P06865 (HEXA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	529 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 component	Lysosome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Gangliosidosis Neurodegeneration
Domain	Signal
Molecular function	Glycosidase Hydrolase
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	adult 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 ganglioside catabolic process Inferred from electronic annotation. Source: Ensembl glycosphingolipid metabolic process Traceable author statement. Source: Reactome hyaluronan catabolic process Traceable author statement. Source: Reactome keratan sulfate catabolic 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
Cellular_component	lysosomal lumen Traceable author statement. Source: Reactome membrane Inferred from electronic annotation. Source: Ensembl
Molecular_function	beta-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

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-723519,EBI-375543
CRK	P46108	1	EBI-723519,EBI-886
FYN	P06241	1	EBI-723519,EBI-515315

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Ref.2

Propeptide

23 – 88

66

PRO_0000011993

Chain

89 – 529

441

Beta-hexosaminidase subunit alpha

PRO_0000011994

Regions

Region

423 – 424

2

Critical for hydrolyzis GM2 gangliosides

Sites

Active site

323

1

Proton donor By similarity

Amino acid modifications

Glycosylation

115

1

N-linked (GlcNAc...) Ref.11 Ref.17

Glycosylation

157

1

N-linked (GlcNAc...) Ref.11 Ref.13 Ref.17

Glycosylation

295

1

N-linked (GlcNAc...) Ref.11 Ref.13 Ref.17

Disulfide bond

58 ↔ 104

Ref.17

Disulfide bond

277 ↔ 328

Ref.17

Disulfide bond

505 ↔ 522

Ref.17

Natural variations

Natural variant

25

1

P → S in GM2G1; late infantile. Ref.29

VAR_003202

Natural variant

39

1

L → R in GM2G1; infantile.

VAR_003203

Natural variant

127

1

L → F in GM2G1. Ref.36

VAR_022439

Natural variant

127

1

L → R in GM2G1; infantile.

VAR_003204

Natural variant

166

1

R → G in GM2G1; late infantile. Ref.33

VAR_003205

Natural variant

170

1

R → Q in GM2G1; infantile; inactive or unstable protein. Ref.37

VAR_003206

Natural variant

170

1

R → W in GM2G1; infantile. Ref.24

VAR_003207

Natural variant

178

1

R → C in GM2G1; infantile; inactive protein.

VAR_003208

Natural variant

178

1

R → H in GM2G1; infantile; inactive protein.

VAR_003209

Natural variant

178

1

R → L in GM2G1; infantile.
Corresponds to variant rs28941770 [ dbSNP | Ensembl ].

VAR_003210

Natural variant

180

1

Y → H in GM2G1. Ref.35
Corresponds to variant rs28941771 [ dbSNP | Ensembl ].

VAR_003211

Natural variant

192

1

V → L in GM2G1; infantile.

VAR_003212

Natural variant

196

1

N → S in GM2G1. Ref.32

VAR_003213

Natural variant

197

1

K → T in GM2G1.

VAR_003214

Natural variant

200

1

V → M in GM2G1.
Corresponds to variant rs1800429 [ dbSNP | Ensembl ].

VAR_003215

Natural variant

204

1

H → R in GM2G1; infantile.

VAR_003216

Natural variant

210

1

S → F in GM2G1; infantile. Ref.21

VAR_003217

Natural variant

211

1

F → S in GM2G1; infantile.

VAR_003218

Natural variant

226

1

S → F in GM2G1. Ref.36

VAR_022440

Natural variant

247

1

R → W in HEXA pseudodeficiency. Ref.23
Corresponds to variant rs121907970 [ dbSNP | Ensembl ].

VAR_003219

Natural variant

249

1

R → W in HEXA pseudodeficiency. Ref.5 Ref.27

VAR_003220

Natural variant

250

1

G → D in GM2G1; juvenile. Ref.25

VAR_003221

Natural variant

250

1

G → S in GM2G1. Ref.32

VAR_003222

Natural variant

252

1

R → H in GM2G1.

