GRB14_MOUSE
ID GRB14_MOUSE Reviewed; 538 AA.
AC Q9JLM9; Q3UI77; Q8VDI2; Q9CR03;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Growth factor receptor-bound protein 14;
DE AltName: Full=GRB14 adapter protein;
GN Name=Grb14;
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].
RX PubMed=10713090; DOI=10.1074/jbc.275.11.7771;
RA Reilly J.F., Mickey G., Maher P.A.;
RT "Association of fibroblast growth factor receptor 1 with the adaptor
RT protein Grb14. Characterization of a new receptor binding partner.";
RL J. Biol. Chem. 275:7771-7778(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic liver, and Heart;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 332-538.
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [4]
RP INTERACTION WITH TEK/TIE2.
RX PubMed=10521483; DOI=10.1074/jbc.274.43.30896;
RA Jones N., Master Z., Jones J., Bouchard D., Gunji Y., Sasaki H., Daly R.,
RA Alitalo K., Dumont D.J.;
RT "Identification of Tek/Tie2 binding partners. Binding to a multifunctional
RT docking site mediates cell survival and migration.";
RL J. Biol. Chem. 274:30896-30905(1999).
RN [5]
RP IDENTIFICATION BY 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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-373, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Liver, Lung, and Testis;
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 cell surface
CC receptor kinases with specific signaling pathways. Binds to, and
CC suppresses signals from, the activated insulin receptor (INSR). Potent
CC inhibitor of insulin-stimulated MAPK3 phosphorylation. Plays a critical
CC role regulating PDPK1 membrane translocation in response to insulin
CC stimulation and serves as an adapter protein to recruit PDPK1 to
CC activated insulin receptor, thus promoting PKB/AKT1 phosphorylation and
CC transduction of the insulin signal (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with the cytoplasmic domain of the
CC autophosphorylated insulin receptor, through the SH2 domain. Interacts
CC with GRB14 (via BPS domain); this interaction protects the tyrosines in
CC the activation loop on INSR from dephosphorylation (By similarity).
CC Binds to the ankyrin repeat region of TNKS2 via its N-terminus.
CC Interacts with activated NRAS (By similarity). Interacts (via SH2
CC domain) with TEK/TIE2 (tyrosine phosphorylated). {ECO:0000250,
CC ECO:0000269|PubMed:10521483}.
CC -!- INTERACTION:
CC Q9JLM9; P29973: CNGA1; Xeno; NbExp=2; IntAct=EBI-8347358, EBI-8417095;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q14449}.
CC Endosome membrane {ECO:0000250|UniProtKB:Q14449}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:Q14449}. Note=Upon insulin stimulation,
CC translocates to the plasma membrane. {ECO:0000250|UniProtKB:Q14449}.
CC -!- DOMAIN: The PH domain binds relatively non-specifically and with low
CC affinity to several phosphoinositides, the best binder being
CC PI(3,4,5)P3. {ECO:0000250}.
CC -!- PTM: Phosphorylated on serine residues. Phosphorylated on tyrosine
CC residues by TEK/TIE2 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
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DR EMBL; AF155647; AAF43996.1; -; mRNA.
DR EMBL; AK010849; BAB27221.3; -; mRNA.
DR EMBL; AK010903; BAB27256.3; -; mRNA.
DR EMBL; AK147041; BAE27629.1; -; mRNA.
DR EMBL; BC021820; AAH21820.1; -; mRNA.
DR CCDS; CCDS16071.1; -.
DR RefSeq; NP_057928.1; NM_016719.1.
DR AlphaFoldDB; Q9JLM9; -.
DR SMR; Q9JLM9; -.
DR BioGRID; 206154; 3.
DR IntAct; Q9JLM9; 1.
DR MINT; Q9JLM9; -.
DR STRING; 10090.ENSMUSP00000028252; -.
DR iPTMnet; Q9JLM9; -.
DR PhosphoSitePlus; Q9JLM9; -.
DR MaxQB; Q9JLM9; -.
DR PaxDb; Q9JLM9; -.
DR PRIDE; Q9JLM9; -.
DR ProteomicsDB; 271294; -.
DR Antibodypedia; 33757; 198 antibodies from 29 providers.
DR DNASU; 50915; -.
DR Ensembl; ENSMUST00000028252; ENSMUSP00000028252; ENSMUSG00000026888.
DR GeneID; 50915; -.
DR KEGG; mmu:50915; -.
DR UCSC; uc008jvx.2; mouse.
DR CTD; 2888; -.
DR MGI; MGI:1355324; Grb14.
DR VEuPathDB; HostDB:ENSMUSG00000026888; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000158609; -.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; Q9JLM9; -.
DR OMA; EDDGAMF; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; Q9JLM9; -.
DR TreeFam; TF317511; -.
DR Reactome; R-MMU-210993; Tie2 Signaling.
DR BioGRID-ORCS; 50915; 1 hit in 71 CRISPR screens.
DR PRO; PR:Q9JLM9; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9JLM9; protein.
DR Bgee; ENSMUSG00000026888; Expressed in interventricular septum and 235 other tissues.
DR ExpressionAtlas; Q9JLM9; baseline and differential.
DR Genevisible; Q9JLM9; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005768; C:endosome; ISO:MGI.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IDA:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0032869; P:cellular response to insulin stimulus; ISO:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:1904145; P:negative regulation of meiotic cell cycle process involved in oocyte maturation; ISO:MGI.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
DR CDD; cd01259; PH_APBB1IP; 1.
DR CDD; cd10414; SH2_Grb14; 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; IPR035035; Grb14.
DR InterPro; IPR035034; Grb14_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:SF22; PTHR11243:SF22; 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 Acetylation; Cytoplasm; Endosome; Membrane; Phosphoprotein;
KW Reference proteome; SH2 domain.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q14449"
FT CHAIN 2..538
FT /note="Growth factor receptor-bound protein 14"
FT /id="PRO_0000150349"
FT DOMAIN 104..190
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 232..340
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 437..533
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0000250|UniProtKB:Q14449"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88900"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
SQ SEQUENCE 538 AA; 60573 MW; 04ABD6CEB6ABC6CB CRC64;
MTTSLQDGQS AAGRAGAQDS PLAVQVCRVA QGKGDAQDPA QVPGLHALSP ASDATLRGAI
DRRKMKDLDV LEKPPIPNPF PELCCSPLTS VLSAGLFPRA NSRKKQVIKV YSEDETSRAL
EVPSDITARD VCQLLILKNH YVDDNSWTLF EHLSHIGLER TVEDHELPTE VLSHWGVEED
NKLYLRKNYA KYEFFKNPMY FFPEHMVSFA AEMNGDRSPT QILQVFLSSS TYPEIHGFLH
AKEQGKKSWK KAYFFLRRSG LYFSTKGTSK EPRHLQLFSE FSTSHVYMSL AGKKKHGAPT
PYGFCLKPNK AGGPRDLKML CAEEEQSRTC WVTAIRLLKD GMQLYQNYMH PYQGRSACNS
QSMSPMRSVS ENSLVAMDFS GEKSRVIDNP TEALSVAVEE GLAWRKKGCL RLGNHGSPSA
PSQSSAVNMA LHRSQPWFHH RISRDEAQRL IIRQGPVDGV FLVRDSQSNP RTFVLSMSHG
QKIKHYQIIP VEDDGELFHT LDDGHTKFTD LIQLVEFYQL NRGVLPCKLK HYCARMAV
