RPGF3_HUMAN
ID RPGF3_HUMAN Reviewed; 923 AA.
AC O95398; A8K2G5; E7EQC8; O95634; Q8WVN0;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 6.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Rap guanine nucleotide exchange factor 3;
DE AltName: Full=Exchange factor directly activated by cAMP 1;
DE AltName: Full=Exchange protein directly activated by cAMP 1;
DE Short=EPAC 1;
DE AltName: Full=Rap1 guanine-nucleotide-exchange factor directly activated by cAMP;
DE AltName: Full=cAMP-regulated guanine nucleotide exchange factor I;
DE Short=cAMP-GEFI;
GN Name=RAPGEF3; Synonyms=CGEF1, EPAC, EPAC1;
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] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP MUTAGENESIS OF ARG-321, AND VARIANT GLY-193.
RX PubMed=9856955; DOI=10.1126/science.282.5397.2275;
RA Kawasaki H., Springett G.M., Mochizuki N., Toki S., Nakaya M., Matsuda M.,
RA Housman D.E., Graybiel A.M.;
RT "A family of cAMP-binding proteins that directly activate rap1.";
RL Science 282:2275-2279(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT GLY-193.
RC TISSUE=Thalamus;
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=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLY-193.
RA Mural R.J., Istrail S., Sutton G.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), AND VARIANTS PRO-16 AND
RP GLY-193.
RC TISSUE=Kidney;
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 [MRNA] OF 43-923 (ISOFORM 1), FUNCTION, AND VARIANT
RP GLY-193.
RC TISSUE=Muscle;
RX PubMed=9853756; DOI=10.1038/24884;
RA de Rooij J., Zwartkruis F.J.T., Verheijen M.H., Cool R.H., Nijman S.M.,
RA Wittinghofer A., Bos J.L.;
RT "Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by
RT cyclic AMP.";
RL Nature 396:474-477(1998).
RN [7]
RP FUNCTION, DOMAIN DEP, AND SUBCELLULAR LOCATION.
RX PubMed=10777494; DOI=10.1074/jbc.m001113200;
RA de Rooij J., Rehmann H., van Triest M., Cool R.H., Wittinghofer A.,
RA Bos J.L.;
RT "Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs.";
RL J. Biol. Chem. 275:20829-20836(2000).
RN [8]
RP MUTAGENESIS OF LEU-315 AND PHE-342.
RX PubMed=12469113; DOI=10.1038/nsb878;
RA Rehmann H., Prakash B., Wolf E., Rueppel A., De Rooij J., Bos J.L.,
RA Wittinghofer A.;
RT "Structure and regulation of the cAMP-binding domains of Epac2.";
RL Nat. Struct. Biol. 10:26-32(2003).
RN [9]
RP FUNCTION.
RX PubMed=21840392; DOI=10.1016/j.cellsig.2011.07.022;
RA Pannekoek W.J., van Dijk J.J., Chan O.Y., Huveneers S., Linnemann J.R.,
RA Spanjaard E., Brouwer P.M., van der Meer A.J., Zwartkruis F.J., Rehmann H.,
RA de Rooij J., Bos J.L.;
RT "Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction
RT control.";
RL Cell. Signal. 23:2056-2064(2011).
RN [10]
RP INTERACTION WITH PDE3B AND PIK3R6, AND MUTAGENESIS OF ASP-412; GLU-415;
RP PHE-417; ASP-420 AND PHE-421.
RX PubMed=21393242; DOI=10.1074/jbc.m110.217026;
RA Wilson L.S., Baillie G.S., Pritchard L.M., Umana B., Terrin A., Zaccolo M.,
RA Houslay M.D., Maurice D.H.;
RT "A phosphodiesterase 3B-based signaling complex integrates exchange protein
RT activated by cAMP 1 and phosphatidylinositol 3-kinase signals in human
RT arterial endothelial cells.";
RL J. Biol. Chem. 286:16285-16296(2011).
RN [11] {ECO:0007744|PDB:6H7E}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 92-360 IN COMPLEX WITH CAMP.
