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 01-MAY-2013, entry version 94.
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;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP 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
RT to R-Ras and Rap1A.";
RL J. Biol. Chem. 274:31941-31946(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH BCAR1 AND
RP 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), INTERACTION WITH BCAR1; NEDD9
RP 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
RT cell 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.,
RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
RA 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.,
RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
RA 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.,
RA She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W.,
RA Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T.,
RA Zhou S., Teague B., Potamousis K., Churas C., Place M., Herschleb J.,
RA Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z.,
RA Lindblad-Toh K., Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of
RT the 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-273, AND MASS
RP SPECTROMETRY.
RX PubMed=12522270; DOI=10.1073/pnas.2436191100;
RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T.,
RA Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
RT "Profiling of tyrosine phosphorylation pathways in human cells using
RT mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
RN [8]
RP PHOSPHORYLATION AT TYR-273; TYR-278 AND TYR-787, MASS SPECTROMETRY,
RP 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
RT but not with Ras GTPases.";
RL J. Biol. Chem. 279:41892-41902(2004).
CC -!- FUNCTION: Eph receptor-binding protein which may be a positive
CC regulator of TCR signaling. Binding to BCAR1 is required to induce
CC membrane ruffling and promote EGF-dependent cell migration.
CC -!- SUBUNIT: Interacts (via C-terminus) with BCAR1/CAS (By
CC similarity). Interacts with PTK2B. Isoform 2 interacts with
CC NEDD9/HEF1.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane
CC protein. Note=Associated with the membrane when EGF-stimulated.
CC Found at ruffling membranes.
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: Isoform 2 is ubiquitously expressed. Isoform 1
CC is expressed in hematopoietic cells from spleen, lymph node and
CC thymus.
CC -!- DOMAIN: The C-terminal Cdc25-homology/Ras-GEF domain adopts a
CC closed conformation rendering it incapable of carrying out
CC canonical exchange factor function, this closed conformation is
CC required for interaction with BCAR1 (By similarity).
CC -!- SIMILARITY: Contains 1 Ras-GEF domain.
CC -!- SIMILARITY: Contains 1 SH2 domain.
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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; CAM16622.1; -; Genomic_DNA.
DR EMBL; BC113203; AAI13204.1; -; mRNA.
DR IPI; IPI00137970; -.
DR IPI; IPI00742349; -.
DR RefSeq; NP_001239476.1; NM_001252547.1.
DR RefSeq; NP_038809.1; NM_013781.3.
DR UniGene; Mm.474256; -.
DR UniGene; Mm.9593; -.
DR ProteinModelPortal; Q9QZS8; -.
DR SMR; Q9QZS8; 214-295, 537-849.
DR MINT; MINT-1503279; -.
DR STRING; 10090.ENSMUSP00000073866; -.
DR PhosphoSite; Q9QZS8; -.
DR PaxDb; Q9QZS8; -.
DR PRIDE; Q9QZS8; -.
DR Ensembl; ENSMUST00000074248; ENSMUSP00000073866; ENSMUSG00000059013.
DR Ensembl; ENSMUST00000113242; ENSMUSP00000108868; ENSMUSG00000059013.
DR GeneID; 27387; -.
DR KEGG; mmu:27387; -.
DR UCSC; uc008jgq.1; mouse.
DR CTD; 10044; -.
DR MGI; MGI:1351631; Sh2d3c.
DR eggNOG; NOG149796; -.
DR GeneTree; ENSGT00390000008976; -.
DR HOGENOM; HOG000231595; -.
DR HOVERGEN; HBG053174; -.
DR InParanoid; Q9QZS8; -.
DR OMA; RLEQTWM; -.
DR OrthoDB; EOG4WH8K7; -.
DR NextBio; 305340; -.
DR ArrayExpress; Q9QZS8; -.
DR Bgee; Q9QZS8; -.
DR CleanEx; MM_CHAT; -.
DR CleanEx; MM_SH2D3C; -.
DR Genevestigator; Q9QZS8; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IEA:InterPro.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; TAS:MGI.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR023578; Ras_GEF_dom.
DR InterPro; IPR001895; RasGRF_CDC25.
DR InterPro; IPR000980; SH2.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00017; SH2; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF48366; Ras_GEF; 1.
DR PROSITE; PS00720; RASGEF; FALSE_NEG.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Membrane;
KW Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1 854 SH2 domain-containing protein 3C.
FT /FTId=PRO_0000228834.
FT DOMAIN 215 314 SH2.
FT DOMAIN 580 848 Ras-GEF.
FT MOD_RES 273 273 Phosphotyrosine.
FT MOD_RES 278 278 Phosphotyrosine.
FT MOD_RES 787 787 Phosphotyrosine.
FT VAR_SEQ 1 166 MTEMPKKTGRKFKFFKFKGLGSLSNLPRSFSLRRSSASASI
FT RSCPEPDTFEATQDDMVTLPKSPPAYARSSDMYSHMGTMPR
FT PNIKKAQKQQAVQKAQEVSRESHLVSRRLPEPPDLEAAKEA
FT GEGTEALLEDTAPSAVEVDPMRELEDLTVDTEKEQVPGDVS
FT PE -> MTAVGRRCSALEPR (in isoform 2).
FT /FTId=VSP_017709.
FT MUTAGEN 787 787 Y->E: Disrupts binding to BCAR1 and
FT inhibits EGF-induced tyrosine
FT phosphorylation.
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
//
