GRB10_HUMAN
ID GRB10_HUMAN Reviewed; 594 AA.
AC Q13322; A4D258; A7VJ95; A8K0E6; D3DVM9; O00427; O00701; O75222; Q92606;
AC Q92907; Q92948;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 2.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Growth factor receptor-bound protein 10;
DE AltName: Full=GRB10 adapter protein;
DE AltName: Full=Insulin receptor-binding protein Grb-IR;
GN Name=GRB10; Synonyms=GRBIR, KIAA0207;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=7479769; DOI=10.1073/pnas.92.22.10287;
RA Liu F., Roth R.A.;
RT "Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor
RT and inhibits its function.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:10287-10291(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Skeletal muscle;
RX PubMed=8798417; DOI=10.1074/jbc.271.37.22506;
RA O'Neill T.J., Rose D.W., Pillay T.S., Hotta K., Olefsky J.M.,
RA Gustafson T.A.;
RT "Interaction of a GRB-IR splice variant (a human GRB10 homolog) with the
RT insulin and insulin-like growth factor I receptors. Evidence for a role in
RT mitogenic signaling.";
RL J. Biol. Chem. 271:22506-22513(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum, and Skeletal muscle;
RX PubMed=9006901; DOI=10.1074/jbc.272.5.2659;
RA Frantz J.D., Giorgetti-Peraldi S., Ottinger E.A., Shoelson S.E.;
RT "Human GRB-IR-beta/GRB10: splice variants of an insulin and growth factor
RT receptor-binding protein with PH and SH2 domains.";
RL J. Biol. Chem. 272:2659-2667(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=9360986; DOI=10.1074/jbc.272.46.29104;
RA Dong L.Q., Du H., Porter S.G., Kolakowski L.F. Jr., Lee A.V.,
RA Mandarino L.J., Fan J., Yee D., Liu F.;
RT "Cloning, chromosome localization, expression, and characterization of an
RT Src homology 2 and pleckstrin homology domain-containing insulin receptor
RT binding protein hGrb10gamma.";
RL J. Biol. Chem. 272:29104-29112(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=9553107; DOI=10.1074/jbc.273.17.10475;
RA Nantel A., Mohammad-Ali K., Sherk J., Posner B.I., Thomas D.Y.;
RT "Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases.";
RL J. Biol. Chem. 273:10475-10484(1998).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PHOSPHORYLATION AT TYR-67.
RX PubMed=9753425; DOI=10.1046/j.1365-2443.1998.00201.x;
RA Mano H., Ohya K., Miyazato A., Yamashita Y., Ogawa W., Inazawa J.,
RA Ikeda U., Shimada K., Hatake K., Kasuga M., Ozawa K., Kajigaya S.;
RT "Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase.";
RL Genes Cells 3:431-441(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORM 3).
RX PubMed=9881709; DOI=10.1038/sj.onc.1202226;
RA Angrist M., Bolk S., Bentley K., Nallasamy S., Halushka M.K.,
RA Chakravarti A.;
RT "Genomic structure of the gene for the SH2 and pleckstrin homology domain-
RT containing protein GRB10 and evaluation of its role in Hirschsprung
RT disease.";
RL Oncogene 17:3065-3070(1998).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING, AND
RP IMPRINTING.
RC TISSUE=Testis;
RX PubMed=10861285; DOI=10.1093/hmg/9.11.1587;
RA Blagitko N., Mergenthaler S., Schulz U., Wollmann H.A., Craigen W.,
RA Eggermann T., Ropers H.-H., Kalscheuer V.M.;
RT "Human GRB10 is imprinted and expressed from the paternal and maternal
RT allele in a highly tissue- and isoform-specific fashion.";
RL Hum. Mol. Genet. 9:1587-1595(2000).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Bone marrow;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Cerebellum;
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [13]
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 [14]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
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 [15]
RP PROTEIN SEQUENCE OF 415-425, PHOSPHORYLATION AT SER-150; SER-418 AND
RP SER-476, AND MUTAGENESIS OF SER-104; SER-150; SER-418 AND SER-476.
RX PubMed=15952796; DOI=10.1021/bi050413i;
RA Langlais P., Wang C., Dong L.Q., Carroll C.A., Weintraub S.T., Liu F.;
RT "Phosphorylation of Grb10 by mitogen-activated protein kinase:
RT identification of Ser150 and Ser476 of human Grb10zeta as major
RT phosphorylation sites.";
RL Biochemistry 44:8890-8897(2005).