VAR_003223

Natural variant

252

1

R → L in GM2G1. Ref.41

VAR_017188

Natural variant

258

1

D → H in GM2G1; infantile. Ref.24

VAR_003224

Natural variant

269

1

G → D in GM2G1. Ref.36

VAR_022441

Natural variant

269

1

G → S in GM2G1; late onset; inhibited subunit dissociation. Ref.19

VAR_003225

Natural variant

279

1

S → P in GM2G1; late infantile. Ref.39

VAR_003226

Natural variant

293

1

S → I.
Corresponds to variant rs1054374 [ dbSNP | Ensembl ].

VAR_058477

Natural variant

295

1

N → S in GM2G1. Ref.41
Corresponds to variant rs199578185 [ dbSNP | Ensembl ].

VAR_017189

Natural variant

301

1

M → R in GM2G1; infantile.

VAR_003227

Natural variant

304

1

Missing in GM2G1; infantile; Moroccan Jewish. Ref.37

VAR_003228

Natural variant

314

1

D → V in GM2G1. Ref.36

VAR_022442

Natural variant

320

1

Missing in GM2G1; late infantile. Ref.22

VAR_003229

Natural variant

335

1

I → F in GM2G1. Ref.30

VAR_003230

Natural variant

347 – 352

6

Missing in GM2G1.

VAR_003231

Natural variant

391

1

V → M in GM2G1; mild; associated with spinal muscular atrophy. Ref.34

VAR_003232

Natural variant

399

1

N → D. Ref.22
Corresponds to variant rs1800430 [ dbSNP | Ensembl ].

VAR_003233

Natural variant

420

1

W → C in GM2G1; infantile; inactive protein. Ref.20 Ref.41

VAR_003234

Natural variant

436

1

I → 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 variant

454

1

G → S in GM2G1; infantile.

VAR_003236

Natural variant

455

1

G → R in GM2G1; late infantile. Ref.38

VAR_003237

Natural variant

458

1

C → Y in GM2G1; infantile. Ref.31

VAR_003238

Natural variant

474

1

W → C in GM2G1; subacute. Ref.40

VAR_003239

Natural variant

482

1

E → K in GM2G1; infantile. Ref.18 Ref.37

VAR_003240

Natural variant

484

1

L → Q in GM2G1; infantile. Ref.31

VAR_003241

Natural variant

485

1

W → R in GM2G1; infantile. Ref.26

VAR_003242

Natural variant

499

1

R → C in GM2G1; infantile. Ref.41

VAR_003243

Natural variant

499

1

R → H in GM2G1; juvenile. Ref.41

VAR_003244

Natural variant

504

1

R → C in GM2G1; infantile. Ref.21
Corresponds to variant rs28942071 [ dbSNP | Ensembl ].

VAR_003245

Natural variant

504

1

R → H in GM2G1; juvenile; inhibited subunit dissociation.

VAR_003246

Experimental info

Mutagenesis

115

1

N → 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

Mutagenesis

157

1

N → 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

Mutagenesis

295

1

N → 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 conflict

331

1

S → P in BAD96222. Ref.4

Secondary structure

1

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529

Helix Strand Turn

Details...

