GRB7_HUMAN
ID GRB7_HUMAN Reviewed; 532 AA.
AC Q14451; B2RAV1; B3KNL0; B3KWP9; B7WP75; J3KQM4; Q53YD3; Q92568; Q96DF9;
AC Q9Y220;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Growth factor receptor-bound protein 7;
DE AltName: Full=B47;
DE AltName: Full=Epidermal growth factor receptor GRB-7;
DE AltName: Full=GRB7 adapter protein;
GN Name=GRB7;
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=Esophageal carcinoma;
RX PubMed=9125150; DOI=10.1006/bbrc.1997.6218;
RA Kishi T., Sasaki H., Akiyama N., Ishizuka T., Sakamoto H., Aizawa S.,
RA Sugimura T., Terada M.;
RT "Molecular cloning of human GRB-7 co-amplified with CAB1 and c-ERBB-2 in
RT primary gastric cancer.";
RL Biochem. Biophys. Res. Commun. 232:5-9(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=9710451; DOI=10.1172/jci2921;
RA Tanaka S., Mori M., Akiyoshi T., Tanaka Y., Mafune K., Wands J.R.,
RA Sugimachi K.;
RT "A novel variant of human Grb7 is associated with invasive esophageal
RT carcinoma.";
RL J. Clin. Invest. 102:821-827(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Whittock N.V., Eady R.A.J., McGrath J.A.;
RT "Genomic organization and amplification of the human GRB7 gene.";
RL Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4).
RC TISSUE=Ovary, Prostate, and Thalamus;
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 130-343.
RX PubMed=8988034;
RA Tanaka S., Mori M., Akiyoshi T., Tanaka Y., Mafune K., Wands J.R.,
RA Sugimachi K.;
RT "Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2
RT in human advanced esophageal carcinoma.";
RL Cancer Res. 57:28-31(1997).
RN [10]
RP INTERACTION WITH ERBB3 AND ERBB4, AND SERINE AND THREONINE PHOSPHORYLATION.
RX PubMed=9516479; DOI=10.1074/jbc.273.13.7717;
RA Fiddes R.J., Campbell D.H., Janes P.W., Sivertsen S.P., Sasaki H.,
RA Wallasch C., Daly R.J.;
RT "Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals
RT a novel target selectivity for erbB3.";
RL J. Biol. Chem. 273:7717-7724(1998).
RN [11]
RP INTERACTION WITH RND1.
RX PubMed=10664463; DOI=10.1016/s0014-5793(99)01530-6;
RA Vayssiere B., Zalcman G., Mahe Y., Mirey G., Ligensa T., Weidner K.M.,
RA Chardin P., Camonis J.;
RT "Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho
RT family.";
RL FEBS Lett. 467:91-96(2000).
RN [12]
RP FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=10893408; DOI=10.1074/jbc.m001997200;
RA Han D.C., Shen T.L., Guan J.L.;
RT "Role of Grb7 targeting to focal contacts and its phosphorylation by focal
RT adhesion kinase in regulation of cell migration.";
RL J. Biol. Chem. 275:28911-28917(2000).
RN [13]
RP INTERACTION WITH INSR.
RX PubMed=10803466; DOI=10.1038/sj.onc.1203469;
RA Kasus-Jacobi A., Bereziat V., Perdereau D., Girard J., Burnol A.F.;
RT "Evidence for an interaction between the insulin receptor and Grb7. A role
RT for two of its binding domains, PIR and SH2.";
RL Oncogene 19:2052-2059(2000).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PTK2/FAK1, MUTAGENESIS OF
RP ARG-239, AND DOMAIN.
RX PubMed=12021278; DOI=10.1074/jbc.m203085200;
RA Shen T.L., Han D.C., Guan J.L.;
RT "Association of Grb7 with phosphoinositides and its role in the regulation
RT of cell migration.";
RL J. Biol. Chem. 277:29069-29077(2002).
RN [15]
RP FUNCTION, PHOSPHORYLATION, AND INTERACTION WITH EPHB1.
