HEXA_PONAB
ID HEXA_PONAB Reviewed; 529 AA.
AC Q5RC84;
DT 10-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 109.
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 Pongo abelii (Sumatran orangutan) (Pongo pygmaeus abelii).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pongo.
OX NCBI_TaxID=9601;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG The German cDNA consortium;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
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; CR858396; CAH90623.1; -; Transcribed_RNA.
DR RefSeq; NP_001192280.1; NM_001205351.1.
DR AlphaFoldDB; Q5RC84; -.
DR SMR; Q5RC84; -.
DR STRING; 9601.ENSPPYP00000007503; -.
DR CAZy; GH20; Glycoside Hydrolase Family 20.
DR GeneID; 100438794; -.
DR KEGG; pon:100438794; -.
DR CTD; 3073; -.
DR eggNOG; KOG2499; Eukaryota.
DR HOGENOM; CLU_007082_0_3_1; -.
DR InParanoid; Q5RC84; -.
DR OMA; QYWVDHA; -.
DR OrthoDB; 545162at2759; -.
DR TreeFam; TF313036; -.
DR Proteomes; UP000001595; Chromosome 15.
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:0016020; C:membrane; IEA:Ensembl.
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: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 3: Inferred from homology;
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_0000011997"
FT CHAIN 89..529
FT /note="Beta-hexosaminidase subunit alpha"
FT /id="PRO_0000011998"
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; 60605 MW; 8D00068F3EBDBA74 CRC64;
MASSRLWFSL LLAAALAGRA TALWPWPQNI QTSDQRYVLY PNNFQFQYDV SSAAQPGCSV
LDEAFQRYRD LLFGSGSWPR PYLTGKRHTL EKNVLVVSVV TPGCNQLPTL ESVENYTLTI
NDDQCLLLSE TVWGALRGLE TFSQLVWKSA EGTFFINKTE IEDFPRFPHR GLLLDTSRHY
LPLSSILDTL DVMAYNKLNV FHWHLVDDPS FPYESFTFPE LMRKGSYNPV THIYTAQDVK
EVIEYARLRG IRVLAEFDTP GHTLSWGPGI PGLLTPCYSG SEPSGTFGPV NPSLNNTYEF
MSTFFLEVSS VFPDFYLHLG GDEVDFTCWK SNPDIQDFMR KKGFGEDFKQ LESFYIQTLL
DIVSSYGKGY VVWQEVFDNK VKIRPDTIIQ VWREDIPVNY MKELELVTKA GFRALLSAPW
YLNRISYGPD WKDFYVVEPL AFEGTPEQKA LVIGGEACMW GEYVDNTNLV PRLWPRAGAV
AERLWSNKLT SDLTFAYERL SHFRCELLRR GVQAQPLNVG FCEQEFEQT
