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P06865 (HEXA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 170. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Beta-hexosaminidase subunit alpha

EC=3.2.1.52
Alternative name(s):
Beta-N-acetylhexosaminidase subunit alpha
Short name=Hexosaminidase subunit A
N-acetyl-beta-glucosaminidase subunit alpha
Gene names
Name:HEXA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length529 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Responsible for the degradation of GM2 gangliosides, and a variety of other molecules containing terminal N-acetyl hexosamines, in the brain and other tissues. The form B is active against certain oligosaccharides. The form S has no measurable activity.

Catalytic activity

Hydrolysis of terminal non-reducing N-acetyl-D-hexosamine residues in N-acetyl-beta-D-hexosaminides.

Subunit structure

There are 3 forms of beta-hexosaminidase: hexosaminidase A is a trimer composed of one subunit alpha, one subunit beta chain A and one subunit beta chain B; hexosaminidase B is a tetramer of two subunit beta chains A and two subunit beta chains B; hexosaminidase S is a homodimer of two alpha subunits. The two beta chains are derived from the cleavage of the beta subunit.

Subcellular location

Lysosome.

Post-translational modification

N-linked glycan at Asn-115 consists of Man(3)-GlcNAc2.

Involvement in disease

GM2-gangliosidosis 1 (GM2G1) [MIM:272800]: An autosomal recessive lysosomal storage disease marked by the accumulation of GM2 gangliosides in the neuronal cells. It is characterized by GM2 gangliosides accumulation in the absence of HEXA activity, leading to neurodegeneration and, in the infantile form, death in early childhood. It exists in several forms: infantile (most common and most severe), juvenile and adult (late-onset).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.24 Ref.25 Ref.26 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37 Ref.38 Ref.39 Ref.40 Ref.41

Sequence similarities

Belongs to the glycosyl hydrolase 20 family.

Ontologies

Keywords
   Cellular componentLysosome
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Gangliosidosis
Neurodegeneration
   DomainSignal
   Molecular functionGlycosidase
Hydrolase
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processadult walking behavior

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cell death

Inferred from electronic annotation. Source: UniProtKB-KW

cell morphogenesis involved in neuron differentiation

Inferred from electronic annotation. Source: Ensembl

chondroitin sulfate catabolic process

Traceable author statement. Source: Reactome

chondroitin sulfate metabolic process

Traceable author statement. Source: Reactome

ganglioside catabolic process

Inferred from electronic annotation. Source: Ensembl

glycosaminoglycan metabolic process

Traceable author statement. Source: Reactome

glycosphingolipid metabolic process

Traceable author statement. Source: Reactome

hyaluronan catabolic process

Traceable author statement. Source: Reactome

hyaluronan metabolic process

Traceable author statement. Source: Reactome

keratan sulfate catabolic process

Traceable author statement. Source: Reactome

keratan sulfate metabolic process

Traceable author statement. Source: Reactome

lipid storage

Inferred from electronic annotation. Source: Ensembl

lysosome organization

Inferred from electronic annotation. Source: Ensembl

myelination

Inferred from electronic annotation. Source: Ensembl

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

neuromuscular process controlling posture

Inferred from electronic annotation. Source: Ensembl

sensory perception of sound

Inferred from electronic annotation. Source: Ensembl

sexual reproduction

Inferred from electronic annotation. Source: Ensembl

skeletal system development

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentlysosomal lumen

Traceable author statement. Source: Reactome

membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionbeta-N-acetylhexosaminidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein heterodimerization activity

Inferred from direct assay PubMed 6230359. Source: MGI

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Ref.2
Propeptide23 – 8866
PRO_0000011993
Chain89 – 529441Beta-hexosaminidase subunit alpha
PRO_0000011994

Regions

Region423 – 4242Critical for hydrolyzis GM2 gangliosides

Sites

Active site3231Proton donor By similarity

Amino acid modifications

Glycosylation1151N-linked (GlcNAc...) Ref.11 Ref.17
Glycosylation1571N-linked (GlcNAc...) Ref.11 Ref.13 Ref.17
Glycosylation2951N-linked (GlcNAc...) Ref.11 Ref.13 Ref.17
Disulfide bond58 ↔ 104 Ref.17
Disulfide bond277 ↔ 328 Ref.17
Disulfide bond505 ↔ 522 Ref.17

