ID SHC1_HUMAN Reviewed; 583 AA.
AC P29353; B5BU19; D3DV78; O15290; Q5T180; Q5T183; Q5T184; Q5T185; Q5T186;
AC Q8N4K5; Q96CL1;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 08-APR-2008, sequence version 4.
DT 27-MAR-2024, entry version 255.
DE RecName: Full=SHC-transforming protein 1;
DE AltName: Full=SHC-transforming protein 3;
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 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] (ISOFORMS P46SHC AND P52SHC).
RX PubMed=1623525; DOI=10.1016/0092-8674(92)90536-l;
RA Pelicci G., Lanfrancone L., Grignani F., McGlade J., Cavallo F., Forni G.,
RA Nicoletti I., Grignani F., Pawson T., Pelicci P.-G.;
RT "A novel transforming protein (SHC) with an SH2 domain is implicated in
RT mitogenic signal transduction.";
RL Cell 70:93-104(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P66SHC).
RX PubMed=9049300; DOI=10.1093/emboj/16.4.706;
RA Migliaccio E., Mele S., Salcini A.E., Pelicci G., Lai K.M.,
RA Superti-Furga G., Pawson T., Di Fiore P.P., Lanfrancone L., Pelicci P.-G.;
RT "Opposite effects of the p52shc/p46shc and p66shc splicing isoforms on the
RT EGF receptor-MAP kinase-fos signalling pathway.";
RL EMBO J. 16:706-716(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Fibroblast;
RX PubMed=9192859; DOI=10.1006/geno.1997.4728;
RA Harun R.B., Smith K.K., Leek J.P., Markham A.F., Norris A., Morrison J.F.;
RT "Characterization of human SHC p66 cDNA and its processed pseudogene
RT mapping to Xq12-q13.1.";
RL Genomics 42:349-352(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P52SHC).
RC TISSUE=Mammary gland, and Synovium;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS P52SHC AND 7).
RC TISSUE=Choriocarcinoma, and Neuroblastoma;
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 [9]
RP INTERACTION WITH PDGFRB AND GRB2, AND PHOSPHORYLATION.
RX PubMed=8195171; DOI=10.1016/s0021-9258(17)36611-5;
RA Yokote K., Mori S., Hansen K., McGlade J., Pawson T., Heldin C.H.,
RA Claesson-Welsh L.;
RT "Direct interaction between Shc and the platelet-derived growth factor
RT beta-receptor.";
RL J. Biol. Chem. 269:15337-15343(1994).
RN [10]
RP INTERACTION WITH NTRK1.
RX PubMed=8155326; DOI=10.1016/0896-6273(94)90223-2;
RA Stephens R.M., Loeb D.M., Copeland T.D., Pawson T., Greene L.A.,
RA Kaplan D.R.;
RT "Trk receptors use redundant signal transduction pathways involving SHC and
RT PLC-gamma 1 to mediate NGF responses.";
RL Neuron 12:691-705(1994).
RN [11]
RP INTERACTION WITH IGF1R.
RX PubMed=7541045; DOI=10.1074/jbc.270.26.15639;
RA Craparo A., O'Neill T.J., Gustafson T.A.;
RT "Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their
RT phosphotyrosine-dependent interaction with the NPEY motif of the insulin-
RT like growth factor I receptor.";
RL J. Biol. Chem. 270:15639-15643(1995).
RN [12]
RP INTERACTION WITH INSR.
RX PubMed=7559478; DOI=10.1074/jbc.270.40.23258;
RA He W., O'Neill T.J., Gustafson T.A.;
RT "Distinct modes of interaction of SHC and insulin receptor substrate-1 with
RT the insulin receptor NPEY region via non-SH2 domains.";
RL J. Biol. Chem. 270:23258-23262(1995).
RN [13]
RP INTERACTION WITH INSR.
RX PubMed=7537849; DOI=10.1128/mcb.15.5.2500;
RA Gustafson T.A., He W., Craparo A., Schaub C.D., O'Neill T.J.;
RT "Phosphotyrosine-dependent interaction of SHC and insulin receptor
RT substrate 1 with the NPEY motif of the insulin receptor via a novel non-SH2
RT domain.";
RL Mol. Cell. Biol. 15:2500-2508(1995).
RN [14]
RP INTERACTION WITH INPP5D.
RX PubMed=8874179;
RA Ware M.D., Rosten P., Damen J.E., Liu L., Humphries R.K., Krystal G.;
RT "Cloning and characterization of human SHIP, the 145-kD inositol 5-
RT phosphatase that associates with SHC after cytokine stimulation.";
RL Blood 88:2833-2840(1996).
RN [15]
RP PHOSPHORYLATION AT TYR-349 AND TYR-350.
RX PubMed=8939605; DOI=10.1016/s0960-9822(96)00748-8;
RA van der Geer P., Wiley S., Gish G.D., Pawson T.;
RT "The Shc adaptor protein is highly phosphorylated at conserved, twin
RT tyrosine residues (Y239/240) that mediate protein-protein interactions.";
RL Curr. Biol. 6:1435-1444(1996).
RN [16]
RP INTERACTION WITH GRB7.
RX PubMed=8940081; DOI=10.1074/jbc.271.48.30942;
RA Yokote K., Margolis B., Heldin C.H., Claesson-Welsh L.;
RT "Grb7 is a downstream signaling component of platelet-derived growth factor
RT alpha- and beta-receptors.";
RL J. Biol. Chem. 271:30942-30949(1996).
RN [17]
RP INTERACTION WITH KIT.
