SHC1_MOUSE
ID SHC1_MOUSE Reviewed; 579 AA.
AC P98083; Q3U2Q7; Q8BFY3; Q8K4C6; Q8K4C7;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 27-MAY-2002, sequence version 3.
DT 03-AUG-2022, entry version 205.
DE RecName: Full=SHC-transforming protein 1;
DE AltName: Full=SHC-transforming protein A;
DE AltName: Full=Src homology 2 domain-containing-transforming protein C1;
DE Short=SH2 domain protein C1;
GN Name=Shc1; Synonyms=Shc, ShcA;
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 [GENOMIC DNA] (ISOFORM P66SHC).
RA Blaikie P.A., Yajnik V., Margolis B.;
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P52SHC).
RX PubMed=7798194; DOI=10.1016/s0021-9258(18)31593-x;
RA Blaikie P.A., Immanuel D., Wu J., Li N., Yajnik V., Margolis B.;
RT "A region in Shc distinct from the SH2 domain can bind tyrosine-
RT phosphorylated growth factor receptors.";
RL J. Biol. Chem. 269:32031-32034(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS P52SHC AND P66SHC).
RC STRAIN=C57BL/6J, and NOD;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P52SHC).
RC STRAIN=FVB/N; TISSUE=Colon;
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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-165 (ISOFORMS P66SHC AND P52SHC).
RC STRAIN=129/SvJ;
RX PubMed=11948181; DOI=10.1074/jbc.m200280200;
RA Ventura A., Luzi L., Pacini S., Baldari C.T., Pelicci P.-G.;
RT "The p66Shc longevity gene is silenced through epigenetic modifications of
RT an alternative promoter.";
RL J. Biol. Chem. 277:22370-22376(2002).
RN [6]
RP INTERACTION WITH INPP5D.
RX PubMed=8654924; DOI=10.1101/gad.10.9.1084;
RA Lioubin M.N., Algate P.A., Tsai S., Carlberg K., Aebersold A.,
RA Rohrschneider L.R.;
RT "p150Ship, a signal transduction molecule with inositol polyphosphate-5-
RT phosphatase activity.";
RL Genes Dev. 10:1084-1095(1996).
RN [7]
RP INTERACTION WITH INPP5D.
RX PubMed=8643691; DOI=10.1073/pnas.93.4.1689;
RA Damen J.E., Liu L., Rosten P., Humphries R.K., Jefferson A.B.,
RA Majerus P.W., Krystal G.;
RT "The 145-kDa protein induced to associate with Shc by multiple cytokines is
RT an inositol tetraphosphate and phosphatidylinositol 3,4,5-triphosphate 5-
RT phosphatase.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:1689-1693(1996).
RN [8]
RP PHOSPHORYLATION AT SER-36.
RX PubMed=9165038; DOI=10.1210/endo.138.6.5203;
RA Kao A.W., Waters S.B., Okada S., Pessin J.E.;
RT "Insulin stimulates the phosphorylation of the 66- and 52-kilodalton Shc
RT isoforms by distinct pathways.";
RL Endocrinology 138:2474-2480(1997).
RN [9]
RP INTERACTION WITH INPP5D.
RX PubMed=9083021; DOI=10.1074/jbc.272.14.8983;
RA Liu L., Damen J.E., Hughes M.R., Babic I., Jirik F.R., Krystal G.;
RT "The Src homology 2 (SH2) domain of SH2-containing inositol phosphatase
RT (SHIP) is essential for tyrosine phosphorylation of SHIP, its association
RT with Shc, and its induction of apoptosis.";
RL J. Biol. Chem. 272:8983-8988(1997).
RN [10]
RP INTERACTION WITH INPPL1.
RX PubMed=9099679; DOI=10.1074/jbc.272.16.10396;
RA Lamkin T.D., Walk S.F., Liu L., Damen J.E., Krystal G., Ravichandran K.S.;
RT "Shc interaction with Src homology 2 domain containing inositol phosphatase
RT (SHIP) in vivo requires the Shc-phosphotyrosine binding domain and two
RT specific phosphotyrosines on SHIP.";
RL J. Biol. Chem. 272:10396-10401(1997).
RN [11]
RP INTERACTION WITH GAB2.
