GRDN_HUMAN
ID GRDN_HUMAN Reviewed; 1871 AA.
AC Q3V6T2; A1IGE7; B7ZM78; C9JG83; Q53SF1; Q581G3; Q5HYD0; Q7Z339; Q7Z3C5;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Girdin;
DE AltName: Full=Akt phosphorylation enhancer;
DE Short=APE;
DE AltName: Full=Coiled-coil domain-containing protein 88A;
DE AltName: Full=G alpha-interacting vesicle-associated protein;
DE Short=GIV;
DE AltName: Full=Girders of actin filament;
DE AltName: Full=Hook-related protein 1;
DE Short=HkRP1;
GN Name=CCDC88A;
GN Synonyms=APE {ECO:0000312|EMBL:BAF44475.1}, GRDN,
GN KIAA1212 {ECO:0000312|EMBL:AAI32737.1, ECO:0000312|HGNC:HGNC:25523};
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] {ECO:0000305, ECO:0000312|EMBL:BAE44387.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, INTERACTION WITH AKT1,
RP INTERACTION WITH PHOSPHOINOSITIDES, HOMOOLIGOMERIZATION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-1417 BY AKT1, AND
RP MUTAGENESIS OF SER-1417.
RC TISSUE=Fetal brain {ECO:0000269|PubMed:16139227};
RX PubMed=16139227; DOI=10.1016/j.devcel.2005.08.001;
RA Enomoto A., Murakami H., Asai N., Morone N., Watanabe T., Kawai K.,
RA Murakumo Y., Usukura J., Kaibuchi K., Takahashi M.;
RT "Akt/PKB regulates actin organization and cell motility via Girdin/APE.";
RL Dev. Cell 9:389-402(2005).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, SUBCELLULAR LOCATION, AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Fetal brain {ECO:0000269|PubMed:15882442};
RX PubMed=15882442; DOI=10.1111/j.1600-0854.2005.00289.x;
RA Simpson F., Martin S., Evans T.M., Kerr M., James D.E., Parton R.G.,
RA Teasdale R.D., Wicking C.;
RT "A novel hook-related protein family and the characterization of hook-
RT related protein 1.";
RL Traffic 6:442-458(2005).
RN [3] {ECO:0000305, ECO:0000312|EMBL:BAF44475.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Anai M.;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000312|EMBL:AAX82029.1}
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 [5] {ECO:0000305, ECO:0000312|EMBL:AAI32737.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 5).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 811-1871 (ISOFORM 2), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 826-1850 (ISOFORM 1), AND NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 851-1871 (ISOFORM 4).
RC TISSUE=Amygdala, and Testis;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7] {ECO:0000305}
RP IDENTIFICATION, AND SUBCELLULAR LOCATION.
RX PubMed=15749703; DOI=10.1074/jbc.m501833200;
RA Le-Niculescu H., Niesman I., Fischer T., DeVries L., Farquhar M.G.;
RT "Identification and characterization of GIV, a novel Galpha i/s-interacting
RT protein found on COPI, endoplasmic reticulum-Golgi transport vesicles.";
RL J. Biol. Chem. 280:22012-22020(2005).
RN [8] {ECO:0000305}
RP REVIEW.
RX PubMed=17185515; DOI=10.1196/annals.1377.016;
RA Enomoto A., Ping J., Takahashi M.;
RT "Girdin, a novel actin-binding protein, and its family of proteins possess
RT versatile functions in the Akt and Wnt signaling pathways.";
RL Ann. N. Y. Acad. Sci. 1086:169-184(2006).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1387; THR-1673 AND SER-1837,
RP AND 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 [10]
RP FUNCTION, INTERACTION WITH GNAI1; GNAI2 AND GNAI3, GBA MOTIF, AND
RP MUTAGENESIS OF PHE-1686 AND GLU-1689.
RX PubMed=19211784; DOI=10.1073/pnas.0900294106;
RA Garcia-Marcos M., Ghosh P., Farquhar M.G.;
RT "GIV is a nonreceptor GEF for G alpha i with a unique motif that regulates
RT Akt signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:3178-3183(2009).
RN [11]
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 [12]
RP FUNCTION, IDENTIFICATION IN COMPLEX WITH EGFR AND GNAI3, AND MUTAGENESIS OF
RP PHE-1686.
RX PubMed=20462955; DOI=10.1091/mbc.e10-01-0028;
RA Ghosh P., Beas A.O., Bornheimer S.J., Garcia-Marcos M., Forry E.P.,
RA Johannson C., Ear J., Jung B.H., Cabrera B., Carethers J.M., Farquhar M.G.;
RT "A G{alpha}i-GIV molecular complex binds epidermal growth factor receptor
RT and determines whether cells migrate or proliferate.";
RL Mol. Biol. Cell 21:2338-2354(2010).
RN [13]
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP FUNCTION, INTERACTION WITH GNAI3 AND PIK3R1, PHOSPHORYLATION AT TYR-1765
RP AND TYR-1799, AND MUTAGENESIS OF SER-1417; TYR-1765 AND TYR-1799.