RX PubMed=12223469; DOI=10.1074/jbc.m203165200;
RA Han D.C., Shen T.L., Miao H., Wang B., Guan J.L.;
RT "EphB1 associates with Grb7 and regulates cell migration.";
RL J. Biol. Chem. 277:45655-45661(2002).
RN [16]
RP REVIEW ON INTERACTION WITH KIT AND ROLE IN KIT SIGNALING.
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 [17]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=16129412; DOI=10.1016/j.bbrc.2005.08.055;
RA Roskoski R. Jr.;
RT "Signaling by Kit protein-tyrosine kinase--the stem cell factor receptor.";
RL Biochem. Biophys. Res. Commun. 337:1-13(2005).
RN [18]
RP SUBUNIT, AND MUTAGENESIS OF PHE-511.
RX PubMed=15841400; DOI=10.1007/s00249-005-0480-1;
RA Porter C.J., Wilce M.C., Mackay J.P., Leedman P., Wilce J.A.;
RT "Grb7-SH2 domain dimerisation is affected by a single point mutation.";
RL Eur. Biophys. J. 34:454-460(2005).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-361, AND IDENTIFICATION BY
RP 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 [20]
RP PHOSPHORYLATION AT TYR-188 AND TYR-338, AND INTERACTION WITH PTK2/FAK1.
RX PubMed=19473962; DOI=10.1074/jbc.m109.018259;
RA Chu P.Y., Huang L.Y., Hsu C.H., Liang C.C., Guan J.L., Hung T.H.,
RA Shen T.L.;
RT "Tyrosine phosphorylation of growth factor receptor-bound protein-7 by
RT focal adhesion kinase in the regulation of cell migration, proliferation,
RT and tumorigenesis.";
RL J. Biol. Chem. 284:20215-20226(2009).
RN [21]
RP INTERACTION WITH FHL2, STRUCTURE BY NMR, MUTAGENESIS OF TYR-259; TYR-260;
RP TYR-284; TYR-480 AND TYR-492, SUBCELLULAR LOCATION, AND TYROSINE
RP PHOSPHORYLATION.
RX PubMed=18853468; DOI=10.1002/jmr.916;
RA Siamakpour-Reihani S., Argiros H.J., Wilmeth L.J., Haas L.L.,
RA Peterson T.A., Johnson D.L., Shuster C.B., Lyons B.A.;
RT "The cell migration protein Grb7 associates with transcriptional regulator
RT FHL2 in a Grb7 phosphorylation-dependent manner.";
RL J. Mol. Recognit. 22:9-17(2009).
RN [22]
RP FUNCTION, SUBUNIT, PHOSPHORYLATION AT TYR-188 AND TYR-338, AND MUTAGENESIS
RP OF TYR-188 AND TYR-338.
RX PubMed=20622016; DOI=10.1074/jbc.c110.114124;
RA Chu P.Y., Li T.K., Ding S.T., Lai I.R., Shen T.L.;
RT "EGF-induced Grb7 recruits and promotes Ras activity essential for the
RT tumorigenicity of Sk-Br3 breast cancer cells.";
RL J. Biol. Chem. 285:29279-29285(2010).
RN [23]
RP INTERACTION WITH HAX1, MUTAGENESIS OF TYR-259; TYR-260; TYR-284; TYR-480
RP AND TYR-492, CIRCULAR DICHROISM, AND TYROSINE PHOSPHORYLATION.
RX PubMed=20665473; DOI=10.1002/jmr.1062;
RA Siamakpour-Reihani S., Peterson T.A., Bradford A.M., Argiros H.J.,
RA Haas L.L., Lor S.N., Haulsee Z.M., Spuches A.M., Johnson D.L.,
RA Rohrschneider L.R., Shuster C.B., Lyons B.A.;
RT "Grb7 binds to Hax-1 and undergoes an intramolecular domain association
RT that offers a model for Grb7 regulation.";
RL J. Mol. Recognit. 24:314-321(2011).
