SH2D3_MOUSE
ID SH2D3_MOUSE Reviewed; 854 AA.
AC Q9QZS8; A2AK84; Q9JME1;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 154.
DE RecName: Full=SH2 domain-containing protein 3C;
DE AltName: Full=Cas/HEF1-associated signal transducer;
DE AltName: Full=SH2 domain-containing Eph receptor-binding protein 1;
GN Name=Sh2d3c; Synonyms=Chat, Shep1;
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 1), INTERACTION WITH EPHB2, TISSUE
RP SPECIFICITY, AND PHOSPHORYLATION.
RX PubMed=10542222; DOI=10.1074/jbc.274.45.31941;
RA Dodelet V.C., Pazzagli C., Zisch A.H., Hauser C.A., Pasquale E.B.;
RT "A novel signaling intermediate, SHEP1, directly couples Eph receptors to
RT R-Ras and Rap1A.";
RL J. Biol. Chem. 274:31941-31946(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, INTERACTION WITH BCAR1
RP AND NEDD9, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=10692442; DOI=10.1074/jbc.275.9.6404;
RA Sakakibara A., Hattori S.;
RT "Chat, a Cas/HEF1-associated adaptor protein that integrates multiple
RT signaling pathways.";
RL J. Biol. Chem. 275:6404-6410(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH BCAR1;
RP NEDD9 AND PTK2B, TISSUE SPECIFICITY, AND PHOSPHORYLATION.
RC TISSUE=Spleen;
RX PubMed=12486027; DOI=10.1074/jbc.m207942200;
RA Sakakibara A., Hattori S., Nakamura S., Katagiri T.;
RT "A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell
RT receptor-mediated interleukin-2 production by Jurkat cells.";
RL J. Biol. Chem. 278:6012-6017(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 AT TYR-273; TYR-278 AND TYR-787, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND MUTAGENESIS OF TYR-787.
RX PubMed=15272013; DOI=10.1074/jbc.m402929200;
RA Dail M., Kalo M.S., Seddon J.A., Cote J.-F., Vuori K., Pasquale E.B.;
RT "SHEP1 function in cell migration is impaired by a single amino acid
RT mutation that disrupts association with the scaffolding protein cas but not
RT with Ras GTPases.";
RL J. Biol. Chem. 279:41892-41902(2004).
RN [8]
RP FUNCTION, INTERACTION WITH BCAR1 AND NEDD9, SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND MUTAGENESIS OF TYR-787.
RX PubMed=17174122; DOI=10.1016/j.immuni.2006.09.014;
RA Regelmann A.G., Danzl N.M., Wanjalla C., Alexandropoulos K.;
RT "The hematopoietic isoform of Cas-Hef1-associated signal transducer
RT regulates chemokine-induced inside-out signaling and T cell trafficking.";
RL Immunity 25:907-918(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; SER-354 AND SER-435, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
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 [11]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=20505138; DOI=10.4049/jimmunol.1000096;
RA Al-Shami A., Wilkins C., Crisostomo J., Seshasayee D., Martin F., Xu N.,
RA Suwanichkul A., Anderson S.J., Oravecz T.;
RT "The adaptor protein Sh2d3c is critical for marginal zone B cell
RT development and function.";
RL J. Immunol. 185:327-334(2010).
RN [12]
RP FUNCTION, INTERACTION WITH IGF1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=20881139; DOI=10.1523/jneurosci.3289-10.2010;
RA Wang L., Vervoort V., Wallez Y., Core N., Cremer H., Pasquale E.B.;
RT "The SRC homology 2 domain protein Shep1 plays an important role in the
RT penetration of olfactory sensory axons into the forebrain.";
RL J. Neurosci. 30:13201-13210(2010).
RN [13]
RP FUNCTION, INTERACTION WITH NEDD9, SUBCELLULAR LOCATION, TISSUE SPECIFICITY,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF TYR-787.
RX PubMed=20956287; DOI=10.1073/pnas.1007558107;
RA Browne C.D., Hoefer M.M., Chintalapati S.K., Cato M.H., Wallez Y.,
RA Ostertag D.V., Pasquale E.B., Rickert R.C.;
RT "SHEP1 partners with CasL to promote marginal zone B-cell maturation.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:18944-18949(2010).
CC -!- FUNCTION: Acts as an adapter protein that mediates cell signaling
CC pathways involved in cellular functions such as cell adhesion and
CC migration, tissue organization, and the regulation of the immune
CC response (PubMed:20505138, PubMed:20881139, PubMed:20956287). Plays a
CC role in integrin-mediated cell adhesion through BCAR1-CRK-RAPGEF1
CC signaling and activation of the small GTPase RAP1 (By similarity).
