HEXA_BOVIN
ID HEXA_BOVIN Reviewed; 529 AA.
AC Q0V8R6;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 1.
DT 03-AUG-2022, entry version 113.
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
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=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:P06865};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47941;
CC Evidence={ECO:0000250|UniProtKB:P06865};
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: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; BT026152; ABG66991.1; -; mRNA.
DR RefSeq; NP_001068632.1; NM_001075164.2.
DR AlphaFoldDB; Q0V8R6; -.
DR SMR; Q0V8R6; -.
DR STRING; 9913.ENSBTAP00000017261; -.
DR ChEMBL; CHEMBL1075052; -.
DR CAZy; GH20; Glycoside Hydrolase Family 20.
DR PaxDb; Q0V8R6; -.
DR PRIDE; Q0V8R6; -.
DR Ensembl; ENSBTAT00000017261; ENSBTAP00000017261; ENSBTAG00000012981.
DR GeneID; 504468; -.
DR KEGG; bta:504468; -.
DR CTD; 3073; -.
DR VEuPathDB; HostDB:ENSBTAG00000012981; -.
DR eggNOG; KOG2499; Eukaryota.
DR GeneTree; ENSGT00390000008107; -.
DR HOGENOM; CLU_007082_0_3_1; -.
DR InParanoid; Q0V8R6; -.
DR OMA; QYWVDHA; -.
DR OrthoDB; 545162at2759; -.
DR TreeFam; TF313036; -.
DR BRENDA; 3.2.1.52; 908.
DR Reactome; R-BTA-1660662; Glycosphingolipid metabolism.
DR Reactome; R-BTA-2022857; Keratan sulfate degradation.
DR Reactome; R-BTA-2024101; CS/DS degradation.
DR Reactome; R-BTA-2160916; Hyaluronan uptake and degradation.
DR PRO; PR:Q0V8R6; -.
DR Proteomes; UP000009136; Chromosome 10.
DR Bgee; ENSBTAG00000012981; Expressed in uterine cervix and 104 other tissues.
DR GO; GO:0042582; C:azurophil granule; IEA:Ensembl.
DR GO; GO:1905379; C:beta-N-acetylhexosaminidase complex; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005764; C:lysosome; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0007628; P:adult walking behavior; IEA:Ensembl.
DR GO; GO:0005975; P:carbohydrate metabolic process; IEA:InterPro.
DR GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; IEA:Ensembl.
DR GO; GO:0006689; P:ganglioside catabolic process; ISS:UniProtKB.
DR GO; GO:0006024; P:glycosaminoglycan biosynthetic process; IEA:Ensembl.
DR GO; GO:0030203; P:glycosaminoglycan metabolic process; IBA:GO_Central.
DR GO; GO:0019915; P:lipid storage; IEA:Ensembl.
DR GO; GO:0007040; P:lysosome organization; IEA:Ensembl.
DR GO; GO:0051651; P:maintenance of location in cell; IEA:Ensembl.
DR GO; GO:0042552; P:myelination; IEA:Ensembl.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IEA:Ensembl.
DR GO; GO:0050884; P:neuromuscular process controlling posture; IEA:Ensembl.
DR GO; GO:0007605; P:sensory perception of sound; IEA:Ensembl.
DR GO; GO:0019953; P:sexual reproduction; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR GO; GO:0060395; P:SMAD protein signal transduction; IEA:Ensembl.
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 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:0000250"
FT PROPEP 23..88
FT /evidence="ECO:0000250"
FT /id="PRO_0000274203"
FT CHAIN 89..529
FT /note="Beta-hexosaminidase subunit alpha"
FT /id="PRO_0000274204"
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; 60353 MW; 878641B502FCD3A9 CRC64;
MAGSTLRFSL LLAAAFAGRA TALWPWPQYI QTSELRYTIF PQSFQFQYHL SSAAQVGCSV
LDEAFQRYRD LLFGSVAFRF PHPIEKRHTS EKNSLVVLVV TPGCDQFPSL GSVENYTLTI
NDEQSLLLSE TVWGALRGLE TFSQLIWRSP EGTFYVNKTD IEDFPRFPHR GLLLDTSRHY
LPLASILDTL DVMAYNKFNV FHWHLVDDSS FPYESFTFPE LTKKGSYNPA THIYTAQDVK
EVIEYARLRG IRVLAEFDTP GHTLSWGPGV PGLLTPCYSG SHPSGTFGPV NPALNNTYEF
MSTFFLEIST VFPDFYLHLG GDEVDFTCWK SNPDIQAFMK KKGFGDDFKK LESFYIQTLL
DIVSAYGKGY VVWQEVFDNK VKVRPDTIIQ VWREEIPVKY VKELALVTRA GFRALLSAPW
YLNHITYGPD WKEIYLVEPL AFEGSPEQKA LVIGGEACMW GEYVDSTNLV PRLWPRAGAV
AERLWSNKMV SNLDFAFKRL AHFRCELLRR GVQAQPLSVG YCDMEFEQT
