SH2D3_HUMAN
ID SH2D3_HUMAN Reviewed; 860 AA.
AC Q8N5H7; A8K5S8; E9PG48; Q5HYE5; Q5JU31; Q6UY42; Q8N6X3; Q9Y2X5;
DT 21-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=SH2 domain-containing protein 3C;
DE AltName: Full=Cas/HEF1-associated signal transducer {ECO:0000303|PubMed:17174122};
DE Short=Chat-H {ECO:0000303|PubMed:17174122};
DE AltName: Full=Novel SH2-containing protein 3;
DE AltName: Full=SH2 domain-containing Eph receptor-binding protein 1;
DE Short=SHEP1;
GN Name=SH2D3C; Synonyms=NSP3; ORFNames=UNQ272/PRO309/PRO34088;
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 2), AND TISSUE SPECIFICITY.
RC TISSUE=Placenta;
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] (ISOFORMS 2 AND 3).
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 5 AND 6).
RC TISSUE=Brain;
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 MRNA] (ISOFORM 4).
RC TISSUE=Cervix;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Pancreas, and Testis;
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 FUNCTION, IDENTIFICATION IN A COMPLEX WITH BCAR1 AND CRK, AND SUBCELLULAR
RP LOCATION.
RX PubMed=12432078; DOI=10.1242/jcs.00207;
RA Sakakibara A., Ohba Y., Kurokawa K., Matsuda M., Hattori S.;
RT "Novel function of Chat in controlling cell adhesion via Cas-Crk-C3G-
RT pathway-mediated Rap1 activation.";
RL J. Cell Sci. 115:4915-4924(2002).
RN [8]
RP INTERACTION WITH BCAR1, AND SUBCELLULAR LOCATION.
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 FUNCTION, AND INTERACTION WITH IGF1.
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-440, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 539-860 IN COMPLEX WITH BCAR1.
RX PubMed=22081014; DOI=10.1038/nsmb.2152;
RA Mace P.D., Wallez Y., Dobaczewska M.K., Lee J.J., Robinson H.,
RA Pasquale E.B., Riedl S.J.;
RT "NSP-Cas protein structures reveal a promiscuous interaction module in cell
RT signaling.";
RL Nat. Struct. Mol. Biol. 18:1381-1387(2011).
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:12432078, PubMed:20881139). Plays a role in integrin-
CC mediated cell adhesion through BCAR1-CRK-RAPGEF1 signaling and
CC activation of the small GTPase RAP1 (PubMed:12432078). Promotes cell
CC 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 (By similarity). Mediates
CC migration and adhesion of B cells in the splenic marginal zone via
CC promoting hyperphosphorylation of NEDD9/CASL (By similarity). Plays a
CC role in CXCL13-induced chemotaxis of B-cells (By similarity). Plays a
CC role in the migration of olfactory sensory neurons (OSNs) into the
CC forebrain and the innervation of the olfactory bulb by the OSN axons
CC during development (By similarity). Required for the efficient tyrosine
CC phosphorylation of BCAR1 in OSN axons (By similarity).
CC {ECO:0000250|UniProtKB:Q9QZS8, ECO:0000269|PubMed:12432078,
CC ECO:0000269|PubMed:20881139}.
CC -!- FUNCTION: [Isoform 1]: Important regulator of chemokine-induced,
CC integrin-mediated T lymphocyte adhesion and migration, acting upstream
CC of RAP1 (By similarity). Required for tissue-specific adhesion of T
CC lymphocytes to peripheral tissues (By similarity). Required for basal
CC and CXCL2 stimulated serine-threonine phosphorylation of NEDD9 (By
CC similarity). May be involved in the regulation of T-cell receptor-
CC mediated IL2 production through the activation of the JNK pathway in T-
CC cells (By similarity). {ECO:0000250|UniProtKB:Q9QZS8}.
CC -!- FUNCTION: [Isoform 2]: May be involved in the BCAR1/CAS-mediated JNK
CC activation pathway. {ECO:0000250|UniProtKB:Q9QZS8}.
CC -!- SUBUNIT: Component of a complex comprised of SH2D3C, BCAR1/CAS, and CRK
CC (PubMed:12432078). Within the complex, interacts with CRK and (via C-
CC terminus) with BCAR1/CAS (via C-terminus) (PubMed:12432078,
CC PubMed:17174122, PubMed:22081014). Interacts with NEDD9/HEF1 (By
CC similarity). Interacts with EPHB2 (By similarity).
CC {ECO:0000250|UniProtKB:Q9QZS8, ECO:0000269|PubMed:12432078,
CC ECO:0000269|PubMed:17174122, ECO:0000269|PubMed:22081014}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with NEDD9/HEF1 (By similarity).