RX PubMed=21954290; DOI=10.1126/scisignal.2002049;
RA Lin C., Ear J., Pavlova Y., Mittal Y., Kufareva I., Ghassemian M.,
RA Abagyan R., Garcia-Marcos M., Ghosh P.;
RT "Tyrosine phosphorylation of the Galpha-interacting protein GIV promotes
RT activation of phosphoinositide 3-kinase during cell migration.";
RL Sci. Signal. 4:RA64-RA64(2011).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233; SER-449; SER-1020;
RP SER-1387; SER-1417; THR-1421; SER-1717 AND SER-1820, AND IDENTIFICATION BY
RP 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 [18]
RP FUNCTION, INTERACTION WITH GNAI3 AND PRKCQ, PHOSPHORYLATION AT SER-1690,
RP AND MUTAGENESIS OF PHE-1686 AND SER-1690.
RX PubMed=23509302; DOI=10.1073/pnas.1303392110;
RA Lopez-Sanchez I., Garcia-Marcos M., Mittal Y., Aznar N., Farquhar M.G.,
RA Ghosh P.;
RT "Protein kinase C-theta (PKCtheta) phosphorylates and inhibits the guanine
RT exchange factor, GIV/Girdin.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:5510-5515(2013).
RN [19]
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 [20]
RP FUNCTION, INTERACTION WITH EGFR; GNAI3; INSR AND KDR, SH2-LIKE REGION, AND
RP MUTAGENESIS OF LYS-1723; LYS-1725; ARG-1746; LYS-1750; PHE-1766 AND
RP GLN-1778.
RX PubMed=25187647; DOI=10.1091/mbc.e14-05-0978;
RA Lin C., Ear J., Midde K., Lopez-Sanchez I., Aznar N., Garcia-Marcos M.,
RA Kufareva I., Abagyan R., Ghosh P.;
RT "Structural basis for activation of trimeric Gi proteins by multiple growth
RT factor receptors via GIV/Girdin.";
RL Mol. Biol. Cell 25:3654-3671(2014).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=27864364; DOI=10.1074/jbc.m116.764431;
RA Parag-Sharma K., Leyme A., DiGiacomo V., Marivin A., Broselid S.,
RA Garcia-Marcos M.;
RT "Membrane recruitment of the non-receptor protein GIV/Girdin (Galpha-
RT interacting, Vesicle-associated Protein/Girdin) is sufficient for
RT activating heterotrimeric G protein signaling.";
RL J. Biol. Chem. 291:27098-27111(2016).
RN [22]
RP FUNCTION, INTERACTION WITH GNAI3 AND GNAS, PHOSPHORYLATION AT SER-1675 AND
RP SER-1690, AND MUTAGENESIS OF SER-1675; PHE-1686 AND SER-1690.
RX PubMed=27621449; DOI=10.1073/pnas.1609502113;
RA Gupta V., Bhandari D., Leyme A., Aznar N., Midde K.K., Lo I.C., Ear J.,
RA Niesman I., Lopez-Sanchez I., Blanco-Canosa J.B., von Zastrow M.,
RA Garcia-Marcos M., Farquhar M.G., Ghosh P.;
RT "GIV/Girdin activates Galphai and inhibits Galphas via the same motif.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E5721-E5730(2016).
RN [23]
RP INVOLVEMENT IN PEHOL.
RX PubMed=26917597; DOI=10.1093/brain/aww014;
RA Nahorski M.S., Asai M., Wakeling E., Parker A., Asai N., Canham N.,
RA Holder S.E., Chen Y.C., Dyer J., Brady A.F., Takahashi M., Woods C.G.;
RT "CCDC88A mutations cause PEHO-like syndrome in humans and mouse.";
RL Brain 139:1036-1044(2016).
RN [24]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=27623382; DOI=10.1016/j.devcel.2016.07.013;
RA Nechipurenko I.V., Olivier-Mason A., Kazatskaya A., Kennedy J.,
RA McLachlan I.G., Heiman M.G., Blacque O.E., Sengupta P.;
RT "A Conserved role for girdin in basal body positioning and ciliogenesis.";
RL Dev. Cell 38:493-506(2016).
RN [25]
RP GBA MOTIF.
RX PubMed=30194280; DOI=10.1074/jbc.ra118.003580;
RA Maziarz M., Broselid S., DiGiacomo V., Park J.C., Luebbers A.,
RA Garcia-Navarrete L., Blanco-Canosa J.B., Baillie G.S., Garcia-Marcos M.;
RT "A biochemical and genetic discovery pipeline identifies PLCdelta4b as a
RT nonreceptor activator of heterotrimeric G-proteins.";
RL J. Biol. Chem. 293:16964-16983(2018).
RN [26] {ECO:0007744|PDB:6MHF}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1672-1702 IN COMPLEX WITH RAT
RP GNAI3, AND MUTAGENESIS OF GLN-1684.
RX PubMed=31363053; DOI=10.1073/pnas.1906658116;
RA Kalogriopoulos N.A., Rees S.D., Ngo T., Kopcho N.J., Ilatovskiy A.V.,
RA Sun N., Komives E.A., Chang G., Ghosh P., Kufareva I.;
RT "Structural basis for GPCR-independent activation of heterotrimeric Gi
RT proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:16394-16403(2019).
