SH21A_MOUSE
ID SH21A_MOUSE Reviewed; 126 AA.
AC O88890; A2ANL8; Q9QWV6;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=SH2 domain-containing protein 1A;
DE AltName: Full=Signaling lymphocytic activation molecule-associated protein;
DE Short=SLAM-associated protein;
DE AltName: Full=T-cell signal transduction molecule SAP;
GN Name=Sh2d1a; Synonyms=Xlp;
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] (ISOFORM LONG).
RC STRAIN=BALB/cJ;
RX PubMed=9774102; DOI=10.1038/26683;
RA Sayos J., Wu C., Morra M., Wang N., Zhang X., Allen D., van Schaik S.,
RA Notarangelo L., Geha R., Roncarolo M.G., Oettgen H., de Vries J.E.,
RA Aversa G., Terhorst C.;
RT "The X-linked lymphoproliferative-disease gene product SAP regulates
RT signals induced through the co-receptor SLAM.";
RL Nature 395:462-469(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORMS LONG AND SHORT).
RC STRAIN=C57BL/6J;
RA Garrity D.B., Amemiya C.T.;
RT "cDNA sequence of the mouse homolog of the human X-linked
RT lymphoproliferative-disease gene.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM LONG).
RX PubMed=10970095; DOI=10.1007/s002510000215;
RA Wu C., Sayos J., Wang N., Howie D., Coyle A., Terhorst C.;
RT "Genomic organization and characterization of mouse SAP, the gene that is
RT altered in X-linked lymphoproliferative disease.";
RL Immunogenetics 51:805-815(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP INTERACTION WITH FYN, AND MUTAGENESIS OF ARG-32; PRO-70; 74-LYS-ARG-75;
RP 78-ARG-LYS-79 AND PRO-90.
RX PubMed=12545173; DOI=10.1038/ncb919;
RA Latour S., Roncagalli R., Chen R., Bakinowski M., Shi X.,
RA Schwartzberg P.L., Davidson D., Veillette A.;
RT "Binding of SAP SH2 domain to FynT SH3 domain reveals a novel mechanism of
RT receptor signalling in immune regulation.";
RL Nat. Cell Biol. 5:149-154(2003).
RN [6]
RP FUNCTION IN NTRK2 SIGNALING, AND INTERACTION WITH NTRK1; NTRK2 AND NTRK3.
RX PubMed=16223723; DOI=10.1074/jbc.m506554200;
RA Lo K.Y., Chin W.H., Ng Y.P., Cheng A.W., Cheung Z.H., Ip N.Y.;
RT "SLAM-associated protein as a potential negative regulator in Trk
RT signaling.";
RL J. Biol. Chem. 280:41744-41752(2005).
RN [7]
RP FUNCTION.
RX PubMed=19648922; DOI=10.1038/ni.1763;
RA Dong Z., Cruz-Munoz M.E., Zhong M.C., Chen R., Latour S., Veillette A.;
RT "Essential function for SAP family adaptors in the surveillance of
RT hematopoietic cells by natural killer cells.";
RL Nat. Immunol. 10:973-980(2009).
RN [8]
RP FUNCTION.
RX PubMed=20962259; DOI=10.4049/jimmunol.1001974;
RA Wang N., Calpe S., Westcott J., Castro W., Ma C., Engel P., Schatzle J.D.,
RA Terhorst C.;
RT "The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-
RT dependent NK cell functions in the C57BL/6 mouse.";
RL J. Immunol. 185:5683-5687(2010).
RN [9]
RP REVIEW.
RX PubMed=21219180; DOI=10.1146/annurev-immunol-030409-101302;
RA Cannons J.L., Tangye S.G., Schwartzberg P.L.;
RT "SLAM family receptors and SAP adaptors in immunity.";
RL Annu. Rev. Immunol. 29:665-705(2011).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF ARG-78.
RX PubMed=22683124; DOI=10.1016/j.immuni.2012.03.023;
RA Dong Z., Davidson D., Perez-Quintero L.A., Kurosaki T., Swat W.,
RA Veillette A.;
RT "The adaptor SAP controls NK cell activation by regulating the enzymes Vav-
RT 1 and SHIP-1 and by enhancing conjugates with target cells.";
RL Immunity 36:974-985(2012).