RA Ferrandez Y., Cherfils J., Peurois F.;
RT "GEF regulatory domain.";
RL Submitted (JUL-2018) to the PDB data bank.
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) for RAP1A and RAP2A
CC small GTPases that is activated by binding cAMP. Through simultaneous
CC binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling
CC complex in which it activates the PI3K gamma complex and which is
CC involved in angiogenesis. Plays a role in the modulation of the cAMP-
CC induced dynamic control of endothelial barrier function through a
CC pathway that is independent on Rho-mediated signaling. Required for the
CC actin rearrangement at cell-cell junctions, such as stress fibers and
CC junctional actin. {ECO:0000269|PubMed:10777494,
CC ECO:0000269|PubMed:21840392, ECO:0000269|PubMed:9853756}.
CC -!- SUBUNIT: Interacts with PDE3B and PIK3R6; form a signaling complex that
CC regulates phosphatidylinositol 3-kinase gamma in angiogenesis.
CC {ECO:0000269|PubMed:21393242}.
CC -!- INTERACTION:
CC O95398; Q13370: PDE3B; NbExp=8; IntAct=EBI-6172806, EBI-6172856;
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000269|PubMed:10777494}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O95398-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O95398-2; Sequence=VSP_007608, VSP_007609;
CC Name=3;
CC IsoId=O95398-3; Sequence=VSP_047007;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in adult
CC kidney, heart, thyroid and brain, and fetal kidney.
CC {ECO:0000269|PubMed:9856955}.
CC -!- DOMAIN: The DEP domain is involved in membrane localization independent
CC from regulation by cAMP. {ECO:0000269|PubMed:10777494}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-43 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD02890.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAD12740.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U78168; AAD12740.1; ALT_INIT; mRNA.
DR EMBL; U78169; AAD02890.1; ALT_INIT; mRNA.
DR EMBL; AK290230; BAF82919.1; -; mRNA.
DR EMBL; AC004241; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC137054; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471111; EAW57944.1; -; Genomic_DNA.
DR EMBL; BC017728; AAH17728.2; -; mRNA.
DR EMBL; AF103905; AAC83381.1; -; mRNA.
DR CCDS; CCDS31784.1; -. [O95398-3]
DR CCDS; CCDS41775.1; -. [O95398-1]
DR RefSeq; NP_001092002.1; NM_001098532.2.
DR RefSeq; NP_006096.2; NM_006105.5.
DR PDB; 6H7E; X-ray; 2.30 A; A/B=92-360.
DR PDBsum; 6H7E; -.
DR AlphaFoldDB; O95398; -.
DR SASBDB; O95398; -.
DR SMR; O95398; -.
DR BioGRID; 115682; 18.
DR IntAct; O95398; 5.
DR MINT; O95398; -.
DR STRING; 9606.ENSP00000395708; -.
DR BindingDB; O95398; -.
DR ChEMBL; CHEMBL2029197; -.
DR GuidetoPHARMACOLOGY; 1292; -.
DR GlyGen; O95398; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95398; -.
DR PhosphoSitePlus; O95398; -.
DR BioMuta; RAPGEF3; -.
DR MassIVE; O95398; -.
DR MaxQB; O95398; -.
DR PaxDb; O95398; -.
DR PeptideAtlas; O95398; -.
DR PRIDE; O95398; -.
DR ProteomicsDB; 17545; -.
DR ProteomicsDB; 50849; -. [O95398-1]
DR ProteomicsDB; 50850; -. [O95398-2]
DR Antibodypedia; 3824; 257 antibodies from 38 providers.
DR DNASU; 10411; -.
DR Ensembl; ENST00000389212.7; ENSP00000373864.3; ENSG00000079337.16. [O95398-1]
DR Ensembl; ENST00000395358.7; ENSP00000378764.3; ENSG00000079337.16. [O95398-2]
DR Ensembl; ENST00000405493.6; ENSP00000384521.2; ENSG00000079337.16. [O95398-3]
DR Ensembl; ENST00000449771.7; ENSP00000395708.2; ENSG00000079337.16. [O95398-1]
DR Ensembl; ENST00000549151.5; ENSP00000448619.1; ENSG00000079337.16. [O95398-3]
DR GeneID; 10411; -.