RN [16]
RP TISSUE SPECIFICITY, AND IMPRINTING.
RX PubMed=11527390; DOI=10.1006/bbrc.2001.5500;
RA McCann J.A., Zheng H., Islam A., Goodyer C.G., Polychronakos C.;
RT "Evidence against GRB10 as the gene responsible for Silver-Russell
RT syndrome.";
RL Biochem. Biophys. Res. Commun. 286:943-948(2001).
RN [17]
RP FUNCTION, INTERACTION WITH INSR, AND MUTAGENESIS OF ARG-520.
RX PubMed=12493740; DOI=10.1074/jbc.m208518200;
RA Wick K.R., Werner E.D., Langlais P., Ramos F.J., Dong L.Q., Shoelson S.E.,
RA Liu F.;
RT "Grb10 inhibits insulin-stimulated insulin receptor substrate (IRS)-
RT phosphatidylinositol 3-kinase/Akt signaling pathway by disrupting the
RT association of IRS-1/IRS-2 with the insulin receptor.";
RL J. Biol. Chem. 278:8460-8467(2003).
RN [18]
RP INTERACTION WITH MAP3K14, AND IDENTIFICATION IN A COMPLEX WITH EGFR AND
RP ERBB2.
RX PubMed=12853971; DOI=10.1038/sj.onc.1206532;
RA Chen D., Xu L.G., Chen L., Li L., Zhai Z., Shu H.B.;
RT "NIK is a component of the EGF/heregulin receptor signaling complexes.";
RL Oncogene 22:4348-4355(2003).
RN [19]
RP FUNCTION, INTERACTION WITH NEDD4, AND MUTAGENESIS OF PRO-136; PRO-139;
RP PRO-141 AND ARG-520.
RX PubMed=15060076; DOI=10.1074/jbc.m311802200;
RA Murdaca J., Treins C., Monthouel-Kartmann M.N., Pontier-Bres R., Kumar S.,
RA Van Obberghen E., Giorgetti-Peraldi S.;
RT "Grb10 prevents Nedd4-mediated vascular endothelial growth factor receptor-
RT 2 degradation.";
RL J. Biol. Chem. 279:26754-26761(2004).
RN [20]
RP INTERACTION WITH YWHAE, PHOSPHORYLATION AT SER-428, AND MUTAGENESIS OF
RP SER-134 AND SER-428.
RX PubMed=15722337; DOI=10.1074/jbc.m501477200;
RA Urschel S., Bassermann F., Bai R.Y., Munch S., Peschel C., Duyster J.;
RT "Phosphorylation of grb10 regulates its interaction with 14-3-3.";
RL J. Biol. Chem. 280:16987-16993(2005).
RN [21]
RP ROLE IN THE UBIQUITINATION OF INSR.
RX PubMed=16434550; DOI=10.1152/ajpendo.00609.2005;
RA Ramos F.J., Langlais P.R., Hu D., Dong L.Q., Liu F.;
RT "Grb10 mediates insulin-stimulated degradation of the insulin receptor: a
RT mechanism of negative regulation.";
RL Am. J. Physiol. 290:E1262-E1266(2006).
RN [22]
RP FUNCTION.
RX PubMed=17376403; DOI=10.1016/j.bbrc.2007.03.019;
RA Tezuka N., Brown A.M., Yanagawa S.;
RT "GRB10 binds to LRP6, the Wnt co-receptor and inhibits canonical Wnt
RT signaling pathway.";
RL Biochem. Biophys. Res. Commun. 356:648-654(2007).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-418, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104 AND SER-418, 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 [25]
RP IMPRINTING.
RX PubMed=19487367; DOI=10.1093/hmg/ddp248;
RA Monk D., Arnaud P., Frost J., Hills F.A., Stanier P., Feil R., Moore G.E.;
RT "Reciprocal imprinting of human GRB10 in placental trophoblast and brain:
RT evolutionary conservation of reversed allelic expression.";
RL Hum. Mol. Genet. 18:3066-3074(2009).
RN [26]
RP IDENTIFICATION BY 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 [27]
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 [28]
RP PHOSPHORYLATION AT SER-150; SER-428 AND SER-476 BY MTOR, AND ACTIVITY
RP REGULATION.
