RPGF2_RAT
ID RPGF2_RAT Reviewed; 1496 AA.
AC F1M386; D3ZD17;
DT 14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=Rap guanine nucleotide exchange factor 2;
DE AltName: Full=Cyclic nucleotide ras GEF;
DE Short=CNrasGEF;
DE AltName: Full=Neural RAP guanine nucleotide exchange protein;
DE Short=nRap GEP;
DE AltName: Full=PDZ domain-containing guanine nucleotide exchange factor 1;
DE Short=PDZ-GEF1;
DE AltName: Full=RA-GEF-1;
DE AltName: Full=Ras/Rap1-associating GEF-1;
GN Name=Rapgef2; Synonyms=Pdzgef1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP INTERACTION WITH MAGI2, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10548487; DOI=10.1006/bbrc.1999.1619;
RA Ohtsuka T., Hata Y., Ide N., Yasuda T., Inoue E., Inoue T., Mizoguchi A.,
RA Takai Y.;
RT "nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein
RT that interacts with synaptic scaffolding molecule (S-SCAM).";
RL Biochem. Biophys. Res. Commun. 265:38-44(1999).
RN [4]
RP TISSUE SPECIFICITY.
RX PubMed=10873669; DOI=10.1006/bbrc.2000.3002;
RA Kawajiri A., Itoh N., Fukata M., Nakagawa M., Yamaga M., Iwamatsu A.,
RA Kaibuchi K.;
RT "Identification of a novel beta-catenin-interacting protein.";
RL Biochem. Biophys. Res. Commun. 273:712-717(2000).
RN [5]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10801446; DOI=10.1016/s0960-9822(00)00473-5;
RA Pham N., Cheglakov I., Koch C.A., de Hoog C.L., Moran M.F., Rotin D.;
RT "The guanine nucleotide exchange factor CNrasGEF activates ras in response
RT to cAMP and cGMP.";
RL Curr. Biol. 10:555-558(2000).
RN [6]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12391161; DOI=10.1128/mcb.22.22.7942-7952.2002;
RA Pak Y., Pham N., Rotin D.;
RT "Direct binding of the beta1 adrenergic receptor to the cyclic AMP-
RT dependent guanine nucleotide exchange factor CNrasGEF leads to Ras
RT activation.";
RL Mol. Cell. Biol. 22:7942-7952(2002).
RN [7]
RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH KIDINS220; MAGI2 AND NTRK1, AND
RP SUBCELLULAR LOCATION.
RX PubMed=17724123; DOI=10.1083/jcb.200610073;
RA Hisata S., Sakisaka T., Baba T., Yamada T., Aoki K., Matsuda M., Takai Y.;
RT "Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes,
RT leading to sustained activation of Rap1 and ERK and neurite outgrowth.";
RL J. Cell Biol. 178:843-860(2007).
RN [8]
RP PHOSPHORYLATION AT THR-644; SER-806; SER-933; SER-1022 AND SER-1175, AND
RP MUTAGENESIS OF THR-644; SER-806; SER-933; SER-1022 AND SER-1175.
RX PubMed=21382555; DOI=10.1016/j.neuron.2011.02.004;
RA Lee K.J., Lee Y., Rozeboom A., Lee J.Y., Udagawa N., Hoe H.S., Pak D.T.;
RT "Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic
RT structural plasticity, and memory.";
RL Neuron 69:957-973(2011).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-501; SER-930 AND SER-1115,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Functions as a guanine nucleotide exchange factor (GEF),
CC which activates Rap and Ras family of small GTPases by exchanging bound
CC GDP for free GTP in a cAMP-dependent manner. Serves as a link between
CC cell surface receptors and Rap/Ras GTPases in intracellular signaling
CC cascades. Acts also as an effector for Rap1 by direct association with
CC Rap1-GTP thereby leading to the amplification of Rap1-mediated
CC signaling. Shows weak activity on HRAS. It is controversial whether
CC RAPGEF2 binds cAMP and cGMP or not. Its binding to ligand-activated
CC beta-1 adrenergic receptor ADRB1 leads to the Ras activation through
CC the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and
CC Erk1/2 signaling pathway that leads to sustained inhibition of long
CC term melanogenesis by reducing dendrite extension and melanin
CC synthesis. Provides also inhibitory signals for cell proliferation of
CC melanoma cells and promotes their apoptosis in a cAMP-independent
CC nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-
CC Raf/ERK signaling through a pathway that is independent on both PKA and
CC RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of
CC the major forebrain fiber connections forming the corpus callosum, the
CC anterior commissure and the hippocampal commissure during brain
CC development. Involved in neuronal growth factor (NGF)-induced sustained
CC activation of Rap1 at late endosomes and in brain-derived neurotrophic
CC factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a
CC role in the regulation of embryonic blood vessel formation and in the
CC establishment of basal junction integrity and endothelial barrier
CC function. May be involved in the regulation of the vascular endothelial
CC growth factor receptor KDR and cadherin CDH5 expression at allantois
CC endothelial cell-cell junctions. {ECO:0000269|PubMed:17724123}.