RX PubMed=9038210; DOI=10.1074/jbc.272.9.5915;
RA Price D.J., Rivnay B., Fu Y., Jiang S., Avraham S., Avraham H.;
RT "Direct association of Csk homologous kinase (CHK) with the
RT diphosphorylated site Tyr568/570 of the activated c-KIT in
RT megakaryocytes.";
RL J. Biol. Chem. 272:5915-5920(1997).
RN [18]
RP PHOSPHORYLATION.
RX PubMed=9148935; DOI=10.1074/jbc.272.20.13189;
RA Schlaepfer D.D., Hunter T.;
RT "Focal adhesion kinase overexpression enhances ras-dependent integrin
RT signaling to ERK2/mitogen-activated protein kinase through interactions
RT with and activation of c-Src.";
RL J. Biol. Chem. 272:13189-13195(1997).
RN [19]
RP PHOSPHORYLATION AT TYR-349; TYR-350 AND TYR-427.
RX PubMed=9121430; DOI=10.1128/mcb.17.4.1824;
RA Gotoh N., Toyoda M., Shibuya M.;
RT "Tyrosine phosphorylation sites at amino acids 239 and 240 of Shc are
RT involved in epidermal growth factor-induced mitogenic signaling that is
RT distinct from Ras/mitogen-activated protein kinase activation.";
RL Mol. Cell. Biol. 17:1824-1831(1997).
RN [20]
RP INTERACTION WITH SH2B2.
RX PubMed=9233773; DOI=10.1038/sj.onc.1201163;
RA Yokouchi M., Suzuki R., Masuhara M., Komiya S., Inoue A., Yoshimura A.;
RT "Cloning and characterization of APS, an adaptor molecule containing PH and
RT SH2 domains that is tyrosine phosphorylated upon B-cell receptor
RT stimulation.";
RL Oncogene 15:7-15(1997).
RN [21]
RP INTERACTION WITH INPP5D AND INPPL1.
RX PubMed=9660833; DOI=10.1074/jbc.273.29.18605;
RA Habib T., Hejna J.A., Moses R.E., Decker S.J.;
RT "Growth factors and insulin stimulate tyrosine phosphorylation of the
RT 51C/SHIP2 protein.";
RL J. Biol. Chem. 273:18605-18609(1998).
RN [22]
RP PHOSPHORYLATION, DEPHOSPHORYLATION BY PTPN2, MUTAGENESIS OF TYR-349 AND
RP TYR-427, AND INTERACTION WITH GRB2.
RX PubMed=9488479; DOI=10.1128/mcb.18.3.1622;
RA Tiganis T., Bennett A.M., Ravichandran K.S., Tonks N.K.;
RT "Epidermal growth factor receptor and the adaptor protein p52Shc are
RT specific substrates of T-cell protein tyrosine phosphatase.";
RL Mol. Cell. Biol. 18:1622-1634(1998).
RN [23]
RP PHOSPHORYLATION AT TYR-349; TYR-350 AND TYR-427.
RX PubMed=9566877; DOI=10.1128/mcb.18.5.2571;
RA Schlaepfer D.D., Jones K.C., Hunter T.;
RT "Multiple Grb2-mediated integrin-stimulated signaling pathways to
RT ERK2/mitogen-activated protein kinase: summation of both c-Src- and focal
RT adhesion kinase-initiated tyrosine phosphorylation events.";
RL Mol. Cell. Biol. 18:2571-2585(1998).
RN [24]
RP INTERACTION WITH INPPL1.
RX PubMed=10194451;
RA Wisniewski D., Strife A., Swendeman S., Erdjument-Bromage H., Geromanos S.,
RA Kavanaugh W.M., Tempst P., Clarkson B.;
RT "A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-
RT phosphatase (SHIP2) is constitutively tyrosine phosphorylated and
RT associated with src homologous and collagen gene (SHC) in chronic
RT myelogenous leukemia progenitor cells.";
RL Blood 93:2707-2720(1999).
RN [25]
RP INTERACTION WITH ERBB4.
RX PubMed=10867024; DOI=10.1074/jbc.c901015199;
RA Sweeney C., Lai C., Riese D.J. II, Diamonti A.J., Cantley L.C.,
RA Carraway K.L. III;
RT "Ligand discrimination in signaling through an ErbB4 receptor homodimer.";
RL J. Biol. Chem. 275:19803-19807(2000).
RN [26]
RP INTERACTION WITH INPPL1.
RX PubMed=11349134; DOI=10.1074/jbc.m103537200;
RA Pesesse X., Dewaste V., De Smedt F., Laffargue M., Giuriato S., Moreau C.,
RA Payrastre B., Erneux C.;
RT "The Src homology 2 domain containing inositol 5-phosphatase SHIP2 is
RT recruited to the epidermal growth factor (EGF) receptor and
RT dephosphorylates phosphatidylinositol 3,4,5-trisphosphate in EGF-stimulated
RT COS-7 cells.";
RL J. Biol. Chem. 276:28348-28355(2001).
RN [27]
RP INTERACTION WITH PTK2/FAK1, AND PHOSPHORYLATION.
RX PubMed=11980671;
RA Hecker T.P., Grammer J.R., Gillespie G.Y., Stewart J. Jr., Gladson C.L.;
RT "Focal adhesion kinase enhances signaling through the Shc/extracellular
RT signal-regulated kinase pathway in anaplastic astrocytoma tumor biopsy
RT samples.";
RL Cancer Res. 62:2699-2707(2002).
RN [28]
RP ALTERNATIVE PROMOTER USAGE.
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 [29]
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 [30]
RP INTERACTION WITH NTRK1.
