RPGF2_MOUSE
ID RPGF2_MOUSE Reviewed; 1496 AA.
AC Q8CHG7; E9QMD0;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 2.
DT 03-AUG-2022, entry version 148.
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=Kiaa0313, Pdzgef1;
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 {ECO:0000312|EMBL:BAC41412.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 359-1496.
RC TISSUE=Brain {ECO:0000269|PubMed:12465718};
RX PubMed=12465718; DOI=10.1093/dnares/9.5.179;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Hara Y., Nagase T., Ohara O.,
RA Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: I.
RT The complete nucleotide sequences of 100 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 9:179-188(2002).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16272156; DOI=10.1074/jbc.m507595200;
RA Amsen E.M., Pham N., Pak Y., Rotin D.;
RT "The guanine nucleotide exchange factor CNrasGEF regulates melanogenesis
RT and cell survival in melanoma cells.";
RL J. Biol. Chem. 281:121-128(2006).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=17826737; DOI=10.1016/j.bbrc.2007.08.149;
RA Wei P., Satoh T., Edamatsu H., Aiba A., Setsu T., Terashima T.,
RA Kitazawa S., Nakao K., Yoshikawa Y., Tamada M., Kataoka T.;
RT "Defective vascular morphogenesis and mid-gestation embryonic death in mice
RT lacking RA-GEF-1.";
RL Biochem. Biophys. Res. Commun. 363:106-112(2007).
RN [6]
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 [7]
RP FUNCTION.
RX PubMed=19635461; DOI=10.1016/j.bbrc.2009.07.108;
RA Kanemura H., Satoh T., Bilasy S.E., Ueda S., Hirashima M., Kataoka T.;
RT "Impaired vascular development in the yolk sac and allantois in mice
RT lacking RA-GEF-1.";
RL Biochem. Biophys. Res. Commun. 387:754-759(2009).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=19453629; DOI=10.1111/j.1460-9568.2009.06754.x;
RA Bilasy S.E., Satoh T., Ueda S., Wei P., Kanemura H., Aiba A., Terashima T.,
RA Kataoka T.;
RT "Dorsal telencephalon-specific RA-GEF-1 knockout mice develop heterotopic
RT cortical mass and commissural fiber defect.";
RL Eur. J. Neurosci. 29:1994-2008(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1022, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1115 AND SER-1119, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Lung, Pancreas, Spleen, and
RC 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).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=21864586; DOI=10.1016/j.neures.2011.08.004;
RA Bilasy S.E., Satoh T., Terashima T., Kataoka T.;
RT "RA-GEF-1 (Rapgef2) is essential for proper development of the midline
RT commissures.";
RL Neurosci. Res. 71:200-209(2011).
RN [12]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=23800469; DOI=10.1126/scisignal.2003993;
RA Emery A.C., Eiden M.V., Mustafa T., Eiden L.E.;
RT "Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in Neuronal
RT and Endocrine Cells.";
RL Sci. Signal. 6:RA51-RA51(2013).
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:16272156,
CC ECO:0000269|PubMed:17826737, ECO:0000269|PubMed:19453629,
CC ECO:0000269|PubMed:19635461, ECO:0000269|PubMed:21864586,
CC ECO:0000269|PubMed:23800469}.
CC -!- SUBUNIT: 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 NEDD4 (via WW domains); this interaction leads to
CC ubiquitination and degradation via the proteasome pathway in a cAMP-
CC independent manner. Interacts with MAGI1 (via PDZ domain). Interacts
CC with ADRB1 (via C-terminal PDZ motif); the interaction is direct.
CC Interacts (via Ras-associating domain) with RAP1A (via GTP-bound active
CC form). Interacts weakly with HRAS (via GDP- and GTP-bound forms).
CC Interacts (via C-terminal domain) with MAGI2 (via PDZ and WW domains).