CC Promotes cell migration and invasion through the extracellular matrix
CC (PubMed:20881139). Required for marginal zone B-cell development and
CC thymus-independent type 2 immune responses (PubMed:20505138,
CC PubMed:20956287). Mediates migration and adhesion of B cells in the
CC splenic marginal zone via promoting hyperphosphorylation of NEDD9/CASL
CC (PubMed:20505138). Plays a role in CXCL13-induced chemotaxis of B-cells
CC (PubMed:20505138, PubMed:20956287). Plays a role in the migration of
CC olfactory sensory neurons (OSNs) into the forebrain and the innervation
CC of the olfactory bulb by the OSN axons during development
CC (PubMed:20881139). Required for the efficient tyrosine phosphorylation
CC of BCAR1 in OSN axons (PubMed:20881139). {ECO:0000250|UniProtKB:Q8N5H7,
CC ECO:0000269|PubMed:20505138, ECO:0000269|PubMed:20881139,
CC ECO:0000269|PubMed:20956287}.
CC -!- FUNCTION: [Isoform 1]: Important regulator of chemokine-induced,
CC integrin-mediated T lymphocyte adhesion and migration, acting upstream
CC of RAP1 (PubMed:17174122). Required for tissue-specific adhesion of T
CC lymphocytes to peripheral tissues (PubMed:17174122). Required for basal
CC and CXCL2 stimulated serine-threonine phosphorylation of NEDD9
CC (PubMed:17174122). May be involved in the regulation of T-cell
CC receptor-mediated IL2 production through the activation of the JNK
CC pathway in T-cells (PubMed:12486027). {ECO:0000269|PubMed:12486027,
CC ECO:0000269|PubMed:17174122}.
CC -!- FUNCTION: [Isoform 2]: May be involved in the BCAR1/CAS-mediated JNK
CC activation pathway. {ECO:0000269|PubMed:10692442}.
CC -!- SUBUNIT: Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK
CC (By similarity). Within the complex, interacts with CRK and (via C-
CC terminus) with BCAR1/CAS (via C-terminus) (PubMed:10692442,
CC PubMed:17174122). Interacts with NEDD9/HEF1 (PubMed:20956287).
CC Interacts with EPHB2 (PubMed:10542222). {ECO:0000250|UniProtKB:Q8N5H7,
CC ECO:0000269|PubMed:10542222, ECO:0000269|PubMed:10692442,
CC ECO:0000269|PubMed:17174122, ECO:0000269|PubMed:20956287}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with NEDD9/HEF1 (PubMed:10692442,
CC PubMed:17174122). Interacts with BCAR1/CAS (PubMed:10692442). Interacts
CC with PTK2B (PubMed:12486027). {ECO:0000269|PubMed:10692442,
CC ECO:0000269|PubMed:12486027, ECO:0000269|PubMed:17174122}.
CC -!- SUBUNIT: [Isoform 2]: Interacts (via C-terminus) with BCAR1/CAS (via C-
CC terminus) (PubMed:10692442). Interacts with IGF1 (PubMed:20881139).
CC {ECO:0000269|PubMed:10692442, ECO:0000269|PubMed:20881139}.
CC -!- INTERACTION:
CC Q9QZS8; O35177: Nedd9; NbExp=2; IntAct=EBI-7964037, EBI-2642891;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10692442,
CC ECO:0000269|PubMed:17174122, ECO:0000269|PubMed:20956287}. Cell
CC membrane {ECO:0000269|PubMed:10692442}; Peripheral membrane protein
CC {ECO:0000269|PubMed:10692442}. Cell projection, axon
CC {ECO:0000269|PubMed:20881139}. Cell projection, ruffle membrane
CC {ECO:0000269|PubMed:10692442}. Note=Associated with the membrane when
CC EGF-stimulated (PubMed:10692442). Expressed at the cortical actin ring
CC in B cells (PubMed:20956287). {ECO:0000269|PubMed:10692442,
CC ECO:0000269|PubMed:20956287}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:17174122}; Peripheral membrane protein
CC {ECO:0000269|PubMed:17174122}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Chat-H;
CC IsoId=Q9QZS8-1; Sequence=Displayed;
CC Name=2; Synonyms=Chat;
CC IsoId=Q9QZS8-2; Sequence=VSP_017709;
CC -!- TISSUE SPECIFICITY: Expressed in the olfactory bulb and olfactory
CC sensory neurons (at protein level) (PubMed:20881139). Expressed in B
CC cells (at protein level) (PubMed:20505138, PubMed:20956287). Expressed
CC in T lymphocytes (PubMed:17174122). {ECO:0000269|PubMed:17174122,
CC ECO:0000269|PubMed:20505138, ECO:0000269|PubMed:20881139,
CC ECO:0000269|PubMed:20956287}.
