SHC1_RAT
ID SHC1_RAT Reviewed; 469 AA.
AC Q5M824;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=SHC-transforming protein 1;
DE AltName: Full=Src homology 2 domain-containing-transforming protein C1;
DE Short=SH2 domain protein C1;
GN Name=Shc1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [2]
RP PHOSPHORYLATION.
RC TISSUE=Brain;
RX PubMed=7544443; DOI=10.1038/376737a0;
RA Lev S., Moreno H., Martinez R., Canoll P., Peles E., Musacchio J.M.,
RA Plowman G.D., Rudy B., Schlessinger J.;
RT "Protein tyrosine kinase PYK2 involved in Ca(2+)-induced regulation of ion
RT channel and MAP kinase functions.";
RL Nature 376:737-745(1995).
RN [3]
RP PHOSPHORYLATION, AND INTERACTION WITH FLT4.
RX PubMed=7675451;
RA Fournier E., Dubreuil P., Birnbaum D., Borg J.P.;
RT "Mutation at tyrosine residue 1337 abrogates ligand-dependent transforming
RT capacity of the FLT4 receptor.";
RL Oncogene 11:921-931(1995).
RN [4]
RP INTERACTION WITH NTRK2.
RX PubMed=9582017; DOI=10.1038/sj.onc.1201688;
RA McCarty J.H., Feinstein S.C.;
RT "Activation loop tyrosines contribute varying roles to TrkB
RT autophosphorylation and signal transduction.";
RL Oncogene 16:1691-1700(1998).
RN [5]
RP INTERACTION WITH CEACAM1.
RX PubMed=11694516; DOI=10.1074/jbc.m108415200;
RA Poy M.N., Ruch R.J., Fernstrom M.A., Okabayashi Y., Najjar S.M.;
RT "Shc and CEACAM1 interact to regulate the mitogenic action of insulin.";
RL J. Biol. Chem. 277:1076-1084(2002).
RN [6]
RP INTERACTION WITH DDR2.
RX PubMed=16186108; DOI=10.1074/jbc.m506921200;
RA Yang K., Kim J.H., Kim H.J., Park I.S., Kim I.Y., Yang B.S.;
RT "Tyrosine 740 phosphorylation of discoidin domain receptor 2 by Src
RT stimulates intramolecular autophosphorylation and Shc signaling complex
RT formation.";
RL J. Biol. Chem. 280:39058-39066(2005).
CC -!- FUNCTION: Signaling adapter that couples activated growth factor
CC receptors to signaling pathways. Participates in a signaling cascade
CC initiated by activated KIT and KITLG/SCF. Participates in signaling
CC downstream of the angiopoietin receptor TEK/TIE2, and plays a role in
CC the regulation of endothelial cell migration and sprouting angiogenesis
CC (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CPNE3; this interaction may mediate the binding
CC of CPNE3 with ERBB2 (By similarity). Interacts with the NPXY motif of
CC tyrosine-phosphorylated IGF1R and INSR in vitro via the PID domain.
CC Once activated, binds to GRB2. Interacts with tyrosine-phosphorylated
CC CD3T and DDR2. Interacts with the N-terminal region of APS. Interacts
CC with phosphorylated LRP1 and IRS4. Interacts with INPP5D/SHIP1 and
CC INPPL1/SHIP2. Interacts with ALK, GAB2, GRB7 and KIT. Interacts with
CC PTPN6/SHP (tyrosine phosphorylated). Identified in a complex containing
CC FGFR4, NCAM1, CDH2, PLCG1, FRS2A, SRC, SHC1, GAP43 and CTTN. Interacts
CC with EPHB1 and GRB2; activates the MAPK/ERK cascade to regulate cell
CC migration. Interacts with PDGFRB (tyrosine-phosphorylated). Interacts
CC with ERBB4. Interacts with TEK/TIE2 (tyrosine-phosphorylated).
