GRB10_MOUSE
ID GRB10_MOUSE Reviewed; 621 AA.
AC Q60760; O35352; Q3TQ71; Q7TSA4; Q8BSH4; Q8BSS5; Q91WC5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 03-AUG-2022, entry version 188.
DE RecName: Full=Growth factor receptor-bound protein 10;
DE AltName: Full=GRB10 adapter protein;
DE AltName: Full=Maternally expressed gene 1 protein;
GN Name=Grb10; Synonyms=Meg1;
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 [MRNA] (ISOFORM 1), INTERACTION WITH EGFR, TISSUE
RP SPECIFICITY, AND PHOSPHORYLATION.
RC STRAIN=SWR/J;
RX PubMed=7731717;
RA Ooi J., Yajnik V., Immanuel D., Gordon M., Moskow J.J., Buchberg A.,
RA Margolis B.;
RT "The cloning of Grb10 reveals a new family of SH2 domain proteins.";
RL Oncogene 10:1621-1630(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH INSR AND IGF1R,
RP AND TISSUE SPECIFICITY.
RX PubMed=9062339; DOI=10.1172/jci119246;
RA Laviola L., Giorgino F., Chow J.C., Baquero J.A., Hansen H., Ooi J.,
RA Zhu J., Riedel H., Smith R.J.;
RT "The adapter protein Grb10 associates preferentially with the insulin
RT receptor as compared with the IGF-I receptor in mouse fibroblasts.";
RL J. Clin. Invest. 99:830-837(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Embryonic head;
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 GENOMIC DNA].
RA Griffiths C., Sycamore N.;
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Eye, and Olfactory epithelium;
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 [6]
RP IMPRINTING, AND DEVELOPMENTAL STAGE.
RX PubMed=9448292; DOI=10.1073/pnas.95.3.1102;
RA Miyoshi N., Kuroiwa Y., Kohda T., Shitara H., Yonekawa H., Kawabe T.,
RA Hasegawa H., Barton S.C., Surani M.A., Kaneko-Ishino T., Ishino F.;
RT "Identification of the Meg1/Grb10 imprinted gene on mouse proximal
RT chromosome 11, a candidate for the Silver-Russell syndrome gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:1102-1107(1998).
RN [7]
RP INTERACTION WITH FGFR1; INSR; IGF1R; MET AND PDGFRB.
RX PubMed=10454568; DOI=10.1128/mcb.19.9.6217;
RA Wang J., Dai H., Yousaf N., Moussaif M., Deng Y., Boufelliga A.,
RA Swamy O.R., Leone M.E., Riedel H.;
RT "Grb10, a positive, stimulatory signaling adapter in platelet-derived
RT growth factor BB-, insulin-like growth factor I-, and insulin-mediated
RT mitogenesis.";
RL Mol. Cell. Biol. 19:6217-6228(1999).
RN [8]
RP IMPRINTING.
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 INTERACTION WITH GIGYF1 AND GIGYF2.
RX PubMed=12771153; DOI=10.1074/jbc.m211572200;
RA Giovannone B., Lee E., Laviola L., Giorgino F., Cleveland K.A., Smith R.J.;
RT "Two novel proteins that are linked to insulin-like growth factor (IGF-I)
RT receptors by the Grb10 adapter and modulate IGF-I signaling.";
RL J. Biol. Chem. 278:31564-31573(2003).
RN [10]
RP FUNCTION, AND INTERACTION WITH IGF1R AND NEDD4.
RX PubMed=12697834; DOI=10.1128/mcb.23.9.3363-3372.2003;
RA Vecchione A., Marchese A., Henry P., Rotin D., Morrione A.;
RT "The Grb10/Nedd4 complex regulates ligand-induced ubiquitination and
RT stability of the insulin-like growth factor I receptor.";
RL Mol. Cell. Biol. 23:3363-3372(2003).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, IMPRINTING, AND DEVELOPMENTAL STAGE.
RX PubMed=12829789; DOI=10.1073/pnas.1532175100;
RA Charalambous M., Smith F.M., Bennett W.R., Crew T.E., Mackenzie F.,
RA Ward A.;
RT "Disruption of the imprinted Grb10 gene leads to disproportionate
RT overgrowth by an Igf2-independent mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:8292-8297(2003).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-96, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [13]
RP INTERACTION WITH AKT1 AND YWHAE, AND PHOSPHORYLATION.