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in hematopoietic cells from
CC spleen, lymph node and thymus (at protein level) (PubMed:10542222,
CC PubMed:10692442, PubMed:12486027). Expressed weakly in the lung (at
CC protein level) (PubMed:10692442). {ECO:0000269|PubMed:10542222,
CC ECO:0000269|PubMed:10692442, ECO:0000269|PubMed:12486027}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the brain, lung, kidney,
CC and weakly expressed in the liver and lung (at protein level).
CC {ECO:0000269|PubMed:10692442}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the developing OSNs at dpc 13.5 and
CC 14.5 with reduced expression at dpc 16.5.
CC {ECO:0000269|PubMed:20881139}.
CC -!- DOMAIN: The C-terminal Cdc25-homology/Ras-GEF domain adopts a closed
CC conformation rendering it incapable of carrying out canonical exchange
CC factor function, this closed conformation is required for interaction
CC with BCAR1. {ECO:0000250}.
CC -!- PTM: [Isoform 1]: Phosphorylated by MAPK/ERK upon T-cell receptor
CC stimulation in T-cells. {ECO:0000269|PubMed:12486027}.
CC -!- DISRUPTION PHENOTYPE: In one study knockout mice are viable and born at
CC the expected Mendelian rate (PubMed:20505138). In another study the
CC majority of knockout mice die after birth, those that survive show
CC severe lamination defects and loss of cellular organization in their
CC olfactory bulb, with a reduction in gonadotropin-releasing hormone in
CC the preoptic region of the hypothalamus (PubMed:20881139). Mice that
CC die at birth are morphologically normal apart from a marked reduction
CC in the size of the olfactory bulb, which exhibits abnormal cellular
CC organization in the outer layers and a lack of innervation of OSNs
CC (PubMed:20881139). At dpc 16.5 OSNs fail to extend into the marginal
CC zone of the forming olfactory bulb from the basement membrane, and show
CC a reduction in tyrosine phosphorylated BCAR1 (PubMed:20881139).
CC Decrease in B cells in the splenic marginal zone (PubMed:20505138,
CC PubMed:20956287). {ECO:0000269|PubMed:20505138,
CC ECO:0000269|PubMed:20881139, ECO:0000269|PubMed:20956287}.
CC -!- CAUTION: It is unclear if the knockout of Sh2d3c causes lethality
CC (PubMed:20505138, PubMed:20881139). One report in genetic knockout mice
CC suggests it is viable (PubMed:20505138). Another report in the same
CC strain but a different genetic knockout model suggests lethality
CC (PubMed:20881139). {ECO:0000269|PubMed:20505138,
CC ECO:0000269|PubMed:20881139}.
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DR EMBL; AF168364; AAF13305.1; -; mRNA.
DR EMBL; AB030442; BAA90557.1; -; mRNA.
DR EMBL; AB043953; BAA96361.1; -; mRNA.
DR EMBL; AK042709; BAC31340.1; -; mRNA.
DR EMBL; AK155165; BAE33088.1; -; mRNA.
DR EMBL; AL772271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC113203; AAI13204.1; -; mRNA.
DR CCDS; CCDS15928.1; -. [Q9QZS8-1]
DR CCDS; CCDS57168.1; -. [Q9QZS8-2]
DR RefSeq; NP_001239476.1; NM_001252547.1. [Q9QZS8-2]
DR RefSeq; NP_038809.1; NM_013781.3. [Q9QZS8-1]
DR AlphaFoldDB; Q9QZS8; -.
DR SMR; Q9QZS8; -.
DR DIP; DIP-42657N; -.
DR IntAct; Q9QZS8; 2.
DR MINT; Q9QZS8; -.
DR STRING; 10090.ENSMUSP00000073866; -.
DR iPTMnet; Q9QZS8; -.
DR PhosphoSitePlus; Q9QZS8; -.
DR EPD; Q9QZS8; -.
DR jPOST; Q9QZS8; -.
DR MaxQB; Q9QZS8; -.
DR PaxDb; Q9QZS8; -.
DR PeptideAtlas; Q9QZS8; -.
DR PRIDE; Q9QZS8; -.
DR ProteomicsDB; 261020; -. [Q9QZS8-1]
DR ProteomicsDB; 261021; -. [Q9QZS8-2]
DR Antibodypedia; 30796; 276 antibodies from 26 providers.
DR DNASU; 27387; -.
DR Ensembl; ENSMUST00000074248; ENSMUSP00000073866; ENSMUSG00000059013. [Q9QZS8-1]
DR Ensembl; ENSMUST00000113242; ENSMUSP00000108868; ENSMUSG00000059013. [Q9QZS8-2]
DR GeneID; 27387; -.
DR KEGG; mmu:27387; -.