RX PubMed=9885561; DOI=10.1016/s1097-2765(00)80288-9;
RA Gu H., Pratt J.C., Burakoff S.J., Neel B.G.;
RT "Cloning of p97/Gab2, the major SHP2-binding protein in hematopoietic
RT cells, reveals a novel pathway for cytokine-induced gene activation.";
RL Mol. Cell 2:729-740(1998).
RN [12]
RP INTERACTION WITH INPP5D.
RX PubMed=10395202; DOI=10.1016/s0161-5890(98)00097-2;
RA Tridandapani S., Phee H., Shivakumar L., Kelley T.W., Coggeshall K.M.;
RT "Role of SHIP in FcgammaRIIb-mediated inhibition of Ras activation in B
RT cells.";
RL Mol. Immunol. 35:1135-1146(1998).
RN [13]
RP INTERACTION WITH INPP5D.
RX PubMed=10068665;
RA Lucas D.M., Rohrschneider L.R.;
RT "A novel spliced form of SH2-containing inositol phosphatase is expressed
RT during myeloid development.";
RL Blood 93:1922-1933(1999).
RN [14]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING, AND INTERACTION WITH GRB2
RP AND PTPN6/SHP.
RX PubMed=10080542; DOI=10.1002/jlb.65.3.372;
RA Zhang S., Mantel C., Broxmeyer H.E.;
RT "Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and
RT their association with Grb2 and Shc in Baf3/Flt3 cells.";
RL J. Leukoc. Biol. 65:372-380(1999).
RN [15]
RP IDENTIFICATION IN A COMPLEX WITH NCAM1; CDH2; PLCG1; FRS2; SRC; SHC1; FGFR4
RP AND CTTN.
RX PubMed=11433297; DOI=10.1038/35083041;
RA Cavallaro U., Niedermeyer J., Fuxa M., Christofori G.;
RT "N-CAM modulates tumour-cell adhesion to matrix by inducing FGF-receptor
RT signalling.";
RL Nat. Cell Biol. 3:650-657(2001).
RN [16]
RP INTERACTION WITH NTRK2.
RX PubMed=12367511; DOI=10.1016/s0896-6273(02)00942-x;
RA Minichiello L., Calella A.M., Medina D.L., Bonhoeffer T., Klein R.,
RA Korte M.;
RT "Mechanism of TrkB-mediated hippocampal long-term potentiation.";
RL Neuron 36:121-137(2002).
RN [17]
RP INTERACTION WITH EPHB1 AND GRB2.
RX PubMed=12925710; DOI=10.1083/jcb.200302073;
RA Vindis C., Cerretti D.P., Daniel T.O., Huynh-Do U.;
RT "EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote
RT chemotaxis.";
RL J. Cell Biol. 162:661-671(2003).
RN [18]
RP FUNCTION.
RX PubMed=12571362; DOI=10.1073/pnas.0336359100;
RA Napoli C., Martin-Padura I., de Nigris F., Giorgio M., Mansueto G.,
RA Somma P., Condorelli M., Sica G., De Rosa G., Pelicci P.-G.;
RT "Deletion of the p66Shc longevity gene reduces systemic and tissue
RT oxidative stress, vascular cell apoptosis, and early atherogenesis in mice
RT fed a high-fat diet.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:2112-2116(2003).
RN [19]
RP INTERACTION WITH CEACAM1.
RX PubMed=15467833; DOI=10.1172/jci200421786;
RA Abou-Rjaily G.A., Lee S.J., May D., Al-Share Q.Y., Deangelis A.M.,
RA Ruch R.J., Neumaier M., Kalthoff H., Lin S.H., Najjar S.M.;
RT "CEACAM1 modulates epidermal growth factor receptor--mediated cell
RT proliferation.";
RL J. Clin. Invest. 114:944-952(2004).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-423, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [22]
RP FUNCTION, SUBCELLULAR LOCATION (ISOFORM P66SHC), AND PHOSPHORYLATION AT
RP SER-36.
RX PubMed=17272725; DOI=10.1126/science.1135380;
RA Pinton P., Rimessi A., Marchi S., Orsini F., Migliaccio E., Giorgio M.,
RA Contursi C., Minucci S., Mantovani F., Wieckowski M.R., Del Sal G.,
RA Pelicci P.G., Rizzuto R.;
RT "Protein kinase C beta and prolyl isomerase 1 regulate mitochondrial
RT effects of the life-span determinant p66Shc.";
RL Science 315:659-663(2007).