RN [24]
RP STRUCTURE BY NMR OF 415-532 IN COMPLEX WITH ERBB2, AND INTERACTION WITH
RP ERBB2.
RX PubMed=12975581; DOI=10.1023/a:1025498409113;
RA Ivancic M., Daly R.J., Lyons B.A.;
RT "Solution structure of the human Grb7-SH2 domain/erbB2 peptide complex and
RT structural basis for Grb7 binding to ErbB2.";
RL J. Biomol. NMR 27:205-219(2003).
RN [25]
RP STRUCTURE BY NMR OF 100-186.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the RA domain of human GRB7 protein.";
RL Submitted (NOV-2004) to the PDB data bank.
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 415-532, INTERACTION WITH THE
RP SYNTHETIC INHIBITOR G7-18NATE, AND SUBUNIT.
RX PubMed=17894853; DOI=10.1186/1472-6807-7-58;
RA Porter C.J., Matthews J.M., Mackay J.P., Pursglove S.E., Schmidberger J.W.,
RA Leedman P.J., Pero S.C., Krag D.N., Wilce M.C., Wilce J.A.;
RT "Grb7 SH2 domain structure and interactions with a cyclic peptide inhibitor
RT of cancer cell migration and proliferation.";
RL BMC Struct. Biol. 7:58-58(2007).
CC -!- FUNCTION: Adapter protein that interacts with the cytoplasmic domain of
CC numerous receptor kinases and modulates down-stream signaling. Promotes
CC activation of down-stream protein kinases, including STAT3, AKT1, MAPK1
CC and/or MAPK3. Promotes activation of HRAS. Plays a role in signal
CC transduction in response to EGF. Plays a role in the regulation of cell
CC proliferation and cell migration. Plays a role in the assembly and
CC stability of RNA stress granules. Binds to the 5'UTR of target mRNA
CC molecules and represses translation of target mRNA species, when not
CC phosphorylated. Phosphorylation impairs RNA binding and promotes stress
CC granule disassembly during recovery after cellular stress (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:10893408,
CC ECO:0000269|PubMed:12021278, ECO:0000269|PubMed:12223469,
CC ECO:0000269|PubMed:20622016}.
CC -!- SUBUNIT: Homodimer. Interacts (via SH2 domain) with EGFR, ERBB2, ERBB3
CC (when phosphorylated), ERBB4 (when phosphorylated), EPHB1, INSR, FGFR1,
CC PDGFRA (tyrosine phosphorylated) and PDGFRB (tyrosine phosphorylated).
CC Interacts with SHC1. Interacts with RND1. Interacts (when tyrosine
CC phosphorylated) with FHL2 and HAX1 (By similarity). Interacts (via SH2
CC domain) with RET and PTK2/FAK1. Interacts (when not phosphorylated)
CC with ELAVL1. In stressed cells, but not in normal cells, part of a
CC complex that contains at least GRB7, PTK2/FAK1, STAU1, ELAVL1 and TIA1.
