ID   HEXA_PONAB              Reviewed;         529 AA.
AC   Q5RC84;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   21-DEC-2004, sequence version 1.
DT   04-NOV-2026, entry version 124.
DE   RecName: Full=Beta-hexosaminidase subunit alpha {ECO:0000250|UniProtKB:P06865};
DE            EC=3.2.1.52 {ECO:0000250|UniProtKB:P06865};
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:0000250|UniProtKB:P06865};
OS   Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Pongo.
OX   NCBI_TaxID=9601;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain cortex;
RG   The German cDNA consortium;
RL   Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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. The isozyme S is as active as the isozyme
CC       A on the anionic bis-sulfated glycans, the chondroitin-6-sulfate
CC       trisaccharide (C6S-3), and the dermatan sulfate pentasaccharide, and
CC       the sulfated glycosphingolipid SM2. The isozyme B does not hydrolyze
CC       each of these substrates, however hydrolyzes efficiently neutral
CC       oligosaccharide. Only the isozyme A is responsible for the degradation
CC       of GM2 gangliosides in the presence of GM2A.
CC       {ECO:0000250|UniProtKB:P06865}.
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:0000250|UniProtKB:P06865};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N-acetyl-beta-D-galactosaminyl-(1->4)-beta-D-3-
CC         sulfogalactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide + H2O = a
CC         beta-D-3-sulfogalactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide +
CC         N-acetyl-beta-D-galactosamine; Xref=Rhea:RHEA:48276,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:28497, ChEBI:CHEBI:90163,
CC         ChEBI:CHEBI:90164; Evidence={ECO:0000250|UniProtKB:P06865};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48277;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ganglioside GM2 (d18:1(4E)) + H2O = a ganglioside GM3
CC         (d18:1(4E)) + N-acetyl-beta-D-galactosamine; Xref=Rhea:RHEA:47940,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:28497, ChEBI:CHEBI:60065,
CC         ChEBI:CHEBI:71502; Evidence={ECO:0000250|UniProtKB:P06865};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47941;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a ganglioside GM2 + H2O = a ganglioside GM3 + N-acetyl-beta-D-
CC         galactosamine; Xref=Rhea:RHEA:47968, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:28497, ChEBI:CHEBI:79210, ChEBI:CHEBI:79218;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47969;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
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:0000250|UniProtKB:P06865};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64373;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=N-acetyl-beta-D-6-sulfogalactosaminyl-(1->4)-alpha-L-iduronyl-
CC         (1->3)-N-acetyl-D-6-sulfogalactosamine + H2O = 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:0000250|UniProtKB:P06865};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64385;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a globoside Gb4Cer + H2O = a globoside Gb3Cer + N-acetyl-beta-
CC         D-galactosamine; Xref=Rhea:RHEA:48040, ChEBI:CHEBI:15377,
CC         ChEBI:CHEBI:28497, ChEBI:CHEBI:88154, ChEBI:CHEBI:88167;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48041;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a globoside Gb4Cer (d18:1(4E)) + H2O = a globoside Gb3Cer
CC         (d18:1(4E)) + N-acetyl-beta-D-galactosamine; Xref=Rhea:RHEA:48036,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:18259, ChEBI:CHEBI:18313,
CC         ChEBI:CHEBI:28497; Evidence={ECO:0000250|UniProtKB:P06865};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48037;
CC         Evidence={ECO:0000250|UniProtKB:P06865};
CC   -!- ACTIVITY REGULATION: Addition of GM2A stimulates the hydrolysis of
CC       sulfated glycosphingolipid SM2 and the ganglioside GM2.
CC       {ECO:0000250|UniProtKB:P06865}.
CC   -!- SUBUNIT: There are 3 beta-hexosaminidase isozymes: isozyme A
CC       (hexosaminidase A) is a heterodimer composed of one subunit alpha and
CC       one subunit beta (chain A and B); isozyme B (hexosaminidase B) is a
CC       homodimer of two beta subunits (two chains A and B); isozyme S
CC       (hexosaminidase S) is a homodimer of two alpha subunits. The
CC       composition of the dimer (isozyme A versus isozyme S) has a significant
CC       effect on the substrate specificity of the alpha subunit active site.
CC       {ECO:0000250|UniProtKB:P06865}.
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 20 family. {ECO:0000305}.
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DR   EMBL; CR858396; CAH90623.1; -; Transcribed_RNA.
DR   RefSeq; NP_001192280.1; NM_001205351.1.
