:rs121907978)"
FT /id="VAR_003236"
FT VARIANT 455
FT /note="G -> R (in GM2G1; late infantile)"
FT /evidence="ECO:0000269|PubMed:9375850"
FT /id="VAR_003237"
FT VARIANT 458
FT /note="C -> Y (in GM2G1; infantile)"
FT /evidence="ECO:0000269|PubMed:7837766"
FT /id="VAR_003238"
FT VARIANT 462
FT /note="E -> V (in GM2G1; dbSNP:rs863225434)"
FT /evidence="ECO:0000269|PubMed:22723944"
FT /id="VAR_077501"
FT VARIANT 474
FT /note="W -> C (in GM2G1; subacute; dbSNP:rs121907981)"
FT /evidence="ECO:0000269|PubMed:9603435"
FT /id="VAR_003239"
FT VARIANT 478
FT /note="G -> R (in GM2G1; dbSNP:rs1057519467)"
FT /evidence="ECO:0000269|PubMed:22723944"
FT /id="VAR_077502"
FT VARIANT 482
FT /note="E -> K (in GM2G1; infantile; loss of processing to a
FT mature form; increased degradation; dbSNP:rs121907952)"
FT /evidence="ECO:0000269|PubMed:27682588,
FT ECO:0000269|PubMed:2970528, ECO:0000269|PubMed:9338583"
FT /id="VAR_003240"
FT VARIANT 484
FT /note="L -> Q (in GM2G1; infantile)"
FT /evidence="ECO:0000269|PubMed:7837766"
FT /id="VAR_003241"
FT VARIANT 485
FT /note="W -> R (in GM2G1; infantile; dbSNP:rs121907968)"
FT /evidence="ECO:0000269|PubMed:1301190"
FT /id="VAR_003242"
FT VARIANT 499
FT /note="R -> C (in GM2G1; infantile; dbSNP:rs121907966)"
FT /evidence="ECO:0000269|PubMed:14566483"
FT /id="VAR_003243"
FT VARIANT 499
FT /note="R -> H (in GM2G1; juvenile; dbSNP:rs121907956)"
FT /evidence="ECO:0000269|PubMed:14566483"
FT /id="VAR_003244"
FT VARIANT 504
FT /note="R -> C (in GM2G1; infantile; dbSNP:rs28942071)"
FT /evidence="ECO:0000269|PubMed:1837283"
FT /id="VAR_003245"
FT VARIANT 504
FT /note="R -> H (in GM2G1; juvenile; fails to associate with
FT the beta-subunit to form the enzymatically active
FT heterodimer; dbSNP:rs121907955)"
FT /evidence="ECO:0000269|PubMed:2140574"
FT /id="VAR_003246"
FT MUTAGEN 115
FT /note="N->Q: No change of the catalytic activity associated
FT with the alpha-chain. No catalytic activity associated with
FT the alpha-chain; when associated with Q-157 and Q-295."
FT /evidence="ECO:0000269|PubMed:1533633"
FT MUTAGEN 157
FT /note="N->Q: No change of the catalytic activity associated
FT with the alpha-chain. No catalytic activity associated with
FT the alpha-chain; when associated with Q-115 and Q-295."
FT /evidence="ECO:0000269|PubMed:1533633"
FT MUTAGEN 295
FT /note="N->Q: No change of the catalytic activity associated
FT with the alpha-chain. No catalytic activity associated with
FT the alpha-chain; when associated with Q-115 and Q-157."
FT /evidence="ECO:0000269|PubMed:1533633"
FT CONFLICT 331
FT /note="S -> P (in Ref. 5; BAD96222)"
FT /evidence="ECO:0000305"
FT STRAND 28..31
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 36..39
FT /evidence="ECO:0007829|PDB:2GJX"
FT TURN 41..43
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 45..48
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 59..73
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 93..100
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 104..106
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 125..131
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 132..145
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 159..163
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 168..175
FT /evidence="ECO:0007829|PDB:2GJX"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 183..195
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 200..204
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 216..218
FT /evidence="ECO:0007829|PDB:2GK1"
FT HELIX 220..225
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:2GK1"
FT TURN 229..231
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 236..248
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 260..262
FT /evidence="ECO:0007829|PDB:2GJX"
FT TURN 264..269
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 274..290
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 295..311
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 314..318
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 327..331
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 333..341
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 349..364
FT /evidence="ECO:0007829|PDB:2GJX"
FT TURN 365..367
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 369..373
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 374..378
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 394..398
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 400..409
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 413..416
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 431..436
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 446..449
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 452..459
FT /evidence="ECO:0007829|PDB:2GJX"
FT TURN 466..468
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 469..473
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 476..485
FT /evidence="ECO:0007829|PDB:2GJX"
FT HELIX 493..509
FT /evidence="ECO:0007829|PDB:2GJX"
FT STRAND 517..519
FT /evidence="ECO:0007829|PDB:2GJX"
SQ SEQUENCE 529 AA; 60703 MW; DACB3E3992E57A47 CRC64;
MTSSRLWFSL LLAAAFAGRA TALWPWPQNF QTSDQRYVLY PNNFQFQYDV SSAAQPGCSV
LDEAFQRYRD LLFGSGSWPR PYLTGKRHTL EKNVLVVSVV TPGCNQLPTL ESVENYTLTI
NDDQCLLLSE TVWGALRGLE TFSQLVWKSA EGTFFINKTE IEDFPRFPHR GLLLDTSRHY
LPLSSILDTL DVMAYNKLNV FHWHLVDDPS FPYESFTFPE LMRKGSYNPV THIYTAQDVK
EVIEYARLRG IRVLAEFDTP GHTLSWGPGI PGLLTPCYSG SEPSGTFGPV NPSLNNTYEF
MSTFFLEVSS VFPDFYLHLG GDEVDFTCWK SNPEIQDFMR KKGFGEDFKQ LESFYIQTLL
DIVSSYGKGY VVWQEVFDNK VKIQPDTIIQ VWREDIPVNY MKELELVTKA GFRALLSAPW
YLNRISYGPD WKDFYIVEPL AFEGTPEQKA LVIGGEACMW GEYVDNTNLV PRLWPRAGAV
AERLWSNKLT SDLTFAYERL SHFRCELLRR GVQAQPLNVG FCEQEFEQT
