GRB14_HUMAN
ID GRB14_HUMAN Reviewed; 540 AA.
AC Q14449; B7Z7F9; Q7Z6I1;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 2.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=Growth factor receptor-bound protein 14;
DE AltName: Full=GRB14 adapter protein;
GN Name=GRB14;
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), AND VARIANT ILE-90.
RX PubMed=8647858; DOI=10.1074/jbc.271.21.12502;
RA Daly R.J., Sanderson G.M., Janes P.W., Sutherland R.L.;
RT "Cloning and characterization of GRB14, a novel member of the GRB7 gene
RT family.";
RL J. Biol. Chem. 271:12502-12510(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 INTERACTION WITH INSR.
RX PubMed=11726652; DOI=10.1074/jbc.m106574200;
RA Bereziat V., Kasus-Jacobi A., Perdereau D., Cariou B., Girard J.,
RA Burnol A.F.;
RT "Inhibition of insulin receptor catalytic activity by the molecular adapter
RT Grb14.";
RL J. Biol. Chem. 277:4845-4852(2002).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PDPK1.
RX PubMed=15210700; DOI=10.1074/jbc.m405340200;
RA King C.C., Newton A.C.;
RT "The adaptor protein Grb14 regulates the localization of 3-
RT phosphoinositide-dependent kinase-1.";
RL J. Biol. Chem. 279:37518-37527(2004).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP FUNCTION, INTERACTION WITH NRAS, PHOSPHOINOSITIDE-BINDING, SUBCELLULAR
RP LOCATION, DOMAIN PH, AND MUTAGENESIS OF LYS-140; GLU-245; GLN-246; LYS-252;
RP GLY-299; GLN-348 AND ASN-349.
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 [10]
RP ERRATUM OF PUBMED:19648926.
RA Depetris R.S., Wu J., Hubbard S.R.;
RL Nat. Struct. Mol. Biol. 16:1331-1331(2009).
RN [11]
RP INTERACTION WITH TEK/TIE2, AND PHOSPHORYLATION.
RX PubMed=20973951; DOI=10.1186/1478-811x-8-30;
RA Sturk C., Dumont D.J.;
RT "Tyrosine phosphorylation of Grb14 by Tie2.";
RL Cell Commun. Signal. 8:30-30(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-9 (ISOFORM 2), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 361-419 AND 433-537 IN COMPLEX
RP WITH INSR.
RX PubMed=16246733; DOI=10.1016/j.molcel.2005.09.001;
RA Depetris R.S., Hu J., Gimpelevich I., Holt L.J., Daly R.J., Hubbard S.R.;
RT "Structural basis for inhibition of the insulin receptor by the adaptor
RT protein Grb14.";
RL Mol. Cell 20:325-333(2005).
RN [14]
RP VARIANTS ILE-90 AND TYR-507.
RX PubMed=21220648; DOI=10.1001/archneurol.2010.351;
RA Daoud H., Valdmanis P.N., Gros-Louis F., Belzil V., Spiegelman D.,
RA Henrion E., Diallo O., Desjarlais A., Gauthier J., Camu W., Dion P.A.,
RA Rouleau G.A.;
RT "Resequencing of 29 candidate genes in patients with familial and sporadic
RT amyotrophic lateral sclerosis.";
RL Arch. Neurol. 68:587-593(2011).
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. {ECO:0000269|PubMed:15210700,
CC ECO:0000269|PubMed:19648926}.
CC -!- SUBUNIT: Interacts with the cytoplasmic domain of the
CC autophosphorylated insulin receptor (INSR), through the SH2 domain (By
CC similarity). Interacts with GRB14 (via BPS domain); this interaction
CC protects the tyrosines in the activation loop on INSR from
CC dephosphorylation. Binds to the ankyrin repeat region of TNKS2 via its
CC N-terminus. Interacts with activated NRAS. Interacts (via SH2 domain)
CC with TEK/TIE2 (tyrosine phosphorylated). {ECO:0000250,
CC ECO:0000269|PubMed:11726652, ECO:0000269|PubMed:15210700,
CC ECO:0000269|PubMed:16246733, ECO:0000269|PubMed:19648926,
CC ECO:0000269|PubMed:20973951}.