Natural variations

Natural variant251P → S in GM2G1; late infantile. Ref.29
VAR_003202
Natural variant391L → R in GM2G1; infantile.
VAR_003203
Natural variant1271L → F in GM2G1. Ref.36
VAR_022439
Natural variant1271L → R in GM2G1; infantile.
VAR_003204
Natural variant1661R → G in GM2G1; late infantile. Ref.33
VAR_003205
Natural variant1701R → Q in GM2G1; infantile; inactive or unstable protein. Ref.37
VAR_003206
Natural variant1701R → W in GM2G1; infantile. Ref.24
VAR_003207
Natural variant1781R → C in GM2G1; infantile; inactive protein.
VAR_003208
Natural variant1781R → H in GM2G1; infantile; inactive protein.
VAR_003209
Natural variant1781R → L in GM2G1; infantile.
Corresponds to variant rs28941770 [ dbSNP | Ensembl ].
VAR_003210
Natural variant1801Y → H in GM2G1. Ref.35
Corresponds to variant rs28941771 [ dbSNP | Ensembl ].
VAR_003211
Natural variant1921V → L in GM2G1; infantile.
VAR_003212
Natural variant1961N → S in GM2G1. Ref.32
VAR_003213
Natural variant1971K → T in GM2G1.
VAR_003214
Natural variant2001V → M in GM2G1.
Corresponds to variant rs1800429 [ dbSNP | Ensembl ].
VAR_003215
Natural variant2041H → R in GM2G1; infantile.
VAR_003216
Natural variant2101S → F in GM2G1; infantile. Ref.21
VAR_003217
Natural variant2111F → S in GM2G1; infantile.
VAR_003218
Natural variant2261S → F in GM2G1. Ref.36
VAR_022440
Natural variant2471R → W in HEXA pseudodeficiency. Ref.23
Corresponds to variant rs121907970 [ dbSNP | Ensembl ].
VAR_003219
Natural variant2491R → W in HEXA pseudodeficiency. Ref.5 Ref.27
VAR_003220
Natural variant2501G → D in GM2G1; juvenile. Ref.25
VAR_003221
Natural variant2501G → S in GM2G1. Ref.32
VAR_003222
Natural variant2521R → H in GM2G1.
VAR_003223
Natural variant2521R → L in GM2G1. Ref.41
VAR_017188
Natural variant2581D → H in GM2G1; infantile. Ref.24
VAR_003224
Natural variant2691G → D in GM2G1. Ref.36
VAR_022441
Natural variant2691G → S in GM2G1; late onset; inhibited subunit dissociation. Ref.19
VAR_003225
Natural variant2791S → P in GM2G1; late infantile. Ref.39
VAR_003226
Natural variant2931S → I.
Corresponds to variant rs1054374 [ dbSNP | Ensembl ].
VAR_058477
Natural variant2951N → S in GM2G1. Ref.41
Corresponds to variant rs199578185 [ dbSNP | Ensembl ].
VAR_017189
Natural variant3011M → R in GM2G1; infantile.
VAR_003227
Natural variant3041Missing in GM2G1; infantile; Moroccan Jewish. Ref.37
VAR_003228
Natural variant3141D → V in GM2G1. Ref.36
VAR_022442
Natural variant3201Missing in GM2G1; late infantile. Ref.22
VAR_003229
Natural variant3351I → F in GM2G1. Ref.30
VAR_003230
Natural variant347 – 3526Missing in GM2G1.
VAR_003231
Natural variant3911V → M in GM2G1; mild; associated with spinal muscular atrophy. Ref.34
VAR_003232
Natural variant3991N → D. Ref.22
Corresponds to variant rs1800430 [ dbSNP | Ensembl ].
VAR_003233
Natural variant4201W → C in GM2G1; infantile; inactive protein. Ref.20 Ref.41
VAR_003234
Natural variant4361I → V. Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 Ref.7 Ref.8 Ref.22 Ref.42
Corresponds to variant rs1800431 [ dbSNP | Ensembl ].
VAR_003235
Natural variant4541G → S in GM2G1; infantile.
VAR_003236
Natural variant4551G → R in GM2G1; late infantile. Ref.38
VAR_003237
Natural variant4581C → Y in GM2G1; infantile. Ref.31
VAR_003238
Natural variant4741W → C in GM2G1; subacute. Ref.40
VAR_003239
Natural variant4821E → K in GM2G1; infantile. Ref.18 Ref.37
VAR_003240
Natural variant4841L → Q in GM2G1; infantile. Ref.31
VAR_003241
Natural variant4851W → R in GM2G1; infantile. Ref.26
VAR_003242
Natural variant4991R → C in GM2G1; infantile. Ref.41
VAR_003243
Natural variant4991R → H in GM2G1; juvenile. Ref.41
VAR_003244
Natural variant5041R → C in GM2G1; infantile. Ref.21
Corresponds to variant rs28942071 [ dbSNP | Ensembl ].
VAR_003245
Natural variant5041R → H in GM2G1; juvenile; inhibited subunit dissociation.
VAR_003246