RN [23]
RP INTERACTION WITH TRIM31.
RX PubMed=19665990; DOI=10.1016/j.bbrc.2009.08.028;
RA Watanabe M., Tsukiyama T., Hatakeyama S.;
RT "TRIM31 interacts with p52(Shc) and inhibits Src-induced anchorage-
RT independent growth.";
RL Biochem. Biophys. Res. Commun. 388:422-427(2009).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139 AND TYR-423, AND
RP IDENTIFICATION BY 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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-423, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Pancreas, 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 [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-154, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Signaling adapter that couples activated growth factor
CC receptors to signaling pathways. Participates in signaling downstream
CC of the angiopoietin receptor TEK/TIE2, and plays a role in the
CC regulation of endothelial cell migration and sprouting angiogenesis (By
CC similarity). Participates in a signaling cascade initiated by activated
CC KIT and KITLG/SCF. Isoform p47Shc and isoform p52Shc, once
CC phosphorylated, couple activated receptor kinases to Ras via the
CC recruitment of the GRB2/SOS complex and are implicated in the
CC cytoplasmic propagation of mitogenic signals. Isoform p47Shc and
CC isoform p52 may thus function as initiators of the Ras signaling
CC cascade in various non-neuronal systems. Isoform p66Shc does not
CC mediate Ras activation, but is involved in signal transduction pathways
CC that regulate the cellular response to oxidative stress and life span.
CC Isoform p66Shc acts as a downstream target of the tumor suppressor p53
CC and is indispensable for the ability of stress-activated p53 to induce
CC elevation of intracellular oxidants, cytochrome c release and
CC apoptosis. The expression of isoform p66Shc has been correlated with
CC life span. {ECO:0000250, ECO:0000269|PubMed:12571362,
CC ECO:0000269|PubMed:17272725}.
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 DDR2 and CD3T. Interacts with the N-terminal region of APS. Interacts
CC with GRB7 and KIT (By similarity). Interacts with PTK2/FAK1 (By
CC similarity). Interacts with phosphorylated LRP1 and IRS4. Interacts
CC with FLT4 (tyrosine-phosphorylated) (By similarity). Interacts with
CC PDGFRB (tyrosine-phosphorylated). Interacts with ERBB4 (By similarity).
CC Interacts with TEK/TIE2 (tyrosine-phosphorylated) (By similarity).
CC Interacts with ALK, GAB2, TRIM31, INPP5D/SHIP1 and INPPL1/SHIP2.
CC Interacts with PTPN6/SHP (tyrosine phosphorylated). Identified in a
CC complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43
CC and CTTN. Interacts with EPHB1 and GRB2; activates the MAPK/ERK cascade
CC to regulate cell migration. 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:15467833). Interacts (via PID domain) with PEAK1 (when
CC phosphorylated at 'Tyr-1177') (By similarity). Found in a complex with
CC PPP1CA, PPP1CC, SHC1 and PEAK1 (By similarity).
CC {ECO:0000250|UniProtKB:P29353, ECO:0000250|UniProtKB:Q5M824,
CC ECO:0000269|PubMed:10068665, ECO:0000269|PubMed:10080542,
CC ECO:0000269|PubMed:10395202, ECO:0000269|PubMed:11433297,
CC ECO:0000269|PubMed:12367511, ECO:0000269|PubMed:12925710,
CC ECO:0000269|PubMed:15467833, ECO:0000269|PubMed:19665990,
CC ECO:0000269|PubMed:8643691, ECO:0000269|PubMed:8654924,
CC ECO:0000269|PubMed:9083021, ECO:0000269|PubMed:9099679,
CC ECO:0000269|PubMed:9885561}.