CC -!- INTERACTION:
CC Q14449; Q08379: GOLGA2; NbExp=3; IntAct=EBI-2680889, EBI-618309;
CC Q14449; P14373: TRIM27; NbExp=3; IntAct=EBI-2680889, EBI-719493;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15210700,
CC ECO:0000269|PubMed:19648926}. Endosome membrane
CC {ECO:0000269|PubMed:15210700, ECO:0000269|PubMed:19648926}; Peripheral
CC membrane protein {ECO:0000269|PubMed:15210700,
CC ECO:0000269|PubMed:19648926}. Note=Upon insulin stimulation,
CC translocates to the plasma membrane. {ECO:0000269|PubMed:15210700,
CC ECO:0000269|PubMed:19648926}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14449-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14449-2; Sequence=VSP_056582, VSP_056583;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in the liver, kidney,
CC pancreas, testis, ovary, heart and skeletal muscle.
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:0000269|PubMed:19648926}.
CC -!- PTM: Phosphorylated on serine residues. Phosphorylated on tyrosine
CC residues by TEK/TIE2. {ECO:0000269|PubMed:20973951}.
CC -!- SIMILARITY: Belongs to the GRB7/10/14 family. {ECO:0000305}.
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DR EMBL; L76687; AAC15861.1; -; mRNA.
DR EMBL; AK301961; BAH13595.1; -; mRNA.
DR EMBL; AC107075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11342.1; -; Genomic_DNA.
DR EMBL; BC053559; AAH53559.1; -; mRNA.
DR CCDS; CCDS2222.1; -. [Q14449-1]
DR RefSeq; NP_001290351.1; NM_001303422.1. [Q14449-2]
DR RefSeq; NP_004481.2; NM_004490.2. [Q14449-1]
DR PDB; 2AUG; X-ray; 2.30 A; A/B=433-537.
DR PDB; 2AUH; X-ray; 3.20 A; B=361-419.
DR PDB; 4K81; X-ray; 2.40 A; A/C/E/G=106-356.
DR PDBsum; 2AUG; -.
DR PDBsum; 2AUH; -.
DR PDBsum; 4K81; -.
DR AlphaFoldDB; Q14449; -.
DR SMR; Q14449; -.
DR BioGRID; 109145; 26.
DR DIP; DIP-42605N; -.
DR IntAct; Q14449; 13.
DR MINT; Q14449; -.
DR STRING; 9606.ENSP00000263915; -.
DR iPTMnet; Q14449; -.
DR PhosphoSitePlus; Q14449; -.
DR BioMuta; GRB14; -.
DR DMDM; 59802920; -.
DR EPD; Q14449; -.
DR MassIVE; Q14449; -.
DR MaxQB; Q14449; -.
DR PaxDb; Q14449; -.
DR PeptideAtlas; Q14449; -.
DR PRIDE; Q14449; -.
DR ProteomicsDB; 59994; -. [Q14449-1]
DR ProteomicsDB; 6865; -.
DR Antibodypedia; 33757; 198 antibodies from 29 providers.
DR DNASU; 2888; -.
DR Ensembl; ENST00000263915.8; ENSP00000263915.3; ENSG00000115290.10. [Q14449-1]
DR GeneID; 2888; -.
DR KEGG; hsa:2888; -.
DR MANE-Select; ENST00000263915.8; ENSP00000263915.3; NM_004490.3; NP_004481.2.
DR UCSC; uc002ucl.4; human. [Q14449-1]
DR CTD; 2888; -.
DR DisGeNET; 2888; -.
DR GeneCards; GRB14; -.
DR HGNC; HGNC:4565; GRB14.
DR HPA; ENSG00000115290; Tissue enhanced (liver, tongue).