CC Interacts (via SH2 domain) with KIT (phosphorylated). Interacts (via
CC SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q14451; P10275: AR; NbExp=3; IntAct=EBI-970191, EBI-608057;
CC Q14451; P54762: EPHB1; NbExp=4; IntAct=EBI-970191, EBI-80252;
CC Q14451; P04626: ERBB2; NbExp=5; IntAct=EBI-970191, EBI-641062;
CC Q14451; P21860: ERBB3; NbExp=7; IntAct=EBI-970191, EBI-720706;
CC Q14451; Q14451: GRB7; NbExp=2; IntAct=EBI-970191, EBI-970191;
CC Q14451; O00165: HAX1; NbExp=2; IntAct=EBI-970191, EBI-357001;
CC Q14451; Q8NC69: KCTD6; NbExp=3; IntAct=EBI-970191, EBI-2511344;
CC Q14451; P10721: KIT; NbExp=4; IntAct=EBI-970191, EBI-1379503;
CC Q14451; Q8IWV1: LAX1; NbExp=4; IntAct=EBI-970191, EBI-10232942;
CC Q14451; Q5SQ64: LY6G6F; NbExp=2; IntAct=EBI-970191, EBI-6963742;
CC Q14451; Q8TAK6: OLIG1; NbExp=3; IntAct=EBI-970191, EBI-3867416;
CC Q14451; P09619: PDGFRB; NbExp=4; IntAct=EBI-970191, EBI-641237;
CC Q14451; Q05397: PTK2; NbExp=3; IntAct=EBI-970191, EBI-702142;
CC Q14451; Q92730: RND1; NbExp=4; IntAct=EBI-970191, EBI-448618;
CC Q14451; Q9NQ86: TRIM36; NbExp=3; IntAct=EBI-970191, EBI-2341518;
CC Q14451; P62157: CALM; Xeno; NbExp=2; IntAct=EBI-970191, EBI-397403;
CC Q14451; P62161: Calm3; Xeno; NbExp=9; IntAct=EBI-970191, EBI-397530;
CC Q14451-3; Q8IUR6: CREBRF; NbExp=3; IntAct=EBI-11991632, EBI-1042699;
CC Q14451-3; Q9H5Z6-2: FAM124B; NbExp=3; IntAct=EBI-11991632, EBI-11986315;
CC Q14451-3; A0A0C3SFZ9: FCHO1; NbExp=3; IntAct=EBI-11991632, EBI-11977403;
CC Q14451-3; Q8NC69: KCTD6; NbExp=3; IntAct=EBI-11991632, EBI-2511344;
CC Q14451-3; Q8IWV1-3: LAX1; NbExp=3; IntAct=EBI-11991632, EBI-12327415;
CC Q14451-3; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-11991632, EBI-79165;
CC Q14451-3; Q96MF2: STAC3; NbExp=3; IntAct=EBI-11991632, EBI-745680;
CC Q14451-3; Q99081-3: TCF12; NbExp=3; IntAct=EBI-11991632, EBI-11952764;
CC Q14451-3; O43548: TGM5; NbExp=3; IntAct=EBI-11991632, EBI-12027348;
CC Q14451-3; Q96BQ3: TRIM43; NbExp=3; IntAct=EBI-11991632, EBI-2129899;
CC Q14451-3; O75604: USP2; NbExp=3; IntAct=EBI-11991632, EBI-743272;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10893408,
CC ECO:0000269|PubMed:12021278, ECO:0000269|PubMed:18853468}. Cell
CC junction, focal adhesion {ECO:0000269|PubMed:10893408,
CC ECO:0000269|PubMed:12021278}. Cell membrane; Peripheral membrane
CC protein; Cytoplasmic side {ECO:0000269|PubMed:10893408,
CC ECO:0000269|PubMed:12021278, ECO:0000269|PubMed:18853468}. Cytoplasmic
CC granule {ECO:0000250|UniProtKB:Q03160}. Cell projection
CC {ECO:0000269|PubMed:18853468}. Note=Predominantly cytoplasmic. Detected
CC in stress granules, where mRNA is stored under stress conditions.
CC {ECO:0000250|UniProtKB:Q03160}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=At least 2 isoforms are produced.;
CC Name=1;
CC IsoId=Q14451-1; Sequence=Displayed;
CC Name=2; Synonyms=Grb7V;
CC IsoId=Q14451-2; Sequence=VSP_035500, VSP_035501;
CC Name=3;
CC IsoId=Q14451-3; Sequence=VSP_041665;
CC Name=4;
CC IsoId=Q14451-4; Sequence=VSP_041666;
CC -!- DOMAIN: The PH domain mediates interaction with membranes containing
CC phosphoinositides. {ECO:0000269|PubMed:12021278}.
CC -!- PTM: Phosphorylated on serine and threonine residues in response to
CC heregulin. Phosphorylated on tyrosine residues by TEK/TIE2.
CC Phosphorylated on tyrosine residues in response to NTN1 signaling.