CC Interacts with CDH1, CTNNB1 and TJP1 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear
CC region {ECO:0000250}. Cell membrane {ECO:0000250}. Late endosome
CC {ECO:0000250}. Cell junction {ECO:0000250}. Note=Associated with the
CC synaptic plasma membrane. Localized diffusely in the cytoplasm before
CC neuronal growth factor (NGF) stimulation. Recruited to late endosomes
CC after NGF stimulation. Colocalized with the high affinity nerve growth
CC factor receptor NTRK1 at late endosomes. Translocated to the
CC perinuclear region in a RAP1A-dependent manner. Translocated to the
CC cell membrane. Colocalized with CTNNB1 at cell-cell contacts (By
CC similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in all layers of the cerebral cortex,
CC hippocampus and cerebellum. Expressed in the cortical plate, cingulate
CC cortex and the subventricular zone. Expressed in neurons and endocrine
CC cells (at protein level). Expressed in melanoma cells.
CC {ECO:0000269|PubMed:16272156, ECO:0000269|PubMed:19453629,
CC ECO:0000269|PubMed:21864586, ECO:0000269|PubMed:23800469}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the yolk sacs at vascular endothelial
CC cells at 7.5 dpc. Expressed in the glial sling (GS) at the cortico-
CC septal boundary at 17.5 dpc (at protein level).
CC {ECO:0000269|PubMed:17826737, ECO:0000269|PubMed:21864586}.
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. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice appear normal until 7.5 dpc, but become
CC grossly abnormal and dead at mid-gestation. Show severe defects in yolk
CC sac blood and major vessels formation. Show impair callosal axons to
CC cross the midline during cortical development. Show disruption of all
CC three midline commissure fibers crossing, the corpus callosum, the
CC anterior commissure and the dorsal hippocampal commissure during
CC cortical develpoment. Conditional knockout mice in which rapgef2 is
CC lacking within the dorsal telencephalon result in malformation of the
CC cortical brain structures: developed an ectopic cortical mass (ECM)
CC extending throughout the rostro-caudal axis of the cerebral hemisphere.
CC Mice show also an enlargement of the lateral ventricles and the
CC agenesis of interhemispheric connections: the corpus callosum, the
CC dorsal hippocampus commissure and the anterior commissure
CC (PubMed:19453629). {ECO:0000269|PubMed:17826737,
CC ECO:0000269|PubMed:19453629, ECO:0000269|PubMed:21864586}.
CC -!- SIMILARITY: Belongs to the RAPGEF2 family. {ECO:0000305}.
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DR EMBL; AC124358; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC157941; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC164560; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AB093228; BAC41412.1; -; mRNA.
DR CCDS; CCDS89637.1; -.
DR RefSeq; XP_006502317.1; XM_006502254.3.
DR AlphaFoldDB; Q8CHG7; -.
DR SMR; Q8CHG7; -.
DR BioGRID; 217954; 23.
DR IntAct; Q8CHG7; 8.
DR MINT; Q8CHG7; -.
DR STRING; 10090.ENSMUSP00000113778; -.
DR iPTMnet; Q8CHG7; -.
DR PhosphoSitePlus; Q8CHG7; -.
DR jPOST; Q8CHG7; -.
DR MaxQB; Q8CHG7; -.
DR PaxDb; Q8CHG7; -.
DR PRIDE; Q8CHG7; -.
DR ProteomicsDB; 260927; -.
DR Antibodypedia; 28211; 135 antibodies from 22 providers.
DR Ensembl; ENSMUST00000118100; ENSMUSP00000114119; ENSMUSG00000062232.
DR UCSC; uc008pnl.1; mouse.
DR MGI; MGI:2659071; Rapgef2.
DR VEuPathDB; HostDB:ENSMUSG00000062232; -.
DR eggNOG; KOG3542; Eukaryota.
DR GeneTree; ENSGT00940000156418; -.
DR InParanoid; Q8CHG7; -.