DR MIM; 601524; gene.
DR neXtProt; NX_Q14449; -.
DR OpenTargets; ENSG00000115290; -.
DR PharmGKB; PA28961; -.
DR VEuPathDB; HostDB:ENSG00000115290; -.
DR eggNOG; KOG3751; Eukaryota.
DR GeneTree; ENSGT00940000158609; -.
DR HOGENOM; CLU_023207_0_1_1; -.
DR InParanoid; Q14449; -.
DR OMA; EDDGAMF; -.
DR OrthoDB; 497681at2759; -.
DR PhylomeDB; Q14449; -.
DR TreeFam; TF317511; -.
DR PathwayCommons; Q14449; -.
DR Reactome; R-HSA-210993; Tie2 Signaling.
DR SignaLink; Q14449; -.
DR SIGNOR; Q14449; -.
DR BioGRID-ORCS; 2888; 7 hits in 1068 CRISPR screens.
DR ChiTaRS; GRB14; human.
DR EvolutionaryTrace; Q14449; -.
DR GeneWiki; GRB14; -.
DR GenomeRNAi; 2888; -.
DR Pharos; Q14449; Tbio.
DR PRO; PR:Q14449; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q14449; protein.
DR Bgee; ENSG00000115290; Expressed in adrenal tissue and 130 other tissues.
DR ExpressionAtlas; Q14449; baseline and differential.
DR Genevisible; Q14449; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IEA:Ensembl.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:CAFA.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:CAFA.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd01259; PH_APBB1IP; 1.
DR CDD; cd10414; SH2_Grb14; 1.
DR DisProt; DP00230; -.
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 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Endosome;
KW Membrane; Phosphoprotein; Reference proteome; SH2 domain.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..540
FT /note="Growth factor receptor-bound protein 14"
FT /id="PRO_0000150348"
FT DOMAIN 106..192
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 234..342
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 439..535
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88900"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9JLM9"
FT VAR_SEQ 1..21
FT /note="MTTSLQDGQSAASRAAARDSP -> MSLSARRVTLPAITPIILQKR (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056582"
FT VAR_SEQ 22..108
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056583"
FT VARIANT 90
FT /note="F -> I (in dbSNP:rs61748245)"
FT /evidence="ECO:0000269|PubMed:21220648,
FT ECO:0000269|PubMed:8647858"
FT /id="VAR_065758"
FT VARIANT 507
FT /note="H -> Y (in a patient with amyotrophic lateral
FT sclerosis; dbSNP:rs144301087)"
FT /evidence="ECO:0000269|PubMed:21220648"
FT /id="VAR_065759"
FT MUTAGEN 140
FT /note="K->A: Partial loss of INSR-binding. Loss of
FT inhibition of AKT1 activation. Loss of inhibition of MAPK3
FT phosphorylation. Loss of NRAS-binding."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 245
FT /note="E->G: 4-fold increase in PI(3,4,5)P3-binding
FT affinity; when associated with S-246."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 246
FT /note="Q->S: 4-fold increase in PI(3,4,5)P3-binding
FT affinity; when associated with G-245."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 252
FT /note="K->A: Partial loss of INSR-binding. Loss of
FT inhibition of AKT1 activation. Loss of inhibition of MAPK3
FT phosphorylation. Loss of translocation to the plasma
FT membrane upon insulin-stimulation. More than 3-fold
FT decrease in PI(3,4,5)P3-binding affinity."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 299
FT /note="G->N: No effect on PI(3,4,5)P3-binding."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 348
FT /note="Q->A: Loss of inhibition of AKT1 activation; when
FT associated with A-349. Loss of inhibition of MAPK3
FT phosphorylation; when associated with A-349. No effect on
FT INSR-binding; when associated with A-349."
FT /evidence="ECO:0000269|PubMed:19648926"
FT MUTAGEN 349
FT /note="N->A: Loss of inhibition of AKT1 activation; when
FT associated with A-348. Loss of inhibition of MAPK3
FT phosphorylation; when associated with A-348. No effect on
FT INSR-binding; when associated with A-348."