CC Phosphorylation promotes stress granule disassembly during recovery
CC after cellular stress (By similarity). Phosphorylated on tyrosine
CC residues by PTK2/FAK1, and possibly also other kinases. Phosphorylation
CC is enhanced by activation of receptor kinases. Tyrosine phosphorylation
CC is essential for activation of down-stream protein kinases.
CC {ECO:0000250, ECO:0000269|PubMed:10893408, ECO:0000269|PubMed:12223469,
CC ECO:0000269|PubMed:19473962, ECO:0000269|PubMed:20622016}.
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
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DR EMBL; D43772; BAA07827.1; -; mRNA.
DR EMBL; AB008789; BAA29059.1; -; mRNA.
DR EMBL; AB008790; BAA29060.1; -; mRNA.
DR EMBL; AF274875; AAG25938.1; -; Genomic_DNA.
DR EMBL; BT006686; AAP35332.1; -; mRNA.
DR EMBL; AK222849; BAD96569.1; -; mRNA.
DR EMBL; AK222870; BAD96590.1; -; mRNA.
DR EMBL; AK290115; BAF82804.1; -; mRNA.
DR EMBL; AK314368; BAG36998.1; -; mRNA.
DR EMBL; AK027729; BAG51372.1; -; mRNA.
DR EMBL; AK125544; BAG54211.1; -; mRNA.
DR EMBL; AC079199; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471152; EAW60600.1; -; Genomic_DNA.
DR EMBL; CH471152; EAW60601.1; -; Genomic_DNA.
DR EMBL; BC006535; AAH06535.1; -; mRNA.
DR EMBL; D87513; BAA13412.1; -; mRNA.
DR CCDS; CCDS11345.1; -. [Q14451-1]
DR CCDS; CCDS56028.1; -. [Q14451-3]
DR CCDS; CCDS82116.1; -. [Q14451-2]
DR PIR; JC5412; JC5412.
DR RefSeq; NP_001025173.1; NM_001030002.2. [Q14451-1]
DR RefSeq; NP_001229371.1; NM_001242442.1. [Q14451-3]
DR RefSeq; NP_001229372.1; NM_001242443.1. [Q14451-1]
DR RefSeq; NP_001317136.1; NM_001330207.1. [Q14451-2]
DR RefSeq; NP_005301.2; NM_005310.3. [Q14451-1]
DR PDB; 1MW4; NMR; -; A=415-532.
DR PDB; 1WGR; NMR; -; A=100-186.
DR PDB; 2L4K; NMR; -; A=415-532.
DR PDB; 2QMS; X-ray; 2.10 A; A/B/C/D=415-532.
DR PDB; 3PQZ; X-ray; 2.41 A; A/B/C/D=416-532.
DR PDB; 4WWQ; X-ray; 1.80 A; A/B=415-532.
DR PDB; 4X6S; X-ray; 2.55 A; A/B=423-529.
DR PDB; 5D0J; X-ray; 2.60 A; A/B/C/D=415-532.
DR PDB; 5EEL; X-ray; 2.47 A; A/B/C/D/E/F=415-532.
DR PDB; 5EEQ; X-ray; 1.60 A; A/B=415-532.
DR PDB; 5TYI; X-ray; 2.15 A; A/B/C/D=415-532.
DR PDB; 5U06; X-ray; 2.10 A; A/B/C/D=415-532.
DR PDB; 5U1Q; X-ray; 2.10 A; A/B/C/D=415-532.
DR PDB; 7MP3; X-ray; 2.55 A; A/B/C/D=415-532.
DR PDBsum; 1MW4; -.
DR PDBsum; 1WGR; -.
DR PDBsum; 2L4K; -.
DR PDBsum; 2QMS; -.
DR PDBsum; 3PQZ; -.
DR PDBsum; 4WWQ; -.
DR PDBsum; 4X6S; -.
DR PDBsum; 5D0J; -.
DR PDBsum; 5EEL; -.
DR PDBsum; 5EEQ; -.
DR PDBsum; 5TYI; -.
DR PDBsum; 5U06; -.
DR PDBsum; 5U1Q; -.
DR PDBsum; 7MP3; -.