CC -!- SUBUNIT: Interacts (via C-terminal domain) with NEDD4 (via WW domains);
CC this interaction leads to ubiquitination and degradation via the
CC proteasome pathway in a cAMP-independent manner. Interacts with MAGI1
CC (via PDZ domain). Interacts with ADRB1 (via C-terminal PDZ motif); the
CC interaction is direct. Interacts (via Ras-associating domain) with
CC RAP1A (via GTP-bound active form). Interacts weakly with HRAS (via
CC GDP- and GTP-bound forms). Interacts (via C-terminal domain) with MAGI2
CC (via PDZ and WW domains). Interacts with CDH1, CTNNB1 and TJP1 (By
CC similarity). Found in a complex, at least composed of KIDINS220, MAGI2,
CC NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a
CC neuronal growth factor (NGF)-dependent manner. Interacts (via C-
CC terminal domain) with MAGI2 (via PDZ and WW domains); the interaction
CC occurs before or after NGF stimulation. Interacts with KIDINS220 and
CC NTRK1; the interactions occur after NGF stimulation. {ECO:0000250,
CC ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:17724123}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10548487,
CC ECO:0000269|PubMed:10801446, ECO:0000269|PubMed:12391161,
CC ECO:0000269|PubMed:17724123}. Cytoplasm {ECO:0000250}. Cytoplasm,
CC perinuclear region {ECO:0000250}. Late endosome {ECO:0000250}. Cell
CC junction {ECO:0000250}. Note=Associated with the synaptic plasma
CC membrane. Localized diffusely in the cytoplasm before neuronal growth
CC factor (NGF) stimulation. Recruited to late endosomes after NGF
CC stimulation. Colocalized with the high affinity nerve growth factor
CC receptor NTRK1 at late endosomes. Translocated to the perinuclear
CC region in a RAP1A-dependent manner. Translocated to the cell membrane.
CC Colocalized with CTNNB1 at cell-cell contacts (By similarity).
CC Colocalizes with ADRB1 at the plasma membrane. Synaptosome. Enriched in
CC synaptic plasma membrane and neuronal cell body. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, heart, lung, liver and
CC stomach. Expressed in the granular layer of the cerebellum. Expressed
CC in Purkinje cells. Expressed in cortical neurons and coronary artery
CC smooth muscle cells (at protein level). Expressed ubiquitously in the
CC brain. {ECO:0000269|PubMed:10548487, ECO:0000269|PubMed:10801446,
CC ECO:0000269|PubMed:10873669, ECO:0000269|PubMed:12391161}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the brain (at protein level).
CC {ECO:0000269|PubMed:10801446}.
CC -!- DOMAIN: The Ras-associating domain is necessary for the Rap guanine
CC nucleotide exchange activity. The N-terminal regionis necessary for
CC cAMP-binding. The PDZ domain is necessary for its targeting to the cell
CC membrane (By similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by NEDD4, leading to proteasomal degradation.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation by PLK2 promotes its activity.
CC {ECO:0000269|PubMed:21382555}.
CC -!- SIMILARITY: Belongs to the RAPGEF2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDM00875.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CH473976; EDM00875.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_001101154.1; NM_001107684.1.
DR RefSeq; XP_006232574.1; XM_006232512.3.
DR AlphaFoldDB; F1M386; -.
DR BioGRID; 259649; 3.
DR CORUM; F1M386; -.
DR IntAct; F1M386; 1.
DR MINT; F1M386; -.
DR STRING; 10116.ENSRNOP00000037119; -.
DR iPTMnet; F1M386; -.
DR PhosphoSitePlus; F1M386; -.
DR PaxDb; F1M386; -.