RX PubMed=21659604; DOI=10.1126/science.1199498;
RA Hsu P.P., Kang S.A., Rameseder J., Zhang Y., Ottina K.A., Lim D.,
RA Peterson T.R., Choi Y., Gray N.S., Yaffe M.B., Marto J.A., Sabatini D.M.;
RT "The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated
RT inhibition of growth factor signaling.";
RL Science 332:1317-1322(2011).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-104 AND SER-418, 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 [30]
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 487-591.
RX PubMed=12551896; DOI=10.1074/jbc.m212026200;
RA Stein E.G., Ghirlando R., Hubbard S.R.;
RT "Structural basis for dimerization of the Grb10 Src homology 2 domain.
RT Implications for ligand specificity.";
RL J. Biol. Chem. 278:13257-13264(2003).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 164-415, INTERACTION WITH NRAS AND
RP PHOSPHOINOSITIDES, AND MUTAGENESIS OF LYS-300; LYS-305; LYS-308 AND
RP ASN-355.
RX PubMed=19648926; DOI=10.1038/nsmb.1642;
RA Depetris R.S., Wu J., Hubbard S.R.;
RT "Structural and functional studies of the Ras-associating and pleckstrin-
RT homology domains of Grb10 and Grb14.";
RL Nat. Struct. Mol. Biol. 16:833-839(2009).
RN [32]
RP ERRATUM OF PUBMED:19648926.
RA Depetris R.S., Wu J., Hubbard S.R.;
RL Nat. Struct. Mol. Biol. 16:1331-1331(2009).
RN [33]
RP VARIANT SER-95, AND IMPRINTING.
RX PubMed=10856193; DOI=10.1086/302997;
RA Yoshihashi H., Maeyama K., Kosaki R., Ogata T., Tsukahara M., Goto Y.,
RA Hata J., Matsuo N., Smith R.J., Kosaki K.;
RT "Imprinting of human GRB10 and its mutations in two patients with Russell-
RT Silver syndrome.";
RL Am. J. Hum. Genet. 67:476-482(2000).
CC -!- FUNCTION: Adapter protein which modulates coupling of a number of cell
CC surface receptor kinases with specific signaling pathways. Binds to,
CC and suppress signals from, activated receptors tyrosine kinases,
CC including the insulin (INSR) and insulin-like growth factor (IGF1R)
CC receptors. The inhibitory effect can be achieved by 2 mechanisms:
CC interference with the signaling pathway and increased receptor
CC degradation. Delays and reduces AKT1 phosphorylation in response to
CC insulin stimulation. Blocks association between INSR and IRS1 and IRS2
CC and prevents insulin-stimulated IRS1 and IRS2 tyrosine phosphorylation.
CC Recruits NEDD4 to IGF1R, leading to IGF1R ubiquitination, increased
CC internalization and degradation by both the proteasomal and lysosomal
CC pathways. May play a role in mediating insulin-stimulated
CC ubiquitination of INSR, leading to proteasomal degradation. Negatively
CC regulates Wnt signaling by interacting with LRP6 intracellular portion
CC and interfering with the binding of AXIN1 to LRP6. Positive regulator
CC of the KDR/VEGFR-2 signaling pathway. May inhibit NEDD4-mediated
CC degradation of KDR/VEGFR-2. {ECO:0000269|PubMed:12493740,
CC ECO:0000269|PubMed:15060076, ECO:0000269|PubMed:16434550,
CC ECO:0000269|PubMed:17376403}.
CC -!- ACTIVITY REGULATION: Phosphorylation by mTORC1 stabilizes and activates
CC GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-
CC dependent signaling. {ECO:0000269|PubMed:21659604}.
CC -!- SUBUNIT: Interacts with ligand-activated tyrosine kinase receptors,
CC including FGFR1, INSR, IGF1R, MET and PDGFRB in a phosphotyrosine-
CC dependent manner through the SH2 domain (By similarity). Poorly binds
CC to the EGFR (By similarity). Directly interacts with MAP3K14/NIK and is
CC recruited to the EGFR-ERBB2 complex. Interacts with GIGYF1/PERQ1 and
CC GIGYF2/TNRC15 (By similarity). When unphosphorylated, interacts with
CC AKT1 and when phosphorylated with YWHAE/14-3-3 epsilon. Interacts with
CC NEDD4. Interacts with LRP6, thus interfering with the binding of AXIN1
CC to LRP6 (By similarity). Binds to activated NRAS. {ECO:0000250,
CC ECO:0000269|PubMed:12493740, ECO:0000269|PubMed:12853971,
CC ECO:0000269|PubMed:15060076, ECO:0000269|PubMed:15722337,
CC ECO:0000269|PubMed:19648926}.