RN [27]
RP ERRATUM OF PUBMED:31363053.
RX PubMed=31570568; DOI=10.1073/pnas.1916094116;
RA Kalogriopoulos N.A., Rees S.D., Ngo T., Kopcho N.J., Ilatovskiy A.V.,
RA Sun N., Komives E.A., Chang G., Ghosh P., Kufareva I.;
RL Proc. Natl. Acad. Sci. U.S.A. 116:20794-20794(2019).
CC -!- FUNCTION: Bifunctional modulator of guanine nucleotide-binding proteins
CC (G proteins) (PubMed:19211784, PubMed:27621449). Acts as a non-receptor
CC guanine nucleotide exchange factor which binds to and activates guanine
CC nucleotide-binding protein G(i) alpha subunits (PubMed:19211784,
CC PubMed:21954290, PubMed:23509302, PubMed:25187647). Also acts as a
CC guanine nucleotide dissociation inhibitor for guanine nucleotide-
CC binding protein G(s) subunit alpha GNAS (PubMed:27621449). Essential
CC for cell migration (PubMed:20462955, PubMed:16139227, PubMed:19211784,
CC PubMed:21954290). Interacts in complex with G(i) alpha subunits with
CC the EGFR receptor, retaining EGFR at the cell membrane following ligand
CC stimulation and promoting EGFR signaling which triggers cell migration
CC (PubMed:20462955). Binding to Gi-alpha subunits displaces the beta and
CC gamma subunits from the heterotrimeric G-protein complex which enhances
CC phosphoinositide 3-kinase (PI3K)-dependent phosphorylation and kinase
CC activity of AKT1/PKB (PubMed:19211784). Phosphorylation of AKT1/PKB
CC induces the phosphorylation of downstream effectors GSK3 and
CC FOXO1/FKHR, and regulates DNA replication and cell proliferation (By
CC similarity). Binds in its tyrosine-phosphorylated form to the
CC phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1 which
CC enables recruitment of PIK3R1 to the EGFR receptor, enhancing PI3K
CC activity and cell migration (PubMed:21954290). Plays a role as a key
CC modulator of the AKT-mTOR signaling pathway, controlling the tempo of
CC the process of newborn neuron integration during adult neurogenesis,
CC including correct neuron positioning, dendritic development and synapse
CC formation (By similarity). Inhibition of G(s) subunit alpha GNAS leads
CC to reduced cellular levels of cAMP and suppression of cell
CC proliferation (PubMed:27621449). Essential for the integrity of the
CC actin cytoskeleton (PubMed:16139227, PubMed:19211784). Required for
CC formation of actin stress fibers and lamellipodia (PubMed:15882442).
CC May be involved in membrane sorting in the early endosome
CC (PubMed:15882442). Plays a role in ciliogenesis and cilium morphology
CC and positioning and this may partly be through regulation of the
CC localization of scaffolding protein CROCC/Rootletin (PubMed:27623382).
CC {ECO:0000250|UniProtKB:Q5SNZ0, ECO:0000269|PubMed:15882442,
CC ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:19211784,
CC ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:21954290,
CC ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:25187647,
CC ECO:0000269|PubMed:27621449, ECO:0000269|PubMed:27623382}.
CC -!- SUBUNIT: Homodimer (PubMed:16139227). Interacts (via GBA motif) with
CC guanine nucleotide-binding protein G(i) alpha subunits GNAI1, GNAI2 and
CC GNAI3 (PubMed:19211784, PubMed:21954290, PubMed:23509302,
CC PubMed:27621449, PubMed:31363053). Also interacts (via GNA motif) with
CC guanine nucleotide-binding protein G(s) alpha subunit GNAS
CC (PubMed:27621449). Interaction with G(i) alpha subunits occurs before
CC interaction with GNAS and is regulated by phosphorylation;
CC phosphorylation at Ser-1675 enhances binding to G(i) alpha subunits
CC while phosphorylation at Ser-1690 abolishes G(i) alpha subunit binding,
CC promoting binding to GNAS (PubMed:27621449). Interacts (via C-terminal
CC SH2-like region) with growth factor receptors EGFR, INSR and KDR/VEGFR2
CC (via their autophosphorylated cytoplasmic tails) (PubMed:25187647).
CC Forms a complex with EGFR and GNAI3 which leads to enhanced EGFR
CC signaling and triggering of cell migration; ligand stimulation is
CC required for recruitment of GNAI3 to the complex (PubMed:20462955,
CC PubMed:25187647). Interacts (tyrosine-phosphorylated form) with
CC phosphatidylinositol 3-kinase (PI3K) regulatory subunit PIK3R1/p85a
CC (via SH2 domains); the interaction enables recruitment of PIK3R1 to the
CC EGFR receptor, enhancing PI3K activity and cell migration
CC (PubMed:21954290). Interacts with serine/threonine-protein kinase
CC PRKCQ; the interaction leads to phosphorylation of CCDC88A and
CC inhibition of its guanine nucleotide exchange factor activity
CC (PubMed:23509302). Interacts (via C-terminus) with DISC1; the
CC interaction is direct (By similarity). Interacts with AKT proteins; the
CC interaction is inhibited in the presence of DISC1 (By similarity).