DR KEGG; hsa:10411; -.
DR MANE-Select; ENST00000449771.7; ENSP00000395708.2; NM_001098531.4; NP_001092001.2.
DR UCSC; uc001rpz.5; human. [O95398-1]
DR CTD; 10411; -.
DR DisGeNET; 10411; -.
DR GeneCards; RAPGEF3; -.
DR HGNC; HGNC:16629; RAPGEF3.
DR HPA; ENSG00000079337; Low tissue specificity.
DR MIM; 606057; gene.
DR neXtProt; NX_O95398; -.
DR OpenTargets; ENSG00000079337; -.
DR PharmGKB; PA134910959; -.
DR VEuPathDB; HostDB:ENSG00000079337; -.
DR eggNOG; KOG2378; Eukaryota.
DR GeneTree; ENSGT00940000159931; -.
DR HOGENOM; CLU_006829_0_0_1; -.
DR InParanoid; O95398; -.
DR OMA; DIYRPDH; -.
DR OrthoDB; 143470at2759; -.
DR PhylomeDB; O95398; -.
DR TreeFam; TF313184; -.
DR PathwayCommons; O95398; -.
DR Reactome; R-HSA-354192; Integrin signaling.
DR Reactome; R-HSA-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-HSA-392517; Rap1 signalling.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR SignaLink; O95398; -.
DR SIGNOR; O95398; -.
DR BioGRID-ORCS; 10411; 8 hits in 1071 CRISPR screens.
DR ChiTaRS; RAPGEF3; human.
DR GeneWiki; RAPGEF3; -.
DR GenomeRNAi; 10411; -.
DR Pharos; O95398; Tchem.
DR PRO; PR:O95398; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O95398; protein.
DR Bgee; ENSG00000079337; Expressed in metanephros cortex and 173 other tissues.
DR ExpressionAtlas; O95398; baseline and differential.
DR Genevisible; O95398; HS.
DR GO; GO:0012505; C:endomembrane system; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005902; C:microvillus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0030552; F:cAMP binding; IEA:UniProtKB-KW.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IMP:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0002250; P:adaptive immune response; TAS:Reactome.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR GO; GO:0019933; P:cAMP-mediated signaling; NAS:BHF-UCL.
DR GO; GO:0071320; P:cellular response to cAMP; IDA:UniProtKB.
DR GO; GO:0061028; P:establishment of endothelial barrier; IMP:UniProtKB.
DR GO; GO:0034242; P:negative regulation of syncytium formation by plasma membrane fusion; IMP:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:1901985; P:positive regulation of protein acetylation; IMP:UniProtKB.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IDA:UniProtKB.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IMP:UniProtKB.
DR GO; GO:0060143; P:positive regulation of syncytium formation by plasma membrane fusion; IMP:UniProtKB.
DR GO; GO:0032486; P:Rap protein signal transduction; IMP:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:2000249; P:regulation of actin cytoskeleton reorganization; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00038; CAP_ED; 1.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 2.60.120.10; -; 1.
DR InterPro; IPR018490; cNMP-bd-like.
DR InterPro; IPR000595; cNMP-bd_dom.
DR InterPro; IPR000591; DEP_dom.
DR InterPro; IPR008937; Ras-like_GEF.
DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR InterPro; IPR019804; Ras_G-nucl-exch_fac_CS.
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 InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR Pfam; PF00027; cNMP_binding; 1.
DR Pfam; PF00610; DEP; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR SMART; SM00100; cNMP; 1.
DR SMART; SM00049; DEP; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF51206; SSF51206; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50042; CNMP_BINDING_3; 1.
DR PROSITE; PS50186; DEP; 1.
