SAP3_MOUSE
ID SAP3_MOUSE Reviewed; 193 AA.
AC Q60648; Q61610; Q61819;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Ganglioside GM2 activator {ECO:0000305};
DE AltName: Full=Cerebroside sulfate activator protein;
DE AltName: Full=GM2-AP;
DE AltName: Full=Sphingolipid activator protein 3;
DE Short=SAP-3;
DE Flags: Precursor;
GN Name=Gm2a {ECO:0000312|MGI:MGI:95762};
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.
RC STRAIN=C57BL/6 X CBA; TISSUE=Liver;
RX PubMed=7713516; DOI=10.1006/geno.1994.1674;
RA Yamanaka S., Johnson O.N., Lyu M.S., Kozak C.A., Proia R.L.;
RT "The mouse gene encoding the GM2 activator protein (Gm2a): cDNA sequence,
RT expression, and chromosome mapping.";
RL Genomics 24:601-604(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7689829; DOI=10.1042/bj2940227;
RA Bellachioma G., Stirling J.L., Orlacchio A., Beccari T.;
RT "Cloning and sequence analysis of a cDNA clone coding for the mouse GM2
RT activator protein.";
RL Biochem. J. 294:227-230(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C57BL/6 X CBA;
RX PubMed=9060405; DOI=10.1007/s003359900364;
RA Bertoni C., Appolloni M.G., Stirling J.L., Li S.C., Li Y.T., Orlacchio A.,
RA Beccari T.;
RT "Structural organization and expression of the gene for the mouse GM2
RT activator protein.";
RL Mamm. Genome 8:90-93(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 32-193 IN COMPLEX WITH
RP LYSOPHOSPHATIDYLCHOLINE, FUNCTION, DISULFIDE BONDS, AND MUTAGENESIS OF
RP TYR-168.
RX PubMed=16216074; DOI=10.1021/bi050668w;
RA Wright C.S., Mi L.Z., Lee S., Rastinejad F.;
RT "Crystal structure analysis of phosphatidylcholine-GM2-activator product
RT complexes: evidence for hydrolase activity.";
RL Biochemistry 44:13510-13521(2005).
CC -!- FUNCTION: Binds gangliosides and stimulates ganglioside GM2
CC degradation. It stimulates only the breakdown of ganglioside GM2 and
CC glycolipid GA2 by beta-hexosaminidase A. It extracts single GM2
CC molecules from membranes and presents them in soluble form to beta-
CC hexosaminidase A for cleavage of N-acetyl-D-galactosamine and
CC conversion to GM3. The large binding pocket can accommodate several
CC single chain phospholipids and fatty acids, GM2A also exhibits some
CC calcium-independent phospholipase activity. Has cholesterol transfer
CC activity (By similarity). {ECO:0000250|UniProtKB:P17900,
CC ECO:0000269|PubMed:16216074}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol(in) = cholesterol(out); Xref=Rhea:RHEA:39747,
CC ChEBI:CHEBI:16113; Evidence={ECO:0000250|UniProtKB:P17900};
CC -!- SUBCELLULAR LOCATION: Lysosome.
CC -!- TISSUE SPECIFICITY: Widely expressed. Most abundant in kidney and
CC testis.
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DR EMBL; U09816; AAA21543.1; -; mRNA.
DR EMBL; L19526; AAA61929.1; -; mRNA.
DR EMBL; U34359; AAB06275.1; ALT_SEQ; Genomic_DNA.
DR EMBL; U34356; AAB06275.1; JOINED; Genomic_DNA.
DR EMBL; U34357; AAB06275.1; JOINED; Genomic_DNA.
DR EMBL; U34358; AAB06275.1; JOINED; Genomic_DNA.
DR EMBL; BC004651; AAH04651.1; -; mRNA.
DR CCDS; CCDS24707.1; -.
DR PIR; S35613; S35613.
DR RefSeq; NP_034429.1; NM_010299.3.
DR PDB; 2AGC; X-ray; 2.50 A; A=32-193.
DR PDBsum; 2AGC; -.
DR AlphaFoldDB; Q60648; -.
DR SMR; Q60648; -.
DR BioGRID; 199959; 1.
DR STRING; 10090.ENSMUSP00000000608; -.
DR GlyGen; Q60648; 1 site.
DR PhosphoSitePlus; Q60648; -.
DR EPD; Q60648; -.
DR jPOST; Q60648; -.
DR MaxQB; Q60648; -.
DR PaxDb; Q60648; -.
DR PRIDE; Q60648; -.
DR ProteomicsDB; 256701; -.
DR Antibodypedia; 2212; 490 antibodies from 33 providers.
DR Ensembl; ENSMUST00000000608; ENSMUSP00000000608; ENSMUSG00000000594.
DR GeneID; 14667; -.
DR KEGG; mmu:14667; -.
