SH23A_HUMAN
ID SH23A_HUMAN Reviewed; 576 AA.
AC Q9BRG2; A8K9R6; B4DRS7; Q9Y2X4;
DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=SH2 domain-containing protein 3A;
DE AltName: Full=Novel SH2-containing protein 1;
GN Name=SH2D3A; Synonyms=NSP1; ORFNames=UNQ175/PRO201;
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] (ISOFORM 1), TISSUE SPECIFICITY,
RP PHOSPHORYLATION, INTERACTION WITH BCAR1, MUTAGENESIS OF TYR-95 AND TYR-231,
RP AND VARIANT ASP-32.
RC TISSUE=Fetal kidney;
RX PubMed=10187783; DOI=10.1074/jbc.274.15.10047;
RA Lu Y., Brush J., Stewart T.A.;
RT "NSP1 defines a novel family of adaptor proteins linking integrin and
RT tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated
RT protein kinase signaling pathway.";
RL J. Biol. Chem. 274:10047-10052(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASP-32.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Tongue, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123; SER-125 AND SER-180, 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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125; SER-147 AND SER-180, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-125; SER-147; SER-180 AND
RP SER-201, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP VARIANT [LARGE SCALE ANALYSIS] GLY-265.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: May play a role in JNK activation.
CC -!- SUBUNIT: Interacts with BCAR1. {ECO:0000269|PubMed:10187783}.
CC -!- INTERACTION:
CC Q9BRG2; P00533: EGFR; NbExp=3; IntAct=EBI-2339271, EBI-297353;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BRG2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BRG2-2; Sequence=VSP_056268, VSP_056269, VSP_056270;
CC -!- TISSUE SPECIFICITY: Weakly expressed in placenta, fetal kidney, fetal
CC lung, adult pancreas, adult kidney and adult lung.
CC {ECO:0000269|PubMed:10187783}.
CC -!- PTM: Phosphorylated on tyrosine. {ECO:0000269|PubMed:10187783}.
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DR EMBL; AF124249; AAD28244.1; -; mRNA.
DR EMBL; AY358406; AAQ88772.1; -; mRNA.
DR EMBL; AK292781; BAF85470.1; -; mRNA.
DR EMBL; AK299406; BAG61389.1; -; mRNA.
DR EMBL; AC008760; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC020954; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69059.1; -; Genomic_DNA.
DR EMBL; BC006281; AAH06281.1; -; mRNA.
DR CCDS; CCDS12173.1; -. [Q9BRG2-1]
DR RefSeq; NP_005481.2; NM_005490.2. [Q9BRG2-1]
DR RefSeq; XP_005259529.1; XM_005259472.2. [Q9BRG2-2]
DR AlphaFoldDB; Q9BRG2; -.
DR SMR; Q9BRG2; -.
DR BioGRID; 115356; 82.
DR IntAct; Q9BRG2; 11.
DR MINT; Q9BRG2; -.
DR STRING; 9606.ENSP00000245908; -.
DR iPTMnet; Q9BRG2; -.
DR PhosphoSitePlus; Q9BRG2; -.
DR BioMuta; SH2D3A; -.
DR DMDM; 74732879; -.
DR EPD; Q9BRG2; -.
DR jPOST; Q9BRG2; -.
DR MassIVE; Q9BRG2; -.
DR MaxQB; Q9BRG2; -.
DR PaxDb; Q9BRG2; -.
DR PeptideAtlas; Q9BRG2; -.
DR PRIDE; Q9BRG2; -.
DR ProteomicsDB; 4969; -.
DR ProteomicsDB; 78763; -. [Q9BRG2-1]
DR Antibodypedia; 24322; 167 antibodies from 33 providers.
DR DNASU; 10045; -.
DR Ensembl; ENST00000245908.11; ENSP00000245908.5; ENSG00000125731.13. [Q9BRG2-1]
DR Ensembl; ENST00000437152.7; ENSP00000393303.2; ENSG00000125731.13. [Q9BRG2-2]
DR GeneID; 10045; -.
DR KEGG; hsa:10045; -.
DR MANE-Select; ENST00000245908.11; ENSP00000245908.5; NM_005490.3; NP_005481.2.
DR UCSC; uc002mft.4; human. [Q9BRG2-1]
DR CTD; 10045; -.
DR DisGeNET; 10045; -.