CC Interacts with AKT1/PKB (via C-terminus) (PubMed:16139227). The non-
CC phosphorylated form interacts with phosphatidylinositol 4-phosphate
CC [PI(4)P] and weakly with phosphatidylinositol 3-phosphate [PI(3)P]
CC (PubMed:16139227). Interacts with microtubules (By similarity).
CC Interacts with actin (PubMed:16139227). {ECO:0000250|UniProtKB:Q5SNZ0,
CC ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:19211784,
CC ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:21954290,
CC ECO:0000269|PubMed:23509302, ECO:0000269|PubMed:25187647,
CC ECO:0000269|PubMed:27621449, ECO:0000269|PubMed:31363053}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15882442,
CC ECO:0000269|PubMed:16139227, ECO:0000269|PubMed:27864364}; Peripheral
CC membrane protein {ECO:0000305}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:27864364}. Cytoplasmic
CC vesicle {ECO:0000269|PubMed:15749703, ECO:0000269|PubMed:15882442,
CC ECO:0000269|PubMed:16139227}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:15882442}. Cytoplasm, cytoskeleton, cilium basal
CC body {ECO:0000269|PubMed:27623382}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome, centriole
CC {ECO:0000269|PubMed:27623382}. Note=Localizes to the cytosol in
CC unstimulated cells while EGF stimulation promotes membrane localization
CC and guanine nucleotide exchange factor activity (PubMed:27864364).
CC Localizes to the cell membrane through interaction with
CC phosphoinositides (PubMed:16139227, PubMed:15882442).
CC {ECO:0000269|PubMed:15882442, ECO:0000269|PubMed:16139227,
CC ECO:0000269|PubMed:27864364}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1 {ECO:0000269|PubMed:16139227};
CC IsoId=Q3V6T2-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15882442};
CC IsoId=Q3V6T2-2; Sequence=VSP_052409;
CC Name=3;
CC IsoId=Q3V6T2-3; Sequence=VSP_040129;
CC Name=4;
CC IsoId=Q3V6T2-4; Sequence=VSP_040129, VSP_052409;
CC Name=5;
CC IsoId=Q3V6T2-5; Sequence=VSP_040129, VSP_044943;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously.
CC {ECO:0000269|PubMed:16139227}.
CC -!- DOMAIN: The GBA (G-alpha binding and activating) motif mediates binding
CC to the alpha subunits of guanine nucleotide-binding proteins (G
CC proteins). {ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:30194280}.
CC -!- DOMAIN: In the presence of tyrosine-autophosphorylated growth factor
CC receptors, the C-terminus folds into an SH2-like region which promotes
CC the stable recruitment of CCDC88A to the growth factor receptors. The
CC SH2-like region is phosphorylated by the growth factor receptors prior
CC to completion of folding. {ECO:0000269|PubMed:25187647}.
CC -!- PTM: Phosphorylation is induced by epidermal growth factor (EGF) in a
CC phosphoinositide 3-kinase (PI3K)-dependent manner (PubMed:16139227).
CC Phosphorylation by AKT1/PKB is necessary for delocalization from the
CC cell membrane and for cell migration (PubMed:16139227). Phosphorylated
CC on tyrosine residues which promotes binding to phosphatidylinositol 3-
CC kinase (PI3K) regulatory subunit PIK3R1/p85a and enhances PI3K activity
CC (PubMed:21954290). Tyrosine-phosphorylated by both receptor and non-
CC receptor tyrosine kinases in vitro (PubMed:21954290). Tyrosine
CC phosphorylation is required for AKT1-dependent phosphorylation of Ser-
CC 1417 (PubMed:21954290). Phosphorylation at Ser-1690 by PRKCQ disrupts
CC interaction with GNAI3 and inhibits guanine nucleotide exchange factor
CC activity (PubMed:23509302). {ECO:0000269|PubMed:16139227,
CC ECO:0000269|PubMed:21954290, ECO:0000269|PubMed:23509302}.
CC -!- DISEASE: PEHO-like syndrome (PEHOL) [MIM:617507]: An autosomal
CC recessive syndrome characterized by microcephaly and moderately severe
CC hypotonia manifesting at birth, seizures that progress into infantile
CC spasms with hypsarrhythmia, brain atrophy with bilateral polymicrogyria
CC and pachygyria, thin corpus callosum, and mild reduction in cerebellar
CC vermis volume. Patients also display optic atrophy, severe cognitive
CC delay, puffiness of the maxillary region of the face, and edema of the
CC dorsum of the hands and feet. {ECO:0000269|PubMed:26917597}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the CCDC88 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAY14932.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAD97945.1; Type=Miscellaneous discrepancy; Note=Intron retention at the C-terminus.; Evidence={ECO:0000305};
CC Sequence=CAI46020.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB201172; BAE44387.1; -; mRNA.