DR AlphaFoldDB; Q14451; -.
DR BMRB; Q14451; -.
DR SMR; Q14451; -.
DR BioGRID; 109143; 132.
DR CORUM; Q14451; -.
DR DIP; DIP-502N; -.
DR IntAct; Q14451; 100.
DR MINT; Q14451; -.
DR STRING; 9606.ENSP00000403459; -.
DR BindingDB; Q14451; -.
DR ChEMBL; CHEMBL1649051; -.
DR GlyGen; Q14451; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q14451; -.
DR PhosphoSitePlus; Q14451; -.
DR BioMuta; GRB7; -.
DR DMDM; 116242503; -.
DR CPTAC; CPTAC-148; -.
DR CPTAC; CPTAC-149; -.
DR EPD; Q14451; -.
DR jPOST; Q14451; -.
DR MassIVE; Q14451; -.
DR MaxQB; Q14451; -.
DR PaxDb; Q14451; -.
DR PeptideAtlas; Q14451; -.
DR PRIDE; Q14451; -.
DR ProteomicsDB; 59995; -. [Q14451-1]
DR ProteomicsDB; 59996; -. [Q14451-2]
DR ProteomicsDB; 59997; -. [Q14451-3]
DR ProteomicsDB; 59998; -. [Q14451-4]
DR Antibodypedia; 3928; 370 antibodies from 38 providers.
DR DNASU; 2886; -.
DR Ensembl; ENST00000309156.9; ENSP00000310771.4; ENSG00000141738.14. [Q14451-1]
DR Ensembl; ENST00000394204.1; ENSP00000377754.1; ENSG00000141738.14. [Q14451-2]
DR Ensembl; ENST00000394209.6; ENSP00000377759.2; ENSG00000141738.14. [Q14451-1]
DR Ensembl; ENST00000394211.7; ENSP00000377761.3; ENSG00000141738.14. [Q14451-1]
DR Ensembl; ENST00000445327.6; ENSP00000403459.2; ENSG00000141738.14. [Q14451-3]
DR GeneID; 2886; -.
DR KEGG; hsa:2886; -.
DR MANE-Select; ENST00000309156.9; ENSP00000310771.4; NM_005310.5; NP_005301.2.
DR UCSC; uc002hsr.4; human. [Q14451-1]
DR CTD; 2886; -.
DR DisGeNET; 2886; -.
DR GeneCards; GRB7; -.
DR HGNC; HGNC:4567; GRB7.
DR HPA; ENSG00000141738; Tissue enhanced (esophagus).
DR MIM; 601522; gene.
DR neXtProt; NX_Q14451; -.
DR OpenTargets; ENSG00000141738; -.
DR PharmGKB; PA28963; -.
DR VEuPathDB; HostDB:ENSG00000141738; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000158710; -.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; Q14451; -.
DR OMA; RCFCFLR; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; Q14451; -.
DR TreeFam; TF317511; -.
DR PathwayCommons; Q14451; -.
DR Reactome; R-HSA-1306955; GRB7 events in ERBB2 signaling.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR Reactome; R-HSA-186763; Downstream signal transduction.
DR Reactome; R-HSA-210993; Tie2 Signaling.
DR Reactome; R-HSA-8853659; RET signaling.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; Q14451; -.
DR SIGNOR; Q14451; -.
DR BioGRID-ORCS; 2886; 21 hits in 1080 CRISPR screens.
DR ChiTaRS; GRB7; human.
DR EvolutionaryTrace; Q14451; -.
DR GeneWiki; GRB7; -.
DR GenomeRNAi; 2886; -.
DR Pharos; Q14451; Tchem.
DR PRO; PR:Q14451; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q14451; protein.
DR Bgee; ENSG00000141738; Expressed in oocyte and 128 other tissues.
DR ExpressionAtlas; Q14451; baseline and differential.
DR Genevisible; Q14451; HS.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-SubCell.
DR GO; GO:0010494; C:cytoplasmic stress granule; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; IEA:UniProtKB-KW.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0034063; P:stress granule assembly; ISS:UniProtKB.
