HEXB_MOUSE
ID HEXB_MOUSE Reviewed; 536 AA.
AC P20060;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Beta-hexosaminidase subunit beta {ECO:0000305};
DE EC=3.2.1.52 {ECO:0000269|PubMed:8253842};
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:0000312|MGI:MGI:96074};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2971567; DOI=10.1016/0014-5793(88)80199-6;
RA Bapat B., Ethier M., Neote K., Mahuran D., Gravel R.A.;
RT "Cloning and sequence analysis of a cDNA encoding the beta-subunit of mouse
RT beta-hexosaminidase.";
RL FEBS Lett. 237:191-195(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=7959736; DOI=10.1006/geno.1994.1318;
RA Yamanaka S., Johnson O.N., Norflus F., Boles D.J., Proia R.L.;
RT "Structure and expression of the mouse beta-hexosaminidase genes, Hexa and
RT Hexb.";
RL Genomics 21:588-596(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv;
RX PubMed=7918686; DOI=10.1016/0925-4439(94)90110-4;
RA Triggs-Raine B.L., Benoit G., Salo T.J., Trasler J.M., Gravel R.A.;
RT "Characterization of the murine beta-hexosaminidase (HEXB) gene.";
RL Biochim. Biophys. Acta 1227:79-86(1994).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=8253842; DOI=10.1083/jcb.123.6.1431;
RA Miller D.J., Gong X., Decker G., Shur B.D.;
RT "Egg cortical granule N-acetylglucosaminidase is required for the mouse
RT zona block to polyspermy.";
RL J. Cell Biol. 123:1431-1440(1993).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. During fertilization is
CC responsible, at least in part, for the zona block to polyspermy.
CC Present in the cortical granules of non-activated oocytes, is
CC 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 (PubMed:8253842). {ECO:0000250|UniProtKB:P07686,
CC ECO:0000269|PubMed:8253842}.
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:0000269|PubMed:8253842};
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=ganglioside GM2 (d18:1(4E)) + H2O = 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=ganglioside GM2 + H2O = 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:0000269|PubMed:8253842}. Note=In oocytes, the enzyme is released
CC from cortical granules after fertilization.
CC {ECO:0000269|PubMed:8253842}.
CC -!- SIMILARITY: Belongs to the glycosyl hydrolase 20 family. {ECO:0000305}.
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DR EMBL; Y00964; CAA68781.1; -; mRNA.
DR EMBL; U07633; AAA18776.1; -; mRNA.
DR EMBL; U07049; AAA74738.1; -; Genomic_DNA.
DR EMBL; U07036; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07037; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07038; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07039; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07040; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07041; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07042; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07043; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07044; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07045; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07046; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07047; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07048; AAA74738.1; JOINED; Genomic_DNA.
DR EMBL; U07742; AAB60667.1; -; Genomic_DNA.
DR EMBL; U07722; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07723; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07724; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07725; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07726; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07727; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07728; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07737; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07738; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07739; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07740; AAB60667.1; JOINED; Genomic_DNA.
DR EMBL; U07741; AAB60667.1; JOINED; Genomic_DNA.
DR CCDS; CCDS26709.1; -.
DR PIR; B54745; B54745.
DR RefSeq; NP_034552.1; NM_010422.2.
DR AlphaFoldDB; P20060; -.
DR SMR; P20060; -.
DR BioGRID; 200281; 14.
DR ComplexPortal; CPX-689; Beta-hexosaminidase A complex.
DR ComplexPortal; CPX-690; Beta-hexosaminidase B complex.
DR STRING; 10090.ENSMUSP00000022169; -.
DR CAZy; GH20; Glycoside Hydrolase Family 20.
DR GlyConnect; 2152; 2 N-Linked glycans (1 site).
DR GlyGen; P20060; 3 sites, 2 N-linked glycans (1 site).
DR PhosphoSitePlus; P20060; -.
DR EPD; P20060; -.
DR PaxDb; P20060; -.
DR PeptideAtlas; P20060; -.
DR PRIDE; P20060; -.
DR ProteomicsDB; 269660; -.
DR Antibodypedia; 24338; 269 antibodies from 34 providers.
DR DNASU; 15212; -.
DR Ensembl; ENSMUST00000022169; ENSMUSP00000022169; ENSMUSG00000021665.
DR GeneID; 15212; -.
DR KEGG; mmu:15212; -.
DR UCSC; uc007roc.2; mouse.
DR CTD; 3074; -.
DR MGI; MGI:96074; Hexb.
DR VEuPathDB; HostDB:ENSMUSG00000021665; -.
DR eggNOG; KOG2499; Eukaryota.
DR GeneTree; ENSGT00390000008107; -.
DR HOGENOM; CLU_007082_0_3_1; -.
DR InParanoid; P20060; -.
DR OMA; GHDVVMC; -.
DR OrthoDB; 545162at2759; -.
DR PhylomeDB; P20060; -.
DR TreeFam; TF313036; -.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-2022857; Keratan sulfate degradation.
DR Reactome; R-MMU-2024101; CS/DS degradation.
DR Reactome; R-MMU-2160916; Hyaluronan uptake and degradation.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 15212; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Hexb; mouse.