DR PRIDE; F1M386; -.
DR GeneID; 310533; -.
DR KEGG; rno:310533; -.
DR UCSC; RGD:1306434; rat.
DR CTD; 9693; -.
DR RGD; 1306434; Rapgef2.
DR eggNOG; KOG3542; Eukaryota.
DR HOGENOM; CLU_002782_0_1_1; -.
DR InParanoid; F1M386; -.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR PRO; PR:F1M386; -.
DR Proteomes; UP000002494; Chromosome 2.
DR Proteomes; UP000234681; Chromosome 2.
DR Bgee; ENSRNOG00000021581; Expressed in Ammon's horn and 19 other tissues.
DR ExpressionAtlas; F1M386; baseline and differential.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0005923; C:bicellular tight junction; ISO:RGD.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030139; C:endocytic vesicle; ISO:RGD.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0031697; F:beta-1 adrenergic receptor binding; ISS:UniProtKB.
DR GO; GO:0030552; F:cAMP binding; ISS:UniProtKB.
DR GO; GO:0005096; F:GTPase activator activity; ISO:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0050699; F:WW domain binding; ISS:UniProtKB.
DR GO; GO:0071880; P:adenylate cyclase-activating adrenergic receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001568; P:blood vessel development; ISS:UniProtKB.
DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0071321; P:cellular response to cGMP; ISS:UniProtKB.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; IDA:UniProtKB.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0090557; P:establishment of endothelial intestinal barrier; ISO:RGD.
DR GO; GO:0021884; P:forebrain neuron development; ISS:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0030033; P:microvillus assembly; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; ISS:UniProtKB.
DR GO; GO:0048022; P:negative regulation of melanin biosynthetic process; ISS:UniProtKB.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; IDA:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISS:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; ISS:UniProtKB.
DR GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; ISS:UniProtKB.
DR GO; GO:0043950; P:positive regulation of cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; ISS:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IMP:UniProtKB.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; ISS:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:RGD.
DR GO; GO:0032486; P:Rap protein signal transduction; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:1901888; P:regulation of cell junction assembly; ISS:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IDA:UniProtKB.
DR GO; GO:0021591; P:ventricular system development; ISS:UniProtKB.
DR CDD; cd00038; CAP_ED; 1.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 2.30.42.10; -; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR030739; RapGEF2.
DR InterPro; IPR008937; Ras-like_GEF.
DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR InterPro; IPR014710; RmlC-like_jellyroll.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR PANTHER; PTHR23113:SF217; PTHR23113:SF217; 1.
DR Pfam; PF00595; PDZ; 1.
DR Pfam; PF00788; RA; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR SMART; SM00100; cNMP; 1.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00314; RA; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell membrane; Cytoplasm; Developmental protein;
KW Differentiation; Endosome; GTPase activation;
KW Guanine-nucleotide releasing factor; Membrane; Neurogenesis;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT CHAIN 1..1496
FT /note="Rap guanine nucleotide exchange factor 2"
FT /id="PRO_0000414717"
FT DOMAIN 267..380
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 385..470
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 606..692
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT DOMAIN 717..944
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 40..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 68..101
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1003..1052
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1093..1127
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1139..1159
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1224..1256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1304..1369
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1390..1496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..96
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1105..1127
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1304..1335
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1338..1352
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 135..252
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 644
FT /note="Phosphothreonine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 806
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 930
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 933
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 1022
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 1079
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4G8"
FT MOD_RES 1088
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4G8"
FT MOD_RES 1094
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4G8"
FT MOD_RES 1115
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1119
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8CHG7"
FT MOD_RES 1158
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y4G8"
FT MOD_RES 1175
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MUTAGEN 644
FT /note="T->A: Blocks the gel mobility shift induced by PLK2
FT and affects stimulation by PLK2; when associated with A-
FT 806; A-933; A-1022 and A-1175."
FT /evidence="ECO:0000269|PubMed:21382555"
FT MUTAGEN 806
FT /note="S->A: Blocks the gel mobility shift induced by PLK2
FT and affects stimulation by PLK2; when associated with A-
FT 644: A-933; A-1022 and A-1175."
FT /evidence="ECO:0000269|PubMed:21382555"
FT MUTAGEN 933
FT /note="S->A: Blocks the gel mobility shift induced by PLK2
FT and affects stimulation by PLK2; when associated with A-
FT 644; A-806; A-1022 and A-1175."
