ID SH22A_HUMAN Reviewed; 389 AA.
AC Q9NP31; O43817; Q5UBZ1; Q5VZS4; Q5VZS5; Q9UPA7;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 3.
DT 24-JAN-2024, entry version 193.
DE RecName: Full=SH2 domain-containing protein 2A;
DE AltName: Full=SH2 domain-containing adapter protein;
DE AltName: Full=T cell-specific adapter protein;
DE Short=TSAd;
DE AltName: Full=VEGF receptor-associated protein;
GN Name=SH2D2A; Synonyms=SCAP, TSAD, VRAP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT SER-52.
RC TISSUE=T-cell;
RX PubMed=9468509; DOI=10.1074/jbc.273.8.4539;
RA Spurkland A., Brinchmann J.E., Markussen G., Pedeutour F., Munthe E.,
RA Lea T., Vartdal F., Aasheim H.-C.;
RT "Molecular cloning of a T cell-specific adapter protein (TSAd) containing
RT an Src homology (SH) 2 domain and putative SH3 and phosphotyrosine binding
RT sites.";
RL J. Biol. Chem. 273:4539-4546(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), ALTERNATIVE SPLICING, AND VARIANT
RP SER-52.
RX PubMed=10752626; DOI=10.1007/s002510050029;
RA Dai K.Z., Vergnaud G., Ando A., Inoko H., Spurkland A.;
RT "The SH2D2A gene encoding the T-cell-specific adapter protein (TSAd) is
RT localized centromeric to the CD1 gene cluster on human Chromosome 1.";
RL Immunogenetics 51:179-185(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH KDR, AND VARIANT
RP SER-52.
RC TISSUE=B-cell;
RX PubMed=10692392; DOI=10.1074/jbc.275.9.6059;
RA Wu L.-W., Mayo L.D., Dunbar J.D., Kessler K.M., Ozes O.N., Warren R.S.,
RA Donner D.B.;
RT "VRAP is an adaptor protein that binds KDR, a receptor for vascular
RT endothelial cell growth factor.";
RL J. Biol. Chem. 275:6059-6062(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND VARIANT SER-52.
RC TISSUE=B-cell;
RA Lee J.-S., Suh K.S., Burr J.G.;
RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Dermoid cancer;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT SER-52.
RC TISSUE=Lung;
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 [8]
RP INTERACTION WITH KDR.
RX PubMed=15962004; DOI=10.1038/sj.emboj.7600709;
RA Matsumoto T., Bohman S., Dixelius J., Berge T., Dimberg A., Magnusson P.,
RA Wang L., Wikner C., Qi J.H., Wernstedt C., Wu J., Bruheim S., Mugishima H.,
RA Mukhopadhyay D., Spurkland A., Claesson-Welsh L.;
RT "VEGF receptor-2 Y951 signaling and a role for the adapter molecule TSAd in
RT tumor angiogenesis.";
RL EMBO J. 24:2342-2353(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217 AND SER-296, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [10]
RP VARIANT [LARGE SCALE ANALYSIS] SER-52, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
CC -!- FUNCTION: Could be a T-cell-specific adapter protein involved in the
CC control of T-cell activation. May play a role in the CD4-p56-LCK-
CC dependent signal transduction pathway. Could also play an important
CC role in normal and pathological angiogenesis. Could be an adapter
CC protein that facilitates and regulates interaction of KDR with effector
CC proteins important to endothelial cell survival and proliferation.