CC -!- INTERACTION:
CC Q13322; P00533: EGFR; NbExp=3; IntAct=EBI-80275, EBI-297353;
CC Q13322; P54762: EPHB1; NbExp=2; IntAct=EBI-80275, EBI-80252;
CC Q13322; P36888: FLT3; NbExp=6; IntAct=EBI-80275, EBI-3946257;
CC Q13322; P06213: INSR; NbExp=3; IntAct=EBI-80275, EBI-475899;
CC Q13322; P27986: PIK3R1; NbExp=2; IntAct=EBI-80275, EBI-79464;
CC Q13322; Q9UKA8: RCAN3; NbExp=3; IntAct=EBI-80275, EBI-9091952;
CC Q13322-3; Q13322-3: GRB10; NbExp=2; IntAct=EBI-15796145, EBI-15796145;
CC Q13322-4; Q16613: AANAT; NbExp=3; IntAct=EBI-12353035, EBI-7451846;
CC Q13322-4; Q86V38: ATN1; NbExp=3; IntAct=EBI-12353035, EBI-11954292;
CC Q13322-4; P51451: BLK; NbExp=3; IntAct=EBI-12353035, EBI-2105445;
CC Q13322-4; P02489: CRYAA; NbExp=3; IntAct=EBI-12353035, EBI-6875961;
CC Q13322-4; O95363: FARS2; NbExp=3; IntAct=EBI-12353035, EBI-2513774;
CC Q13322-4; P01100: FOS; NbExp=3; IntAct=EBI-12353035, EBI-852851;
CC Q13322-4; P50440: GATM; NbExp=3; IntAct=EBI-12353035, EBI-2552594;
CC Q13322-4; P14136: GFAP; NbExp=3; IntAct=EBI-12353035, EBI-744302;
CC Q13322-4; Q13322-4: GRB10; NbExp=3; IntAct=EBI-12353035, EBI-12353035;
CC Q13322-4; P62993: GRB2; NbExp=3; IntAct=EBI-12353035, EBI-401755;
CC Q13322-4; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-12353035, EBI-1055254;
CC Q13322-4; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-12353035, EBI-2556193;
CC Q13322-4; O00505: KPNA3; NbExp=3; IntAct=EBI-12353035, EBI-358297;
CC Q13322-4; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-12353035, EBI-11742507;
CC Q13322-4; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-12353035, EBI-10271199;
CC Q13322-4; Q13153: PAK1; NbExp=3; IntAct=EBI-12353035, EBI-1307;
CC Q13322-4; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-12353035, EBI-79165;
CC Q13322-4; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-12353035, EBI-9090795;
CC Q13322-4; P12931: SRC; NbExp=3; IntAct=EBI-12353035, EBI-621482;
CC Q13322-4; Q8WW24: TEKT4; NbExp=3; IntAct=EBI-12353035, EBI-750487;
CC Q13322-4; Q96N21: TEPSIN; NbExp=3; IntAct=EBI-12353035, EBI-11139477;
CC Q13322-4; Q13470-2: TNK1; NbExp=3; IntAct=EBI-12353035, EBI-11018037;
CC Q13322-4; P42681: TXK; NbExp=3; IntAct=EBI-12353035, EBI-7877438;
CC Q13322-4; P61981: YWHAG; NbExp=3; IntAct=EBI-12353035, EBI-359832;
CC Q13322-4; Q96E35: ZMYND19; NbExp=3; IntAct=EBI-12353035, EBI-746595;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Note=When complexed with
CC NEDD4 and IGF1R, follows IGF1R internalization, remaining associated
CC with early endosomes. Uncouples from IGF1R-containing endosomes before
CC the sorting of the receptor to the lysosomal compartment (By
CC similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist, many of which involve
CC splicing of 5' non-coding exons.;
CC Name=3; Synonyms=Zeta;
CC IsoId=Q13322-1; Sequence=Displayed;
CC Name=1; Synonyms=Beta;
CC IsoId=Q13322-2; Sequence=VSP_001843;
CC Name=2; Synonyms=Gamma, Beta, SV-1;
CC IsoId=Q13322-3; Sequence=VSP_001842;
CC Name=4; Synonyms=Epsilon;
CC IsoId=Q13322-4; Sequence=VSP_038784;
CC -!- TISSUE SPECIFICITY: Widely expressed in fetal and adult tissues,
CC including fetal and postnatal liver, lung, kidney, skeletal muscle,
CC heart, spleen, skin and brain. {ECO:0000269|PubMed:11527390}.