RX PubMed=15488758; DOI=10.1016/j.ccr.2004.09.011;
RA Tacconelli A., Farina A.R., Cappabianca L., Desantis G., Tessitore A.,
RA Vetuschi A., Sferra R., Rucci N., Argenti B., Screpanti I., Gulino A.,
RA Mackay A.R.;
RT "TrkA alternative splicing: a regulated tumor-promoting switch in human
RT neuroblastoma.";
RL Cancer Cell 6:347-360(2004).
RN [31]
RP REVIEW ON ROLE IN KIT SIGNALING, AND PHOSPHORYLATION.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [32]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH TEK.
RX PubMed=14665640; DOI=10.1074/jbc.m307456200;
RA Audero E., Cascone I., Maniero F., Napione L., Arese M., Lanfrancone L.,
RA Bussolino F.;
RT "Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates
RT migration and sprouting but not survival of endothelial cells.";
RL J. Biol. Chem. 279:13224-13233(2004).
RN [33]
RP INTERACTION WITH FLT4.
RX PubMed=15102829; DOI=10.1074/jbc.m314015200;
RA Wang J.F., Zhang X., Groopman J.E.;
RT "Activation of vascular endothelial growth factor receptor-3 and its
RT downstream signaling promote cell survival under oxidative stress.";
RL J. Biol. Chem. 279:27088-27097(2004).
RN [34]
RP INTERACTION WITH IRS4.
RX PubMed=15316024; DOI=10.1074/jbc.m404537200;
RA Hinsby A.M., Olsen J.V., Mann M.;
RT "Tyrosine phosphoproteomics of fibroblast growth factor signaling: a role
RT for insulin receptor substrate-4.";
RL J. Biol. Chem. 279:46438-46447(2004).
RN [35]
RP SUBCELLULAR LOCATION (ISOFORM P46SHC).
RX PubMed=14573619; DOI=10.1074/jbc.m307655200;
RA Ventura A., Maccarana M., Raker V.A., Pelicci P.-G.;
RT "A cryptic targeting signal induces isoform-specific localization of p46Shc
RT to mitochondria.";
RL J. Biol. Chem. 279:2299-2306(2004).
RN [36]
RP INTERACTION WITH LRP1.
RX PubMed=15272003; DOI=10.1074/jbc.m407592200;
RA Ranganathan S., Liu C.-X., Migliorini M.M., Von Arnim C.A.F., Peltan I.D.,
RA Mikhailenko I., Hyman B.T., Strickland D.K.;
RT "Serine and threonine phosphorylation of the low density lipoprotein
RT receptor-related protein by protein kinase Calpha regulates endocytosis and
RT association with adaptor molecules.";
RL J. Biol. Chem. 279:40536-40544(2004).
RN [37]
RP PHOSPHORYLATION AT SER-36.
RX PubMed=15837797; DOI=10.1083/jcb.200410041;
RA Smith W.W., Norton D.D., Gorospe M., Jiang H., Nemoto S., Holbrook N.J.,
RA Finkel T., Kusiak J.W.;
RT "Phosphorylation of p66Shc and forkhead proteins mediates Abeta toxicity.";
RL J. Cell Biol. 169:331-339(2005).
RN [38]
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 [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [40]
RP INTERACTION WITH ALK, AND PHOSPHORYLATION.
RX PubMed=17274988; DOI=10.1016/j.febslet.2007.01.039;
RA Degoutin J., Vigny M., Gouzi J.Y.;
RT "ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic
RT outcomes in PC12 cells differentiation.";
RL FEBS Lett. 581:727-734(2007).
RN [41]
RP INTERACTION WITH GAB2.
RX PubMed=19172738; DOI=10.1038/emboj.2008.159;
RA Brummer T., Larance M., Herrera Abreu M.T., Lyons R.J., Timpson P.,
RA Emmerich C.H., Fleuren E.D.G., Lehrbach G.M., Schramek D., Guilhaus M.,
RA James D.E., Daly R.J.;
RT "Phosphorylation-dependent binding of 14-3-3 terminates signalling by the
RT Gab2 docking protein.";
RL EMBO J. 27:2305-2316(2008).
RN [42]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139 AND TYR-427, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [43]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [44]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-427, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [45]
RP INTERACTION WITH CPNE3.
RX PubMed=20010870; DOI=10.1038/onc.2009.456;
RA Heinrich C., Keller C., Boulay A., Vecchi M., Bianchi M., Sack R.,
RA Lienhard S., Duss S., Hofsteenge J., Hynes N.E.;
RT "Copine-III interacts with ErbB2 and promotes tumor cell migration.";
RL Oncogene 29:1598-1610(2010).
RN [46]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [47]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [48]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [49]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, ACETYLATION [LARGE SCALE
RP ANALYSIS] AT MET-1 (ISOFORMS 7 AND P52SHC), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139; TYR-427 AND SER-453, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [51]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 UL46 (MICROBIAL INFECTION).
RX PubMed=23946459; DOI=10.1128/jvi.01702-13;
RA Strunk U., Saffran H.A., Wu F.W., Smiley J.R.;
RT "Role of herpes simplex virus VP11/12 tyrosine-based motifs in binding and
RT activation of the Src family kinase Lck and recruitment of p85, Grb2, and
RT Shc.";
RL J. Virol. 87:11276-11286(2013).
RN [52]
RP INTERACTION WITH PEAK1, INTERACTION WITH PPP1CA, PPP1CC AND PEAK1, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=23846654; DOI=10.1038/nature12308;
RA Zheng Y., Zhang C., Croucher D.R., Soliman M.A., St-Denis N.,
RA Pasculescu A., Taylor L., Tate S.A., Hardy W.R., Colwill K., Dai A.Y.,
RA Bagshaw R., Dennis J.W., Gingras A.C., Daly R.J., Pawson T.;
RT "Temporal regulation of EGF signalling networks by the scaffold protein
RT Shc1.";
RL Nature 499:166-171(2013).