CC -!- FUNCTION: Cytoplasmic adapter regulating receptors of the signaling
CC lymphocytic activation molecule (SLAM) family such as SLAMF1, CD244,
CC LY9, CD84, SLAMF6 and SLAMF7. In SLAM signaling seems to cooperate with
CC SH2D1B/EAT-2. Initially it has been proposed that association with
CC SLAMF1 prevents SLAMF1 binding to inhibitory effectors including
CC INPP5D/SHIP1 and PTPN11/SHP-2. However, by simultaneous interactions,
CC recruits FYN which subsequently phosphorylates and activates SLAMF1 (By
CC similarity). Positively regulates CD244/2B4- and CD84-mediated natural
CC killer (NK) cell functions (PubMed:22683124). Can also promote CD48-,
CC SLAMF6 -, LY9-, and SLAMF7-mediated NK cell activation
CC (PubMed:19648922). In the context of NK cell-mediated cytotoxicity
CC enhances conjugate formation with target cells (PubMed:22683124). May
CC also regulate the activity of the neurotrophin receptors NTRK1, NTRK2
CC and NTRK3. {ECO:0000250|UniProtKB:B2RZ59, ECO:0000250|UniProtKB:O60880,
CC ECO:0000269|PubMed:16223723, ECO:0000269|PubMed:19648922,
CC ECO:0000269|PubMed:20962259, ECO:0000269|PubMed:22683124,
CC ECO:0000305|PubMed:21219180}.
CC -!- SUBUNIT: Interacts with CD84, CD244, LY9, SLAMF1 and FYN (By
CC similarity). Interacts with NTRK1, NTRK2 and NTRK3.
CC {ECO:0000250|UniProtKB:B2RZ59, ECO:0000250|UniProtKB:O60880,
CC ECO:0000269|PubMed:16223723}.
CC -!- INTERACTION:
CC O88890; Q9QUM4: Slamf1; NbExp=3; IntAct=EBI-7910438, EBI-7910086;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=O88890-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=O88890-2; Sequence=VSP_004391;
CC -!- TISSUE SPECIFICITY: T-cells.
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DR EMBL; AF072903; AAC62629.1; -; mRNA.
DR EMBL; AF097633; AAC95999.1; -; mRNA.
DR EMBL; AF097632; AAC95998.1; -; mRNA.
DR EMBL; AF154505; AAF14526.1; -; Genomic_DNA.
DR EMBL; AF154503; AAF14526.1; JOINED; Genomic_DNA.
DR EMBL; AF154504; AAF14526.1; JOINED; Genomic_DNA.
DR EMBL; AL831716; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS30099.1; -. [O88890-1]
DR CCDS; CCDS85770.1; -. [O88890-2]
DR RefSeq; NP_001300617.1; NM_001313688.1.
DR RefSeq; NP_001300618.1; NM_001313689.1. [O88890-2]
DR RefSeq; NP_001300620.1; NM_001313691.1.
DR RefSeq; NP_035494.1; NM_011364.4. [O88890-1]
DR AlphaFoldDB; O88890; -.
DR SMR; O88890; -.
DR CORUM; O88890; -.
DR IntAct; O88890; 3.
DR MINT; O88890; -.
DR STRING; 10090.ENSMUSP00000005839; -.
DR iPTMnet; O88890; -.
DR PhosphoSitePlus; O88890; -.
DR EPD; O88890; -.
DR jPOST; O88890; -.
DR MaxQB; O88890; -.
DR PaxDb; O88890; -.
DR PRIDE; O88890; -.
DR ProteomicsDB; 261017; -. [O88890-1]
DR ProteomicsDB; 261018; -. [O88890-2]
DR Antibodypedia; 30053; 469 antibodies from 41 providers.
DR DNASU; 20400; -.
DR Ensembl; ENSMUST00000005839; ENSMUSP00000005839; ENSMUSG00000005696. [O88890-1]
DR Ensembl; ENSMUST00000115070; ENSMUSP00000110722; ENSMUSG00000005696. [O88890-2]
DR Ensembl; ENSMUST00000189753; ENSMUSP00000141070; ENSMUSG00000005696. [O88890-1]
DR GeneID; 20400; -.