CC -!- DOMAIN: The PH domain binds relatively non-specifically to several
CC phosphoinositides, including PI(5)P, PI(4,5)P2, PI(3,4)P2 and
CC PI(3,4,5)P3, with modest affinities.
CC -!- PTM: Phosphorylated on serine residues upon EGF, FGF and PDGF
CC stimulation (By similarity). Phosphorylated at Tyr-67 by TEC.
CC {ECO:0000250, ECO:0000269|PubMed:15722337, ECO:0000269|PubMed:15952796,
CC ECO:0000269|PubMed:21659604, ECO:0000269|PubMed:9753425}.
CC -!- MISCELLANEOUS: The GRB10 locus is imprinted. During embryonic
CC development, the expression in the brain and spinal cord is from the
CC paternal allele, while in placental villous trophoblasts and skeletal
CC muscle, it is from the maternal one. Expression is biallelic in most
CC other tissues. Paternal expression in the brain is maintained
CC throughout adulthood. Imprinting often is isoform-specific.
CC -!- MISCELLANEOUS: GRB10 is unlikely to be responsible for Silver-Russell
CC syndrome (SRS).
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13198.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GRB10ID278.html";
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DR EMBL; U34355; AAA88819.1; -; mRNA.
DR EMBL; U66065; AAC50671.1; -; mRNA.
DR EMBL; U69276; AAB08431.1; -; mRNA.
DR EMBL; AF001534; AAB81134.1; -; mRNA.
DR EMBL; AF000017; AAC19748.1; -; mRNA.
DR EMBL; AB000731; BAF76353.1; -; mRNA.
DR EMBL; AJ271366; CAB96542.1; -; mRNA.
DR EMBL; D86962; BAA13198.2; ALT_INIT; mRNA.
DR EMBL; AK289511; BAF82200.1; -; mRNA.
DR EMBL; AF073378; AAC83655.1; -; Genomic_DNA.
DR EMBL; AF073363; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073364; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073365; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073366; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073367; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073368; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073369; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073370; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073371; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073372; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073373; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073374; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073375; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073376; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073377; AAC83655.1; JOINED; Genomic_DNA.
DR EMBL; AF073378; AAC83654.1; -; Genomic_DNA.
DR EMBL; AF073363; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073364; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073365; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073366; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073367; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073368; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073369; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073371; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073372; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073373; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073374; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073375; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073376; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AF073377; AAC83654.1; JOINED; Genomic_DNA.
DR EMBL; AC005153; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH236955; EAL23897.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW60964.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW60965.1; -; Genomic_DNA.
DR EMBL; CH471128; EAW60967.1; -; Genomic_DNA.
DR EMBL; BC024285; AAH24285.1; -; mRNA.
DR CCDS; CCDS43582.1; -. [Q13322-1]
DR CCDS; CCDS43583.1; -. [Q13322-3]
DR CCDS; CCDS47586.1; -. [Q13322-2]
DR CCDS; CCDS87503.1; -. [Q13322-3]
DR PIR; I39175; I39175.
DR RefSeq; NP_001001549.1; NM_001001549.2. [Q13322-2]
DR RefSeq; NP_001001550.1; NM_001001550.2. [Q13322-3]
DR RefSeq; NP_001001555.1; NM_001001555.2. [Q13322-3]
DR RefSeq; NP_005302.3; NM_005311.4.
DR RefSeq; XP_011513606.1; XM_011515304.1.
DR RefSeq; XP_011513614.1; XM_011515312.2.
DR RefSeq; XP_011513618.1; XM_011515316.1. [Q13322-3]
DR RefSeq; XP_016867534.1; XM_017012045.1. [Q13322-3]
DR RefSeq; XP_016867535.1; XM_017012046.1. [Q13322-1]
DR RefSeq; XP_016867552.1; XM_017012063.1. [Q13322-3]
DR RefSeq; XP_016867553.1; XM_017012064.1. [Q13322-3]
DR RefSeq; XP_016867554.1; XM_017012065.1. [Q13322-3]
DR RefSeq; XP_016867555.1; XM_017012066.1.
DR RefSeq; XP_016867556.1; XM_017012067.1. [Q13322-3]
DR RefSeq; XP_016867557.1; XM_017012068.1. [Q13322-3]
DR PDB; 1NRV; X-ray; 1.65 A; A/B=487-591.
