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   24-JAN-2024, entry version 159.
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,
RC   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).
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.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
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   GlyCosmos; Q60648; 1 site, No reported glycans.
DR   GlyGen; Q60648; 1 site.
DR   PhosphoSitePlus; Q60648; -.
DR   SwissPalm; Q60648; -.
DR   EPD; Q60648; -.
DR   jPOST; Q60648; -.
DR   MaxQB; Q60648; -.
DR   PaxDb; 10090-ENSMUSP00000000608; -.
DR   ProteomicsDB; 256701; -.
DR   Pumba; Q60648; -.
DR   Antibodypedia; 2212; 506 antibodies from 33 providers.
DR   Ensembl; ENSMUST00000000608.8; ENSMUSP00000000608.8; ENSMUSG00000000594.8.
DR   GeneID; 14667; -.
DR   KEGG; mmu:14667; -.
DR   UCSC; uc007iyw.2; mouse.
DR   AGR; MGI:95762; -.
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; WIKVPCV; -.
DR   OrthoDB; 23272at2759; -.
DR   PhylomeDB; Q60648; -.
DR   TreeFam; TF353575; -.
DR   Reactome; R-MMU-6798695; Neutrophil degranulation.
DR   Reactome; R-MMU-9840310; Glycosphingolipid catabolism.
DR   BioGRID-ORCS; 14667; 3 hits in 80 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 267 other cell types or tissues.
DR   ExpressionAtlas; Q60648; baseline and differential.
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; Ganglioside GM2 activator; 1.
DR   InterPro; IPR028996; GM2-AP.
DR   InterPro; IPR036846; GM2-AP_sf.
DR   InterPro; IPR003172; ML_dom.
DR   PANTHER; PTHR17357:SF0; GANGLIOSIDE GM2 ACTIVATOR; 1.
DR   PANTHER; PTHR17357; GM2 GANGLIOSIDE ACTIVATOR PROTEIN; 1.
DR   Pfam; PF02221; E1_DerP2_DerF2; 1.
DR   SMART; SM00737; ML; 1.
DR   SUPFAM; SSF63707; Ganglioside M2 (gm2) activator; 1.
DR   Genevisible; Q60648; MM.
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
//