Experimental info

Mutagenesis1151N → Q: No change of the catalytic activity associated with the alpha-chain. No catalytic activity associated with the alpha-chain; when associated with Q-157 and Q-295. Ref.11
Mutagenesis1571N → Q: No change of the catalytic activity associated with the alpha-chain. No catalytic activity associated with the alpha-chain; when associated with Q-115 and Q-295. Ref.11
Mutagenesis2951N → Q: No change of the catalytic activity associated with the alpha-chain. No catalytic activity associated with the alpha-chain; when associated with Q-115 and Q-157. Ref.11
Sequence conflict3311S → P in BAD96222. Ref.4

Secondary structure

....................................................................................... 529
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P06865 [UniParc].

Last modified November 2, 2010. Version 2.
Checksum: DACB3E3992E57A47

FASTA52960,703
        10         20         30         40         50         60 
MTSSRLWFSL LLAAAFAGRA TALWPWPQNF QTSDQRYVLY PNNFQFQYDV SSAAQPGCSV 

        70         80         90        100        110        120 
LDEAFQRYRD LLFGSGSWPR PYLTGKRHTL EKNVLVVSVV TPGCNQLPTL ESVENYTLTI 

       130        140        150        160        170        180 
NDDQCLLLSE TVWGALRGLE TFSQLVWKSA EGTFFINKTE IEDFPRFPHR GLLLDTSRHY 

       190        200        210        220        230        240 
LPLSSILDTL DVMAYNKLNV FHWHLVDDPS FPYESFTFPE LMRKGSYNPV THIYTAQDVK 

       250        260        270        280        290        300 
EVIEYARLRG IRVLAEFDTP GHTLSWGPGI PGLLTPCYSG SEPSGTFGPV NPSLNNTYEF 

       310        320        330        340        350        360 
MSTFFLEVSS VFPDFYLHLG GDEVDFTCWK SNPEIQDFMR KKGFGEDFKQ LESFYIQTLL 

       370        380        390        400        410        420 
DIVSSYGKGY VVWQEVFDNK VKIQPDTIIQ VWREDIPVNY MKELELVTKA GFRALLSAPW 

       430        440        450        460        470        480 
YLNRISYGPD WKDFYIVEPL AFEGTPEQKA LVIGGEACMW GEYVDNTNLV PRLWPRAGAV 