RN [53]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-139, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [54]
RP INTERACTION WITH PEAK1, AND SUBCELLULAR LOCATION.
RX PubMed=35687021; DOI=10.1083/jcb.202108027;
RA Zuidema A., Atherton P., Kreft M., Hoekman L., Bleijerveld O.B.,
RA Nagaraj N., Chen N., Faessler R., Sonnenberg A.;
RT "PEAK1 Y635 phosphorylation regulates cell migration through association
RT with Tensin3 and integrins.";
RL J. Cell Biol. 221:0-0(2022).
RN [55]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 482-583.
RX PubMed=7473762; DOI=10.1006/jmbi.1995.0601;
RA Mikol V., Baumann G., Zurini M.G.M., Hommel U.;
RT "Crystal structure of the SH2 domain from the adaptor protein SHC: a model
RT for peptide binding based on X-ray and NMR data.";
RL J. Mol. Biol. 254:86-95(1995).
RN [56]
RP STRUCTURE BY NMR OF 127-317.
RX PubMed=8524391; DOI=10.1038/378584a0;
RA Zhou M.-M., Ravichandran K.S., Olejniczak E.F., Petros A.M., Meadows R.P.,
RA Sattler M., Harlan J.E., Wade W.S., Burakoff S.J., Fesik S.W.;
RT "Structure and ligand recognition of the phosphotyrosine binding domain of
RT Shc.";
RL Nature 378:584-592(1995).
RN [57]
RP STRUCTURE BY NMR OF 480-583 IN COMPLEX WITH TYROSINE-PHOSPHORYLATED CD3Z.
RX PubMed=7544002; DOI=10.1073/pnas.92.17.7784;
RA Zhou M.-M., Meadows R.P., Logan T.M., Yoon H.S., Wade W.S.,
RA Ravichandran K.S., Burakoff S.J., Fesik S.W.;
RT "Solution structure of the Shc SH2 domain complexed with a tyrosine-
RT phosphorylated peptide from the T-cell receptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:7784-7788(1995).
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. Isoform p46Shc and isoform
CC p52Shc, once phosphorylated, couple activated receptor tyrosine kinases
CC to Ras via the recruitment of the GRB2/SOS complex and are implicated
CC in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and
CC isoform p52Shc 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 (By similarity). Participates in signaling downstream of the
CC angiopoietin receptor TEK/TIE2, and plays a role in the regulation of
CC endothelial cell migration and sprouting angiogenesis. {ECO:0000250,
CC ECO:0000269|PubMed:14665640}.
CC -!- SUBUNIT: Interacts with CPNE3; this interaction may mediate the binding
CC of CPNE3 with ERBB2 (PubMed:20010870). 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 SH2B2. Interacts
CC with phosphorylated LRP1 and IRS4. Interacts with INPP5D/SHIP1 and
CC INPPL1/SHIP2. Interacts with TRIM31. Interacts with PTPN6/SHP (tyrosine
CC phosphorylated). Identified in a complex containing FGFR4, NCAM1, CDH2,
CC PLCG1, FRS2, SRC, SHC1, GAP43 and CTT (By similarity). Interacts with
CC ALK, GAB2, GRB7 and KIT. Interacts with FLT4 (tyrosine-phosphorylated).
CC Interacts with EPHB1 and GRB2; activates the MAPK/ERK cascade to
CC regulate cell migration. Interacts with PDGFRB (tyrosine-
CC phosphorylated). Interacts with ERBB4. Interacts with TEK/TIE2
CC (tyrosine-phosphorylated). Interacts with the Trk receptors NTRK1,
CC NTRK2 and NTRK3; in a phosphotyrosine-dependent manner. Interacts with
CC PTK2/FAK1. Interacts with CEACAM1; this interaction is CEACAM1-
CC phosphorylation-dependent and mediates interaction with EGFR or INSR
CC resulting in decrease coupling of SHC1 to the MAPK3/ERK1-MAPK1/ERK2
CC pathway (By similarity). Interacts (via PID domain) with PEAK1 (when
CC phosphorylated at 'Tyr-1188') (PubMed:23846654, PubMed:35687021). Found
CC in a complex with PPP1CA, PPP1CC, SHC1 and PEAK1 (PubMed:23846654).
CC {ECO:0000250|UniProtKB:P98083, ECO:0000250|UniProtKB:Q5M824,
CC ECO:0000269|PubMed:10194451, ECO:0000269|PubMed:10867024,
CC ECO:0000269|PubMed:11349134, ECO:0000269|PubMed:11980671,
CC ECO:0000269|PubMed:12925710, ECO:0000269|PubMed:14665640,
CC ECO:0000269|PubMed:15102829, ECO:0000269|PubMed:15272003,
CC ECO:0000269|PubMed:15316024, ECO:0000269|PubMed:15488758,
CC ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:19172738,
CC ECO:0000269|PubMed:20010870, ECO:0000269|PubMed:23846654,
CC ECO:0000269|PubMed:35687021, ECO:0000269|PubMed:7537849,
CC ECO:0000269|PubMed:7541045, ECO:0000269|PubMed:7544002,
CC ECO:0000269|PubMed:7559478, ECO:0000269|PubMed:8155326,
CC ECO:0000269|PubMed:8195171, ECO:0000269|PubMed:8874179,
CC ECO:0000269|PubMed:8940081, ECO:0000269|PubMed:9038210,
CC ECO:0000269|PubMed:9233773, ECO:0000269|PubMed:9488479,
CC ECO:0000269|PubMed:9660833}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus 1
CC UL46. {ECO:0000269|PubMed:23946459}.