FT /evidence="ECO:0000269|PubMed:19648926"
FT STRAND 107..113
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 119..125
FT /evidence="ECO:0007829|PDB:4K81"
FT HELIX 130..141
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 149..155
FT /evidence="ECO:0007829|PDB:4K81"
FT TURN 156..159
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 160..163
FT /evidence="ECO:0007829|PDB:4K81"
FT HELIX 170..175
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 184..189
FT /evidence="ECO:0007829|PDB:4K81"
FT HELIX 195..198
FT /evidence="ECO:0007829|PDB:4K81"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:4K81"
FT TURN 206..208
FT /evidence="ECO:0007829|PDB:4K81"
FT HELIX 221..229
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 236..244
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 251..259
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 262..268
FT /evidence="ECO:0007829|PDB:4K81"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 283..291
FT /evidence="ECO:0007829|PDB:4K81"
FT TURN 297..299
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 301..303
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 305..310
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 320..323
FT /evidence="ECO:0007829|PDB:4K81"
FT HELIX 327..342
FT /evidence="ECO:0007829|PDB:4K81"
FT HELIX 344..351
FT /evidence="ECO:0007829|PDB:4K81"
FT STRAND 377..380
FT /evidence="ECO:0007829|PDB:2AUH"
FT STRAND 382..385
FT /evidence="ECO:0007829|PDB:2AUH"
FT HELIX 392..407
FT /evidence="ECO:0007829|PDB:2AUH"
FT HELIX 434..436
FT /evidence="ECO:0007829|PDB:2AUG"
FT HELIX 446..454
FT /evidence="ECO:0007829|PDB:2AUG"
FT TURN 455..457
FT /evidence="ECO:0007829|PDB:2AUG"
FT STRAND 462..467
FT /evidence="ECO:0007829|PDB:2AUG"
FT STRAND 469..472
FT /evidence="ECO:0007829|PDB:2AUG"
FT STRAND 475..481
FT /evidence="ECO:0007829|PDB:2AUG"
FT STRAND 484..495
FT /evidence="ECO:0007829|PDB:2AUG"
FT STRAND 498..504
FT /evidence="ECO:0007829|PDB:2AUG"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:2AUG"
FT HELIX 513..520
FT /evidence="ECO:0007829|PDB:2AUG"
FT STRAND 527..529
FT /evidence="ECO:0007829|PDB:2AUG"
FT MOD_RES Q14449-2:9
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
SQ SEQUENCE 540 AA; 60988 MW; 00472988650F7C6C CRC64;
MTTSLQDGQS AASRAAARDS PLAAQVCGAA QGRGDAHDLA PAPWLHARAL LPLPDGTRGC
AADRRKKKDL DVPEMPSIPN PFPELCCSPF TSVLSADLFP KANSRKKQVI KVYSEDETSR
ALDVPSDITA RDVCQLLILK NHYIDDHSWT LFEHLPHIGV ERTIEDHELV IEVLSNWGIE
EENKLYFRKN YAKYEFFKNP MYFFPEHMVS FATETNGEIS PTQILQMFLS SSTYPEIHGF
LHAKEQGKKS WKKIYFFLRR SGLYFSTKGT SKEPRHLQFF SEFGNSDIYV SLAGKKKHGA
PTNYGFCFKP NKAGGPRDLK MLCAEEEQSR TCWVTAIRLL KYGMQLYQNY MHPYQGRSGC
SSQSISPMRS ISENSLVAMD FSGQKSRVIE NPTEALSVAV EEGLAWRKKG CLRLGTHGSP
TASSQSSATN MAIHRSQPWF HHKISRDEAQ RLIIQQGLVD GVFLVRDSQS NPKTFVLSMS
HGQKIKHFQI IPVEDDGEMF HTLDDGHTRF TDLIQLVEFY QLNKGVLPCK LKHYCARIAL