       490        500        510        520 
AERLWSNKLT SDLTFAYERL SHFRCELLRR GVQAQPLNVG FCEQEFEQT 

« Hide

References

« Hide 'large scale' references
[1]"Human beta-hexosaminidase alpha chain: coding sequence and homology with the beta chain."
Myerowitz R., Piekarz R., Neufeld E.F., Shows T.B., Suzuki K.
Proc. Natl. Acad. Sci. U.S.A. 82:7830-7834(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-436.
[2]"Organization of the gene encoding the human beta-hexosaminidase alpha-chain."
Proia R.L., Soravia E.
J. Biol. Chem. 262:5677-5681(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-436.
[3]"Sequence of DNA flanking the exons of the HEXA gene, and identification of mutations in Tay-Sachs disease."
Triggs-Raine B.L., Akerman B.R., Clarke J.T.R., Gravel R.A.
Am. J. Hum. Genet. 49:1041-1054(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-436.
[4]Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-436.
Tissue: Adipose tissue.
[5]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS PSEUDODEFICIENCY TRP-249 AND VAL-436.
[6]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-436.
Tissue: Brain and Eye.
[8]"Isolation of cDNA clones coding for the alpha-subunit of human beta-hexosaminidase. Extensive homology between the alpha- and beta-subunits and studies on Tay-Sachs disease."
Korneluk R.G., Mahuran D.J., Neote K., Klavins M.H., O'Dowd B.F., Tropak M., Willard H.F., Anderson M.-J., Lowden J.A., Gravel R.A.
J. Biol. Chem. 261:8407-8413(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 40-529, VARIANT VAL-436.
[9]"Proteolytic processing of pro-alpha and pro-beta precursors from human beta-hexosaminidase. Generation of the mature alpha and beta a beta b subunits."
Mahuran D.J., Neote K., Klavins M.H., Leung A., Gravel R.A.
J. Biol. Chem. 263:4612-4618(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 89-99.
[10]"Oligosaccharide structure and amino acid sequence of the major glycopeptides of mature human beta-hexosaminidase."
O'Dowd B.F., Cumming D.A., Gravel R.A., Mahuran D.J.
Biochemistry 27:5216-5226(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 96-105, STRUCTURE OF CARBOHYDRATES.
[11]"Analysis of the glycosylation and phosphorylation of the alpha-subunit of the lysosomal enzyme, beta-hexosaminidase A, by site-directed mutagenesis."
Weitz G., Proia R.L.
J. Biol. Chem. 267:10039-10044(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-115; ASN-157 AND ASN-295, MUTAGENESIS OF ASN-115; ASN-157 AND ASN-295.
[12]"Identification of an active acidic residue in the catalytic site of beta-hexosaminidase."
Tse R., Vavougios G., Hou Y., Mahuran D.J.
Biochemistry 35:7599-7607(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITES.
[13]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-157 AND ASN-295.
Tissue: Liver.
[14]"Bacterial chitobiase structure provides insight into catalytic mechanism and the basis of Tay-Sachs disease."
Tews I., Perrakis A., Oppenheim A., Dauter Z., Wilson K.S., Vorgias C.E.
Nat. Struct. Biol. 3:638-648(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING.
[15]"The biochemistry of HEXA and HEXB gene mutations causing GM2 gangliosidosis."
Mahuran D.J.
Biochim. Biophys. Acta 1096:87-94(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[16]"Tay-Sachs disease-causing mutations and neutral polymorphisms in the Hex A gene."
Myerowitz R.
Hum. Mutat. 9:195-208(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
[17]"Crystallographic structure of human beta-hexosaminidase A: interpretation of Tay-Sachs mutations and loss of GM2 ganglioside hydrolysis."
Lemieux M.J., Mark B.L., Cherney M.M., Withers S.G., Mahuran D.J., James M.N.
J. Mol. Biol. 359:913-929(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 23-529 IN COMPLEX WITH HEXB, GLYCOSYLATION AT ASN-115; ASN-157 AND ASN-295, DISULFIDE BONDS.
[18]"A point mutation in the coding sequence of the beta-hexosaminidase alpha gene results in defective processing of the enzyme protein in an unusual GM2-gangliosidosis variant."
Nakano T., Muscillo M., Ohno K., Hoffman A.J., Suzuki K.
J. Neurochem. 51:984-987(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 LYS-482.
[19]"The mutations in Ashkenazi Jews with adult GM2 gangliosidosis, the adult form of Tay-Sachs disease."
Navon R., Proia R.L.
Science 243:1471-1474(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 SER-269.
[20]"A new point mutation in the beta-hexosaminidase alpha subunit gene responsible for infantile Tay-Sachs disease in a non-Jewish Caucasian patient (a Kpn mutant)."
Tanaka A., Punnett H.H., Suzuki K.
Am. J. Hum. Genet. 47:568-574(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 CYS-420.
[21]"Seven novel Tay-Sachs mutations detected by chemical mismatch cleavage of PCR-amplified cDNA fragments."
Akli S., Lacorte J.-M., Poenaru L., Khan A.
Genomics 11:124-134(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1 PHE-210 AND CYS-504.
[22]"Six novel deleterious and three neutral mutations in the gene encoding the alpha-subunit of hexosaminidase A in non-Jewish individuals."
Mules E.H., Hayflick S., Miller C.S., Reynolds L.W., Thomas G.H.
Am. J. Hum. Genet. 50:834-841(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 GLY-320 DEL, VARIANTS ASP-399 AND VAL-436.
[23]"A pseudodeficiency allele common in non-Jewish Tay-Sachs carriers: implications for carrier screening."