DR UCSC; uc007iyw.2; mouse.
DR CTD; 2760; -.
DR MGI; MGI:95762; Gm2a.
DR VEuPathDB; HostDB:ENSMUSG00000000594; -.
DR eggNOG; ENOG502S05S; Eukaryota.
DR GeneTree; ENSGT00390000003288; -.
DR HOGENOM; CLU_108261_0_0_1; -.
DR InParanoid; Q60648; -.
DR OMA; GNYRIQS; -.
DR OrthoDB; 1548356at2759; -.
DR PhylomeDB; Q60648; -.
DR TreeFam; TF353575; -.
DR Reactome; R-MMU-1660662; Glycosphingolipid metabolism.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 14667; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Gm2a; mouse.
DR EvolutionaryTrace; Q60648; -.
DR PRO; PR:Q60648; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q60648; protein.
DR Bgee; ENSMUSG00000000594; Expressed in gastrula and 265 other tissues.
DR ExpressionAtlas; Q60648; baseline and differential.
DR Genevisible; Q60648; MM.
DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0004563; F:beta-N-acetylhexosaminidase activity; IMP:MGI.
DR GO; GO:0008047; F:enzyme activator activity; IDA:MGI.
DR GO; GO:0005319; F:lipid transporter activity; IBA:GO_Central.
DR GO; GO:0006689; P:ganglioside catabolic process; IMP:MGI.
DR GO; GO:0007611; P:learning or memory; IMP:MGI.
DR GO; GO:0019915; P:lipid storage; IMP:MGI.
DR GO; GO:0006869; P:lipid transport; IBA:GO_Central.
DR GO; GO:0051651; P:maintenance of location in cell; IMP:MGI.
DR GO; GO:0050877; P:nervous system process; IMP:MGI.
DR GO; GO:0050885; P:neuromuscular process controlling balance; IMP:MGI.
DR GO; GO:0009313; P:oligosaccharide catabolic process; IMP:MGI.
DR Gene3D; 2.70.220.10; -; 1.
DR InterPro; IPR028996; GM2-AP.
DR InterPro; IPR036846; GM2-AP_sf.
DR InterPro; IPR003172; ML_dom.
DR PANTHER; PTHR17357; PTHR17357; 1.
DR Pfam; PF02221; E1_DerP2_DerF2; 1.
DR SMART; SM00737; ML; 1.
DR SUPFAM; SSF63707; SSF63707; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Hydrolase; Lipid metabolism;
KW Lysosome; Reference proteome; Signal; Sphingolipid metabolism.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..193
FT /note="Ganglioside GM2 activator"
FT /id="PRO_0000031643"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 39..183
FT /evidence="ECO:0000269|PubMed:16216074"
FT DISULFID 99..106
FT /evidence="ECO:0000269|PubMed:16216074"
FT DISULFID 112..138
FT /evidence="ECO:0000269|PubMed:16216074"
FT DISULFID 125..136
FT /evidence="ECO:0000269|PubMed:16216074"
FT MUTAGEN 168
FT /note="Y->S: Abolishes phospholipid binding."
FT /evidence="ECO:0000269|PubMed:16216074"
FT CONFLICT 53
FT /note="I -> T (in Ref. 1; AAA21543)"
FT /evidence="ECO:0000305"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:2AGC"
FT HELIX 40..42
FT /evidence="ECO:0007829|PDB:2AGC"
FT STRAND 44..58
FT /evidence="ECO:0007829|PDB:2AGC"
FT STRAND 60..74
FT /evidence="ECO:0007829|PDB:2AGC"
FT STRAND 81..90
FT /evidence="ECO:0007829|PDB:2AGC"
FT STRAND 93..96
FT /evidence="ECO:0007829|PDB:2AGC"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:2AGC"
FT HELIX 111..118
FT /evidence="ECO:0007829|PDB:2AGC"
FT TURN 127..133
FT /evidence="ECO:0007829|PDB:2AGC"
FT STRAND 142..153
FT /evidence="ECO:0007829|PDB:2AGC"
FT STRAND 165..176
FT /evidence="ECO:0007829|PDB:2AGC"
FT STRAND 179..190
FT /evidence="ECO:0007829|PDB:2AGC"
SQ SEQUENCE 193 AA; 20824 MW; 59CC4ABE56FA1FC7 CRC64;
MHRLPLLLLL GLLLAGSVAP ARLVPKRLSQ LGGFSWDNCD EGKDPAVIKS LTIQPDPIVV
PGDVVVSLEG KTSVPLTAPQ KVELTVEKEV AGFWVKIPCV EQLGSCSYEN ICDLIDEYIP
PGESCPEPLH TYGLPCHCPF KEGTYSLPTS NFTVPDLELP SWLSTGNYRI QSILSSGGKR
LGCIKIAASL KGR