DR EMBL; AB125644; BAF44475.1; -; mRNA.
DR EMBL; AC019198; AAY14932.1; ALT_INIT; Genomic_DNA.
DR EMBL; AC092176; AAX82029.1; -; Genomic_DNA.
DR EMBL; AC012358; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC132736; AAI32737.1; -; mRNA.
DR EMBL; BC144320; AAI44321.1; -; mRNA.
DR EMBL; BX537985; CAD97945.1; ALT_SEQ; mRNA.
DR EMBL; BX538154; CAD98038.1; -; mRNA.
DR EMBL; BX648138; CAI46020.1; ALT_INIT; mRNA.
DR CCDS; CCDS33203.1; -. [Q3V6T2-2]
DR CCDS; CCDS46288.1; -. [Q3V6T2-3]
DR CCDS; CCDS58710.1; -. [Q3V6T2-5]
DR RefSeq; NP_001129069.1; NM_001135597.1. [Q3V6T2-3]
DR RefSeq; NP_001241872.1; NM_001254943.1. [Q3V6T2-5]
DR RefSeq; NP_060554.3; NM_018084.4. [Q3V6T2-2]
DR RefSeq; XP_011531267.1; XM_011532965.2.
DR RefSeq; XP_011531268.1; XM_011532966.2. [Q3V6T2-1]
DR RefSeq; XP_011531269.1; XM_011532967.2. [Q3V6T2-2]
DR PDB; 6MHF; X-ray; 2.00 A; C=1672-1702.
DR PDBsum; 6MHF; -.
DR AlphaFoldDB; Q3V6T2; -.
DR SMR; Q3V6T2; -.
DR BioGRID; 120829; 180.
DR CORUM; Q3V6T2; -.
DR DIP; DIP-50784N; -.
DR IntAct; Q3V6T2; 79.
DR MINT; Q3V6T2; -.
DR STRING; 9606.ENSP00000338728; -.
DR iPTMnet; Q3V6T2; -.
DR PhosphoSitePlus; Q3V6T2; -.
DR BioMuta; CCDC88A; -.
DR DMDM; 147644956; -.
DR EPD; Q3V6T2; -.
DR jPOST; Q3V6T2; -.
DR MassIVE; Q3V6T2; -.
DR MaxQB; Q3V6T2; -.
DR PaxDb; Q3V6T2; -.
DR PeptideAtlas; Q3V6T2; -.
DR PRIDE; Q3V6T2; -.
DR ProteomicsDB; 61886; -. [Q3V6T2-1]
DR ProteomicsDB; 61887; -. [Q3V6T2-2]
DR ProteomicsDB; 61888; -. [Q3V6T2-3]
DR ProteomicsDB; 61889; -. [Q3V6T2-4]
DR ProteomicsDB; 7248; -.
DR Antibodypedia; 47423; 255 antibodies from 33 providers.
DR DNASU; 55704; -.
DR Ensembl; ENST00000263630.13; ENSP00000263630.8; ENSG00000115355.18. [Q3V6T2-2]
DR Ensembl; ENST00000336838.10; ENSP00000338728.6; ENSG00000115355.18. [Q3V6T2-3]
DR Ensembl; ENST00000436346.7; ENSP00000410608.1; ENSG00000115355.18. [Q3V6T2-1]
DR Ensembl; ENST00000642200.1; ENSP00000495919.1; ENSG00000115355.18. [Q3V6T2-1]
DR Ensembl; ENST00000643413.1; ENSP00000494811.1; ENSG00000115355.18. [Q3V6T2-4]
DR Ensembl; ENST00000646796.1; ENSP00000493703.1; ENSG00000115355.18. [Q3V6T2-5]
DR GeneID; 55704; -.
DR KEGG; hsa:55704; -.
DR MANE-Select; ENST00000436346.7; ENSP00000410608.1; NM_001365480.1; NP_001352409.1.
DR UCSC; uc002ryv.3; human. [Q3V6T2-1]
DR CTD; 55704; -.
DR DisGeNET; 55704; -.
DR GeneCards; CCDC88A; -.
DR HGNC; HGNC:25523; CCDC88A.
DR HPA; ENSG00000115355; Tissue enhanced (brain).
DR MalaCards; CCDC88A; -.
DR MIM; 609736; gene.
DR MIM; 617507; phenotype.
DR neXtProt; NX_Q3V6T2; -.
DR OpenTargets; ENSG00000115355; -.
DR Orphanet; 99807; PEHO-like syndrome.
DR PharmGKB; PA162381751; -.
DR VEuPathDB; HostDB:ENSG00000115355; -.
DR eggNOG; KOG4643; Eukaryota.
DR GeneTree; ENSGT00940000155559; -.
DR HOGENOM; CLU_001421_1_0_1; -.
DR InParanoid; Q3V6T2; -.
DR OMA; XEEKTEQ; -.
DR OrthoDB; 59187at2759; -.
DR PhylomeDB; Q3V6T2; -.
DR TreeFam; TF320231; -.
DR PathwayCommons; Q3V6T2; -.
DR Reactome; R-HSA-9696264; RND3 GTPase cycle.
