RPGF3_MOUSE
ID RPGF3_MOUSE Reviewed; 918 AA.
AC Q8VCC8; Q8BZK9; Q8R1R1;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 154.
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=cAMP-regulated guanine nucleotide exchange factor I;
DE Short=cAMP-GEFI;
GN Name=Rapgef3; Synonyms=Epac, Epac1;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 640-918 (ISOFORM 2).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 466-918 (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Diencephalon;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-79; SER-531 AND SER-859, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, and Pancreas;
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).
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 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PDE3B and PIK3R6; form a signaling complex that
CC regulates phosphatidylinositol 3-kinase gamma in angiogenesis.
CC {ECO:0000250|UniProtKB:O95398}.
CC -!- INTERACTION:
CC Q8VCC8; E9Q9K8: Akap6; NbExp=2; IntAct=EBI-6902706, EBI-6902745;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8VCC8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8VCC8-2; Sequence=VSP_007610;
CC -!- DOMAIN: The DEP domain is involved in membrane localization independent
CC from regulation by cAMP. {ECO:0000250}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-43 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH20532.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; BC020532; AAH20532.1; ALT_INIT; mRNA.
DR EMBL; BC020311; AAH20311.1; -; mRNA.
DR EMBL; AK034265; BAC28653.1; -; mRNA.
DR CCDS; CCDS37187.2; -. [Q8VCC8-1]
DR CCDS; CCDS49714.1; -. [Q8VCC8-2]
DR RefSeq; NP_001171281.1; NM_001177810.1. [Q8VCC8-2]
DR RefSeq; NP_001171282.1; NM_001177811.1.
DR RefSeq; NP_659099.2; NM_144850.2. [Q8VCC8-1]
DR AlphaFoldDB; Q8VCC8; -.
DR SMR; Q8VCC8; -.
DR BioGRID; 230205; 1.
DR IntAct; Q8VCC8; 1.
DR STRING; 10090.ENSMUSP00000116426; -.
DR iPTMnet; Q8VCC8; -.
DR PhosphoSitePlus; Q8VCC8; -.
DR MaxQB; Q8VCC8; -.
DR PaxDb; Q8VCC8; -.
DR PRIDE; Q8VCC8; -.
DR ProteomicsDB; 299944; -. [Q8VCC8-1]
DR ProteomicsDB; 299945; -. [Q8VCC8-2]
DR Antibodypedia; 3824; 257 antibodies from 38 providers.
DR DNASU; 223864; -.
DR Ensembl; ENSMUST00000126854; ENSMUSP00000116426; ENSMUSG00000022469. [Q8VCC8-2]
DR Ensembl; ENSMUST00000129223; ENSMUSP00000118148; ENSMUSG00000022469. [Q8VCC8-1]
DR GeneID; 223864; -.
DR KEGG; mmu:223864; -.
DR UCSC; uc007xkz.2; mouse. [Q8VCC8-2]
DR UCSC; uc007xla.2; mouse. [Q8VCC8-1]
DR CTD; 10411; -.
DR MGI; MGI:2441741; Rapgef3.
DR VEuPathDB; HostDB:ENSMUSG00000022469; -.
DR eggNOG; KOG2378; Eukaryota.
DR GeneTree; ENSGT00940000159931; -.
DR InParanoid; Q8VCC8; -.
DR OMA; DIYRPDH; -.
DR OrthoDB; 143470at2759; -.
DR PhylomeDB; Q8VCC8; -.
DR TreeFam; TF313184; -.
DR Reactome; R-MMU-354192; Integrin signaling.
DR Reactome; R-MMU-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-MMU-392517; Rap1 signalling.
DR Reactome; R-MMU-422356; Regulation of insulin secretion.
DR BioGRID-ORCS; 223864; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Rapgef3; mouse.
DR PRO; PR:Q8VCC8; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8VCC8; protein.
DR Bgee; ENSMUSG00000022469; Expressed in aortic valve and 218 other tissues.
DR ExpressionAtlas; Q8VCC8; baseline and differential.
DR Genevisible; Q8VCC8; MM.
DR GO; GO:0045177; C:apical part of cell; ISO:MGI.
DR GO; GO:0043679; C:axon terminus; ISO:MGI.
DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI.
DR GO; GO:1990794; C:basolateral part of cell; ISO:MGI.
DR GO; GO:0031526; C:brush border membrane; ISO:MGI.
DR GO; GO:0071944; C:cell periphery; ISO:MGI.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISO:MGI.
DR GO; GO:0030175; C:filopodium; ISO:MGI.