DR CDD; cd01259; PH_APBB1IP; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR IDEAL; IID00566; -.
DR InterPro; IPR015042; BPS-dom.
DR InterPro; IPR039664; GRB/APBB1IP.
DR InterPro; IPR035032; Grb7.
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:SF25; PTHR11243:SF25; 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; Cell junction; Cell membrane;
KW Cell projection; Cytoplasm; Lipid-binding; Membrane; Phosphoprotein;
KW Reference proteome; Repressor; RNA-binding; SH2 domain.
FT CHAIN 1..532
FT /note="Growth factor receptor-bound protein 7"
FT /id="PRO_0000150344"
FT DOMAIN 100..186
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 229..338
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 431..527
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..96
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 18..33
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 239
FT /note="Important for lipid binding and for stimulation of
FT cell migration"
FT SITE 511
FT /note="Important for dimerization and for HRAS activation"
FT MOD_RES 188
FT /note="Phosphotyrosine; by FAK1"
FT /evidence="ECO:0000269|PubMed:19473962,
FT ECO:0000269|PubMed:20622016"
FT MOD_RES 338
FT /note="Phosphotyrosine; by FAK1"
FT /evidence="ECO:0000269|PubMed:19473962,
FT ECO:0000269|PubMed:20622016"
FT MOD_RES 361
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1
FT /note="M -> MGKWRPGQGHTTGSVKPLSCSDAM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041665"
FT VAR_SEQ 48..81
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041666"
FT VAR_SEQ 425..447
FT /note="IHRTQLWFHGRISREESQRLIGQ -> CSWSGRVSGTPRALSSLCATCRK
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9710451"
FT /id="VSP_035500"
FT VAR_SEQ 448..532
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9710451"
FT /id="VSP_035501"
FT MUTAGEN 188
FT /note="Y->F: Abolishes Ras activity increase and ERK1/2
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:20622016"
FT MUTAGEN 239
FT /note="R->L: Abolishes phosphoinositide binding."
FT /evidence="ECO:0000269|PubMed:12021278"
FT MUTAGEN 259
FT /note="Y->F: Global loss of tyrosine phosphorylation.
FT Abolishes interaction with FHL2 and HAX1."
FT /evidence="ECO:0000269|PubMed:18853468,
FT ECO:0000269|PubMed:20665473"
FT MUTAGEN 260
FT /note="Y->F: Global loss of tyrosine phosphorylation.
FT Abolishes interaction with FHL2 and HAX1."
FT /evidence="ECO:0000269|PubMed:18853468,
FT ECO:0000269|PubMed:20665473"
FT MUTAGEN 284
FT /note="Y->F: Global loss of tyrosine phosphorylation.
FT Abolishes interaction with FHL2 and HAX1."
FT /evidence="ECO:0000269|PubMed:18853468,
FT ECO:0000269|PubMed:20665473"
FT MUTAGEN 338
FT /note="Y->F: Abolishes Ras activity increase and ERK1/2
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:20622016"
FT MUTAGEN 458
FT /note="R->L: Impairs phosphotyrosine binding by SH2
FT domain."
FT MUTAGEN 480
FT /note="Y->F: Global loss of tyrosine phosphorylation.
FT Abolishes interaction with FHL2 and HAX1."
FT /evidence="ECO:0000269|PubMed:18853468,
FT ECO:0000269|PubMed:20665473"
FT MUTAGEN 492
FT /note="Y->F: Global loss of tyrosine phosphorylation.
FT Abolishes interaction with FHL2 and HAX1."
FT /evidence="ECO:0000269|PubMed:18853468,
FT ECO:0000269|PubMed:20665473"
FT MUTAGEN 511
FT /note="F->R: Abolishes dimerization. Abolishes activation
FT of HRAS."