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 [14]
RP FUNCTION, AND INTERACTION WITH INSR.
RX PubMed=15664450; DOI=10.1016/j.mce.2004.11.004;
RA Mori K., Giovannone B., Smith R.J.;
RT "Distinct Grb10 domain requirements for effects on glucose uptake and
RT insulin signaling.";
RL Mol. Cell. Endocrinol. 230:39-50(2005).
RN [15]
RP FUNCTION, AND INTERACTION WITH LRP6.
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18286479; DOI=10.1002/jcp.21405;
RA Monami G., Emiliozzi V., Morrione A.;
RT "Grb10/Nedd4-mediated multiubiquitination of the insulin-like growth factor
RT receptor regulates receptor internalization.";
RL J. Cell. Physiol. 216:426-437(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458 AND SER-503, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, and
RC 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).
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. A similar role in the mediation of ubiquitination has also
CC been suggested with INSR. Negatively regulates Wnt signaling by
CC interacting with LRP6 intracellular portion and interfering with the
CC binding of AXIN1 to LRP6. Positive regulator of the KDR/VEGFR-2
CC signaling pathway. May inhibit NEDD4-mediated degradation of KDR/VEGFR-
CC 2. {ECO:0000269|PubMed:12697834, ECO:0000269|PubMed:12829789,
CC ECO:0000269|PubMed:15664450, ECO:0000269|PubMed:17376403,
CC ECO:0000269|PubMed:18286479}.
CC -!- ACTIVITY REGULATION: Phosphorylation by mTORC1 stabilizes and activates
CC GRB10 constituting a feedback pathway by which mTORC1 inhibits INSR-
CC dependent signaling. {ECO:0000250}.
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. Poorly binds to the EGFR.
CC Directly interacts with MAP3K14/NIK and is recruited to the EGFR-ERBB2
CC complex (By similarity). Interacts with GIGYF1/PERQ1 and GIGYF2/TNRC15.
CC When unphosphorylated, interacts with AKT1 and when phosphorylated with
CC YWHAE/14-3-3 epsilon. Interacts with NEDD4. Interacts with LRP6, thus
CC interfering with the binding of AXIN1 to LRP6. Binds to activated NRAS
CC (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q60760; P15208: Insr; NbExp=6; IntAct=EBI-861810, EBI-6999015;
CC Q60760; P46935: Nedd4; NbExp=6; IntAct=EBI-861810, EBI-773516;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18286479}.
CC Note=When complexed with NEDD4 and IGF1R, follows IGF1R
CC internalization, remaining associated with early endosomes. Uncouples
CC from IGF1R before the sorting of the receptor to the lysosomal
CC compartment.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q60760-1; Sequence=Displayed;
CC Name=2; Synonyms=Delta;
CC IsoId=Q60760-2; Sequence=VSP_001844;
CC Name=3;
CC IsoId=Q60760-3; Sequence=VSP_012379;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:7731717,
CC ECO:0000269|PubMed:9062339}.
CC -!- DEVELOPMENTAL STAGE: At 13.5 dpc, expressed in most embryonic tissues
CC and in placenta. At 14.5 dpc, expressed at high levels in a variety of
CC muscle tissues, including that of the face and trunk, the intercostal
CC muscles, the diaphragm and cardiac muscle, the tongue and limbs (at
CC protein level). In the brain, most abundant expression in the
CC subependymal layers, in the meninges and in the choroid plexus (both
CC epithelium and mesenchyme) (at protein level). High levels in the
CC liver, bronchioles and the cartilage of the atlas, ribs and long bones
CC (at protein level). In the kidney, expression limited to the developing
CC tubules and mesenchyme (at protein level). Also detected in the adrenal
CC gland and pancreatic bud (at protein level). At 12.5 dpc, paternal
CC allele expression detected in the cartilage of the limbs, ribs and face
CC and in the meninges. At 14.5 dpc, paternal allele expressed in the
CC cartilage of the axis, ribs, head, and long bones, in the heart, lungs,
CC gut, umbilicus and tongue, as well as in the meninges of the fourth
CC ventricle. Not detected in the skeletal muscle. In most tissues,
CC paternal expression is lower than maternal.