CC -!- INTERACTION:
CC P98083; P0DMN7: Amd1; NbExp=7; IntAct=EBI-300201, EBI-644529;
CC P98083; Q60631: Grb2; NbExp=8; IntAct=EBI-300201, EBI-1688;
CC P98083; Q9JKF1: Iqgap1; NbExp=5; IntAct=EBI-300201, EBI-644633;
CC P98083; P35831: Ptpn12; NbExp=2; IntAct=EBI-300201, EBI-2642957;
CC P98083; Q9Z179: Shcbp1; NbExp=5; IntAct=EBI-300201, EBI-644352;
CC P98083-1; P98083-1: Shc1; NbExp=4; IntAct=EBI-7533258, EBI-7533258;
CC P98083-1; Q62312: Tgfbr2; NbExp=2; IntAct=EBI-7533258, EBI-2899332;
CC P98083-2; Q64729: Tgfbr1; NbExp=7; IntAct=EBI-1019301, EBI-2899393;
CC P98083-2; Q62312: Tgfbr2; NbExp=3; IntAct=EBI-1019301, EBI-2899332;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform p47Shc]: Mitochondrion matrix
CC {ECO:0000250}. Note=Targeting of isoform p47Shc to mitochondria is
CC mediated by its first 32 amino acids, which behave as a bona fide
CC mitochondrial targeting sequence. Isoform p52Shc and isoform p66Shc,
CC that contain the same sequence but more internally located, display a
CC different subcellular localization (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Isoform p66Shc]: Mitochondrion
CC {ECO:0000269|PubMed:17272725}. Note=In case of oxidative conditions,
CC phosphorylation at 'Ser-36' of isoform p66Shc, leads to mitochondrial
CC accumulation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=3;
CC Comment=In human, it is alternative promoter usage that produces such
CC isoforms.;
CC Name=p66Shc; Synonyms=p66;
CC IsoId=P98083-1; Sequence=Displayed;
CC Name=p52Shc; Synonyms=p52;
CC IsoId=P98083-2; Sequence=VSP_018791;
CC Name=p47Shc; Synonyms=p47;
CC IsoId=P98083-3; Sequence=VSP_018792;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in neural stem cells
CC but absent in mature neurons.
CC -!- DOMAIN: In response to a variety of growth factors, isoform p47Shc and
CC isoform p52 bind to phosphorylated receptors through their
CC phosphotyrosine binding (PID) and/or SH2 domains. The PID and SH2
CC domains bind to specific phosphorylated tyrosine residues in the Asn-
CC Pro-Xaa-Tyr(P) motif. Isoform p47Shc and isoform p52Shc are in turn
CC phosphorylated on three tyrosine residues within the extended proline-
CC rich domain. These phosphotyrosines act as docking site for GRB2 and
CC thereby are involved in Ras activation.
CC -!- PTM: Phosphorylated in response to FLT4 signaling (By similarity).
CC Tyrosine phosphorylated by ligand-activated PDGFRB (By similarity). May
CC be tyrosine phosphorylated by activated PTK2/FAK1 (By similarity).
CC Tyrosine phosphorylated by TEK/TIE2 (By similarity). Tyrosine
CC phosphorylated by activated PTK2B/PYK2 (By similarity).
CC Dephosphorylation by PTPN2 may regulate interaction with GRB2 (By
CC similarity). Phosphorylated by activated epidermal growth factor
CC receptor. Phosphorylated in response to KIT signaling. Isoform p47Shc
CC and isoform p52Shc are phosphorylated on tyrosine residues of the Pro-
CC rich domain. Isoform p66Shc is phosphorylated on Ser-36 by PRKCB upon
CC treatment with insulin, hydrogen peroxide or irradiation with
CC ultraviolet light. FLT3 signaling promotes tyrosine phosphorylation of
CC isoform p47Shc and isoform p52Shc. Also tyrosine phosphorylated by
CC ligand-activated ALK. {ECO:0000250, ECO:0000269|PubMed:10080542,
CC ECO:0000269|PubMed:9165038}.
CC -!- MISCELLANEOUS: [Isoform p52Shc]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform p47Shc]: Produced by alternative initiation at
CC Met-46 of isoform p52. {ECO:0000305}.
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DR EMBL; U46956; AAA91777.2; -; Genomic_DNA.
DR EMBL; U15784; AAC52146.1; -; mRNA.
DR EMBL; AK049357; BAC33706.1; -; mRNA.
DR EMBL; AK155158; BAE33083.1; -; mRNA.
DR EMBL; BC036172; AAH36172.1; -; mRNA.
DR EMBL; AF455140; AAM61857.1; -; Genomic_DNA.
DR EMBL; AF455140; AAM61858.1; -; Genomic_DNA.
DR CCDS; CCDS17508.1; -. [P98083-2]
DR CCDS; CCDS50962.1; -. [P98083-1]
DR PIR; A55484; A55484.