CC -!- INTERACTION:
CC P29353; P05067: APP; NbExp=5; IntAct=EBI-78835, EBI-77613;
CC P29353; P10275: AR; NbExp=14; IntAct=EBI-78835, EBI-608057;
CC P29353; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-78835, EBI-739580;
CC P29353; P13569: CFTR; NbExp=6; IntAct=EBI-78835, EBI-349854;
CC P29353; P00533: EGFR; NbExp=37; IntAct=EBI-78835, EBI-297353;
CC P29353; P04626: ERBB2; NbExp=11; IntAct=EBI-78835, EBI-641062;
CC P29353; P21860: ERBB3; NbExp=6; IntAct=EBI-78835, EBI-720706;
CC P29353; Q15303: ERBB4; NbExp=2; IntAct=EBI-78835, EBI-80371;
CC P29353; P03372-4: ESR1; NbExp=2; IntAct=EBI-78835, EBI-4309277;
CC P29353; Q13480: GAB1; NbExp=9; IntAct=EBI-78835, EBI-517684;
CC P29353; P62993: GRB2; NbExp=28; IntAct=EBI-78835, EBI-401755;
CC P29353; P06213: INSR; NbExp=2; IntAct=EBI-78835, EBI-475899;
CC P29353; P10721: KIT; NbExp=8; IntAct=EBI-78835, EBI-1379503;
CC P29353; P08581: MET; NbExp=5; IntAct=EBI-78835, EBI-1039152;
CC P29353; Q05209: PTPN12; NbExp=8; IntAct=EBI-78835, EBI-2266035;
CC P29353; Q07889: SOS1; NbExp=2; IntAct=EBI-78835, EBI-297487;
CC P29353; Q62120: Jak2; Xeno; NbExp=2; IntAct=EBI-78835, EBI-646604;
CC P29353; P03495: NS; Xeno; NbExp=2; IntAct=EBI-78835, EBI-2548993;
CC P29353-1; P62993: GRB2; NbExp=3; IntAct=EBI-8160716, EBI-401755;
CC P29353-2; P08069: IGF1R; NbExp=2; IntAct=EBI-1000553, EBI-475981;
CC P29353-2; P28482: MAPK1; NbExp=4; IntAct=EBI-1000553, EBI-959949;
CC P29353-7; Q9UQM7: CAMK2A; NbExp=3; IntAct=EBI-9691288, EBI-1383687;
CC P29353-7; P00533: EGFR; NbExp=4; IntAct=EBI-9691288, EBI-297353;
CC P29353-7; P43405-2: SYK; NbExp=3; IntAct=EBI-9691288, EBI-25892332;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell junction, focal adhesion
CC {ECO:0000269|PubMed:35687021}.
CC -!- SUBCELLULAR LOCATION: [Isoform p46Shc]: Mitochondrion matrix
CC {ECO:0000269|PubMed:14573619}. Note=Localized to the mitochondria
CC matrix. Targeting of isoform p46Shc to mitochondria is mediated by its
CC first 32 amino acids, which behave as a bona fide mitochondrial
CC targeting sequence. Isoform p52Shc and isoform p66Shc, that contain the
CC same sequence but more internally located, display a different
CC subcellular localization.
CC -!- SUBCELLULAR LOCATION: [Isoform p66Shc]: Mitochondrion {ECO:0000250}.
CC Note=In case of oxidative conditions, phosphorylation at 'Ser-36' of
CC isoform p66Shc, leads to mitochondrial accumulation. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6;
CC Name=p66Shc;
CC IsoId=P29353-1; Sequence=Displayed;
CC Name=p52Shc;
CC IsoId=P29353-2; Sequence=VSP_016108;
CC Name=p46Shc;
CC IsoId=P29353-3; Sequence=VSP_016107;
CC Name=5;
CC IsoId=P29353-5; Sequence=VSP_040090, VSP_040091;
CC Name=6;
CC IsoId=P29353-6; Sequence=VSP_040092;
CC Name=7;
CC IsoId=P29353-7; Sequence=VSP_016108, VSP_040092;
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 p46Shc and
CC isoform p52Shc bind to phosphorylated Trk 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 of the Trk receptors. Isoform p46Shc and isoform
CC p52Shc are in turn phosphorylated on three tyrosine residues within the
CC extended proline-rich domain. These phosphotyrosines act as docking
CC site for GRB2 and thereby are involved in Ras activation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by activated epidermal growth factor receptor.
CC Phosphorylated in response to FLT4 and KIT signaling. Isoform p46Shc
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 (By similarity). Tyrosine phosphorylated in response
CC to FLT3 signaling (By similarity). Tyrosine phosphorylated by activated
CC PTK2B/PYK2 (By similarity). Tyrosine phosphorylated by ligand-activated
CC ALK. Tyrosine phosphorylated by ligand-activated PDGFRB. Tyrosine
CC phosphorylated by TEK/TIE2. May be tyrosine phosphorylated by activated
CC PTK2/FAK1; tyrosine phosphorylation was seen in an astrocytoma biopsy,
CC where PTK2/FAK1 kinase activity is high, but not in normal brain
CC tissue. Isoform p52Shc dephosphorylation by PTPN2 may regulate
CC interaction with GRB2. {ECO:0000250, ECO:0000269|PubMed:11980671,
CC ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15526160,
CC ECO:0000269|PubMed:15837797, ECO:0000269|PubMed:17274988,
CC ECO:0000269|PubMed:8195171, ECO:0000269|PubMed:8939605,
CC ECO:0000269|PubMed:9121430, ECO:0000269|PubMed:9148935,
CC ECO:0000269|PubMed:9488479, ECO:0000269|PubMed:9566877}.
CC -!- MISCELLANEOUS: [Isoform p66Shc]: Regulated by epigenetic modifications
CC of its promoter region.