CC {ECO:0000269|PubMed:12829789, ECO:0000269|PubMed:9448292}.
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. {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues upon EGF, FGF and PDGF
CC stimulation. {ECO:0000269|PubMed:15722337, ECO:0000269|PubMed:7731717}.
CC -!- DISRUPTION PHENOTYPE: Disruption of the maternal allele results in
CC overgrowth of both the embryo and placenta such that mutant mice are at
CC birth about 30% larger than normal. This effect occurs during
CC embryogenesis and results in addition in disproportionate overgrowth of
CC the liver with relative sparing of the brain. The major part of the
CC growth phenotype seems to be IGF2-independent.
CC {ECO:0000269|PubMed:12829789}.
CC -!- MISCELLANEOUS: The GRB10 locus is imprinted. The maternal allele is
CC expressed in most tissues, except the brain where it is expressed from
CC the paternal allele. Expression from the maternal allele in fetal and
CC adult brain was however described in PubMed:10861285.
CC -!- MISCELLANEOUS: [Isoform 2]: Predominant isoform in most tissues.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH53842.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAE37514.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; U18996; AAB53687.1; -; mRNA.
DR EMBL; AF022072; AAB72103.1; -; mRNA.
DR EMBL; AK030727; BAC27100.1; -; mRNA.
DR EMBL; AK032927; BAC28088.1; -; mRNA.
DR EMBL; AK163841; BAE37514.1; ALT_INIT; mRNA.
DR EMBL; AL645803; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL663087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016111; AAH16111.1; -; mRNA.
DR EMBL; BC053842; AAH53842.1; ALT_INIT; mRNA.
DR CCDS; CCDS24440.1; -. [Q60760-2]
DR CCDS; CCDS48754.1; -. [Q60760-3]
DR PIR; I49199; I49199.
DR RefSeq; NP_001171100.1; NM_001177629.1. [Q60760-3]
DR RefSeq; NP_034475.2; NM_010345.4. [Q60760-2]
DR RefSeq; XP_006514592.1; XM_006514529.1.
DR RefSeq; XP_011241966.1; XM_011243664.1. [Q60760-3]
DR PDB; 3M7F; X-ray; 2.00 A; A=514-621.
DR PDBsum; 3M7F; -.
DR AlphaFoldDB; Q60760; -.
DR SMR; Q60760; -.
DR BioGRID; 200045; 5.
DR DIP; DIP-446N; -.
DR IntAct; Q60760; 7.
DR MINT; Q60760; -.
DR STRING; 10090.ENSMUSP00000091011; -.
DR iPTMnet; Q60760; -.
DR PhosphoSitePlus; Q60760; -.
DR MaxQB; Q60760; -.
DR PaxDb; Q60760; -.
DR PeptideAtlas; Q60760; -.
DR PRIDE; Q60760; -.
DR ProteomicsDB; 271291; -. [Q60760-1]
DR ProteomicsDB; 271292; -. [Q60760-2]
DR ProteomicsDB; 271293; -. [Q60760-3]
DR Antibodypedia; 27751; 495 antibodies from 37 providers.
DR DNASU; 14783; -.
DR Ensembl; ENSMUST00000093321; ENSMUSP00000091011; ENSMUSG00000020176. [Q60760-2]
DR Ensembl; ENSMUST00000109654; ENSMUSP00000105281; ENSMUSG00000020176. [Q60760-3]
DR GeneID; 14783; -.
DR KEGG; mmu:14783; -.
DR UCSC; uc007iaz.2; mouse. [Q60760-3]
DR UCSC; uc007iba.2; mouse. [Q60760-2]
DR CTD; 2887; -.
DR MGI; MGI:103232; Grb10.
DR VEuPathDB; HostDB:ENSMUSG00000020176; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000155909; -.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; Q60760; -.
DR OMA; QXRCLED; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; Q60760; -.
DR TreeFam; TF317511; -.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-74713; IRS activation.
DR Reactome; R-MMU-74749; Signal attenuation.
DR Reactome; R-MMU-74751; Insulin receptor signalling cascade.
DR Reactome; R-MMU-8853659; RET signaling.
DR Reactome; R-MMU-9607240; FLT3 Signaling.
DR BioGRID-ORCS; 14783; 4 hits in 72 CRISPR screens.