DR RefSeq; NP_001106802.1; NM_001113331.2. [P98083-1]
DR RefSeq; NP_035498.2; NM_011368.5. [P98083-2]
DR AlphaFoldDB; P98083; -.
DR BMRB; P98083; -.
DR SMR; P98083; -.
DR BioGRID; 203215; 33.
DR CORUM; P98083; -.
DR DIP; DIP-271N; -.
DR IntAct; P98083; 27.
DR MINT; P98083; -.
DR STRING; 10090.ENSMUSP00000091940; -.
DR iPTMnet; P98083; -.
DR PhosphoSitePlus; P98083; -.
DR EPD; P98083; -.
DR jPOST; P98083; -.
DR MaxQB; P98083; -.
DR PaxDb; P98083; -.
DR PeptideAtlas; P98083; -.
DR PRIDE; P98083; -.
DR ProteomicsDB; 261225; -. [P98083-1]
DR ProteomicsDB; 261226; -. [P98083-2]
DR ProteomicsDB; 261227; -. [P98083-3]
DR Antibodypedia; 731; 1210 antibodies from 45 providers.
DR DNASU; 20416; -.
DR Ensembl; ENSMUST00000039110; ENSMUSP00000035361; ENSMUSG00000042626. [P98083-2]
DR Ensembl; ENSMUST00000094378; ENSMUSP00000091940; ENSMUSG00000042626. [P98083-1]
DR Ensembl; ENSMUST00000107417; ENSMUSP00000103040; ENSMUSG00000042626. [P98083-3]
DR Ensembl; ENSMUST00000191485; ENSMUSP00000140336; ENSMUSG00000042626. [P98083-2]
DR GeneID; 20416; -.
DR KEGG; mmu:20416; -.
DR UCSC; uc008pzm.2; mouse. [P98083-1]
DR CTD; 6464; -.
DR MGI; MGI:98296; Shc1.
DR VEuPathDB; HostDB:ENSMUSG00000042626; -.
DR eggNOG; KOG3697; Eukaryota.
DR GeneTree; ENSGT00950000182870; -.
DR HOGENOM; CLU_029532_2_0_1; -.
DR InParanoid; P98083; -.
DR OMA; FFPRMSS; -.
DR OrthoDB; 1351843at2759; -.
DR PhylomeDB; P98083; -.
DR TreeFam; TF315807; -.
DR Reactome; R-MMU-1250196; SHC1 events in ERBB2 signaling. [P98083-3]
DR Reactome; R-MMU-1250347; SHC1 events in ERBB4 signaling. [P98083-3]
DR Reactome; R-MMU-167044; Signalling to RAS. [P98083-3]
DR Reactome; R-MMU-180336; SHC1 events in EGFR signaling. [P98083-3]
DR Reactome; R-MMU-201556; Signaling by ALK. [P98083-3]
DR Reactome; R-MMU-210993; Tie2 Signaling. [P98083-3]
DR Reactome; R-MMU-2424491; DAP12 signaling. [P98083-3]
DR Reactome; R-MMU-2428933; SHC-related events triggered by IGF1R. [P98083-3]
DR Reactome; R-MMU-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. [P98083-3]
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation. [P98083-3]
DR Reactome; R-MMU-2871809; FCERI mediated Ca+2 mobilization. [P98083-3]
DR Reactome; R-MMU-354192; Integrin signaling. [P98083-3]
DR Reactome; R-MMU-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling. [P98083-3]
DR Reactome; R-MMU-5654688; SHC-mediated cascade:FGFR1. [P98083-3]
DR Reactome; R-MMU-5654699; SHC-mediated cascade:FGFR2. [P98083-3]
DR Reactome; R-MMU-5654704; SHC-mediated cascade:FGFR3. [P98083-3]
DR Reactome; R-MMU-5654719; SHC-mediated cascade:FGFR4. [P98083-3]
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade. [P98083-3]
DR Reactome; R-MMU-74749; Signal attenuation. [P98083-3]
DR Reactome; R-MMU-74751; Insulin receptor signalling cascade. [P98083-3]
DR Reactome; R-MMU-8851805; MET activates RAS signaling. [P98083-3]
DR Reactome; R-MMU-8853659; RET signaling. [P98083-3]
DR Reactome; R-MMU-8983432; Interleukin-15 signaling. [P98083-3]
DR Reactome; R-MMU-9009391; Extra-nuclear estrogen signaling. [P98083-3]
DR Reactome; R-MMU-9020558; Interleukin-2 signaling. [P98083-3]
DR Reactome; R-MMU-9027284; Erythropoietin activates RAS. [P98083-3]
DR Reactome; R-MMU-912526; Interleukin receptor SHC signaling. [P98083-3]
DR Reactome; R-MMU-9634597; GPER1 signaling. [P98083-3]
DR Reactome; R-MMU-9674555; Signaling by CSF3 (G-CSF). [P98083-3]
DR BioGRID-ORCS; 20416; 6 hits in 74 CRISPR screens.