CC -!- MISCELLANEOUS: [Isoform 5]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 6]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 7]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/42287/SHC1";
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DR EMBL; X68148; CAA48251.1; -; mRNA.
DR EMBL; U73377; AAB49972.1; -; mRNA.
DR EMBL; Y09847; CAA70977.1; -; Genomic_DNA.
DR EMBL; AK292143; BAF84832.1; -; mRNA.
DR EMBL; AK315842; BAF98733.1; -; mRNA.
DR EMBL; AB451255; BAG70069.1; -; mRNA.
DR EMBL; AB451379; BAG70193.1; -; mRNA.
DR EMBL; AL451085; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471121; EAW53168.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53169.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53170.1; -; Genomic_DNA.
DR EMBL; CH471121; EAW53171.1; -; Genomic_DNA.
DR EMBL; BC014158; AAH14158.1; -; mRNA.
DR EMBL; BC033925; AAH33925.1; -; mRNA.
DR CCDS; CCDS1076.1; -. [P29353-7]
DR CCDS; CCDS30881.1; -. [P29353-1]
DR CCDS; CCDS44233.1; -. [P29353-6]
DR CCDS; CCDS44234.1; -. [P29353-2]
DR PIR; S25776; S25776.
DR RefSeq; NP_001123512.1; NM_001130040.1. [P29353-6]
DR RefSeq; NP_001123513.1; NM_001130041.1. [P29353-2]
DR RefSeq; NP_001189788.1; NM_001202859.1. [P29353-3]
DR RefSeq; NP_003020.2; NM_003029.4. [P29353-7]
DR RefSeq; NP_892113.4; NM_183001.4. [P29353-1]
DR PDB; 1MIL; X-ray; 2.70 A; A=482-583.
DR PDB; 1N3H; NMR; -; A=111-317.
DR PDB; 1OY2; NMR; -; A=111-317.
DR PDB; 1QG1; NMR; -; I=423-435.
DR PDB; 1SHC; NMR; -; A=127-317.
DR PDB; 1TCE; NMR; -; A=480-583.
DR PDB; 2L1C; NMR; -; A=127-317.
DR PDB; 4JMH; X-ray; 2.41 A; B=344-356.
DR PDB; 4XWX; X-ray; 1.87 A; A=147-311.
DR PDB; 5CZI; X-ray; 2.60 A; B=345-353.
DR PDB; 6DM4; X-ray; 1.90 A; E/G/H=425-431.
DR PDBsum; 1MIL; -.
DR PDBsum; 1N3H; -.
DR PDBsum; 1OY2; -.
DR PDBsum; 1QG1; -.
DR PDBsum; 1SHC; -.
DR PDBsum; 1TCE; -.
DR PDBsum; 2L1C; -.
DR PDBsum; 4JMH; -.
DR PDBsum; 4XWX; -.
DR PDBsum; 5CZI; -.
DR PDBsum; 6DM4; -.
DR AlphaFoldDB; P29353; -.
DR BMRB; P29353; -.
DR SMR; P29353; -.
DR BioGRID; 112361; 347.
DR CORUM; P29353; -.
DR DIP; DIP-699N; -.
DR ELM; P29353; -.
DR IntAct; P29353; 169.
DR MINT; P29353; -.
DR STRING; 9606.ENSP00000401303; -.
DR BindingDB; P29353; -.
DR ChEMBL; CHEMBL5626; -.
DR GlyGen; P29353; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P29353; -.
DR PhosphoSitePlus; P29353; -.
DR SwissPalm; P29353; -.
DR BioMuta; SHC1; -.
DR DMDM; 182676455; -.
DR CPTAC; CPTAC-1366; -.
DR CPTAC; CPTAC-1559; -.
DR EPD; P29353; -.
DR jPOST; P29353; -.
DR MassIVE; P29353; -.
DR MaxQB; P29353; -.
DR PaxDb; 9606-ENSP00000401303; -.
DR PeptideAtlas; P29353; -.
DR ProteomicsDB; 54546; -. [P29353-1]
DR ProteomicsDB; 54547; -. [P29353-2]
DR ProteomicsDB; 54548; -. [P29353-3]
DR ProteomicsDB; 54549; -. [P29353-5]
DR ProteomicsDB; 54550; -. [P29353-6]
DR ProteomicsDB; 54551; -. [P29353-7]
DR Pumba; P29353; -.
DR ABCD; P29353; 9 sequenced antibodies.
DR Antibodypedia; 731; 1348 antibodies from 45 providers.
DR DNASU; 6464; -.
DR Ensembl; ENST00000368445.9; ENSP00000357430.5; ENSG00000160691.19. [P29353-1]
DR Ensembl; ENST00000368450.5; ENSP00000357435.1; ENSG00000160691.19. [P29353-2]
DR Ensembl; ENST00000368453.8; ENSP00000357438.4; ENSG00000160691.19. [P29353-7]
DR Ensembl; ENST00000448116.7; ENSP00000401303.3; ENSG00000160691.19. [P29353-6]
DR GeneID; 6464; -.
DR KEGG; hsa:6464; -.
DR MANE-Select; ENST00000448116.7; ENSP00000401303.3; NM_001130040.2; NP_001123512.1. [P29353-6]
DR UCSC; uc001ffv.4; human. [P29353-1]
DR AGR; HGNC:10840; -.
DR CTD; 6464; -.
DR DisGeNET; 6464; -.
DR GeneCards; SHC1; -.
DR HGNC; HGNC:10840; SHC1.
DR HPA; ENSG00000160691; Low tissue specificity.
DR MalaCards; SHC1; -.
DR MIM; 600560; gene.