Triggs-Raine B.L., Mules E.H., Kaback M.M., Lim-Steele J.S.T., Dowling C.E., Akerman B.R., Natowicz M.R., Grebner E.E., Navon R., Welch J.P., Greenberg C.R., Thomas G.H., Gravel R.A.
Am. J. Hum. Genet. 51:793-801(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PSEUDODEFICIENCY TRP-247.
[24]"A new Tay-Sachs disease B1 allele in exon 7 in two compound heterozygotes each with a second novel mutation."
Fernandes M., Kaplan F., Natowicz M., Prence E., Kolodny E., Kaback M., Hechtman P.
Hum. Mol. Genet. 1:759-761(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1 TRP-170 AND HIS-258.
[25]"A glycine250--> aspartate substitution in the alpha-subunit of hexosaminidase A causes juvenile-onset Tay-Sachs disease in a Lebanese-Canadian family."
Trop I., Kaplan F., Brown C., Mahuran D., Hechtman P.
Hum. Mutat. 1:35-39(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 ASP-250.
[26]"Novel Tay-Sachs disease mutations from China."
Akalin N., Shi H.-P., Vavougios G., Hechtman P., Lo W., Scriver C.R., Mahuran D., Kaplan F.
Hum. Mutat. 1:40-46(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 ARG-485.
[27]"A second mutation associated with apparent beta-hexosaminidase A pseudodeficiency: identification and frequency estimation."
Cao Z., Natowicz M.R., Kaback M.M., Lim-Steele J.S.T., Prence E.M., Brown D., Chabot T., Triggs-Raine B.L.
Am. J. Hum. Genet. 53:1198-1205(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PSEUDODEFICIENCY TRP-249.
[28]"Ten novel mutations in the HEXA gene in non-Jewish Tay-Sachs patients."
Akli S., Chomel J.-C., Lacorte J.-M., Bachner L., Poenaru A., Poenaru L.
Hum. Mol. Genet. 2:61-67(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1.
[29]"Two new mutations in a late infantile Tay-Sachs patient are both in exon 1 of the beta-hexosaminidase alpha subunit gene."
Harmon D.L., Gardner-Medwin D., Stirling J.L.
J. Med. Genet. 30:123-128(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 SER-25.
[30]"Three novel beta-hexosaminidase A mutations in obligate carriers of Tay-Sachs disease."
Tomczak J., Grebner E.E.
Hum. Mutat. 4:71-72(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1 PHE-335 AND 347-ASP--GLU-352 DEL.
[31]"Molecular genetics of Tay-Sachs disease in Japan."
Tanaka A., Sakazaki H., Murakami H., Isshiki G., Suzuki K.
J. Inherit. Metab. Dis. 17:593-600(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1 TYR-458 AND GLN-484.
[32]"Mutational analyses of Tay-Sachs disease: studies on Tay-Sachs carriers of French Canadian background living in New England."
Triggs-Raine B.L., Richard M., Wasel N., Prence E.M., Natowicz M.R.
Am. J. Hum. Genet. 56:870-879(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1 SER-196 AND SER-250.
[33]"GM2 gangliosidosis B1 variant: biochemical and molecular characterization of hexosaminidase A."
Peleg L., Meltzer F., Karpati M., Goldman B.
Biochem. Mol. Med. 54:126-132(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 GLY-166.
[34]"A new mutation in the HEXA gene associated with a spinal muscular atrophy phenotype."
Navon R., Khosravi R., Korczyn T., Masson M., Sonnino S., Fardeau M., Eymard B., Lefevre N., Turpin J.C., Rondot P.
Neurology 45:539-543(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 MET-391.
[35]"Late-onset GM2 gangliosidosis: Ashkenazi Jewish family with an exon 5 mutation (Tyr180-->His) in the Hex A alpha-chain gene."
de Gasperi R., Gama Sosa M.A., Battistini S., Yeretsian J., Raghavan S., Zelnik N., Leshinsky E., Kolodny E.H.
Neurology 47:547-552(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 HIS-180.
[36]"Novel mutations and DNA-based screening in non-Jewish carriers of Tay-Sachs disease."
Akerman B.R., Natowicz M.R., Kaback M.M., Loyer M., Campeau E., Gravel R.A.
Am. J. Hum. Genet. 60:1099-1106(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1 PHE-127; PHE-226; ASP-269 AND VAL-314.
[37]"Tay-Sachs disease and HEXA mutations among Moroccan Jews."
Kaufman M., Grinshpun-Cohen J., Karpati M., Peleg L., Goldman B., Akstein E., Adam A., Navon R.
Hum. Mutat. 10:295-300(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1 GLN-170; PHE-304 DEL AND LYS-482.
[38]"Two novel (1334delC and 1363G to A, G455R) mutations in exon 12 of the beta-hexosaminidase alpha-chain gene in two Portuguese patients."
Ribeiro M.G., Pinto R.A., Suzuki K., Sa Miranda M.C.
Hum. Mutat. 10:359-360(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 ARG-455.
[39]"Two mutated HEXA alleles in a Druze patient with late-infantile Tay-Sachs disease."
Drucker L., Hemli J.A., Navon R.
Hum. Mutat. 10:451-457(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 PRO-279.
[40]"W474C amino acid substitution affects early processing of the alpha-subunit of beta-hexosaminidase A and is associated with subacute G(M2) gangliosidosis."
Petroulakis E., Cao Z., Clarke J.T.R., Mahuran D.J., Lee G., Triggs-Raine B.
Hum. Mutat. 11:432-442(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GM2G1 CYS-474.
[41]"Different attenuated phenotypes of GM2 gangliosidosis variant B in Japanese patients with HEXA mutations at codon 499, and five novel mutations responsible for infantile acute form."
Tanaka A., Hoang L.T., Nishi Y., Maniwa S., Oka M., Yamano T.
J. Hum. Genet. 48:571-574(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GM2G1 LEU-252; SER-295; CYS-420; CYS-499 AND HIS-499.
[42]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-436, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