DR ChiTaRS; Grb10; mouse.
DR PRO; PR:Q60760; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q60760; protein.
DR Bgee; ENSMUSG00000020176; Expressed in associated mesenchyme of midgut and 258 other tissues.
DR ExpressionAtlas; Q60760; baseline and differential.
DR Genevisible; Q60760; MM.
DR GO; GO:0005829; C:cytosol; TAS:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0005158; F:insulin receptor binding; IPI:BHF-UCL.
DR GO; GO:0001784; F:phosphotyrosine residue binding; TAS:BHF-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:MGI.
DR GO; GO:0030159; F:signaling receptor complex adaptor activity; IPI:BHF-UCL.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IMP:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; IPI:MGI.
DR GO; GO:0046325; P:negative regulation of glucose import; IMP:BHF-UCL.
DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; ISO:MGI.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0042326; P:negative regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; IMP:YuBioLab.
DR GO; GO:0042327; P:positive regulation of phosphorylation; ISO:MGI.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032868; P:response to insulin; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
DR GO; GO:1904738; P:vascular associated smooth muscle cell migration; IMP:MGI.
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; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT CHAIN 1..621
FT /note="Growth factor receptor-bound protein 10"
FT /id="PRO_0000150347"
FT DOMAIN 194..278
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 318..427
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 520..601
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..114
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 50
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 96
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15345747"
FT MOD_RES 455
FT /note="Phosphoserine; by MTOR and PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:Q13322"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 503
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 117..196
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012379"
FT VAR_SEQ 117..141
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:9062339"
FT /id="VSP_001844"
FT CONFLICT 491..492
FT /note="KR -> NG (in Ref. 1; AAB53687)"
FT /evidence="ECO:0000305"
FT CONFLICT 555
FT /note="A -> T (in Ref. 3; BAC28088)"
FT /evidence="ECO:0000305"
FT HELIX 515..517
FT /evidence="ECO:0007829|PDB:3M7F"
FT HELIX 527..536
FT /evidence="ECO:0007829|PDB:3M7F"
FT STRAND 543..548
FT /evidence="ECO:0007829|PDB:3M7F"
FT STRAND 556..562
FT /evidence="ECO:0007829|PDB:3M7F"
FT STRAND 565..576
FT /evidence="ECO:0007829|PDB:3M7F"
FT STRAND 579..585
FT /evidence="ECO:0007829|PDB:3M7F"
FT STRAND 588..593
FT /evidence="ECO:0007829|PDB:3M7F"
FT HELIX 594..601
FT /evidence="ECO:0007829|PDB:3M7F"
FT STRAND 608..610
FT /evidence="ECO:0007829|PDB:3M7F"
SQ SEQUENCE 621 AA; 70585 MW; 6FC737E8F35468BB CRC64;
MNNDINSSVE SLNSACNMQS DTDTAPLLED GQHASNQGAA SSSRGQPQAS PRQKMQRSQP
VHILRRLQEE DQQLRTASLP AIPNPFPELT GAAPGSPPSV APSSLPPPPS QPPAKHCGRC
EKWIPGENTR GNGKRKIWRW QFPPGFQLSK LTRPGLWTKT TARFSKKQPK NQCPTDTVNP
VARMPTSQME KLRLRKDVKV FSEDGTSKVV EILTDMTARD LCQLLVYKSH CVDDNSWTLV
EHHPQLGLER CLEDHEIVVQ VESTMPSESK FLFRKNYAKY EFFKNPVNFF PDQMVNWCQQ
SNGGQAQLLQ NFLNTSSCPE IQGFLQVKEV GRKSWKKLYV CLRRSGLYYS TKGTSKEPRH
LQLLADLEES SIFYLIAGKK QYNAPNEHGM CIKPNKAKTE MKELRLLCAE DEQIRTCWMT
AFRLLKYGML LYQNYRIPQR KGLPPPFNAP MRSVSENSLV AMDFSGQIGR VIDNPAEAQS
AALEEGHAWR KRSTRMNILS SQSPLHPSTL NAVIHRTQHW FHGRISREES HRIIKQQGLV
DGLFLLRDSQ SNPKAFVLTL CHHQKIKNFQ ILPCEDDGQT FFTLDDGNTK FSDLIQLVDF
YQLNKGVLPC KLKHHCIRVA L