DR PROSITE; PS00720; RASGEF; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; cAMP; cAMP-binding;
KW Guanine-nucleotide releasing factor; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..923
FT /note="Rap guanine nucleotide exchange factor 3"
FT /id="PRO_0000068867"
FT DOMAIN 110..186
FT /note="DEP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00066"
FT DOMAIN 384..518
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 662..889
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 218..242
FT /note="Interaction with PDE3B"
FT /evidence="ECO:0000269|PubMed:21393242"
FT REGION 398..422
FT /note="Interaction with PDE3B"
FT /evidence="ECO:0000269|PubMed:21393242"
FT BINDING 311..314
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0007744|PDB:6H7E"
FT BINDING 321..322
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0007744|PDB:6H7E"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCC8"
FT MOD_RES 528
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCC8"
FT MOD_RES 864
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCC8"
FT VAR_SEQ 1..42
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_047007"
FT VAR_SEQ 533..598
FT /note="ARNLPVWLPNQDEPLPGSSCAIQVGDKVPYDICRPDHSVLTLQLPVTASVRE
FT VMAALAQEDGWTKG -> VSAWPQFLSSAPPGLQAPPSPPDPEGLCGRGKLSSHRHTLG
FT SLIGVHGALAACGALGQAVPGGAEA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9856955"
FT /id="VSP_007608"
FT VAR_SEQ 599..923
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9856955"
FT /id="VSP_007609"
FT VARIANT 16
FT /note="A -> P (in dbSNP:rs11168230)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_047924"
FT VARIANT 193
FT /note="R -> G (in dbSNP:rs2016123)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9853756,
FT ECO:0000269|PubMed:9856955, ECO:0000269|Ref.4"
FT /id="VAR_047925"
FT VARIANT 374
FT /note="G -> S (in dbSNP:rs12422983)"
FT /id="VAR_047926"
FT VARIANT 517
FT /note="C -> Y (in dbSNP:rs61709815)"
FT /id="VAR_061784"
FT MUTAGEN 315
FT /note="L->W: Abolishes activation of RAP1A."
FT /evidence="ECO:0000269|PubMed:12469113"
FT MUTAGEN 321
FT /note="R->K: Reduces activation of RAP1A."
FT /evidence="ECO:0000269|PubMed:9856955"
FT MUTAGEN 342
FT /note="F->A,T: Diminishes GEF activity dependence on cAMP
FT concentration."
FT /evidence="ECO:0000269|PubMed:12469113"
FT MUTAGEN 412
FT /note="D->A: Abolishes interaction with PDE3B."
FT /evidence="ECO:0000269|PubMed:21393242"
FT MUTAGEN 415
FT /note="E->A: Abolishes interaction with PDE3B."
FT /evidence="ECO:0000269|PubMed:21393242"
FT MUTAGEN 417
FT /note="F->A: Abolishes interaction with PDE3B."
FT /evidence="ECO:0000269|PubMed:21393242"
FT MUTAGEN 420
FT /note="D->A: Abolishes interaction with PDE3B."
FT /evidence="ECO:0000269|PubMed:21393242"
FT MUTAGEN 421
FT /note="F->A: Abolishes interaction with PDE3B."