DR PDB; 3HK0; X-ray; 2.60 A; A/B=164-415.
DR PDBsum; 1NRV; -.
DR PDBsum; 3HK0; -.
DR AlphaFoldDB; Q13322; -.
DR SMR; Q13322; -.
DR BioGRID; 109144; 150.
DR DIP; DIP-31657N; -.
DR ELM; Q13322; -.
DR IntAct; Q13322; 122.
DR MINT; Q13322; -.
DR STRING; 9606.ENSP00000381793; -.
DR BindingDB; Q13322; -.
DR ChEMBL; CHEMBL3621028; -.
DR GlyGen; Q13322; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13322; -.
DR PhosphoSitePlus; Q13322; -.
DR BioMuta; GRB10; -.
DR DMDM; 6166186; -.
DR CPTAC; CPTAC-1247; -.
DR EPD; Q13322; -.
DR jPOST; Q13322; -.
DR MassIVE; Q13322; -.
DR MaxQB; Q13322; -.
DR PaxDb; Q13322; -.
DR PeptideAtlas; Q13322; -.
DR PRIDE; Q13322; -.
DR ProteomicsDB; 59307; -. [Q13322-1]
DR ProteomicsDB; 59308; -. [Q13322-2]
DR ProteomicsDB; 59309; -. [Q13322-3]
DR ProteomicsDB; 59310; -. [Q13322-4]
DR Antibodypedia; 27751; 495 antibodies from 37 providers.
DR DNASU; 2887; -.
DR Ensembl; ENST00000335866.7; ENSP00000338543.3; ENSG00000106070.20. [Q13322-3]
DR Ensembl; ENST00000357271.9; ENSP00000349818.5; ENSG00000106070.20. [Q13322-2]
DR Ensembl; ENST00000398810.6; ENSP00000381790.2; ENSG00000106070.20. [Q13322-3]
DR Ensembl; ENST00000398812.6; ENSP00000381793.2; ENSG00000106070.20. [Q13322-1]
DR Ensembl; ENST00000401949.6; ENSP00000385770.1; ENSG00000106070.20. [Q13322-1]
DR Ensembl; ENST00000402497.6; ENSP00000385748.1; ENSG00000106070.20. [Q13322-3]
DR Ensembl; ENST00000402578.5; ENSP00000385189.1; ENSG00000106070.20. [Q13322-3]
DR Ensembl; ENST00000403097.6; ENSP00000385544.2; ENSG00000106070.20. [Q13322-3]
DR Ensembl; ENST00000406641.5; ENSP00000385366.1; ENSG00000106070.20. [Q13322-3]
DR Ensembl; ENST00000407526.6; ENSP00000385046.1; ENSG00000106070.20. [Q13322-3]
DR Ensembl; ENST00000643299.1; ENSP00000496245.1; ENSG00000106070.20. [Q13322-3]
DR Ensembl; ENST00000645075.2; ENSP00000495341.2; ENSG00000106070.20. [Q13322-3]
DR GeneID; 2887; -.
DR KEGG; hsa:2887; -.
DR MANE-Select; ENST00000401949.6; ENSP00000385770.1; NM_001350814.2; NP_001337743.1.
DR UCSC; uc003tph.4; human. [Q13322-1]
DR CTD; 2887; -.
DR DisGeNET; 2887; -.
DR GeneCards; GRB10; -.
DR HGNC; HGNC:4564; GRB10.
DR HPA; ENSG00000106070; Low tissue specificity.
DR MIM; 601523; gene.
DR neXtProt; NX_Q13322; -.
DR OpenTargets; ENSG00000106070; -.
DR PharmGKB; PA28960; -.
DR VEuPathDB; HostDB:ENSG00000106070; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000155909; -.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; Q13322; -.
DR OMA; QXRCLED; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; Q13322; -.
DR TreeFam; TF317511; -.
DR PathwayCommons; Q13322; -.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR Reactome; R-HSA-74713; IRS activation.
DR Reactome; R-HSA-74749; Signal attenuation.
DR Reactome; R-HSA-74751; Insulin receptor signalling cascade.
DR Reactome; R-HSA-8853659; RET signaling.
DR Reactome; R-HSA-9607240; FLT3 Signaling.
DR Reactome; R-HSA-9648895; Response of EIF2AK1 (HRI) to heme deficiency.
DR SignaLink; Q13322; -.
DR SIGNOR; Q13322; -.
DR BioGRID-ORCS; 2887; 16 hits in 1080 CRISPR screens.