FT /evidence="ECO:0000269|PubMed:21382555"
FT MUTAGEN 1022
FT /note="S->A: Blocks the gel mobility shift induced by PLK2
FT and affects stimulation by PLK2; when associated with A-
FT 644; A-806; A-933 and A-1175."
FT /evidence="ECO:0000269|PubMed:21382555"
FT MUTAGEN 1175
FT /note="S->A: Blocks the gel mobility shift induced by PLK2
FT and affects stimulation by PLK2; when associated with A-
FT 644; A-806; A-933 and A-1022."
FT /evidence="ECO:0000269|PubMed:21382555"
SQ SEQUENCE 1496 AA; 166388 MW; 1F0799FC63293A75 CRC64;
MKPLAAPANH GVLGQQEKQS LPADFTKLHL TDSLHPQVTH VSSSHSGCSI TSDSGSSSLS
DIYQATESEA GDMDLSGLPE TAVDSEDDDD EEDIERASDP LMSRDIVRDC LEKDPIDRTD
DDIEQLLEFM HQLPAFANMT MSVRRELCAV MVFAVVERAG TIVLNDGEEL DSWSVILNGS
VEVTYPDGKA EILCMGNSFG VSPTMDKEYM KGVMRTKVDD CQFVCIAQQD YCRILNQVEK
NMQKVEEEGE IVMVKEHREL DRTGTRKGHI VIKGTSERLT MHLVEEHSVV DPTFIEDFLL
TYRTFLSSPM EVGKKLLEWF NDPSLRDKVT RVVLLWVNNH FNDFEGDPAM TRFLEEFENN
LEREKMGGHL RLLNIACAAK AKRRSMTLTK PSREAPLPFI LLGGSEKGFG IFVDSVDSSS
KATEAGLKRG DQILEVNGQN FENIQLSKAM EILRNNTHLS ITVKTNLFVF KELLTRLSEE
KRNGAPHLPK IGDIKKASRY SIPDLAVDVE QVIGLEKVNK KSKANTVGGR NKLKKILDKT
RISILPQKPY NDIGIGQSQD DSIVGLRQTK HIPAALPVSG TLSSSNPDLL QSHHRILDFS
TTPDLPDQVL RVFKADQQSR YIMISKDTTA KEVVIQAIRE FAVTATPEQY SLCEVSVTPE
GVIKQRRLPD QLSKLADRIQ LSGRYYLKNN METETLCSDE DAQELLRESQ ISLLQLSTVE
VATQLSMRNF ELFRNIEPTE YIDDLFKLKS KTSCANLKKF EEVINQETFW VASEILRETN
QLKRMKIIKH FIKIALHCRE CKNFNSMFAI ISGLNLAPVA RLRTTWEKLP NKYEKLFQDL
QDLFDPSRNM AKYRNVLSGQ NLQPPVIPLF PVIKKDLTFL HEGNDSKVDG LVNFEKLRMI
AKEIRHVGRM ASVNMDPALM FRTRKKKWRS LGSLSQGSAN ATVLDVAQTG GHKKRVRRSS
FLNAKKLYED AQMARKVKQY LSNLELEMDE ESLQTLSLQC EPATSTLPKN PADRKPVKSE
TSPVAPRAGP QQKAQPQQPL APPQPSHKVS QGLQVPAVSL YPSRKKVPVK DLPPFGINSP
QALKKILSLS EEGSLERHRK QAEDTISNAS SQLSSPPTSP QSSPRKGYAL ALSGTVDNFS
DSGHSEISSR SSIVSNSSFD SVPVSLHDER RQRHSVSIVE SNLGVGRMER RTLMEPDQYS
LGSYAPVSES RGLYAAATVI SSPSTEELSH DQGDRASLDA ADSGRGSWTS CSSGSHDNIQ
TIQHQRSWET LPFGHTHFDY SGDATGIWAS GGHMDQIMFS DHSTKYNRQN QSRESLEQAQ
SRASWASSTG YWGEDSEGDT GTIKRRGGKD VSTEAESSSM VPVTTEEAKP VPMPAHIAVT
PSTTKGLIAR KEGRYREPPP TPPGYVGIPI ADFPEGPCHP ARKPPDYNVA LQRSRMVARP
TEAPAPGQTP PAATASRPGS KPQWHKPSDA DPRLAPFQPQ GFAGAEEDED EQVSAV