FT /evidence="ECO:0000269|PubMed:21393242"
FT CONFLICT 64
FT /note="R -> H (in Ref. 1; AAD12740/AAD02890)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="R -> Q (in Ref. 1; AAD12740/AAD02890)"
FT /evidence="ECO:0000305"
FT CONFLICT 116
FT /note="I -> T (in Ref. 6; AAC83381)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="D -> Y (in Ref. 1; AAD12740/AAD02890)"
FT /evidence="ECO:0000305"
FT CONFLICT 394
FT /note="E -> D (in Ref. 1; AAD12740/AAD02890)"
FT /evidence="ECO:0000305"
FT CONFLICT 406
FT /note="P -> L (in Ref. 1; AAD12740/AAD02890)"
FT /evidence="ECO:0000305"
FT CONFLICT 414
FT /note="T -> K (in Ref. 1; AAD12740/AAD02890)"
FT /evidence="ECO:0000305"
FT CONFLICT 491
FT /note="Q -> H (in Ref. 1; AAD12740)"
FT /evidence="ECO:0000305"
FT CONFLICT 638
FT /note="V -> A (in Ref. 6; AAC83381)"
FT /evidence="ECO:0000305"
FT CONFLICT 736
FT /note="R -> K (in Ref. 1; AAD12740)"
FT /evidence="ECO:0000305"
FT CONFLICT 751
FT /note="L -> V (in Ref. 1; AAD12740)"
FT /evidence="ECO:0000305"
FT CONFLICT 765
FT /note="A -> P (in Ref. 1; AAD12740)"
FT /evidence="ECO:0000305"
FT HELIX 94..111
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 115..121
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 124..131
FT /evidence="ECO:0007829|PDB:6H7E"
FT HELIX 132..142
FT /evidence="ECO:0007829|PDB:6H7E"
FT HELIX 149..161
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:6H7E"
FT HELIX 200..222
FT /evidence="ECO:0007829|PDB:6H7E"
FT HELIX 230..240
FT /evidence="ECO:0007829|PDB:6H7E"
FT HELIX 244..246
FT /evidence="ECO:0007829|PDB:6H7E"
FT HELIX 251..260
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 262..265
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 282..295
FT /evidence="ECO:0007829|PDB:6H7E"
FT TURN 296..298
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 299..305
FT /evidence="ECO:0007829|PDB:6H7E"
FT HELIX 312..317
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 322..327
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:6H7E"
FT STRAND 333..338
FT /evidence="ECO:0007829|PDB:6H7E"
FT HELIX 339..346
FT /evidence="ECO:0007829|PDB:6H7E"
SQ SEQUENCE 923 AA; 103751 MW; 8B3A24341F20515F CRC64;
MKVGWPGESC WQVGLAVEDS PALGAPRVGA LPDVVPEGTL LNMVLRRMHR PRSCSYQLLL
EHQRPSCIQG LRWTPLTNSE ESLDFSESLE QASTERVLRA GRQLHRHLLA TCPNLIRDRK
YHLRLYRQCC SGRELVDGIL ALGLGVHSRS QVVGICQVLL DEGALCHVKH DWAFQDRDAQ
FYRFPGPEPE PVRTHEMEEE LAEAVALLSQ RGPDALLTVA LRKPPGQRTD EELDLIFEEL
LHIKAVAHLS NSVKRELAAV LLFEPHSKAG TVLFSQGDKG TSWYIIWKGS VNVVTHGKGL
VTTLHEGDDF GQLALVNDAP RAATIILRED NCHFLRVDKQ DFNRIIKDVE AKTMRLEEHG
KVVLVLERAS QGAGPSRPPT PGRNRYTVMS GTPEKILELL LEAMGPDSSA HDPTETFLSD
FLLTHRVFMP SAQLCAALLH HFHVEPAGGS EQERSTYVCN KRQQILRLVS QWVALYGSML
HTDPVATSFL QKLSDLVGRD TRLSNLLREQ WPERRRCHRL ENGCGNASPQ MKARNLPVWL
PNQDEPLPGS SCAIQVGDKV PYDICRPDHS VLTLQLPVTA SVREVMAALA QEDGWTKGQV
LVKVNSAGDA IGLQPDARGV ATSLGLNERL FVVNPQEVHE LIPHPDQLGP TVGSAEGLDL
VSAKDLAGQL TDHDWSLFNS IHQVELIHYV LGPQHLRDVT TANLERFMRR FNELQYWVAT
ELCLCPVPGP RAQLLRKFIK LAAHLKEQKN LNSFFAVMFG LSNSAISRLA HTWERLPHKV
RKLYSALERL LDPSWNHRVY RLALAKLSPP VIPFMPLLLK DMTFIHEGNH TLVENLINFE
KMRMMARAAR MLHHCRSHNP VPLSPLRSRV SHLHEDSQVA RISTCSEQSL STRSPASTWA
YVQQLKVIDN QRELSRLSRE LEP
