ID   HEXA_RAT                Reviewed;         528 AA.
AC   Q641X3;
DT   10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT   25-OCT-2004, sequence version 1.
DT   27-MAR-2024, entry version 133.
DE   RecName: Full=Beta-hexosaminidase subunit alpha {ECO:0000305};
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:0000312|RGD:2792};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis;
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).
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=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: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=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:0000250|UniProtKB:P06865};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64385;
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 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. 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; BC082097; AAH82097.1; -; mRNA.
DR   RefSeq; NP_001004443.1; NM_001004443.1.
DR   AlphaFoldDB; Q641X3; -.
DR   SMR; Q641X3; -.
DR   IntAct; Q641X3; 1.
DR   STRING; 10116.ENSRNOP00000013747; -.
DR   CAZy; GH20; Glycoside Hydrolase Family 20.
DR   GlyCosmos; Q641X3; 4 sites, No reported glycans.
DR   GlyGen; Q641X3; 4 sites.
DR   PhosphoSitePlus; Q641X3; -.
DR   jPOST; Q641X3; -.
DR   PaxDb; 10116-ENSRNOP00000013747; -.
DR   Ensembl; ENSRNOT00000108506.1; ENSRNOP00000084550.1; ENSRNOG00000010252.5.
DR   Ensembl; ENSRNOT00055046863; ENSRNOP00055038495; ENSRNOG00055027102.
DR   Ensembl; ENSRNOT00060027496; ENSRNOP00060022084; ENSRNOG00060016046.
DR   Ensembl; ENSRNOT00065010982; ENSRNOP00065008066; ENSRNOG00065007034.
DR   GeneID; 300757; -.
DR   KEGG; rno:300757; -.
DR   UCSC; RGD:2792; rat.
DR   AGR; RGD:2792; -.
DR   CTD; 3073; -.
DR   RGD; 2792; Hexa.
DR   eggNOG; KOG2499; Eukaryota.
DR   GeneTree; ENSGT00390000008107; -.
DR   HOGENOM; CLU_007082_0_0_1; -.
DR   InParanoid; Q641X3; -.
DR   OMA; KMWPRAA; -.
DR   OrthoDB; 178991at2759; -.
DR   PhylomeDB; Q641X3; -.
DR   TreeFam; TF313036; -.
DR   Reactome; R-RNO-2022857; Keratan sulfate degradation.
DR   Reactome; R-RNO-2024101; CS/DS degradation.
DR   Reactome; R-RNO-2160916; Hyaluronan uptake and degradation.
DR   Reactome; R-RNO-9840310; Glycosphingolipid catabolism.
DR   SABIO-RK; Q641X3; -.
DR   PRO; PR:Q641X3; -.
DR   Proteomes; UP000002494; Chromosome 8.
DR   Bgee; ENSRNOG00000010252; Expressed in adult mammalian kidney and 19 other cell types or tissues.
DR   GO; GO:0042582; C:azurophil granule; ISO:RGD.
DR   GO; GO:1905379; C:beta-N-acetylhexosaminidase complex; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0005764; C:lysosome; ISO:RGD.
DR   GO; GO:0016020; C:membrane; ISO:RGD.
DR   GO; GO:0008375; F:acetylglucosaminyltransferase activity; ISO:RGD.
DR   GO; GO:0004563; F:beta-N-acetylhexosaminidase activity; ISS:UniProtKB.
DR   GO; GO:0102148; F:N-acetyl-beta-D-galactosaminidase activity; IEA:UniProtKB-EC.
DR   GO; GO:0046982; F:protein heterodimerization activity; ISO:RGD.
DR   GO; GO:0007628; P:adult walking behavior; ISO:RGD.
DR   GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; ISO:RGD.
DR   GO; GO:0030209; P:dermatan sulfate catabolic process; ISO:RGD.
DR   GO; GO:0006689; P:ganglioside catabolic process; ISS:UniProtKB.
DR   GO; GO:0006024; P:glycosaminoglycan biosynthetic process; ISO:RGD.
DR   GO; GO:0030203; P:glycosaminoglycan metabolic process; ISO:RGD.
DR   GO; GO:0030214; P:hyaluronan catabolic process; ISO:RGD.
DR   GO; GO:0019915; P:lipid storage; ISO:RGD.
DR   GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR   GO; GO:0007040; P:lysosome organization; ISO:RGD.
DR   GO; GO:0051651; P:maintenance of location in cell; ISO:RGD.
DR   GO; GO:0042552; P:myelination; ISO:RGD.
DR   GO; GO:0050885; P:neuromuscular process controlling balance; ISO:RGD.
DR   GO; GO:0050884; P:neuromuscular process controlling posture; ISO:RGD.
DR   GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR   GO; GO:0019953; P:sexual reproduction; ISO:RGD.
DR   GO; GO:0001501; P:skeletal system development; ISO:RGD.
DR   CDD; cd06562; GH20_HexA_HexB-like; 1.
DR   Gene3D; 3.30.379.10; Chitobiase/beta-hexosaminidase domain 2-like; 1.
DR   Gene3D; 3.20.20.80; Glycosidases; 1.
DR   InterPro; IPR025705; Beta_hexosaminidase_sua/sub.
DR   InterPro; IPR015883; Glyco_hydro_20_cat.
DR   InterPro; IPR017853; Glycoside_hydrolase_SF.
DR   InterPro; IPR029018; Hex-like_dom2.
DR   InterPro; IPR029019; HEX_eukaryotic_N.
DR   PANTHER; PTHR22600; BETA-HEXOSAMINIDASE; 1.
DR   PANTHER; PTHR22600: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.
DR   Genevisible; Q641X3; RN.
PE   2: Evidence at transcript level;
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_0000011999"
FT   CHAIN           89..528
FT                   /note="Beta-hexosaminidase subunit alpha"
FT                   /id="PRO_0000012000"
FT   REGION          422..423
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   CARBOHYD        487
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        504..521
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   528 AA;  60538 MW;  B87DD9A21260DCA3 CRC64;
     MAGCRLWVSL LLAAALACLA TALWPWPQYI QTSHRRYTLY PNNFQFRYHA GSAAQAGCVV
     LDEAFRRYRS LLFGSGSWPR PSFSKKQQPL GKNILMVSVV TAECNEFPNL ESVENYTLTI
     NDDQCLLSSE TVWGALRGLE TFSQLVWKSA EGTFFINKTK ITDFPRFPHR GILLDTSRHY
     LPLSSILNTL DVMAYNKFNV FHWHLVDDSS FPYESFTFPE LTRKGSFNPV THIYTAQDVK
     EVIEYARLRG IRVLAEFDTP GHTLSWGAGV PGLLTPCYSG SRLSGTYGPV NPSLNSTYDF
     MSTFFLEISS VFPDFYLHLG GDEVDFTCWK SNPNIQAFMK KKGFTDYKQL ESFYIQTLLD
     IVSDYDKGYV VWQEVFDNKV KVRPDTIIQV WREEMPVQYM KEIEAITQAG FRALLSAPWY
     LNRVKYGPDW KEMYKVEPLA FRGTPAQKAL VIGGEACMWG EYVDSTNLVP RLWPRAGAIA
     ERLWSSNLTT NMDFAFKRLS HFRCELLRRG IQAQPISVGY CEQEFEHT
//