CC Interacts with PTK2/FAK1 (By similarity). Interacts with FLT4
CC (tyrosine-phosphorylated). Interacts with the Trk receptors NTRK1,
CC NTRK2 and NTRK3; in a phosphotyrosine-dependent manner. Interacts with
CC CEACAM1; this interaction is CEACAM1-phosphorylation-dependent and
CC mediates interaction with EGFR or INSR resulting in decrease coupling
CC of SHC1 to the MAPK3/ERK1-MAPK1/ERK2 pathway (By similarity)
CC (PubMed:11694516). Interacts (via PID domain) with PEAK1 (when
CC phosphorylated) (By similarity). Found in a complex with PPP1CA,
CC PPP1CC, SHC1 and PEAK1 (By similarity). {ECO:0000250|UniProtKB:P29353,
CC ECO:0000250|UniProtKB:P98083, ECO:0000269|PubMed:11694516,
CC ECO:0000269|PubMed:16186108, ECO:0000269|PubMed:7675451,
CC ECO:0000269|PubMed:9582017}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- PTM: Phosphorylated by activated epidermal growth factor receptor.
CC Phosphorylated in response to KIT signaling. Tyrosine phosphorylated in
CC response to FLT3 signaling and by ligand-activated ALK. Tyrosine
CC phosphorylated by TEK/TIE2 (By similarity). Tyrosine phosphorylated by
CC ligand-activated PDGFRB (By similarity). May be tyrosine phosphorylated
CC by activated PTK2/FAK1 (By similarity). Dephosphorylation by PTPN2 may
CC regulate interaction with GRB2 (By similarity). Phosphorylated in
CC response to FLT4 signaling. Tyrosine phosphorylated by activated
CC PTK2B/PYK2. {ECO:0000250, ECO:0000269|PubMed:7544443,
CC ECO:0000269|PubMed:7675451}.
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DR EMBL; BC088298; AAH88298.1; -; mRNA.
DR RefSeq; NP_445969.2; NM_053517.2.
DR AlphaFoldDB; Q5M824; -.
DR BMRB; Q5M824; -.
DR SMR; Q5M824; -.
DR BioGRID; 250090; 9.
DR CORUM; Q5M824; -.
DR IntAct; Q5M824; 7.
DR MINT; Q5M824; -.
DR STRING; 10116.ENSRNOP00000028038; -.
DR iPTMnet; Q5M824; -.
DR jPOST; Q5M824; -.
DR PaxDb; Q5M824; -.
DR PeptideAtlas; Q5M824; -.
DR GeneID; 85385; -.
DR KEGG; rno:85385; -.
DR UCSC; RGD:620446; rat.
DR CTD; 6464; -.
DR RGD; 620446; Shc1.
DR eggNOG; KOG3697; Eukaryota.
DR InParanoid; Q5M824; -.
DR PhylomeDB; Q5M824; -.
DR Reactome; R-RNO-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-RNO-1250347; SHC1 events in ERBB4 signaling.
DR Reactome; R-RNO-167044; Signalling to RAS.
DR Reactome; R-RNO-180336; SHC1 events in EGFR signaling.
DR Reactome; R-RNO-201556; Signaling by ALK.
DR Reactome; R-RNO-210993; Tie2 Signaling.
DR Reactome; R-RNO-2424491; DAP12 signaling.
DR Reactome; R-RNO-2428933; SHC-related events triggered by IGF1R.
DR Reactome; R-RNO-2730905; Role of LAT2/NTAL/LAB on calcium mobilization.
DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR Reactome; R-RNO-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-RNO-354192; Integrin signaling.
DR Reactome; R-RNO-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-RNO-5654688; SHC-mediated cascade:FGFR1.
DR Reactome; R-RNO-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-RNO-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-RNO-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-74749; Signal attenuation.
DR Reactome; R-RNO-74751; Insulin receptor signalling cascade.