CC Interacts with BCAR1/CAS (By similarity). Interacts with PTK2B (By
CC similarity). {ECO:0000250|UniProtKB:Q9QZS8}.
CC -!- SUBUNIT: [Isoform 2]: Interacts (via C-terminus) with BCAR1/CAS (via C-
CC terminus) (By similarity). Interacts with IGF1 (PubMed:20881139).
CC {ECO:0000250|UniProtKB:Q9QZS8, ECO:0000269|PubMed:20881139}.
CC -!- INTERACTION:
CC Q8N5H7; P10721: KIT; NbExp=4; IntAct=EBI-745980, EBI-1379503;
CC Q8N5H7; P08581: MET; NbExp=4; IntAct=EBI-745980, EBI-1039152;
CC Q8N5H7-2; P56945: BCAR1; NbExp=8; IntAct=EBI-15952996, EBI-702093;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12432078,
CC ECO:0000269|PubMed:17174122}. Cell membrane
CC {ECO:0000269|PubMed:12432078}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q9QZS8}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q9QZS8}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:Q9QZS8}. Note=Associated with the membrane when
CC EGF-stimulated (By similarity). Expressed at the cortical actin ring in
CC B cells (By similarity). {ECO:0000250|UniProtKB:Q9QZS8}.
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=6;
CC Name=1; Synonyms=Chat-H {ECO:0000303|PubMed:17174122};
CC IsoId=Q8N5H7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8N5H7-2; Sequence=VSP_017707;
CC Name=3;
CC IsoId=Q8N5H7-3; Sequence=VSP_017706;
CC Name=4;
CC IsoId=Q8N5H7-4; Sequence=VSP_017708;
CC Name=5;
CC IsoId=Q8N5H7-5; Sequence=VSP_044581, VSP_044582;
CC Name=6;
CC IsoId=Q8N5H7-6; Sequence=VSP_044581;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Ubiquitously expressed.
CC {ECO:0000269|PubMed:10187783}.
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.
CC -!- PTM: [Isoform 1]: Phosphorylated by MAPK/ERK upon T-cell receptor
CC stimulation in T-cells. {ECO:0000250|UniProtKB:Q9QZS8}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAQ88456.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF124251; AAD28246.1; -; mRNA.
DR EMBL; AY358089; AAQ88456.1; ALT_INIT; Transcribed_RNA.
DR EMBL; AY358440; AAQ89948.1; -; mRNA.
DR EMBL; AK056068; BAG51614.1; -; mRNA.
DR EMBL; AK291393; BAF84082.1; -; mRNA.
DR EMBL; BX647905; CAI46101.1; -; mRNA.
DR EMBL; AL162586; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162426; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027962; AAH27962.1; -; mRNA.
DR EMBL; BC032365; AAH32365.1; -; mRNA.
DR CCDS; CCDS48026.1; -. [Q8N5H7-5]
DR CCDS; CCDS48027.1; -. [Q8N5H7-6]
DR CCDS; CCDS48028.1; -. [Q8N5H7-3]
DR CCDS; CCDS59145.1; -. [Q8N5H7-4]
DR CCDS; CCDS6877.1; -. [Q8N5H7-1]
DR CCDS; CCDS6878.1; -. [Q8N5H7-2]
DR RefSeq; NP_001136004.1; NM_001142532.1. [Q8N5H7-3]
DR RefSeq; NP_001136005.1; NM_001142533.1. [Q8N5H7-5]
DR RefSeq; NP_001136006.1; NM_001142534.1. [Q8N5H7-6]
DR RefSeq; NP_001239263.1; NM_001252334.1. [Q8N5H7-4]
DR RefSeq; NP_005480.2; NM_005489.3. [Q8N5H7-2]
DR RefSeq; NP_733745.1; NM_170600.2. [Q8N5H7-1]
DR RefSeq; XP_005251696.1; XM_005251639.1.
DR RefSeq; XP_011516419.1; XM_011518117.2.
DR RefSeq; XP_016869663.1; XM_017014174.1.
DR PDB; 3T6G; X-ray; 2.50 A; A/C=539-860.
DR PDBsum; 3T6G; -.
DR AlphaFoldDB; Q8N5H7; -.
DR SMR; Q8N5H7; -.
DR BioGRID; 115355; 168.
DR DIP; DIP-59443N; -.
DR IntAct; Q8N5H7; 163.
DR MINT; Q8N5H7; -.
DR STRING; 9606.ENSP00000317817; -.
DR iPTMnet; Q8N5H7; -.
DR PhosphoSitePlus; Q8N5H7; -.
DR BioMuta; SH2D3C; -.
DR DMDM; 74751027; -.
DR EPD; Q8N5H7; -.
DR jPOST; Q8N5H7; -.
DR MassIVE; Q8N5H7; -.
DR MaxQB; Q8N5H7; -.
DR PaxDb; Q8N5H7; -.
