ID A0A8C4Z7H1_GADMO Unreviewed; 535 AA.
AC A0A8C4Z7H1;
DT 19-JAN-2022, integrated into UniProtKB/TrEMBL.
DT 19-JAN-2022, sequence version 1.
DT 28-JAN-2026, entry version 20.
DE RecName: Full=Beta-hexosaminidase {ECO:0000256|PIRNR:PIRNR001093};
DE EC=3.2.1.52 {ECO:0000256|PIRNR:PIRNR001093};
GN Name=hexa {ECO:0000313|Ensembl:ENSGMOP00000008926.2};
OS Gadus morhua (Atlantic cod).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Neoteleostei; Acanthomorphata;
OC Zeiogadaria; Gadariae; Gadiformes; Gadoidei; Gadidae; Gadus.
OX NCBI_TaxID=8049 {ECO:0000313|Ensembl:ENSGMOP00000008926.2, ECO:0000313|Proteomes:UP000694546};
RN [1] {ECO:0000313|Ensembl:ENSGMOP00000008926.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (AUG-2025) to UniProtKB.
RN [2] {ECO:0000313|Ensembl:ENSGMOP00000008926.2}
RP IDENTIFICATION.
RG Ensembl;
RL Submitted (SEP-2025) to UniProtKB.
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:0000256|ARBA:ARBA00045782}.
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:0000256|ARBA:ARBA00001231,
CC ECO:0000256|PIRNR:PIRNR001093};
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:0000256|ARBA:ARBA00049464};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64385;
CC Evidence={ECO:0000256|ARBA:ARBA00049464};
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:0000256|ARBA:ARBA00047301};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48277;
CC Evidence={ECO:0000256|ARBA:ARBA00047301};
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:0000256|ARBA:ARBA00043767};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47941;
CC Evidence={ECO:0000256|ARBA:ARBA00043767};
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:0000256|ARBA:ARBA00043827};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47969;
CC Evidence={ECO:0000256|ARBA:ARBA00043827};
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:0000256|ARBA:ARBA00023505};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64373;
CC Evidence={ECO:0000256|ARBA:ARBA00023505};
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:0000256|ARBA:ARBA00046515}.
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000256|ARBA:ARBA00004371}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 20 family.
CC {ECO:0000256|ARBA:ARBA00006285, ECO:0000256|PIRNR:PIRNR001093}.
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DR AlphaFoldDB; A0A8C4Z7H1; -.
DR SMR; A0A8C4Z7H1; -.
DR Ensembl; ENSGMOT00000009172.2; ENSGMOP00000008926.2; ENSGMOG00000008345.2.
DR GeneTree; ENSGT00390000008107; -.
DR OMA; RLWSNEK; -.
DR Proteomes; UP000694546; Chromosome 9.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:TreeGrafter.
DR GO; GO:0004563; F:beta-N-acetylhexosaminidase activity; IEA:UniProtKB-EC.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0006689; P:ganglioside catabolic process; IEA:TreeGrafter.
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:000063; Beta-hexosaminidase; 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; IPR017853; GH.
DR InterPro; IPR015883; Glyco_hydro_20_cat.
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 {ECO:0000256|ARBA:ARBA00023157,
KW ECO:0000256|PIRSR:PIRSR001093-2};
KW Glycoprotein {ECO:0000256|ARBA:ARBA00023180};
KW Glycosidase {ECO:0000256|ARBA:ARBA00023295, ECO:0000256|PIRNR:PIRNR001093};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|PIRNR:PIRNR001093};
KW Lipid metabolism {ECO:0000256|ARBA:ARBA00023098};
KW Lysosome {ECO:0000256|ARBA:ARBA00023228};
KW Reference proteome {ECO:0000313|Proteomes:UP000694546};
KW Signal {ECO:0000256|ARBA:ARBA00022729};
KW Zymogen {ECO:0000256|ARBA:ARBA00023145}.
FT DOMAIN 36..151
FT /note="Beta-hexosaminidase eukaryotic type N-terminal"
FT /evidence="ECO:0000259|Pfam:PF14845"
FT DOMAIN 173..492
FT /note="Glycoside hydrolase family 20 catalytic"
FT /evidence="ECO:0000259|Pfam:PF00728"
FT ACT_SITE 329
FT /note="Proton donor"
FT /evidence="ECO:0000256|PIRSR:PIRSR001093-1"
FT DISULFID 72..110
FT /evidence="ECO:0000256|PIRSR:PIRSR001093-2"
FT DISULFID 283..334
FT /evidence="ECO:0000256|PIRSR:PIRSR001093-2"
FT DISULFID 511..528
FT /evidence="ECO:0000256|PIRSR:PIRSR001093-2"
SQ SEQUENCE 535 AA; 60920 MW; 1C54182090A606C4 CRC64;
RCPRCIPPPR RRTHSYSPRP SPFLGVVING VTSTDVWPLP QKLAISEERY PLSPTHFNFY
YGEDQASIMK DCSLLDSAFT RYFPLIFPDL TSGKPEKAFS LVVTMHQKDC DGYPNEGSSE
RYQLNVSAGQ AVLNSDTVWG ALRGLETFSQ LVQQEEDGTY FINKTEIEDF PSFQYRGILL
DTSRHFLPLK AILNTLDAMA YSKFNVFHWH IVDDPSFPYQ SRTFPDLSSK GAYHPMSHIY
TQSDVRRVLT HARLRGIRVI PEFDSPGHTQ SWGKGQPNLL TPCYKGSSPS GTFGPINPAS
ALSYIFMSQF LKEVTSVFPD PYFHLGGDEV NFSCWQSNPD VRAFMQKMGF GKDYTKLESF
YMENIVNITS NLNKTSIVWQ DVFDYHERIP KDTILHIWKG LPAQYKAETS RMTKAGHRVL
LGAPWYINHI AYGQDWRISY NVQPLNFSGT EEQKKLVIGG EVSMWGEYVD ATNLSPRLWP
RACAAAERLW SDESQTRSAE AAFPRLQAFR CSLLRRGVRA EPLSPGHCSD EYRGI
//