DR Reactome; R-HSA-9696273; RND1 GTPase cycle.
DR SignaLink; Q3V6T2; -.
DR SIGNOR; Q3V6T2; -.
DR BioGRID-ORCS; 55704; 15 hits in 1081 CRISPR screens.
DR ChiTaRS; CCDC88A; human.
DR GeneWiki; CCDC88A; -.
DR GenomeRNAi; 55704; -.
DR Pharos; Q3V6T2; Tbio.
DR PRO; PR:Q3V6T2; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q3V6T2; protein.
DR Bgee; ENSG00000115355; Expressed in medial globus pallidus and 160 other tissues.
DR ExpressionAtlas; Q3V6T2; baseline and differential.
DR Genevisible; Q3V6T2; HS.
DR GO; GO:0005814; C:centriole; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IBA:GO_Central.
DR GO; GO:0036064; C:ciliary basal body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0051959; F:dynein light intermediate chain binding; IBA:GO_Central.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; IPI:UniProtKB.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IPI:UniProtKB.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0005158; F:insulin receptor binding; IPI:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0043422; F:protein kinase B binding; IPI:UniProtKB.
DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB.
DR GO; GO:0042169; F:SH2 domain binding; IPI:UniProtKB.
DR GO; GO:0043184; F:vascular endothelial growth factor receptor 2 binding; IPI:UniProtKB.
DR GO; GO:0032147; P:activation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; IMP:UniProtKB.
DR GO; GO:0031122; P:cytoplasmic microtubule organization; IBA:GO_Central.
DR GO; GO:0030705; P:cytoskeleton-dependent intracellular transport; IBA:GO_Central.
DR GO; GO:0006260; P:DNA replication; IEA:UniProtKB-KW.
DR GO; GO:0030032; P:lamellipodium assembly; IMP:UniProtKB.
DR GO; GO:0072660; P:maintenance of protein location in plasma membrane; IDA:UniProtKB.
DR GO; GO:0061024; P:membrane organization; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0045724; P:positive regulation of cilium assembly; IMP:UniProtKB.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:1903566; P:positive regulation of protein localization to cilium; IMP:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:CACAO.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0006275; P:regulation of DNA replication; ISS:UniProtKB.
DR GO; GO:0010975; P:regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0001932; P:regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA:UniProtKB.
DR GO; GO:0031929; P:TOR signaling; ISS:UniProtKB.
DR Gene3D; 1.10.418.10; -; 1.
DR InterPro; IPR001715; CH-domain.
DR InterPro; IPR036872; CH_dom_sf.
DR InterPro; IPR027717; Girdin.
DR InterPro; IPR043936; HOOK_N.
DR PANTHER; PTHR18947:SF30; PTHR18947:SF30; 1.
DR Pfam; PF19047; HOOK_N; 1.
DR PROSITE; PS50021; CH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Cilium biogenesis/degradation; Coiled coil; Cytoplasm; Cytoplasmic vesicle;
KW Cytoskeleton; DNA replication; Epilepsy;
KW Guanine-nucleotide releasing factor; Intellectual disability; Membrane;
KW Neurodegeneration; Neurogenesis; Phosphoprotein; Reference proteome.
FT CHAIN 1..1871
FT /note="Girdin"
FT /id="PRO_0000287429"
FT DOMAIN 12..132
FT /note="Calponin-homology (CH)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00044"
FT REGION 816..842
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1010..1035
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1390..1408
FT /note="Phosphoinositide-binding"
FT /evidence="ECO:0000269|PubMed:16139227"
FT REGION 1407..1459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1559..1601
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1713..1823
FT /note="SH2-like; required for interaction with growth
FT factor receptors"
FT /evidence="ECO:0000269|PubMed:25187647"
FT REGION 1736..1871
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 196..425
FT /evidence="ECO:0000255"
FT COILED 458..1385
FT /evidence="ECO:0000255"
FT MOTIF 1672..1702
FT /note="GBA"
FT /evidence="ECO:0000269|PubMed:30194280"
FT COMPBIAS 1416..1459
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1743..1759
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1767..1819
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1839..1856
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1857..1871
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q5SNZ0"
FT MOD_RES 449
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1020
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1387
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1417
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:16139227,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1421
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1673
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1675
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:27621449"
FT MOD_RES 1690
FT /note="Phosphoserine; by PKC/PRKCQ"
FT /evidence="ECO:0000269|PubMed:23509302,
FT ECO:0000269|PubMed:27621449"
FT MOD_RES 1717
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1765
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21954290"
FT MOD_RES 1799
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21954290"
FT MOD_RES 1820
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1837
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 952
FT /note="Missing (in isoform 3, isoform 4 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16139227, ECO:0000303|PubMed:17974005"
FT /id="VSP_040129"
FT VAR_SEQ 1463..1491
FT /note="MVALKRLPFLRNRPKDKDKMKACYRRSMS -> T (in isoform 2 and
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:15882442, ECO:0000303|PubMed:17974005,
FT ECO:0000303|Ref.3"
FT /id="VSP_052409"
FT VAR_SEQ 1733..1806
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_044943"
FT MUTAGEN 1417
FT /note="S->A: Phosphorylation-deficient mutant which
FT disrupts actin organization, cell migration and
FT lamellipodia formation but has no effect on tyrosine
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:16139227,
FT ECO:0000269|PubMed:21954290"
FT MUTAGEN 1417
FT /note="S->D: Phosphomimetic mutant which has no effect on
FT tyrosine phosphorylation."