FT /evidence="ECO:0000269|PubMed:15841400"
FT CONFLICT 18
FT /note="C -> W (in Ref. 1; BAA07827, 2; BAA29059/BAA29060
FT and 3; AAG25938)"
FT /evidence="ECO:0000305"
FT CONFLICT 118
FT /note="V -> A (in Ref. 5; BAG36998)"
FT /evidence="ECO:0000305"
FT CONFLICT 120
FT /note="A -> T (in Ref. 5; BAG54211)"
FT /evidence="ECO:0000305"
FT CONFLICT 147
FT /note="E -> G (in Ref. 5; BAG51372)"
FT /evidence="ECO:0000305"
FT CONFLICT 164
FT /note="V -> L (in Ref. 5; BAG36998)"
FT /evidence="ECO:0000305"
FT CONFLICT 510
FT /note="E -> D (in Ref. 5; BAG36998)"
FT /evidence="ECO:0000305"
FT STRAND 102..108
FT /evidence="ECO:0007829|PDB:1WGR"
FT STRAND 113..118
FT /evidence="ECO:0007829|PDB:1WGR"
FT HELIX 124..132
FT /evidence="ECO:0007829|PDB:1WGR"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:1WGR"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:1WGR"
FT TURN 150..152
FT /evidence="ECO:0007829|PDB:1WGR"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:1WGR"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:1WGR"
FT HELIX 164..168
FT /evidence="ECO:0007829|PDB:1WGR"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:1WGR"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:1WGR"
FT HELIX 421..424
FT /evidence="ECO:0007829|PDB:2QMS"
FT HELIX 425..428
FT /evidence="ECO:0007829|PDB:5U1Q"
FT HELIX 429..431
FT /evidence="ECO:0007829|PDB:2L4K"
FT STRAND 432..436
FT /evidence="ECO:0007829|PDB:2QMS"
FT HELIX 438..447
FT /evidence="ECO:0007829|PDB:5EEQ"
FT STRAND 454..459
FT /evidence="ECO:0007829|PDB:5EEQ"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:5U06"
FT STRAND 466..473
FT /evidence="ECO:0007829|PDB:5EEQ"
FT STRAND 476..487
FT /evidence="ECO:0007829|PDB:5EEQ"
FT STRAND 490..496
FT /evidence="ECO:0007829|PDB:5EEQ"
FT STRAND 502..504
FT /evidence="ECO:0007829|PDB:5EEQ"
FT HELIX 505..512
FT /evidence="ECO:0007829|PDB:5EEQ"
FT STRAND 513..515
FT /evidence="ECO:0007829|PDB:1MW4"
FT STRAND 519..521
FT /evidence="ECO:0007829|PDB:5EEQ"
FT CONFLICT Q14451-3:20
FT /note="C -> R (in Ref. 5; BAG54211)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 532 AA; 59681 MW; A6867C20AFD46F74 CRC64;
MELDLSPPHL SSSPEDLCPA PGTPPGTPRP PDTPLPEEVK RSQPLLIPTT GRKLREEERR
ATSLPSIPNP FPELCSPPSQ SPILGGPSSA RGLLPRDASR PHVVKVYSED GACRSVEVAA
GATARHVCEM LVQRAHALSD ETWGLVECHP HLALERGLED HESVVEVQAA WPVGGDSRFV
FRKNFAKYEL FKSSPHSLFP EKMVSSCLDA HTGISHEDLI QNFLNAGSFP EIQGFLQLRG
SGRKLWKRFF CFLRRSGLYY STKGTSKDPR HLQYVADVNE SNVYVVTQGR KLYGMPTDFG
FCVKPNKLRN GHKGLRIFCS EDEQSRTCWL AAFRLFKYGV QLYKNYQQAQ SRHLHPSCLG
SPPLRSASDN TLVAMDFSGH AGRVIENPRE ALSVALEEAQ AWRKKTNHRL SLPMPASGTS
LSAAIHRTQL WFHGRISREE SQRLIGQQGL VDGLFLVRES QRNPQGFVLS LCHLQKVKHY
LILPSEEEGR LYFSMDDGQT RFTDLLQLVE FHQLNRGILP CLLRHCCTRV AL
