ID   HEXB_FELCA              Reviewed;         531 AA.
AC   P49614;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   10-MAY-2005, sequence version 2.
DT   27-MAR-2024, entry version 127.
DE   RecName: Full=Beta-hexosaminidase subunit beta {ECO:0000250|UniProtKB:P07686};
DE            EC=3.2.1.52 {ECO:0000250|UniProtKB:P07686};
DE   AltName: Full=Beta-N-acetylhexosaminidase subunit beta;
DE            Short=Hexosaminidase subunit B;
DE   AltName: Full=N-acetyl-beta-glucosaminidase subunit beta;
DE   Flags: Precursor;
GN   Name=HEXB {ECO:0000250|UniProtKB:P07686};
OS   Felis catus (Cat) (Felis silvestris catus).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX   NCBI_TaxID=9685;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND DISEASE.
RC   STRAIN=Korat; TISSUE=Liver;
RX   PubMed=8178934;
RA   Muldoon L.L., Neuwelt E.A., Pagel M.A., Weiss D.L.;
RT   "Characterization of the molecular defect in a feline model for type II
RT   GM2-gangliosidosis (Sandhoff disease).";
RL   Am. J. Pathol. 144:1109-1118(1994).
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 B does not hydrolyze each of
CC       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 (By similarity). During
CC       fertilization is responsible, at least in part, for the zona block to
CC       polyspermy. Present in the cortical granules of non-activated oocytes,
CC       is exocytosed during the cortical reaction in response to oocyte
CC       activation and inactivates the sperm galactosyltransferase-binding
CC       site, accounting for the block in sperm binding to the zona pellucida
CC       (By similarity). {ECO:0000250|UniProtKB:P07686,
CC       ECO:0000250|UniProtKB:P20060}.
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:P07686};
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:P07686};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48277;
CC         Evidence={ECO:0000250|UniProtKB:P07686};
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:P07686};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47941;
CC         Evidence={ECO:0000250|UniProtKB:P07686};
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:P07686};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47969;
CC         Evidence={ECO:0000250|UniProtKB:P07686};
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:P07686};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64373;
CC         Evidence={ECO:0000250|UniProtKB:P07686};
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:P07686};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64385;
CC         Evidence={ECO:0000250|UniProtKB:P07686};
CC   -!- ACTIVITY REGULATION: Addition of GM2A stimulates the hydrolysis of
CC       sulfated glycosphingolipid SM2 and the ganglioside GM2.
CC       {ECO:0000250|UniProtKB:P07686}.
CC   -!- SUBUNIT: There are 3 forms of beta-hexosaminidase: hexosaminidase A is
CC       an heterodimer composed of one subunit alpha and one subunit beta
CC       (chain A and B); hexosaminidase B is an homodimer of two beta subunits
CC       (two chains A and B); hexosaminidase S is a homodimer of two alpha
CC       subunits (By similarity). The composition of the dimer (isozyme A
CC       versus isozyme S) has a significant effect on the substrate specificity
CC       of the alpha subunit active site (By similarity).
CC       {ECO:0000250|UniProtKB:P06865, ECO:0000250|UniProtKB:P07686}.
CC   -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000250|UniProtKB:P07686}.
CC       Cytoplasmic vesicle, secretory vesicle, Cortical granule
CC       {ECO:0000250|UniProtKB:P20060}.
CC   -!- DISEASE: Note=Defects in HEXB are responsible for Sandhoff disease
CC       (GM2-gangliosidosis type-II). This disorder is found in Korat cats
CC       (initially imported from Thailand). {ECO:0000269|PubMed:8178934}.
CC   -!- SIMILARITY: Belongs to the glycosyl hydrolase 20 family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB30707.2; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; S70340; AAB30707.2; ALT_FRAME; mRNA.
DR   RefSeq; NP_001009333.2; NM_001009333.2.
DR   AlphaFoldDB; P49614; -.
DR   SMR; P49614; -.
DR   STRING; 9685.ENSFCAP00000016100; -.
DR   CAZy; GH20; Glycoside Hydrolase Family 20.
DR   GlyCosmos; P49614; 4 sites, No reported glycans.
DR   PaxDb; 9685-ENSFCAP00000016100; -.
DR   GeneID; 493928; -.
DR   KEGG; fca:493928; -.
DR   eggNOG; KOG2499; Eukaryota.
DR   HOGENOM; CLU_007082_0_0_1; -.
DR   InParanoid; P49614; -.
DR   OrthoDB; 178991at2759; -.
DR   BRENDA; 3.2.1.52; 2235.
DR   Proteomes; UP000011712; Unplaced.
DR   GO; GO:0060473; C:cortical granule; ISS:UniProtKB.
DR   GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
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: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; IBA:GO_Central.
DR   GO; GO:0007338; P:single fertilization; ISS:UniProtKB.
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:SF38; BETA-HEXOSAMINIDASE SUBUNIT BETA; 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   2: Evidence at transcript level;
KW   Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Glycosidase; Hydrolase;
KW   Lipid metabolism; Lysosome; Reference proteome; Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..531
FT                   /note="Beta-hexosaminidase subunit beta"
FT                   /id="PRO_0000012001"
FT   ACT_SITE        329
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250"
FT   CARBOHYD        50
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        116
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        164
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        301
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        65..111
FT                   /evidence="ECO:0000250"
FT   DISULFID        283..334
FT                   /evidence="ECO:0000250"
FT   DISULFID        508..525
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   531 AA;  60427 MW;  AC6E0C8C6509509B CRC64;
     MRHRGLGLAA LLALLAAVAP RSSAAAGAAL WPMPLSVKTS PRLLHLSRDN FSIGYGPSST
     AGPTCSLLQE AFRRYHEYIF GFDKRQRRPA KPNSAIELQQ LLVTVVLDSE CDLFPNITSD
     ESYTLLVKEP VAFLKANRVW GVLRGLETFS QLIYQDSYGT FTVNESDIID SPRFPHRGIL
     IDTARHFLPV KSILKTLDAM AFNKFNVLHW HIVDDQSFPY QSVTFPELSN KGSYSLSHVY
     TPNDVHTVIE YARLRGIRVI PEFDSPGHTQ SWGKGQKDLL TPCYNEHKQS GTFGPINPIL
     NSTYNFLSQF FKEVSMVFPD HFVHLGGDEV EFQCWESNPE IQGFMKQKGF GKDFRRLESF
     YLQKLLGIVS TVKKGSIVWQ EVFDDHVKLL PGTIVQVWKN QVYTEELREV TAAGFPVILS
     APWYLDWISY GQDWRNYYKV DPLHFDGSQE QKKLVIGGEA CLWGEFVDAT NLTPRLWPRA
     SAVGERLWSP EDITSVGNAY NRLTVHRCRM VRRGISAEPL FTGYCDYEYK T
//