DR GO; GO:0030426; C:growth cone; ISO:MGI.
DR GO; GO:0030027; C:lamellipodium; ISO:MGI.
DR GO; GO:0005902; C:microvillus; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0031090; C:organelle membrane; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:1990796; C:photoreceptor cell terminal bouton; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0097470; C:ribbon synapse; ISO:MGI.
DR GO; GO:1990795; C:rod bipolar cell terminal bouton; ISO:MGI.
DR GO; GO:0030552; F:cAMP binding; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0008306; P:associative learning; IMP:MGI.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; ISO:MGI.
DR GO; GO:0034242; P:negative regulation of syncytium formation by plasma membrane fusion; ISO:MGI.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; ISO:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:1904427; P:positive regulation of calcium ion transmembrane transport; ISO:MGI.
DR GO; GO:0045793; P:positive regulation of cell size; ISO:MGI.
DR GO; GO:1904426; P:positive regulation of GTP binding; ISO:MGI.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:1904453; P:positive regulation of potassium:proton exchanging ATPase activity; ISO:MGI.
DR GO; GO:1901985; P:positive regulation of protein acetylation; ISO:MGI.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; ISO:MGI.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; ISS:UniProtKB.
DR GO; GO:0060143; P:positive regulation of syncytium formation by plasma membrane fusion; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; 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:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
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 Alternative splicing; Angiogenesis; cAMP; cAMP-binding; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..918
FT /note="Rap guanine nucleotide exchange factor 3"
FT /id="PRO_0000068868"
FT DOMAIN 110..186
FT /note="DEP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00066"
FT DOMAIN 384..521
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 665..884
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 218..242
FT /note="Interaction with PDE3B"
FT /evidence="ECO:0000250"
FT REGION 369..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..422
FT /note="Interaction with PDE3B"
FT /evidence="ECO:0000250"
FT COMPBIAS 373..387
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 311..314
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:O95398"
FT BINDING 321..322
FT /ligand="3',5'-cyclic AMP"
FT /ligand_id="ChEBI:CHEBI:58165"
FT /evidence="ECO:0000250|UniProtKB:O95398"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 859
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT VAR_SEQ 688..689
FT /note="QE -> ELIHYVLGPQ (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_007610"
SQ SEQUENCE 918 AA; 103533 MW; DB774BBF7CB4428E CRC64;
MKVSWPGENH WQVGPAVVES PAVGAPQVGG LPDVVPEGTL LNMVLKRMHR PRCCSYQLVF
EHRRPSCIQG LRWTPLTNSE DSLDFRVSLE QATTEHVHKA GKLLHRHLLA TYPTLIRDRK
YHLRLYRHCC SGRELVDGIL ALGLGVHSRS QAVGICQVLL DEGALCHVKH DWTFQDRDAQ
FYRFPGPEPE PTGTQDVEEE LVEAMALLSQ RGPDALLTVA LRKPPGQRTD EELDLIFEEL
LHIKAVAHLS NSVKRELAAV LLFEPHSKAG TVLFSQGDKG TSWYIIWKGS VNVVTHGKGL
VTTLHEGDDF GQLALVNDAP RAATIILREN NCHFLRVDKQ DFNRIIKDVE AKTMRLEEHG
KVVLVLERTS QGAGPSRPPT PGRNRYTVMS GTPEKILELL LEAMRPDSSA HDPTETFLSD
FLLTHSVFMP STQLFTALLH HFHVEPADPA GGSEQEHSTY ICNKRQQILR LVGRWVALYS
PMLHSDPVAT SFLQKLSDLV SRDARLSNLL REQYPERRRH HRLENGCGNV SPQTKARNAP
VWLPNQEEPL PSSAGAIRVG DKVPYDICRP DHSVLTLHLP VTASVREVMA ALAHEDHWTK
GQVLVKVNSA GDVVGLQPDA RGVATSLGLN ERLFVVDPQE VHELTPHPEQ LGPTLGSSEM
LDLVSAKDLA GQLTDHDWNL FNRIHQVQEH LRDVTTANLE RFMRRFNELQ YWVATELCLC
PVPGSRAQLL RKFIKLAAHL KEQKNLNSFF AVMFGLSNSA ISRLAHTWER LPHKVRKLYS
ALERLLDPSW NHRVYRLALT KLSPPVIPFM PLLLKDVTFI HEGNHTLVEN LINFEKMRMM
ARAVRMLHHC RSHSTAPLSP LRSRVSHIHE DSQGSRISTC SEQSLSTRSP ASTWAYVQQL
KVIDNQRELS RLSRELEP