DR OrthoDB; 31139at2759; -.
DR PhylomeDB; Q8CHG7; -.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 76089; 1 hit in 58 CRISPR screens.
DR ChiTaRS; Rapgef2; mouse.
DR PRO; PR:Q8CHG7; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q8CHG7; protein.
DR Bgee; ENSMUSG00000062232; Expressed in olfactory tubercle and 223 other tissues.
DR ExpressionAtlas; Q8CHG7; baseline and differential.
DR Genevisible; Q8CHG7; MM.
DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI.
DR GO; GO:0005923; C:bicellular tight junction; ISO:MGI.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0030139; C:endocytic vesicle; ISO:MGI.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; ISS: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:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0030165; F:PDZ domain binding; ISS:UniProtKB.
DR GO; GO:0070300; F:phosphatidic acid binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
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; IMP:UniProtKB.
DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0071321; P:cellular response to cGMP; ISS:UniProtKB.
DR GO; GO:1990090; P:cellular response to nerve growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0090557; P:establishment of endothelial intestinal barrier; ISO:MGI.
DR GO; GO:0021884; P:forebrain neuron development; IMP:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0030033; P:microvillus assembly; ISO:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:UniProtKB.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; IMP:UniProtKB.
DR GO; GO:0048022; P:negative regulation of melanin biosynthetic process; IMP:UniProtKB.
DR GO; GO:0038180; P:nerve growth factor signaling pathway; ISS:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR GO; GO:0007218; P:neuropeptide signaling pathway; IDA:UniProtKB.
DR GO; GO:2000481; P:positive regulation of cAMP-dependent protein kinase activity; IMP: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; IMP:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:2001224; P:positive regulation of neuron migration; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISS:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; IMP:UniProtKB.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0021591; P:ventricular system development; IMP: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_0000068866"
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 1002..1051
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1093..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 1303..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 1025..1049
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1105..1128
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1135..1159
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1303..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..254
FT /ligand="a nucleoside 3',5'-cyclic phosphate"
FT /ligand_id="ChEBI:CHEBI:58464"
FT MOD_RES 501
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M386"
FT MOD_RES 644
FT /note="Phosphothreonine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:F1M386"
FT MOD_RES 806
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:F1M386"
FT MOD_RES 930
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F1M386"
FT MOD_RES 933
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:F1M386"
FT MOD_RES 1022
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0007744|PubMed:19144319"
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:21183079"
FT MOD_RES 1119
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
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:0000250|UniProtKB:F1M386"
SQ SEQUENCE 1496 AA; 166415 MW; C2FDE48E5E21A86F 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 AKRRLMTLTK PSREAPLPFI LLGGSEKGFG IFVDSVDSCS
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 PGDKKPVKSE
TSPVAPRAGP QQKVQPQQPL AQPQPPHKVS QGLQVPAVSL YPSRKKVPVK DLPPFGINSP
QALKKILSLS EEGSLERHRK QAEDTISNAS SQLSSPPTSP QSSPRKGYAL ALSGTVDNFS
DSGHSEISSR SSIVSNSSFD SVPVSLHDER RQRHSVSIVE SNLGVGRMER RTLMEPDQYS
LGSYAPVSES RGLYAAATVI SSPSTEELSH DQGDRASLDA ADSGRGSWTS CSSGSHDNIQ
TIQHQRSWET LPFGHTHFDY SGDAASIWAS GGHMDQMMFS DHSTKYNRQN QSRESLEQAQ
SRASWASSTG YWGEDSEGDT GTIKRRGGKD VSAEAESSSM VPVTTEEAKP VPMPAHIAVT
PSTTKGLIAR KEGRYREPPP TPPGYVGIPI ADFPEGPCHP ARKPPDYNVA LQRSRMVARP
TEAPAPGQTP PAAAASRPGS KPQWHKPSDA DPRLAPFQPQ GFAGAEEDED EQVSAV