DR neXtProt; NX_P29353; -.
DR OpenTargets; ENSG00000160691; -.
DR PharmGKB; PA35746; -.
DR VEuPathDB; HostDB:ENSG00000160691; -.
DR eggNOG; KOG3697; Eukaryota.
DR GeneTree; ENSGT00950000182870; -.
DR HOGENOM; CLU_029532_2_0_1; -.
DR InParanoid; P29353; -.
DR OMA; DKPRMEH; -.
DR OrthoDB; 2903566at2759; -.
DR PhylomeDB; P29353; -.
DR TreeFam; TF315807; -.
DR PathwayCommons; P29353; -.
DR Reactome; R-HSA-1236382; Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants.
DR Reactome; R-HSA-1250196; SHC1 events in ERBB2 signaling.
DR Reactome; R-HSA-1250347; SHC1 events in ERBB4 signaling.
DR Reactome; R-HSA-167044; Signalling to RAS.
DR Reactome; R-HSA-180336; SHC1 events in EGFR signaling.
DR Reactome; R-HSA-201556; Signaling by ALK.
DR Reactome; R-HSA-210993; Tie2 Signaling.
DR Reactome; R-HSA-2424491; DAP12 signaling. [P29353-2]
DR Reactome; R-HSA-2428933; SHC-related events triggered by IGF1R.
DR Reactome; R-HSA-2730905; Role of LAT2/NTAL/LAB on calcium mobilization. [P29353-2]
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation. [P29353-2]
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization. [P29353-2]
DR Reactome; R-HSA-354192; Integrin signaling.
DR Reactome; R-HSA-381038; XBP1(S) activates chaperone genes.
DR Reactome; R-HSA-512988; Interleukin-3, Interleukin-5 and GM-CSF signaling.
DR Reactome; R-HSA-5637810; Constitutive Signaling by EGFRvIII.
DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1.
DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2.
DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3.
DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-74749; Signal attenuation.
DR Reactome; R-HSA-74751; Insulin receptor signalling cascade.
DR Reactome; R-HSA-8851805; MET activates RAS signaling. [P29353-2]
DR Reactome; R-HSA-8853659; RET signaling.
DR Reactome; R-HSA-8983432; Interleukin-15 signaling.
DR Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR Reactome; R-HSA-9020558; Interleukin-2 signaling.
DR Reactome; R-HSA-9026519; Activated NTRK2 signals through RAS.
DR Reactome; R-HSA-9027284; Erythropoietin activates RAS.
DR Reactome; R-HSA-9034864; Activated NTRK3 signals through RAS.
DR Reactome; R-HSA-912526; Interleukin receptor SHC signaling.
DR Reactome; R-HSA-9634285; Constitutive Signaling by Overexpressed ERBB2.
DR Reactome; R-HSA-9634597; GPER1 signaling.
DR Reactome; R-HSA-9664565; Signaling by ERBB2 KD Mutants.
DR Reactome; R-HSA-9665348; Signaling by ERBB2 ECD mutants.
DR Reactome; R-HSA-9665686; Signaling by ERBB2 TMD/JMD mutants.
DR Reactome; R-HSA-9674555; Signaling by CSF3 (G-CSF).
DR Reactome; R-HSA-9680350; Signaling by CSF1 (M-CSF) in myeloid cells.
DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants.
DR SignaLink; P29353; -.
DR SIGNOR; P29353; -.
DR BioGRID-ORCS; 6464; 53 hits in 1161 CRISPR screens.
DR ChiTaRS; SHC1; human.
DR EvolutionaryTrace; P29353; -.
DR GeneWiki; SHC1; -.
DR GenomeRNAi; 6464; -.
DR Pharos; P29353; Tchem.
DR PRO; PR:P29353; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P29353; Protein.
DR Bgee; ENSG00000160691; Expressed in stromal cell of endometrium and 206 other cell types or tissues.
DR ExpressionAtlas; P29353; baseline and differential.
DR Genevisible; P29353; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0070435; C:Shc-EGFR complex; ISS:BHF-UCL.
DR GO; GO:0046875; F:ephrin receptor binding; IPI:UniProtKB.
DR GO; GO:0048408; F:epidermal growth factor binding; IEA:Ensembl.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISS:BHF-UCL.
DR GO; GO:0005158; F:insulin receptor binding; IPI:UniProtKB.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0005168; F:neurotrophin TRKA receptor binding; IPI:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; TAS:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0005068; F:transmembrane receptor protein tyrosine kinase adaptor activity; TAS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0098609; P:cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0042742; P:defense response to bacterium; IMP:CAFA.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IGI:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:CAFA.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IMP:CAFA.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISS:BHF-UCL.
DR GO; GO:0071864; P:positive regulation of cell proliferation in bone marrow; IGI:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IMP:CAFA.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:CAFA.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0090322; P:regulation of superoxide metabolic process; IGI:BHF-UCL.
DR CDD; cd01209; PTB_Shc; 1.
DR CDD; cd09925; SH2_SHC; 1.
DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1.
DR Gene3D; 3.30.505.10; SH2 domain; 1.
DR IDEAL; IID00511; -.
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; IPR035676; SHC_SH2.
DR PANTHER; PTHR10337; SHC TRANSFORMING PROTEIN; 1.