DR KEGG; mmu:20400; -.
DR UCSC; uc009tbb.1; mouse. [O88890-1]
DR CTD; 4068; -.
DR MGI; MGI:1328352; Sh2d1a.
DR VEuPathDB; HostDB:ENSMUSG00000005696; -.
DR eggNOG; KOG0565; Eukaryota.
DR GeneTree; ENSGT00940000155920; -.
DR HOGENOM; CLU_125532_1_0_1; -.
DR InParanoid; O88890; -.
DR OMA; CVLCNGY; -.
DR OrthoDB; 1417830at2759; -.
DR PhylomeDB; O88890; -.
DR TreeFam; TF343096; -.
DR Reactome; R-MMU-198933; Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.
DR BioGRID-ORCS; 20400; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Sh2d1a; mouse.
DR PRO; PR:O88890; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; O88890; protein.
DR Bgee; ENSMUSG00000005696; Expressed in thymus and 43 other tissues.
DR ExpressionAtlas; O88890; baseline and differential.
DR Genevisible; O88890; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007267; P:cell-cell signaling; IEA:InterPro.
DR GO; GO:0006968; P:cellular defense response; IEA:InterPro.
DR GO; GO:0006959; P:humoral immune response; IMP:MGI.
DR GO; GO:0042267; P:natural killer cell mediated cytotoxicity; IMP:MGI.
DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISO:MGI.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IMP:MGI.
DR GO; GO:0050776; P:regulation of immune response; ISO:MGI.
DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central.
DR CDD; cd10400; SH2_SAP1a; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR017289; SH2_prot_1A.
DR InterPro; IPR035876; SH2D1A_SH2.
DR Pfam; PF00017; SH2; 1.
DR PIRSF; PIRSF037828; SH2_p1A; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Adaptive immunity; Alternative splicing; Cytoplasm; Immunity;
KW Innate immunity; Reference proteome; SH2 domain.
FT CHAIN 1..126
FT /note="SH2 domain-containing protein 1A"
FT /id="PRO_0000097723"
FT DOMAIN 6..104
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 67..92
FT /note="Interaction with FYN SH3 domain"
FT /evidence="ECO:0000269|PubMed:12545173"
FT REGION 100..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 89
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O60880"
FT VAR_SEQ 44..46
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_004391"
FT MUTAGEN 32
FT /note="R->K: No effect on interaction with FYN SH3 domain."
FT /evidence="ECO:0000269|PubMed:12545173"
FT MUTAGEN 68
FT /note="T->I: No effect on interaction with FYN SH3 domain."
FT /evidence="ECO:0000269|PubMed:12545173"
FT MUTAGEN 70
FT /note="P->A: No effect on interaction with FYN SH3 domain."
FT /evidence="ECO:0000269|PubMed:12545173"
FT MUTAGEN 74..75
FT /note="KR->AA: Disrupts interaction with FYN SH3 domain."
FT /evidence="ECO:0000269|PubMed:12545173"
FT MUTAGEN 78..79
FT /note="RK->AA: Disrupts interaction with FYN SH3 domain."
FT /evidence="ECO:0000269|PubMed:12545173"
FT MUTAGEN 78
FT /note="R->A: No effect on NK cell development, impairs
FT promotion of NK cell cytotoxicity and IFN-gamma production
FT in response to hematopoietic cells."
FT /evidence="ECO:0000269|PubMed:22683124"
FT MUTAGEN 90
FT /note="P->K: No effect on interaction with FYN SH3 domain."
FT /evidence="ECO:0000269|PubMed:12545173"
SQ SEQUENCE 126 AA; 13904 MW; D78FA7CE425AA680 CRC64;
MDAVTVYHGK ISRETGEKLL LATGLDGSYL LRDSESVPGV YCLCVLYQGY IYTYRVSQTE
TGSWSAETAP GVHKRFFRKV KNLISAFQKP DQGIVTPLQY PVEKSSGRGP QAPTGRRDSD
ICLNAP