Beta strand

28 – 31

4

Beta strand

36 – 39

4

Turn

41 – 43

3

Beta strand

45 – 48

4

Helix

59 – 73

15

Beta strand

93 – 100

8

Beta strand

104 – 106

3

Beta strand

116 – 123

8

Beta strand

125 – 131

7

Helix

132 – 145

14

Beta strand

146 – 148

3

Beta strand

154 – 157

4

Beta strand

159 – 163

5

Beta strand

168 – 175

8

Turn

176 – 178

3

Helix

183 – 195

13

Beta strand

200 – 204

5

Beta strand

216 – 218

3

Helix

220 – 225

6

Beta strand

226 – 228

3

Turn

229 – 231

3

Helix

236 – 248

13

Beta strand

252 – 256

5

Beta strand

260 – 262

3

Turn

264 – 269

6

Beta strand

274 – 290

17

Helix

295 – 311

17

Beta strand

314 – 318

5

Helix

327 – 331

5

Helix

333 – 341

9

Helix

349 – 364

16

Turn

365 – 367

3

Beta strand

369 – 373

5

Helix

374 – 378

5

Beta strand

388 – 391

4

Beta strand

394 – 398

5

Helix

400 – 409

10

Beta strand

413 – 416

4

Beta strand

426 – 428

3

Helix

431 – 436

6

Helix

446 – 449

4

Beta strand

452 – 459

8

Turn

466 – 468

3

Helix

469 – 473

5

Helix

476 – 485

10

Helix

493 – 509

17

Beta strand

517 – 519

3

Sequences

	Sequence		Length	Mass (Da)
	P06865 [UniParc]. Last modified November 2, 2010. Version 2. Checksum: DACB3E3992E57A47	FASTA	529	60,703
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

HEXAdb

HEXA mutation database

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M16424 , M16411, M16412, M16413, M16414, M16415, M16416, M16417, M16418, M16419, M16420, M16421, M16422, M16423 Genomic DNA. Translation: AAB00965.1.
S62076 , 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.

IPI

IPI00027851.

PIR

AOHUBA. A23561.

RefSeq

NP_000511.2. NM_000520.4.

UniGene

Hs.604479.
Hs.709495.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QBC	model	-	A	109-529	[»]
2GJX	X-ray	2.80	A/D/E/H	23-529	[»]
2GK1	X-ray	3.25	A/C/E/G	23-529	[»]

ProteinModelPortal

P06865.

SMR

P06865. Positions 23-528.

ModBase

Search...

Protein-protein interaction databases

IntAct

P06865. 6 interactions.

MINT

MINT-1393072.

STRING

9606.ENSP00000268097.

Protein family/group databases

CAZy

GH20. Glycoside Hydrolase Family 20.

PTM databases

PhosphoSite

P06865.

Polymorphism databases

DMDM

311033393.

Proteomic databases

PaxDb

P06865.

PeptideAtlas

P06865.

PRIDE

P06865.

Protocols and materials databases

DNASU

3073.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000268097; ENSP00000268097; ENSG00000213614.

GeneID

3073.

KEGG

hsa:3073.

UCSC

uc002aun.4. human.

Organism-specific databases

CTD

3073.

GeneCards

GC15M072635.

H-InvDB

HIX0012407.

HGNC

HGNC:4878. HEXA.

HPA

HPA054583.

MIM

272800. phenotype.
606869. gene.

neXtProt

NX_P06865.

Orphanet

309192. 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.

PharmGKB

PA29256.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3525.

HOGENOM

HOG000157972.

HOVERGEN

HBG005961.

InParanoid

P06865.

KO

K12373.

OrthoDB

EOG7KDFB6.

PhylomeDB

P06865.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000140495-MONOMER.

Reactome

REACT_111217. Metabolism.
REACT_116125. Disease.

SABIO-RK

P06865.

Gene expression databases

ArrayExpress

P06865.

Bgee

P06865.

CleanEx

HS_HEXA.

Genevestigator

P06865.

Family and domain databases

Gene3D

3.20.20.80. 1 hit.

InterPro

IPR025705. Beta_hexosaminidase_sua/sub.
IPR015883. Glyco_hydro_20_cat-core.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
[Graphical view]

Pfam

PF00728. Glyco_hydro_20. 1 hit.
[Graphical view]

PIRSF

PIRSF001093. B-hxosamndse_ab_euk_. 1 hit.

PRINTS

PR00738. GLHYDRLASE20.

SUPFAM

SSF51445. SSF51445. 1 hit.

ProtoNet

Search...

Other

BindingDB

P06865.

ChEMBL

CHEMBL1250415.

EvolutionaryTrace

P06865.

GeneWiki

HEXA.

GenomeRNAi

3073.

NextBio

12155.

PRO

P06865.

SOURCE

Search...

Entry information

Entry name

HEXA_HUMAN

Accession

Primary (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:	November 13, 2013
This is version 165 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.