DR Reactome; R-RNO-8851805; MET activates RAS signaling.
DR Reactome; R-RNO-8853659; RET signaling.
DR Reactome; R-RNO-8983432; Interleukin-15 signaling.
DR Reactome; R-RNO-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-RNO-9020558; Interleukin-2 signaling.
DR Reactome; R-RNO-9027284; Erythropoietin activates RAS.
DR Reactome; R-RNO-912526; Interleukin receptor SHC signaling.
DR Reactome; R-RNO-9634597; GPER1 signaling.
DR Reactome; R-RNO-9674555; Signaling by CSF3 (G-CSF).
DR PRO; PR:Q5M824; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0070435; C:Shc-EGFR complex; IDA:BHF-UCL.
DR GO; GO:0046875; F:ephrin receptor binding; ISO:RGD.
DR GO; GO:0048408; F:epidermal growth factor binding; ISO:RGD.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005158; F:insulin receptor binding; ISO:RGD.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISO:RGD.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; ISO:RGD.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:RGD.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:RGD.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISO:RGD.
DR GO; GO:0007568; P:aging; IPI:RGD.
DR GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR GO; GO:0031100; P:animal organ regeneration; IEP:RGD.
DR GO; GO:0098609; P:cell-cell adhesion; ISO:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0042742; P:defense response to bacterium; ISO:RGD.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; IMP:RGD.
DR GO; GO:0031175; P:neuron projection development; IMP:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; IMP:RGD.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; IMP:RGD.
DR GO; GO:1990839; P:response to endothelin; IMP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0042542; P:response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0001666; P:response to hypoxia; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IEP:RGD.
DR GO; GO:0009636; P:response to toxic substance; IEP:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd01209; PTB_Shc; 1.
DR CDD; cd09925; SH2_SHC; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006019; PID_Shc-like.
DR InterPro; IPR006020; PTB/PI_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR029586; Shc1/ShcA.
DR InterPro; IPR035676; SHC_SH2.
DR PANTHER; PTHR10337:SF2; PTHR10337:SF2; 1.
DR Pfam; PF00640; PID; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00629; SHCPIDOMAIN.
DR SMART; SM00462; PTB; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS01179; PID; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Angiogenesis; Cytoplasm; Growth regulation; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT CHAIN 1..469
FT /note="SHC-transforming protein 1"
FT /id="PRO_0000327222"
FT DOMAIN 46..229
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 374..465
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 230..373
FT /note="CH1"
FT REGION 322..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
FT MOD_RES 44
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P98083"
FT MOD_RES 239
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
FT MOD_RES 240
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
FT MOD_RES 313
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
FT MOD_RES 339
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
SQ SEQUENCE 469 AA; 51503 MW; 9BFEE9D33E07B3F9 CRC64;
MNKLSGGGGR RTRVEGGQLG GEEWTRHGSF VNKPTRGWLH PNDKVMGPGV SYLVRYMGCV
EVLQSMRALD FNTRTQVTRE AISLVCEAVP GAKGAMRRRK PCSRPLSSIL GRSNLKFAGM
PITLTVSTSS LNLMAADCKQ IIANHHMQSI SFASGGDPDT AEYVAYVAKD PVNQRACHIL
ECPEGLAQDV ISTIGQAFEL RFKQYLRNPP KLVTPHDRMA GFDGSAWDEE EEELPDHQYY
NDFPGKEPPL GGVVDMRLRE GAARPTLPST QMPSHLGATL PIGQHVTGDH EVRKQMLPPP
PCPGRELFDD PSYVNIQNLD KARQAGGGAG PPNPSVNGSA PRDLFDMKPF EDALRVPPAP
QSMSMAEQLQ GESWFHGKLS RREAEALLQL NGDFLVREST TTPGQYVLTG LQSGQPKHLL
LVDPEGVVRT KDHRFESVSH LISYHMDNHL PIISAGSELC LQQPVDRKV