DR ChiTaRS; Shc1; mouse.
DR PRO; PR:P98083; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P98083; protein.
DR Bgee; ENSMUSG00000042626; Expressed in lens of camera-type eye and 63 other tissues.
DR ExpressionAtlas; P98083; baseline and differential.
DR Genevisible; P98083; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; ISO:MGI.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0070435; C:Shc-EGFR complex; ISO:MGI.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0048408; F:epidermal growth factor binding; IPI:UniProtKB.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005158; F:insulin receptor binding; ISO:MGI.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; ISO:MGI.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; ISO:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0051721; F:protein phosphatase 2A binding; ISO:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:MGI.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; IMP:MGI.
DR GO; GO:0007568; P:aging; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; ISO:MGI.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IDA:MGI.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0030182; P:neuron differentiation; ISO:MGI.
DR GO; GO:0031175; P:neuron projection development; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0071864; P:positive regulation of cell proliferation in bone marrow; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0045907; P:positive regulation of vasoconstriction; ISO:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0040008; P:regulation of growth; IEA:UniProtKB-KW.
DR GO; GO:0006940; P:regulation of smooth muscle contraction; ISO:MGI.
DR GO; GO:0090322; P:regulation of superoxide metabolic process; ISO:MGI.
DR GO; GO:1990839; P:response to endothelin; ISO:MGI.
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; Alternative initiation; Alternative splicing; Angiogenesis;
KW Cytoplasm; Growth regulation; Mitochondrion; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT CHAIN 1..579
FT /note="SHC-transforming protein 1"
FT /id="PRO_0000022339"
FT DOMAIN 156..339
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 484..575
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 337..357
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..483
FT /note="CH1"
FT REGION 432..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 13..36
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9165038"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 154
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 349
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
FT MOD_RES 350
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
FT MOD_RES 423
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P29353"
FT VAR_SEQ 1..155
FT /note="Missing (in isoform p47Shc)"
FT /evidence="ECO:0000305"
FT /id="VSP_018792"
FT VAR_SEQ 1..110
FT /note="Missing (in isoform p52Shc)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:7798194"
FT /id="VSP_018791"
SQ SEQUENCE 579 AA; 62608 MW; 99C22E64412B6236 CRC64;
MDLLPPKPKY NPLRNESLSS LEEGASGSTP PEELPSPSAS SLGPILPPLP GDDSPTTLCS
FFPRMSNLKL ANPAGGRLGP KGEPGKAAED GEGSAGAALR DSGLLPLLQD MNKLSGGGGR
RTRVEGGQLG GEEWTRHGSF VNKPTRGWLH PNDKVMGPGV SYLVRYMGCV EVLQSMRALD
FNTRTQVTRE AISLVCEAVP GAKGATRRRK PCSRPLSSIL GRSNLKFAGM PITLTVSTSS
LNLMAADCKQ IIANHHMQSI SFASGGDPDT AEYVAYVAKD PVNQRACHIL ECPEGLAQDV
ISTIGQAFEL RFKQYLRNPP KLVTPHDRMA GFDGSAWDEE EEEPPDHQYY NDFPGKEPPL
GGVVDMRLRE GAARPTLPSA QMSSHLGATL PIGQHAAGDH EVRKQMLPPP PCPGRELFDD
PSYVNIQNLD KARQAGGGAG PPNPSLNGSA PRDLFDMKPF EDALRVPPPP QSMSMAEQLQ
GEPWFHGKLS RREAEALLQL NGDFLVREST TTPGQYVLTG LQSGQPKHLL LVDPEGVVRT
KDHRFESVSH LISYHMDNHL PIISAGSELC LQQPVDRKV