DR PRO; PR:P20060; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; P20060; protein.
DR Bgee; ENSMUSG00000021665; Expressed in lacrimal gland and 240 other tissues.
DR ExpressionAtlas; P20060; baseline and differential.
DR Genevisible; P20060; MM.
DR GO; GO:0001669; C:acrosomal vesicle; IDA:MGI.
DR GO; GO:0042582; C:azurophil granule; ISO:MGI.
DR GO; GO:1905379; C:beta-N-acetylhexosaminidase complex; ISO:MGI.
DR GO; GO:0060473; C:cortical granule; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0043202; C:lysosomal lumen; IC:ComplexPortal.
DR GO; GO:0005764; C:lysosome; IDA:MGI.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; ISO:MGI.
DR GO; GO:0016231; F:beta-N-acetylglucosaminidase activity; ISO:MGI.
DR GO; GO:0004563; F:beta-N-acetylhexosaminidase activity; IDA:UniProtKB.
DR GO; GO:0030246; F:carbohydrate binding; ISO:MGI.
DR GO; GO:0015929; F:hexosaminidase activity; ISO:MGI.
DR GO; GO:0016787; F:hydrolase activity; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:MGI.
DR GO; GO:0102148; F:N-acetyl-beta-D-galactosaminidase activity; IEA:UniProtKB-EC.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0043615; P:astrocyte cell migration; IMP:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
DR GO; GO:0006689; P:ganglioside catabolic process; IMP:MGI.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; IMP:ComplexPortal.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; IMP:MGI.
DR GO; GO:0030214; P:hyaluronan catabolic process; IMP:MGI.
DR GO; GO:0019915; P:lipid storage; IMP:MGI.
DR GO; GO:0007626; P:locomotory behavior; IMP:MGI.
DR GO; GO:0007040; P:lysosome organization; IMP:MGI.
DR GO; GO:0051651; P:maintenance of location in cell; IMP:MGI.
DR GO; GO:0008049; P:male courtship behavior; IMP:MGI.
DR GO; GO:0042552; P:myelination; IGI:MGI.
DR GO; GO:0006044; P:N-acetylglucosamine metabolic process; ISO:MGI.
DR GO; GO:0050905; P:neuromuscular process; IMP:MGI.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IMP:MGI.
DR GO; GO:0070050; P:neuron cellular homeostasis; IMP:MGI.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IMP:MGI.
DR GO; GO:0048477; P:oogenesis; IMP:MGI.
DR GO; GO:0007341; P:penetration of zona pellucida; IMP:MGI.
DR GO; GO:0008654; P:phospholipid biosynthetic process; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0019538; P:protein metabolic process; IMP:MGI.
DR GO; GO:0008360; P:regulation of cell shape; IMP:UniProtKB.
DR GO; GO:0007605; P:sensory perception of sound; IGI:MGI.
DR GO; GO:0019953; P:sexual reproduction; IMP:MGI.
DR GO; GO:0007338; P:single fertilization; IDA:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IGI:MGI.
DR Gene3D; 3.30.379.10; -; 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; PTHR22600; 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; SSF51445; 1.
DR SUPFAM; SSF55545; SSF55545; 1.
PE 1: Evidence at protein level;
KW Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Glycosidase; Hydrolase;
KW Lipid metabolism; Lysosome; Reference proteome; Signal.
FT SIGNAL 1..31
FT /evidence="ECO:0000255"
FT CHAIN 32..536
FT /note="Beta-hexosaminidase subunit beta"
FT /id="PRO_0000012006"
FT ACT_SITE 334
FT /note="Proton donor"
FT /evidence="ECO:0000250"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 169
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 70..116
FT /evidence="ECO:0000250"
FT DISULFID 288..339
FT /evidence="ECO:0000250"
FT DISULFID 513..530
FT /evidence="ECO:0000250"
SQ SEQUENCE 536 AA; 61116 MW; 579BBEEE9CB508BC CRC64;
MPQSPRSAPG LLLLQALVSL VSLALVAPAR LQPALWPFPR SVQMFPRLLY ISAEDFSIDH
SPNSTAGPSC SLLQEAFRRY YNYVFGFYKR HHGPARFRAE PQLQKLLVSI TLESECESFP
SLSSDETYSL LVQEPVAVLK ANSVWGALRG LETFSQLVYQ DSFGTFTINE SSIADSPRFP
HRGILIDTSR HFLPVKTILK TLDAMAFNKF NVLHWHIVDD QSFPYQSTTF PELSNKGSYS
LSHVYTPNDV RMVLEYARLR GIRVIPEFDT PGHTQSWGKG QKNLLTPCYN QKTKTQVFGP
VDPTVNTTYA FFNTFFKEIS SVFPDQFIHL GGDEVEFQCW ASNPNIQGFM KRKGFGSDFR
RLESFYIKKI LEIISSLKKN SIVWQEVFDD KVELQPGTVV EVWKSEHYSY ELKQVTGSGF
PAILSAPWYL DLISYGQDWK NYYKVEPLNF EGSEKQKQLV IGGEACLWGE FVDATNLTPR
LWPRASAVGE RLWSPKTVTD LENAYKRLAV HRCRMVSRGI AAQPLYTGYC NYENKI