DR ChiTaRS; GRB10; human.
DR EvolutionaryTrace; Q13322; -.
DR GeneWiki; GRB10; -.
DR GenomeRNAi; 2887; -.
DR Pharos; Q13322; Tbio.
DR PRO; PR:Q13322; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q13322; protein.
DR Bgee; ENSG00000106070; Expressed in body of pancreas and 195 other tissues.
DR ExpressionAtlas; Q13322; baseline and differential.
DR Genevisible; Q13322; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005158; F:insulin receptor binding; ISS:BHF-UCL.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010467; P:gene expression; 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:0046325; P:negative regulation of glucose import; ISS:BHF-UCL.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISS:BHF-UCL.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IEA:Ensembl.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISS:BHF-UCL.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0032868; P:response to insulin; ISS:BHF-UCL.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; IEA:Ensembl.
DR CDD; cd01259; PH_APBB1IP; 1.
DR CDD; cd10415; SH2_Grb10; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR015042; BPS-dom.
DR InterPro; IPR039664; GRB/APBB1IP.
DR InterPro; IPR035036; Grb10.
DR InterPro; IPR035037; Grb10_SH2.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR039665; PH_APBB1IP.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR11243; PTHR11243; 1.
DR PANTHER; PTHR11243:SF4; PTHR11243:SF4; 1.
DR Pfam; PF08947; BPS; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00788; RA; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00233; PH; 1.
DR SMART; SM00314; RA; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..594
FT /note="Growth factor receptor-bound protein 10"
FT /id="PRO_0000150346"
FT DOMAIN 166..250
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 290..399
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 493..574
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 18..41
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 82..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 82..111
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 67
FT /note="Phosphotyrosine; by TEC"
FT /evidence="ECO:0000269|PubMed:9753425"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 150
FT /note="Phosphoserine; by MTOR, MAPK1 and MAPK3"
FT /evidence="ECO:0000269|PubMed:15952796,
FT ECO:0000269|PubMed:21659604"
FT MOD_RES 418
FT /note="Phosphoserine; by MAPK1 and MAPK3; in vitro"
FT /evidence="ECO:0000269|PubMed:15952796,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 428
FT /note="Phosphoserine; by MTOR and PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:15722337,
FT ECO:0000269|PubMed:21659604"
FT MOD_RES 431
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60760"
FT MOD_RES 476
FT /note="Phosphoserine; by MTOR, MAPK1 and MAPK3"
FT /evidence="ECO:0000269|PubMed:15952796,
FT ECO:0000269|PubMed:21659604"
FT VAR_SEQ 1..58
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8798417,
FT ECO:0000303|PubMed:9006901"
FT /id="VSP_001842"
FT VAR_SEQ 1..17
FT /note="MALAGCPDSFLHHPYYQ -> MQAAGPLFRSK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:9039502"
FT /id="VSP_038784"
FT VAR_SEQ 283..328
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:7479769,
FT ECO:0000303|PubMed:9753425"
FT /id="VSP_001843"
FT VARIANT 36
FT /note="P -> L (in dbSNP:rs35647889)"
FT /id="VAR_053112"
FT VARIANT 95
FT /note="P -> S (in dbSNP:rs80244589)"
FT /evidence="ECO:0000269|PubMed:10856193"
FT /id="VAR_062864"
FT VARIANT 558
FT /note="D -> H (in dbSNP:rs11768472)"
FT /id="VAR_053113"
FT MUTAGEN 104
FT /note="S->G: No effect on phosphorylation."
FT /evidence="ECO:0000269|PubMed:15952796"
FT MUTAGEN 134
FT /note="S->A: No effect on YWHAE-binding."
FT /evidence="ECO:0000269|PubMed:15722337"
FT MUTAGEN 136
FT /note="P->A: No effect on NEDD4-binding; when associated
FT with A-139 and A-141."
FT /evidence="ECO:0000269|PubMed:15060076"
FT MUTAGEN 139
FT /note="P->A: No effect on NEDD4-binding; when associated
FT with A-136 and A-141."
FT /evidence="ECO:0000269|PubMed:15060076"
FT MUTAGEN 141
FT /note="P->S: No effect on NEDD4-binding; when associated
FT with A-136 and A-139."