DR PANTHER; PTHR10337:SF2; SHC-TRANSFORMING PROTEIN 1; 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; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR PROSITE; PS01179; PID; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative promoter usage;
KW Alternative splicing; Angiogenesis; Cell junction; Cytoplasm;
KW Growth regulation; Host-virus interaction; Mitochondrion; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT CHAIN 1..583
FT /note="SHC-transforming protein 1"
FT /id="PRO_0000097731"
FT DOMAIN 156..339
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 488..579
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..92
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..487
FT /note="CH1"
FT REGION 372..415
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:0007744|PubMed:22814378"
FT MOD_RES 36
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15837797"
FT MOD_RES 139
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 154
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P98083"
FT MOD_RES 349
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:8939605,
FT ECO:0000269|PubMed:9121430, ECO:0000269|PubMed:9566877"
FT MOD_RES 350
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:8939605,
FT ECO:0000269|PubMed:9121430, ECO:0000269|PubMed:9566877"
FT MOD_RES 427
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:9121430,
FT ECO:0000269|PubMed:9566877, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 453
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..214
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_040090"
FT VAR_SEQ 1..155
FT /note="Missing (in isoform p46Shc)"
FT /evidence="ECO:0000303|PubMed:1623525"
FT /id="VSP_016107"
FT VAR_SEQ 1..110
FT /note="Missing (in isoform p52Shc and isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:1623525"
FT /id="VSP_016108"
FT VAR_SEQ 215..221
FT /note="PLSSILG -> MSLCHRW (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_040091"
FT VAR_SEQ 417
FT /note="P -> PA (in isoform 7 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:19054851"
FT /id="VSP_040092"
FT VARIANT 205
FT /note="A -> V (in dbSNP:rs8191981)"
FT /id="VAR_042428"
FT VARIANT 410
FT /note="M -> V (in dbSNP:rs8191979)"
FT /id="VAR_051353"
FT MUTAGEN 349
FT /note="Y->F: Alters interaction with GRB2; isoform p52Shc
FT (in vitro)."
FT /evidence="ECO:0000269|PubMed:9488479"
FT MUTAGEN 427
FT /note="Y->F: No effect on interaction with GRB2; isoform
FT p52Shc (in vitro)."
FT /evidence="ECO:0000269|PubMed:9488479"
FT CONFLICT 2
FT /note="D -> N (in Ref. 3; CAA70977)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="L -> M (in Ref. 3; CAA70977)"
FT /evidence="ECO:0000305"
FT CONFLICT 38
FT /note="S -> P (in Ref. 3; CAA70977)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="V -> D (in Ref. 2; AAB49972)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="D -> E (in Ref. 2; AAB49972)"
FT /evidence="ECO:0000305"
FT CONFLICT 430
FT /note="V -> A (in Ref. 5; BAG70069/BAG70193)"
FT /evidence="ECO:0000305"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:1N3H"
FT STRAND 142..145
FT /evidence="ECO:0007829|PDB:1SHC"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:1N3H"
FT HELIX 152..156
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 160..172
FT /evidence="ECO:0007829|PDB:4XWX"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:4XWX"
FT HELIX 181..198
FT /evidence="ECO:0007829|PDB:4XWX"
FT HELIX 200..202
FT /evidence="ECO:0007829|PDB:1OY2"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:1SHC"
FT TURN 215..219
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 220..224
FT /evidence="ECO:0007829|PDB:4XWX"
FT TURN 226..229
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 230..236
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 238..245
FT /evidence="ECO:0007829|PDB:4XWX"
FT TURN 246..249
FT /evidence="ECO:0007829|PDB:1N3H"
FT STRAND 251..256
FT /evidence="ECO:0007829|PDB:4XWX"
FT HELIX 257..259
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:4XWX"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 273..280
FT /evidence="ECO:0007829|PDB:4XWX"
FT TURN 281..283
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 284..291
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:1N3H"
FT HELIX 296..310
FT /evidence="ECO:0007829|PDB:4XWX"
FT STRAND 311..314
FT /evidence="ECO:0007829|PDB:1N3H"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:5CZI"
FT TURN 483..485
FT /evidence="ECO:0007829|PDB:1MIL"
FT STRAND 487..489
FT /evidence="ECO:0007829|PDB:1TCE"
FT HELIX 495..499
FT /evidence="ECO:0007829|PDB:1MIL"
FT STRAND 507..512
FT /evidence="ECO:0007829|PDB:1MIL"
FT STRAND 514..516
FT /evidence="ECO:0007829|PDB:1TCE"
FT STRAND 518..526
FT /evidence="ECO:0007829|PDB:1MIL"
FT STRAND 529..536
FT /evidence="ECO:0007829|PDB:1MIL"
FT STRAND 540..543
FT /evidence="ECO:0007829|PDB:1MIL"
FT STRAND 548..551
FT /evidence="ECO:0007829|PDB:1MIL"
FT HELIX 552..562
FT /evidence="ECO:0007829|PDB:1MIL"
FT STRAND 566..568
FT /evidence="ECO:0007829|PDB:1MIL"
FT STRAND 571..573
FT /evidence="ECO:0007829|PDB:1MIL"
FT MOD_RES P29353-2:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES P29353-7:1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
SQ SEQUENCE 583 AA; 62822 MW; 7EFA5CB185A548D1 CRC64;
MDLLPPKPKY NPLRNESLSS LEEGASGSTP PEELPSPSAS SLGPILPPLP GDDSPTTLCS
FFPRMSNLRL ANPAGGRPGS KGEPGRAADD GEGIVGAAMP DSGPLPLLQD 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 GAAPGAARPT APNAQTPSHL GATLPVGQPV GGDPEVRKQM PPPPPCPGRE
LFDDPSYVNV QNLDKARQAV GGAGPPNPAI NGSAPRDLFD MKPFEDALRV PPPPQSVSMA
EQLRGEPWFH GKLSRREAEA LLQLNGDFLV RESTTTPGQY VLTGLQSGQP KHLLLVDPEG
VVRTKDHRFE SVSHLISYHM DNHLPIISAG SELCLQQPVE RKL
//