DR   AlphaFoldDB; Q5RC84; -.
DR   SMR; Q5RC84; -.
DR   FunCoup; Q5RC84; 1347.
DR   STRING; 9601.ENSPPYP00000007503; -.
DR   GlyCosmos; Q5RC84; 3 sites, No reported glycans.
DR   GeneID; 100438794; -.
DR   KEGG; pon:100438794; -.
DR   CTD; 3073; -.
DR   eggNOG; KOG2499; Eukaryota.
DR   HOGENOM; CLU_007082_0_3_1; -.
DR   InParanoid; Q5RC84; -.
DR   OMA; AADTIWG; -.
DR   OrthoDB; 428480at2759; -.
DR   Proteomes; UP000001595; Chromosome 15.
DR   GO; GO:0042582; C:azurophil granule; IEA:UniProtKB-ARBA.
DR   GO; GO:0043202; C:lysosomal lumen; IEA:UniProtKB-ARBA.
DR   GO; GO:0016020; C:membrane; IEA:TreeGrafter.
DR   GO; GO:0008375; F:acetylglucosaminyltransferase activity; IEA:UniProtKB-ARBA.
DR   GO; GO:0004563; F:beta-N-acetylhexosaminidase activity; ISS:UniProtKB.
DR   GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR   GO; GO:0006689; P:ganglioside catabolic process; ISS:UniProtKB.
DR   GO; GO:0030203; P:glycosaminoglycan metabolic process; IEA:TreeGrafter.
DR   CDD; cd06562; GH20_HexA_HexB-like; 1.
DR   FunFam; 3.20.20.80:FF:000049; Beta-hexosaminidase A; 1.
DR   FunFam; 3.30.379.10:FF:000001; Beta-hexosaminidase subunit beta; 1.
DR   Gene3D; 3.30.379.10; Chitobiase/beta-hexosaminidase domain 2-like; 1.
DR   Gene3D; 3.20.20.80; Glycosidases; 1.
DR   InterPro; IPR025705; GH20.
DR   InterPro; IPR015883; GH20_cat.
DR   InterPro; IPR017853; GH_hydrolase_sf.
DR   InterPro; IPR029018; Hex-like_dom2.
DR   InterPro; IPR029019; HEX_eukaryotic_N.
DR   PANTHER; PTHR22600; BETA-HEXOSAMINIDASE; 1.
DR   PANTHER; PTHR22600:SF39; BETA-HEXOSAMINIDASE SUBUNIT ALPHA; 1.
DR   Pfam; PF00728; Glyco_hydro_20; 1.
DR   Pfam; PF14845; Glycohydro_20b2; 1.
DR   PIRSF; PIRSF001093; B-hxosamndse_ab_euk; 1.
DR   PRINTS; PR00738; GLHYDRLASE20.
DR   SUPFAM; SSF51445; (Trans)glycosidases; 1.
DR   SUPFAM; SSF55545; beta-N-acetylhexosaminidase-like domain; 1.
PE   3: Inferred from homology;
KW   Disulfide bond; Glycoprotein; Glycosidase; Hydrolase; Lipid metabolism;
KW   Lysosome; Reference proteome; Signal; Zymogen.
FT   SIGNAL          1..22
FT                   /evidence="ECO:0000255"
FT   PROPEP          23..88
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000011997"
FT   CHAIN           89..529
FT                   /note="Beta-hexosaminidase subunit alpha"
FT                   /id="PRO_0000011998"
FT   REGION          423..424
FT                   /note="Critical for hydrolysis GM2 gangliosides"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        323
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        115
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        157
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        295
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        58..104
FT                   /evidence="ECO:0000250"
FT   DISULFID        277..328
FT                   /evidence="ECO:0000250"
FT   DISULFID        505..522
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   529 AA;  60605 MW;  8D00068F3EBDBA74 CRC64;
     MASSRLWFSL LLAAALAGRA TALWPWPQNI 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 SNPDIQDFMR KKGFGEDFKQ LESFYIQTLL
     DIVSSYGKGY VVWQEVFDNK VKIRPDTIIQ VWREDIPVNY MKELELVTKA GFRALLSAPW
     YLNRISYGPD WKDFYVVEPL AFEGTPEQKA LVIGGEACMW GEYVDNTNLV PRLWPRAGAV
     AERLWSNKLT SDLTFAYERL SHFRCELLRR GVQAQPLNVG FCEQEFEQT
//