FT /evidence="ECO:0000269|PubMed:21954290"
FT MUTAGEN 1675
FT /note="S->A: Phosphorylation-deficient mutant which
FT disrupts binding to GNAI3 and GNAS."
FT /evidence="ECO:0000269|PubMed:27621449"
FT MUTAGEN 1675
FT /note="S->D: Phosphomimetic mutant which results in slight
FT increase in binding to GNAI3 and GNAS. Increased inhibition
FT of GNAS; when associated with D-1690."
FT /evidence="ECO:0000269|PubMed:27621449"
FT MUTAGEN 1684
FT /note="Q->A: No effect on guanine nucleotide exchange
FT factor activity."
FT /evidence="ECO:0000269|PubMed:31363053"
FT MUTAGEN 1686
FT /note="F->A: Abolishes interaction with and activation of
FT GNAI3 and also abolishes recruitment of GNAI3 to EGFR.
FT Reduced EGFR autophosphorylation and SH2 adapter
FT recruitment, reduced localization of EGFR at the cell
FT membrane following ligand stimulation with increased
FT endosomal localization, reduced cell migration and
FT increased cell proliferation. Abolishes enhancement of AKT
FT signaling. Abolishes interaction with GNAS."
FT /evidence="ECO:0000269|PubMed:19211784,
FT ECO:0000269|PubMed:20462955, ECO:0000269|PubMed:23509302,
FT ECO:0000269|PubMed:27621449"
FT MUTAGEN 1689
FT /note="E->A: Abolishes interaction with GNAI3."
FT /evidence="ECO:0000269|PubMed:19211784"
FT MUTAGEN 1690
FT /note="S->A: Phosphorylation-deficient mutant which retains
FT the ability to bind GNAI3."
FT /evidence="ECO:0000269|PubMed:23509302"
FT MUTAGEN 1690
FT /note="S->D: Phosphomimetic mutant which abolishes
FT interaction with GNAI3, inhibits guanine nucleotide
FT exchange factor activity, inhibits cell migration and
FT triggers cell proliferation. Retains ability to bind to
FT GNAS. Increased inhibition of GNAS; when associated with D-
FT 1675."
FT /evidence="ECO:0000269|PubMed:23509302,
FT ECO:0000269|PubMed:27621449"
FT MUTAGEN 1723
FT /note="K->E: Abolishes binding to phosphorylated EGFR."
FT /evidence="ECO:0000269|PubMed:25187647"
FT MUTAGEN 1725
FT /note="K->E: Does not affect binding to phosphorylated
FT EGFR."
FT /evidence="ECO:0000269|PubMed:25187647"
FT MUTAGEN 1746
FT /note="R->K,L: Abolishes binding to phosphorylated EGFR."
FT /evidence="ECO:0000269|PubMed:25187647"
FT MUTAGEN 1750
FT /note="K->E: Abolishes binding to phosphorylated EGFR."
FT /evidence="ECO:0000269|PubMed:25187647"
FT MUTAGEN 1765
FT /note="Y->F: Abolishes phosphorylation and leads to reduced
FT AKT phosphorylation, impaired formation of actin stress
FT fibers and impaired cell migration abolishes interaction
FT with PIK3R1 and activation of PI3K, reduces phosphorylation
FT of Ser-1417 but does not affect interaction with or
FT activation of GNAI3; when associated with F-1799."
FT /evidence="ECO:0000269|PubMed:21954290"
FT MUTAGEN 1766
FT /note="F->T: Increases binding to phosphorylated EGFR."
FT /evidence="ECO:0000269|PubMed:25187647"
FT MUTAGEN 1778
FT /note="Q->E: Abolishes binding to phosphorylated EGFR."
FT /evidence="ECO:0000269|PubMed:25187647"
FT MUTAGEN 1799
FT /note="Y->F: Abolishes phosphorylation and leads to reduced
FT AKT phosphorylation, impaired formation of actin stress
FT fibers and impaired cell migration, abolishes interaction
FT with PIK3R1 and activation of PI3K activity, reduces
FT phosphorylation of Ser-1417 but does not affect interaction
FT with or activation of GNAI3; when associated with F-1765."