CC -!- SUBUNIT: Interacts with KDR. Interacts with TXK and ITK (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9NP31; P10275: AR; NbExp=6; IntAct=EBI-490630, EBI-608057;
CC Q9NP31; Q9Y575: ASB3; NbExp=3; IntAct=EBI-490630, EBI-2875625;
CC Q9NP31; Q5VU92: DCAF12L1; NbExp=3; IntAct=EBI-490630, EBI-10694873;
CC Q9NP31; P04626: ERBB2; NbExp=2; IntAct=EBI-490630, EBI-641062;
CC Q9NP31; O95073-2: FSBP; NbExp=3; IntAct=EBI-490630, EBI-10696047;
CC Q9NP31; Q13480: GAB1; NbExp=6; IntAct=EBI-490630, EBI-517684;
CC Q9NP31; P10721: KIT; NbExp=10; IntAct=EBI-490630, EBI-1379503;
CC Q9NP31; Q14847: LASP1; NbExp=2; IntAct=EBI-490630, EBI-742828;
CC Q9NP31; P06239: LCK; NbExp=12; IntAct=EBI-490630, EBI-1348;
CC Q9NP31; P08581: MET; NbExp=7; IntAct=EBI-490630, EBI-1039152;
CC Q9NP31; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-490630, EBI-9090282;
CC Q9NP31; Q92569: PIK3R3; NbExp=4; IntAct=EBI-490630, EBI-79893;
CC Q9NP31; Q9UF11-4: PLEKHB1; NbExp=3; IntAct=EBI-490630, EBI-9089825;
CC Q9NP31; Q05397: PTK2; NbExp=3; IntAct=EBI-490630, EBI-702142;
CC Q9NP31; P43405: SYK; NbExp=3; IntAct=EBI-490630, EBI-78302;
CC Q9NP31; Q96IP4: TENT5A; NbExp=3; IntAct=EBI-490630, EBI-954084;
CC Q9NP31; Q96A09: TENT5B; NbExp=3; IntAct=EBI-490630, EBI-752030;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=2;
CC IsoId=Q9NP31-1; Sequence=Displayed;
CC Name=1;
CC IsoId=Q9NP31-2; Sequence=VSP_003966;
CC Name=3;
CC IsoId=Q9NP31-3; Sequence=VSP_003965;
CC Name=4;
CC IsoId=Q9NP31-4; Sequence=VSP_046378;
CC -!- TISSUE SPECIFICITY: Expression limited to tissues of the immune system
CC and, in particular, activated T-cells. Expressed in peripheral blood
CC leukocytes, thymus and spleen. Much lower expression or undetectable,
CC in brain, placenta, skeletal muscle, prostate, testis, ovary, small
CC intestine, and colon. Expressed at low levels in unstimulated T-cells,
CC but not expressed in normal resting or activated B-cells. According to
CC PubMed:10692392, expression is not restricted to activated T-cells, but
CC strongly expressed in blood cell lineages, the endothelium and other
CC cell and tissue types, such as heart, lung, and liver.
CC -!- INDUCTION: Rapidly induced after activation of T-cells. However, the
CC gene continues to be expressed in long-term cultures of activated T-
CC cells.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC99298.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF106072; AAF69027.1; -; Genomic_DNA.
DR EMBL; AJ000553; CAA04185.1; -; mRNA.
DR EMBL; AY763100; AAV34675.1; -; mRNA.
DR EMBL; AF097744; AAF43260.1; -; mRNA.
DR EMBL; AF051325; AAC99298.1; ALT_INIT; mRNA.
DR EMBL; AK222737; BAD96457.1; -; mRNA.
DR EMBL; AL158169; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590666; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC012107; AAH12107.1; -; mRNA.
DR CCDS; CCDS1159.1; -. [Q9NP31-1]
DR CCDS; CCDS53380.1; -. [Q9NP31-4]
DR CCDS; CCDS53381.1; -. [Q9NP31-2]
DR RefSeq; NP_001154914.1; NM_001161442.1. [Q9NP31-4]
DR RefSeq; NP_001154916.1; NM_001161444.1. [Q9NP31-1]
DR RefSeq; NP_003966.2; NM_003975.3. [Q9NP31-1]
DR AlphaFoldDB; Q9NP31; -.
DR SMR; Q9NP31; -.
DR BioGRID; 114509; 47.
DR IntAct; Q9NP31; 40.
DR MINT; Q9NP31; -.
DR STRING; 9606.ENSP00000376123; -.
DR ChEMBL; CHEMBL3217401; -.
DR MoonDB; Q9NP31; Predicted.
DR iPTMnet; Q9NP31; -.
DR PhosphoSitePlus; Q9NP31; -.
DR BioMuta; SH2D2A; -.
DR DMDM; 143811460; -.
DR EPD; Q9NP31; -.
DR jPOST; Q9NP31; -.
DR MassIVE; Q9NP31; -.
DR MaxQB; Q9NP31; -.
DR PaxDb; 9606-ENSP00000376123; -.
DR PeptideAtlas; Q9NP31; -.
DR ProteomicsDB; 65721; -.
DR ProteomicsDB; 81881; -. [Q9NP31-1]
DR ProteomicsDB; 81882; -. [Q9NP31-2]
DR ProteomicsDB; 81883; -. [Q9NP31-3]
DR Pumba; Q9NP31; -.
DR Antibodypedia; 20445; 388 antibodies from 29 providers.
DR DNASU; 9047; -.
DR Ensembl; ENST00000368198.7; ENSP00000357181.3; ENSG00000027869.12. [Q9NP31-4]
DR Ensembl; ENST00000368199.8; ENSP00000357182.3; ENSG00000027869.12. [Q9NP31-1]
DR Ensembl; ENST00000392306.2; ENSP00000376123.2; ENSG00000027869.12. [Q9NP31-2]
DR GeneID; 9047; -.
DR KEGG; hsa:9047; -.
DR MANE-Select; ENST00000368199.8; ENSP00000357182.3; NM_003975.4; NP_003966.2.