DR UCSC; uc008jgp.2; mouse. [Q9QZS8-1]
DR UCSC; uc008jgr.2; mouse. [Q9QZS8-2]
DR CTD; 10044; -.
DR MGI; MGI:1351631; Sh2d3c.
DR VEuPathDB; HostDB:ENSMUSG00000059013; -.
DR eggNOG; ENOG502QPX3; Eukaryota.
DR GeneTree; ENSGT00940000154130; -.
DR HOGENOM; CLU_015281_0_0_1; -.
DR InParanoid; Q9QZS8; -.
DR OMA; HTDEAFS; -.
DR OrthoDB; 138275at2759; -.
DR PhylomeDB; Q9QZS8; -.
DR TreeFam; TF323756; -.
DR BioGRID-ORCS; 27387; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Sh2d3c; mouse.
DR PRO; PR:Q9QZS8; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9QZS8; protein.
DR Bgee; ENSMUSG00000059013; Expressed in granulocyte and 147 other tissues.
DR Genevisible; Q9QZS8; MM.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
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:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; TAS:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
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; PF00617; RasGEF; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm; Membrane;
KW Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..854
FT /note="SH2 domain-containing protein 3C"
FT /id="PRO_0000228834"
FT DOMAIN 215..314
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 580..848
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 34..129
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 330..384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..417
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 422..520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 85..101
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 102..128
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 330..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 401..417
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 422..447
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 469..488
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 504..520
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 273
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15272013"
FT MOD_RES 278
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15272013"
FT MOD_RES 354
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 787
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:15272013"
FT VAR_SEQ 1..166
FT /note="MTEMPKKTGRKFKFFKFKGLGSLSNLPRSFSLRRSSASASIRSCPEPDTFEA
FT TQDDMVTLPKSPPAYARSSDMYSHMGTMPRPNIKKAQKQQAVQKAQEVSRESHLVSRRL
FT PEPPDLEAAKEAGEGTEALLEDTAPSAVEVDPMRELEDLTVDTEKEQVPGDVSPE ->
FT MTAVGRRCSALEPR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10692442,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_017709"
FT MUTAGEN 787
FT /note="Y->E: Abolishes interaction with NEDD9. Abolishes
FT interaction with BCAR1. Abolishes phosphorylation of NEDD9.
FT Abolishes promotion of migration and adhesion in T cells."
FT /evidence="ECO:0000269|PubMed:17174122,
FT ECO:0000269|PubMed:20956287"
FT MUTAGEN 787
FT /note="Y->E: Disrupts binding to BCAR1 and inhibits EGF-
FT induced tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:15272013"
SQ SEQUENCE 854 AA; 94323 MW; FA8FC2FDEAE32FF5 CRC64;
MTEMPKKTGR KFKFFKFKGL GSLSNLPRSF SLRRSSASAS IRSCPEPDTF EATQDDMVTL
PKSPPAYARS SDMYSHMGTM PRPNIKKAQK QQAVQKAQEV SRESHLVSRR LPEPPDLEAA
KEAGEGTEAL LEDTAPSAVE VDPMRELEDL TVDTEKEQVP GDVSPERTAA ELEAAGDYVK
FSKEKYILDS SPEKLHKELE EELKLSSTDL RSHAWYHGRI PREVSETLVQ RNGDFLIRDS
LTSLGDYVLT CRWHNQALHF KINKVVVKAG ESYTHIRYLF EQESFDHVPA LVRYHVGSRK
AVSEQSGAII YCPVNRTFPL RYLEASYGLS QGSSKTASPA SPSGSKGSHM KRRSITMTDG
LTTDKVTRSD GCPNSTSLPH PRDSIRNCAL SMDQIPDLHS PLSPISESPS SPAYSTVTRV
HAPSATPSTS AQPASPVARR SSEPQLCPGN TPKPPGESDR APHASPSHTL CKASPSPSLS
SYSDPDSGHY CQLQPPVRGS REQAAGETPR KARGSGERQK ELLENGVSDG EWGKTFTVPV
VEATSSFNLA TFQSQLIPKE NRPLEVALLR KVKELLSEVD ARTLARHVTK VDCLVARILG
VTKEMQTLMG VRWGMELLTL PHGRQLRLDL LERFHTMSIM LAVDILGCTG SAEERAALLH
KTIQLAAELR GTMGNMFSFA AVMGALEMAQ ISRLEQTWMT LRQRHTEGAI LYEKKLKPFL
KSLNEGKEGP PLSNTTFPHV LPFITLLECD SAPAEGPEPW GSTEHGVEVV LAHLEAARTV
AHHGGLYHTN AEVKLQGFQA RPELLEVFST EFQMRLLWGS QGANSSQAWR YEKFDKVLTA
LSHKLEPAIR SSEL