FT /evidence="ECO:0000269|PubMed:21954290"
FT CONFLICT 1066
FT /note="K -> E (in Ref. 6; CAI46020)"
FT /evidence="ECO:0000305"
FT CONFLICT 1081
FT /note="A -> T (in Ref. 6; CAD97945)"
FT /evidence="ECO:0000305"
FT CONFLICT 1661
FT /note="S -> P (in Ref. 6; CAD97945)"
FT /evidence="ECO:0000305"
FT CONFLICT 1710
FT /note="V -> I (in Ref. 6; CAI46020)"
FT /evidence="ECO:0000305"
FT CONFLICT 1799
FT /note="Y -> H (in Ref. 6; CAD98038)"
FT /evidence="ECO:0000305"
FT CONFLICT 1836
FT /note="D -> G (in Ref. 6; CAI46020)"
FT /evidence="ECO:0000305"
FT STRAND 1679..1682
FT /evidence="ECO:0007829|PDB:6MHF"
FT HELIX 1683..1690
FT /evidence="ECO:0007829|PDB:6MHF"
SQ SEQUENCE 1871 AA; 216042 MW; 9DD2E06F2A235AA5 CRC64;
MENEIFTPLL EQFMTSPLVT WVKTFGPLAA GNGTNLDEYV ALVDGVFLNQ VMLQINPKLE
SQRVNKKVNN DASLRMHNLS ILVRQIKFYY QETLQQLIMM SLPNVLIIGK NPFSEQGTEE
VKKLLLLLLG CAVQCQKKEE FIERIQGLDF DTKAAVAAHI QEVTHNQENV FDLQWMEVTD
MSQEDIEPLL KNMALHLKRL IDERDEHSET IIELSEERDG LHFLPHASSS AQSPCGSPGM
KRTESRQHLS VELADAKAKI RRLRQELEEK TEQLLDCKQE LEQMEIELKR LQQENMNLLS
DARSARMYRD ELDALREKAV RVDKLESEVS RYKERLHDIE FYKARVEELK EDNQVLLETK
TMLEDQLEGT RARSDKLHEL EKENLQLKAK LHDMEMERDM DRKKIEELME ENMTLEMAQK
QSMDESLHLG WELEQISRTS ELSEAPQKSL GHEVNELTSS RLLKLEMENQ SLTKTVEELR
TTVDSVEGNA SKILKMEKEN QRLSKKVEIL ENEIVQEKQS LQNCQNLSKD LMKEKAQLEK
TIETLRENSE RQIKILEQEN EHLNQTVSSL RQRSQISAEA RVKDIEKENK ILHESIKETS
SKLSKIEFEK RQIKKELEHY KEKGERAEEL ENELHHLEKE NELLQKKITN LKITCEKIEA
LEQENSELER ENRKLKKTLD SFKNLTFQLE SLEKENSQLD EENLELRRNV ESLKCASMKM
AQLQLENKEL ESEKEQLKKG LELLKASFKK TERLEVSYQG LDIENQRLQK TLENSNKKIQ
QLESELQDLE MENQTLQKNL EELKISSKRL EQLEKENKSL EQETSQLEKD KKQLEKENKR
LRQQAEIKDT TLEENNVKIG NLEKENKTLS KEIGIYKESC VRLKELEKEN KELVKRATID
IKTLVTLRED LVSEKLKTQQ MNNDLEKLTH ELEKIGLNKE RLLHDEQSTD DSRYKLLESK
LESTLKKSLE IKEEKIAALE ARLEESTNYN QQLRQELKTV KKNYEALKQR QDEERMVQSS
PPISGEDNKW ERESQETTRE LLKVKDRLIE VERNNATLQA EKQALKTQLK QLETQNNNLQ
AQILALQRQT VSLQEQNTTL QTQNAKLQVE NSTLNSQSTS LMNQNAQLLI QQSSLENENE
SVIKEREDLK SLYDSLIKDH EKLELLHERQ ASEYESLISK HGTLKSAHKN LEVEHRDLED
RYNQLLKQKG QLEDLEKMLK VEQEKMLLEN KNHETVAAEY KKLCGENDRL NHTYSQLLKE
TEVLQTDHKN LKSLLNNSKL EQTRLEAEFS KLKEQYQQLD ITSTKLNNQC ELLSQLKGNL
EEENRHLLDQ IQTLMLQNRT LLEQNMESKD LFHVEQRQYI DKLNELRRQK EKLEEKIMDQ
YKFYDPSPPR RRGNWITLKM RKLIKSKKDI NRERQKSLTL TPTRSDSSEG FLQLPHQDSQ
DSSSVGSNSL EDGQTLGTKK SSMVALKRLP FLRNRPKDKD KMKACYRRSM SMNDLVQSMV
LAGQWTGSTE NLEVPDDIST GKRRKELGAM AFSTTAINFS TVNSSAGFRS KQLVNNKDTT
SFEDISPQGV SDDSSTGSRV HASRPASLDS GRTSTSNSNN NASLHEVKAG AVNNQSRPQS
HSSGEFSLLH DHEAWSSSGS SPIQYLKRQT RSSPVLQHKI SETLESRHHK IKTGSPGSEV
VTLQQFLEES NKLTSVQIKS SSQENLLDEV MKSLSVSSDF LGKDKPVSCG LARSVSGKTP
GDFYDRRTTK PEFLRPGPRK TEDTYFISSA GKPTPGTQGK IKLVKESSLS RQSKDSNPYA
TLPRASSVIS TAEGTTRRTS IHDFLTKDSR LPISVDSPPA AADSNTTAAS NVDKVQESRN
SKSRSREQQS S