DR PeptideAtlas; Q8N5H7; -.
DR PRIDE; Q8N5H7; -.
DR ProteomicsDB; 20244; -.
DR ProteomicsDB; 72054; -. [Q8N5H7-1]
DR ProteomicsDB; 72055; -. [Q8N5H7-2]
DR ProteomicsDB; 72056; -. [Q8N5H7-3]
DR ProteomicsDB; 72057; -. [Q8N5H7-4]
DR ProteomicsDB; 72058; -. [Q8N5H7-5]
DR Antibodypedia; 30796; 276 antibodies from 26 providers.
DR DNASU; 10044; -.
DR Ensembl; ENST00000314830.13; ENSP00000317817.8; ENSG00000095370.20. [Q8N5H7-1]
DR Ensembl; ENST00000373276.7; ENSP00000362373.3; ENSG00000095370.20. [Q8N5H7-4]
DR Ensembl; ENST00000373277.8; ENSP00000362374.4; ENSG00000095370.20. [Q8N5H7-2]
DR Ensembl; ENST00000420366.5; ENSP00000388536.1; ENSG00000095370.20. [Q8N5H7-5]
DR Ensembl; ENST00000429553.5; ENSP00000394632.1; ENSG00000095370.20. [Q8N5H7-3]
DR Ensembl; ENST00000629203.2; ENSP00000485866.1; ENSG00000095370.20. [Q8N5H7-6]
DR GeneID; 10044; -.
DR KEGG; hsa:10044; -.
DR MANE-Select; ENST00000314830.13; ENSP00000317817.8; NM_170600.3; NP_733745.1.
DR UCSC; uc004bry.4; human. [Q8N5H7-1]
DR CTD; 10044; -.
DR DisGeNET; 10044; -.
DR GeneCards; SH2D3C; -.
DR HGNC; HGNC:16884; SH2D3C.
DR HPA; ENSG00000095370; Tissue enhanced (lung).
DR MIM; 604722; gene.
DR neXtProt; NX_Q8N5H7; -.
DR OpenTargets; ENSG00000095370; -.
DR PharmGKB; PA38191; -.
DR VEuPathDB; HostDB:ENSG00000095370; -.
DR eggNOG; ENOG502QPX3; Eukaryota.
DR GeneTree; ENSGT00940000154130; -.
DR HOGENOM; CLU_015281_0_0_1; -.
DR InParanoid; Q8N5H7; -.
DR OMA; HTDEAFS; -.
DR OrthoDB; 138275at2759; -.
DR PhylomeDB; Q8N5H7; -.
DR TreeFam; TF323756; -.
DR PathwayCommons; Q8N5H7; -.
DR SignaLink; Q8N5H7; -.
DR BioGRID-ORCS; 10044; 9 hits in 1071 CRISPR screens.
DR ChiTaRS; SH2D3C; human.
DR GeneWiki; SH2D3C; -.
DR GenomeRNAi; 10044; -.
DR Pharos; Q8N5H7; Tbio.
DR PRO; PR:Q8N5H7; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q8N5H7; protein.
DR Bgee; ENSG00000095370; Expressed in granulocyte and 139 other tissues.
DR ExpressionAtlas; Q8N5H7; baseline and differential.
DR Genevisible; Q8N5H7; HS.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
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: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; 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 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cytoplasm; Membrane; Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..860
FT /note="SH2 domain-containing protein 3C"
FT /id="PRO_0000228833"
FT DOMAIN 220..319
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 586..854
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 51..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..180
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 335..537
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 84..98
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 151..180
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 365..387
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 406..422
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 468..493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 508..522
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 22
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZS8"
FT MOD_RES 278
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZS8"
FT MOD_RES 283
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZS8"
FT MOD_RES 359
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZS8"
FT MOD_RES 440
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 793
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9QZS8"
FT VAR_SEQ 1..354
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309"
FT /id="VSP_017706"
FT VAR_SEQ 1..185
FT /note="MTEGTKKTSKKFKFFKFKGFGSLSNLPRSFTLRRSSASISRQSHLEPDTFEA
FT TQDDMVTVPKSPPAYARSSDMYSHMGTMPRPSIKKAQNSQAARQAQEAGPKPNLVPGGV
FT PDPPGLEAAKEVMVKATGPLEDTPAMEPNPSAVEVDPIRKPEVPTGDVEEERPPRDVHS
FT ERAAGEPEAGSDYVK -> MTERCSLWSALSAAACCFYRGSFVQ (in isoform 5