FT /evidence="ECO:0000269|PubMed:15060076"
FT MUTAGEN 150
FT /note="S->I: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:15952796"
FT MUTAGEN 300
FT /note="K->A: 2-fold loss of inositide-binding."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 305
FT /note="K->A: 5-fold loss of inositide-binding."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 308
FT /note="K->A: 5-fold loss of inositide-binding."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 355
FT /note="N->G: 5-fold loss of inositide-binding."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 418
FT /note="S->A: No net loss of phosphorylation, this may be
FT due to a compensatory phosphorylation of T-422 in vitro."
FT /evidence="ECO:0000269|PubMed:15952796"
FT MUTAGEN 428
FT /note="S->A: Impairs YWHAE-binding."
FT /evidence="ECO:0000269|PubMed:15722337"
FT MUTAGEN 476
FT /note="S->A: Loss of phosphorylation."
FT /evidence="ECO:0000269|PubMed:15952796"
FT MUTAGEN 520
FT /note="R->K: No effect on NEDD4-binding. No effect on the
FT disruption of the interaction between INSR and IRS1 and
FT IRS2."
FT /evidence="ECO:0000269|PubMed:12493740,
FT ECO:0000269|PubMed:15060076"
FT CONFLICT 152
FT /note="P -> A (in Ref. 9; BAA13198)"
FT /evidence="ECO:0000305"
FT CONFLICT 400
FT /note="G -> E (in Ref. 3; AAB08431)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="S -> F (in Ref. 10; BAF82200)"
FT /evidence="ECO:0000305"
FT CONFLICT 498
FT /note="I -> F (in Ref. 3; AAB08431)"
FT /evidence="ECO:0000305"
FT CONFLICT 541
FT /note="N -> I (in Ref. 2; AAC50671)"
FT /evidence="ECO:0000305"
FT STRAND 168..174
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 179..184
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 190..198
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:3HK0"
FT TURN 216..219
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 230..235
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 242..247
FT /evidence="ECO:0007829|PDB:3HK0"
FT TURN 249..252
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 253..256
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 281..285
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 291..300
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 307..315
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 318..324
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 330..332
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 333..337
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 342..349
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 351..354
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 357..366
FT /evidence="ECO:0007829|PDB:3HK0"
FT STRAND 377..383
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 384..399
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 401..407
FT /evidence="ECO:0007829|PDB:3HK0"
FT HELIX 500..509
FT /evidence="ECO:0007829|PDB:1NRV"
FT STRAND 516..521
FT /evidence="ECO:0007829|PDB:1NRV"
FT STRAND 529..535
FT /evidence="ECO:0007829|PDB:1NRV"
FT STRAND 538..546
FT /evidence="ECO:0007829|PDB:1NRV"
FT STRAND 555..558
FT /evidence="ECO:0007829|PDB:1NRV"
FT STRAND 564..566
FT /evidence="ECO:0007829|PDB:1NRV"
FT HELIX 567..574
FT /evidence="ECO:0007829|PDB:1NRV"
FT STRAND 581..583
FT /evidence="ECO:0007829|PDB:1NRV"
SQ SEQUENCE 594 AA; 67231 MW; 53A5F885E17C6C6B CRC64;
MALAGCPDSF LHHPYYQDKV EQTPRSQQDP AGPGLPAQSD RLANHQEDDV DLEALVNDMN
ASLESLYSAC SMQSDTVPLL QNGQHARSQP RASGPPRSIQ PQVSPRQRVQ RSQPVHILAV
RRLQEEDQQF RTSSLPAIPN PFPELCGPGS PPVLTPGSLP PSQAAAKQDV KVFSEDGTSK
VVEILADMTA RDLCQLLVYK SHCVDDNSWT LVEHHPHLGL ERCLEDHELV VQVESTMASE
SKFLFRKNYA KYEFFKNPMN FFPEQMVTWC QQSNGSQTQL LQNFLNSSSC PEIQGFLHVK
ELGKKSWKKL YVCLRRSGLY CSTKGTSKEP RHLQLLADLE DSNIFSLIAG RKQYNAPTDH
GLCIKPNKVR NETKELRLLC AEDEQTRTCW MTAFRLLKYG MLLYQNYRIP QQRKALLSPF
STPVRSVSEN SLVAMDFSGQ TGRVIENPAE AQSAALEEGH AWRKRSTRMN ILGSQSPLHP
STLSTVIHRT QHWFHGRISR EESHRIIKQQ GLVDGLFLLR DSQSNPKAFV LTLCHHQKIK
NFQILPCEDD GQTFFSLDDG NTKFSDLIQL VDFYQLNKGV LPCKLKHHCI RVAL