DR GeneCards; SH2D3A; -.
DR HGNC; HGNC:16885; SH2D3A.
DR HPA; ENSG00000125731; Tissue enhanced (esophagus).
DR MIM; 604721; gene.
DR neXtProt; NX_Q9BRG2; -.
DR OpenTargets; ENSG00000125731; -.
DR PharmGKB; PA38192; -.
DR VEuPathDB; HostDB:ENSG00000125731; -.
DR eggNOG; ENOG502QS5X; Eukaryota.
DR GeneTree; ENSGT00940000154130; -.
DR HOGENOM; CLU_015281_2_0_1; -.
DR InParanoid; Q9BRG2; -.
DR OMA; WWEANEE; -.
DR OrthoDB; 138275at2759; -.
DR PhylomeDB; Q9BRG2; -.
DR TreeFam; TF323756; -.
DR PathwayCommons; Q9BRG2; -.
DR SignaLink; Q9BRG2; -.
DR BioGRID-ORCS; 10045; 10 hits in 1074 CRISPR screens.
DR GeneWiki; SH2D3A; -.
DR GenomeRNAi; 10045; -.
DR Pharos; Q9BRG2; Tbio.
DR PRO; PR:Q9BRG2; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9BRG2; protein.
DR Bgee; ENSG00000125731; Expressed in buccal mucosa cell and 161 other tissues.
DR ExpressionAtlas; Q9BRG2; baseline and differential.
DR Genevisible; Q9BRG2; HS.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:InterPro.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:InterPro.
DR GO; GO:0007254; P:JNK cascade; TAS:ProtInc.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR CDD; cd10337; SH2_BCAR3; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR044102; SH2_SHEP1/BCAR3/NSP1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..576
FT /note="SH2 domain-containing protein 3A"
FT /id="PRO_0000233132"
FT DOMAIN 15..114
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 145..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..227
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 123
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 147
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 201
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..17
FT /note="MQVPQDGEDLAGQPWYH -> MEKTLLANLGTTASCPA (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056268"
FT VAR_SEQ 18..139
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056269"
FT VAR_SEQ 423
FT /note="P -> PQVRGEQGLEEAGVRVTGKTGEEACSDLFS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056270"
FT VARIANT 32
FT /note="N -> D (in dbSNP:rs7258236)"
FT /evidence="ECO:0000269|PubMed:10187783,
FT ECO:0000269|PubMed:12975309"
FT /id="VAR_026054"
FT VARIANT 223
FT /note="D -> G (in dbSNP:rs12608960)"
FT /id="VAR_051349"
FT VARIANT 265
FT /note="E -> G (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035989"
FT MUTAGEN 95
FT /note="Y->F: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:10187783"
FT MUTAGEN 231
FT /note="Y->F: Weak phosphorylation."
FT /evidence="ECO:0000269|PubMed:10187783"
SQ SEQUENCE 576 AA; 63093 MW; 2909F7632B61F18D CRC64;
MQVPQDGEDL AGQPWYHGLL SRQKAEALLQ QNGDFLVRAS GSRGGNPVIS CRWRGSALHF
EVFRVALRPR PGRPTALFQL EDEQFPSIPA LVHSYMTGRR PLSQATGAVV SRPVTWQGPL
RRSFSEDTLM DGPARIEPLR ARKWSNSQPA DLAHMGRSRE DPAGMEASTM PISALPRTSS
DPVLLKAPAP LGTVADSLRA SDGQLQAKAP TKPPRTPSFE LPDASERPPT YCELVPRVPS
VQGTSPSQSC PEPEAPWWEA EEDEEEENRC FTRPQAEISF CPHDAPSCLL GPQNRPLEPQ
VLHTLRGLFL EHHPGSTALH LLLVDCQATG LLGVTRDQRG NMGVSSGLEL LTLPHGHHLR
LELLERHQTL ALAGALAVLG CSGPLEERAA ALRGLVELAL ALRPGAAGDL PGLAAVMGAL
LMPQVSRLEH TWRQLRRSHT EAALAFEQEL KPLMRALDEG AGPCDPGEVA LPHVAPMVRL
LEGEEVAGPL DESCERLLRT LHGARHMVRD APKFRKVAAQ RLRGFRPNPE LREALTTGFV
RRLLWGSRGA GAPRAERFEK FQRVLGVLSQ RLEPDR