FT and isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044581"
FT VAR_SEQ 1..172
FT /note="MTEGTKKTSKKFKFFKFKGFGSLSNLPRSFTLRRSSASISRQSHLEPDTFEA
FT TQDDMVTVPKSPPAYARSSDMYSHMGTMPRPSIKKAQNSQAARQAQEAGPKPNLVPGGV
FT PDPPGLEAAKEVMVKATGPLEDTPAMEPNPSAVEVDPIRKPEVPTGDVEEERPPRDVHS
FT ER -> MTAVGRRCPALGSRG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10187783,
FT ECO:0000303|PubMed:12975309, ECO:0000303|PubMed:15489334"
FT /id="VSP_017707"
FT VAR_SEQ 1..172
FT /note="MTEGTKKTSKKFKFFKFKGFGSLSNLPRSFTLRRSSASISRQSHLEPDTFEA
FT TQDDMVTVPKSPPAYARSSDMYSHMGTMPRPSIKKAQNSQAARQAQEAGPKPNLVPGGV
FT PDPPGLEAAKEVMVKATGPLEDTPAMEPNPSAVEVDPIRKPEVPTGDVEEERPPRDVHS
FT ER -> MAPALPSPHKAVARPELLLDTAAHSGKLRAPDGGEGAECAGHNGGPSWGVGQG
FT QSQEPSRQGIPQAPWLVSWQRRGFPPSSFCPGPLRTEKLRAGRCPLLLCGG (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_017708"
FT VAR_SEQ 186
FT /note="F -> VQF (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044582"
FT VARIANT 23
FT /note="L -> F (in dbSNP:rs10760500)"
FT /id="VAR_051352"
FT CONFLICT 445
FT /note="R -> C (in Ref. 1; AAD28246 and 2; AAQ89948)"
FT /evidence="ECO:0000305"
FT CONFLICT 723
FT /note="K -> E (in Ref. 3; BAF84082)"
FT /evidence="ECO:0000305"
FT HELIX 555..557
FT /evidence="ECO:0007829|PDB:3T6G"
FT STRAND 561..563
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 572..583
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 587..601
FT /evidence="ECO:0007829|PDB:3T6G"
FT STRAND 604..606
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 609..615
FT /evidence="ECO:0007829|PDB:3T6G"
FT STRAND 616..618
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 620..623
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 627..629
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 630..652
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 658..677
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 682..692
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 695..698
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 701..710
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 712..720
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 722..730
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 738..740
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 747..752
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 773..787
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 790..800
FT /evidence="ECO:0007829|PDB:3T6G"
FT TURN 801..803
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 808..813
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 816..824
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 828..830
FT /evidence="ECO:0007829|PDB:3T6G"
FT HELIX 833..851
FT /evidence="ECO:0007829|PDB:3T6G"
FT CONFLICT Q8N5H7-3:29
FT /note="L -> T (in Ref. 4; CAI46101)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 860 AA; 94411 MW; 62598F2F643147C5 CRC64;
MTEGTKKTSK KFKFFKFKGF GSLSNLPRSF TLRRSSASIS RQSHLEPDTF EATQDDMVTV
PKSPPAYARS SDMYSHMGTM PRPSIKKAQN SQAARQAQEA GPKPNLVPGG VPDPPGLEAA
KEVMVKATGP LEDTPAMEPN PSAVEVDPIR KPEVPTGDVE EERPPRDVHS ERAAGEPEAG
SDYVKFSKEK YILDSSPEKL HKELEEELKL SSTDLRSHAW YHGRIPREVS ETLVQRNGDF
LIRDSLTSLG DYVLTCRWRN QALHFKINKV VVKAGESYTH IQYLFEQESF DHVPALVRYH
VGSRKAVSEQ SGAIIYCPVN RTFPLRYLEA SYGLGQGSSK PASPVSPSGP KGSHMKRRSV
TMTDGLTADK VTRSDGCPTS TSLPRPRDSI RSCALSMDQI PDLHSPMSPI SESPSSPAYS
TVTRVHAAPA APSATALPAS PVARRSSEPQ LCPGSAPKTH GESDKGPHTS PSHTLGKASP
SPSLSSYSDP DSGHYCQLQP PVRGSREWAA TETSSQQARS YGERLKELSE NGAPEGDWGK
TFTVPIVEVT SSFNPATFQS LLIPRDNRPL EVGLLRKVKE LLAEVDARTL ARHVTKVDCL
VARILGVTKE MQTLMGVRWG MELLTLPHGR QLRLDLLERF HTMSIMLAVD ILGCTGSAEE
RAALLHKTIQ LAAELRGTMG NMFSFAAVMG ALDMAQISRL EQTWVTLRQR HTEGAILYEK
KLKPFLKSLN EGKEGPPLSN TTFPHVLPLI TLLECDSAPP EGPEPWGSTE HGVEVVLAHL
EAARTVAHHG GLYHTNAEVK LQGFQARPEL LEVFSTEFQM RLLWGSQGAS SSQARRYEKF
DKVLTALSHK LEPAVRSSEL