DR UCSC; uc001fqd.3; human. [Q9NP31-1]
DR AGR; HGNC:10821; -.
DR CTD; 9047; -.
DR DisGeNET; 9047; -.
DR GeneCards; SH2D2A; -.
DR HGNC; HGNC:10821; SH2D2A.
DR HPA; ENSG00000027869; Tissue enhanced (lymphoid).
DR MIM; 604514; gene.
DR neXtProt; NX_Q9NP31; -.
DR OpenTargets; ENSG00000027869; -.
DR PharmGKB; PA35729; -.
DR VEuPathDB; HostDB:ENSG00000027869; -.
DR eggNOG; ENOG502RE0K; Eukaryota.
DR GeneTree; ENSGT00940000161903; -.
DR HOGENOM; CLU_709723_0_0_1; -.
DR InParanoid; Q9NP31; -.
DR OMA; YSPVIKQ; -.
DR OrthoDB; 5360547at2759; -.
DR PhylomeDB; Q9NP31; -.
DR TreeFam; TF336893; -.
DR PathwayCommons; Q9NP31; -.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR SignaLink; Q9NP31; -.
DR SIGNOR; Q9NP31; -.
DR BioGRID-ORCS; 9047; 6 hits in 1155 CRISPR screens.
DR ChiTaRS; SH2D2A; human.
DR GeneWiki; SH2D2A; -.
DR GenomeRNAi; 9047; -.
DR Pharos; Q9NP31; Tbio.
DR PRO; PR:Q9NP31; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NP31; Protein.
DR Bgee; ENSG00000027869; Expressed in granulocyte and 103 other cell types or tissues.
DR Genevisible; Q9NP31; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0042098; P:T cell proliferation; IEA:Ensembl.
DR CDD; cd10416; SH2_SH2D2A; 1.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035884; SH2D2A_SH2.
DR PANTHER; PTHR14388:SF9; SH2 DOMAIN-CONTAINING PROTEIN 2A; 1.
DR PANTHER; PTHR14388; T CELL-SPECIFIC ADAPTER PROTEIN TSAD; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Angiogenesis; Cytoplasm; Developmental protein;
KW Differentiation; Phosphoprotein; Reference proteome; SH2 domain;
KW SH3-binding.
FT CHAIN 1..389
FT /note="SH2 domain-containing protein 2A"
FT /id="PRO_0000097726"
FT DOMAIN 95..186
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 41..63
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 190..295
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..389
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 244..250
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT MOTIF 272..278
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 196..220
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..280
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..347
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:9468509, ECO:0000303|Ref.4"
FT /id="VSP_003965"
FT VAR_SEQ 1..21
FT /note="MEFPLAQICPQGSHEAPIPTF -> MSP (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10752626"
FT /id="VSP_046378"
FT VAR_SEQ 102
FT /note="R -> RRVRPPLSVTH (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:9468509"
FT /id="VSP_003966"
FT VARIANT 52
FT /note="N -> S (in dbSNP:rs926103)"
FT /evidence="ECO:0000269|PubMed:10692392,
FT ECO:0000269|PubMed:10752626, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:9468509, ECO:0000269|Ref.4,
FT ECO:0007744|PubMed:15592455"
FT /id="VAR_024349"
FT VARIANT 272
FT /note="R -> C (in dbSNP:rs12072861)"
FT /id="VAR_056986"
FT CONFLICT 42..44
FT /note="ASP -> GIS (in Ref. 1; AAF69027)"
FT /evidence="ECO:0000305"
FT CONFLICT 111
FT /note="P -> S (in Ref. 2; AAV34675)"
FT /evidence="ECO:0000305"
FT CONFLICT 385
FT /note="L -> F (in Ref. 2; AAV34675)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 389 AA; 42934 MW; 986670BE084072CB CRC64;
MEFPLAQICP QGSHEAPIPT FSTFQITDMT RRSCQNLGYT AASPQAPEAA SNTGNAERAE
EVPGEGSLFL QAETRAWFQK TQAHWLLQHG AAPAWFHGFI TRREAERLLE PKPQGCYLVR
FSESAVTFVL TYRSRTCCRH FLLAQLRDGR HVVLGEDSAH ARLQDLLLHY TAHPLSPYGE
TLTEPLARQT PEPAGLSLRT EESNFGSKSQ DPNPQYSPII KQGQAPVPMQ KEGAGEKEPS
QLLRPKPPIP AKPQLPPEVY TIPVPRHRPA PRPKPSNPIY NEPDEPIAFY AMGRGSPGEA
PSNIYVEVED EGLPATLGHP VLRKSWSRPV PGGQNTGGSQ LHSENSVIGQ GPPLPHQPPP
AWRHTLPHNL SRQVLQDRGQ AWLPLGPPQ
//