HEXAdb

HEXA mutation database

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M16424 expand/collapse EMBL AC list , M16411, M16412, M16413, M16414, M16415, M16416, M16417, M16418, M16419, M16420, M16421, M16422, M16423 Genomic DNA. Translation: AAB00965.1.
S62076 expand/collapse EMBL AC list , S62047, S62049, S62051, S62053, S62055, S62057, S62059, S62061, S62063, S62066, S62068, S62070, S62072 Genomic DNA. Translation: AAD13932.1.
AK222502 mRNA. Translation: BAD96222.1.
CR627386 mRNA. Translation: CAH10482.1.
AC009690 Genomic DNA. No translation available.
BC018927 mRNA. Translation: AAH18927.1.
BC084537 mRNA. Translation: AAH84537.1.
M13520 mRNA. Translation: AAA51827.1.
PIRAOHUBA. A23561.
RefSeqNP_000511.2. NM_000520.4.
UniGeneHs.604479.
Hs.709495.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1QBCmodel-A109-529[»]
2GJXX-ray2.80A/D/E/H23-529[»]
2GK1X-ray3.25A/C/E/G23-529[»]
ProteinModelPortalP06865.
SMRP06865. Positions 23-528.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109322. 25 interactions.
IntActP06865. 6 interactions.
MINTMINT-1393072.
STRING9606.ENSP00000268097.

Chemistry

BindingDBP06865.
ChEMBLCHEMBL1250415.

Protein family/group databases

CAZyGH20. Glycoside Hydrolase Family 20.

PTM databases

PhosphoSiteP06865.

Polymorphism databases

DMDM311033393.

Proteomic databases

PaxDbP06865.
PeptideAtlasP06865.
PRIDEP06865.

Protocols and materials databases

DNASU3073.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000268097; ENSP00000268097; ENSG00000213614.
GeneID3073.
KEGGhsa:3073.
UCSCuc002aun.4. human.

Organism-specific databases

CTD3073.
GeneCardsGC15M072635.
H-InvDBHIX0012407.
HGNCHGNC:4878. HEXA.
HPAHPA054583.
MIM272800. phenotype.
606869. gene.
neXtProtNX_P06865.
Orphanet309192. Tay-Sachs disease, B variant, adult form.
309178. Tay-Sachs disease, B variant, infantile form.
309185. Tay-Sachs disease, B variant, juvenile form.
309239. Tay-Sachs disease, B1 variant.
PharmGKBPA29256.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3525.
HOGENOMHOG000157972.
HOVERGENHBG005961.
InParanoidP06865.
KOK12373.
OrthoDBEOG7KDFB6.
PhylomeDBP06865.
TreeFamTF313036.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000140495-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKP06865.

Gene expression databases

ArrayExpressP06865.
BgeeP06865.
CleanExHS_HEXA.
GenevestigatorP06865.

Family and domain databases

Gene3D3.20.20.80. 1 hit.
InterProIPR025705. Beta_hexosaminidase_sua/sub.
IPR015883. Glyco_hydro_20_cat-core.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]
PfamPF00728. Glyco_hydro_20. 1 hit.
[Graphical view]
PIRSFPIRSF001093. B-hxosamndse_ab_euk_. 1 hit.
PRINTSPR00738. GLHYDRLASE20.
SUPFAMSSF51445. SSF51445. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP06865.
GeneWikiHEXA.
GenomeRNAi3073.
NextBio12155.
PROP06865.
SOURCESearch...

Entry information

Entry nameHEXA_HUMAN
AccessionPrimary (citable) accession number: P06865
Secondary accession number(s): Q53HS8, Q6AI32
Entry history
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 2, 2010
Last modified: April 16, 2014
This is version 170 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries