RPGF3_RAT
ID RPGF3_RAT Reviewed; 926 AA.
AC Q9Z1C8;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-2008, sequence version 2.
DT 03-AUG-2022, entry version 143.
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 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 [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
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).
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 -!- 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=Q9Z1C8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9Z1C8-2; Sequence=VSP_034367;
CC -!- TISSUE SPECIFICITY: Expressed at low levels in adult brain. Strongly
CC expressed in parts of the neonatal brain, including the septum and the
CC thalamus. {ECO:0000269|PubMed:9856955}.
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}.
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DR EMBL; AABR03056109; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03058672; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; U78167; AAD12739.1; -; mRNA.
DR RefSeq; NP_067722.1; NM_021690.1. [Q9Z1C8-2]
DR AlphaFoldDB; Q9Z1C8; -.
DR SMR; Q9Z1C8; -.
DR BioGRID; 248769; 1.
DR STRING; 10116.ENSRNOP00000061597; -.
DR iPTMnet; Q9Z1C8; -.
DR PhosphoSitePlus; Q9Z1C8; -.
DR PaxDb; Q9Z1C8; -.
DR PRIDE; Q9Z1C8; -.
DR GeneID; 59326; -.
DR KEGG; rno:59326; -.
DR UCSC; RGD:621869; rat. [Q9Z1C8-1]
DR CTD; 10411; -.
DR RGD; 621869; Rapgef3.
DR eggNOG; KOG2378; Eukaryota.
DR InParanoid; Q9Z1C8; -.
DR OrthoDB; 143470at2759; -.
DR PhylomeDB; Q9Z1C8; -.
DR Reactome; R-RNO-354192; Integrin signaling.
DR Reactome; R-RNO-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR Reactome; R-RNO-392517; Rap1 signalling.
DR Reactome; R-RNO-422356; Regulation of insulin secretion.
DR PRO; PR:Q9Z1C8; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0043679; C:axon terminus; IDA:RGD.
DR GO; GO:0009925; C:basal plasma membrane; IDA:RGD.
DR GO; GO:1990794; C:basolateral part of cell; IDA:RGD.
DR GO; GO:0031526; C:brush border membrane; IDA:RGD.
DR GO; GO:0071944; C:cell periphery; IDA:RGD.
DR GO; GO:0030175; C:filopodium; IDA:UniProtKB.
DR GO; GO:0030426; C:growth cone; IDA:RGD.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0031090; C:organelle membrane; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:1990796; C:photoreceptor cell terminal bouton; IDA:RGD.
DR GO; GO:0097470; C:ribbon synapse; IDA:RGD.
DR GO; GO:1990795; C:rod bipolar cell terminal bouton; IDA:RGD.
DR GO; GO:0030552; F:cAMP binding; IPI:RGD.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISO:RGD.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:RGD.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0060840; P:artery development; IEP:RGD.
DR GO; GO:0008306; P:associative learning; ISO:RGD.
DR GO; GO:0007420; P:brain development; IEP:RGD.
DR GO; GO:0071320; P:cellular response to cAMP; ISS:UniProtKB.
DR GO; GO:1904474; P:cellular response to L-dopa; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IEP:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEP:RGD.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:1990791; P:dorsal root ganglion development; IEP:RGD.
DR GO; GO:0061028; P:establishment of endothelial barrier; ISS:UniProtKB.
DR GO; GO:0097421; P:liver regeneration; IEP:RGD.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:RGD.
DR GO; GO:0032966; P:negative regulation of collagen biosynthetic process; IMP:RGD.
DR GO; GO:0034242; P:negative regulation of syncytium formation by plasma membrane fusion; ISO:RGD.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IMP:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:1904427; P:positive regulation of calcium ion transmembrane transport; IMP:RGD.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:RGD.
DR GO; GO:1904426; P:positive regulation of GTP binding; IMP:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:1904453; P:positive regulation of potassium:proton exchanging ATPase activity; IMP:RGD.
DR GO; GO:1901985; P:positive regulation of protein acetylation; ISO:RGD.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:RGD.
DR GO; GO:0014911; P:positive regulation of smooth muscle cell migration; IMP:RGD.
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:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP: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:2000249; P:regulation of actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0035094; P:response to nicotine; IEP:RGD.
DR GO; GO:0021510; P:spinal cord development; IEP:RGD.
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 2: Evidence at transcript level;
KW Alternative splicing; Angiogenesis; cAMP; cAMP-binding; Cytoplasm;
KW Guanine-nucleotide releasing factor; Membrane; Nucleotide-binding;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..926
FT /note="Rap guanine nucleotide exchange factor 3"
FT /id="PRO_0000068869"
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..892
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:0000250|UniProtKB:Q8VCC8"
FT MOD_RES 531
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCC8"
FT MOD_RES 867
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8VCC8"
FT VAR_SEQ 1..42
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9856955"
FT /id="VSP_034367"
SQ SEQUENCE 926 AA; 104559 MW; B5D250C580883BF7 CRC64;
MKVSWPGENH WQVGPAVVES PAVGAPQVGG LPDVVPEGTL LNMVLKRMHR PRCCSYQLVF
EHRRPSCIQG LRWTPLTNSE GSLDFRVSLE QATTEHVHKA GKLLYRHLLA TYPTLIRDRK
YHLRLHRQCC SGRELVDGIL ALGLGVHSRS QAVGICQVLL DEGALCHVKH DWTFQDRDAQ
FYRFPGPEPQ PAGTHDVEEE LVEAMALLSQ RGPDALLTVA LRKSPGQRTD EELDLIFEEL
VHIKAVAHLS NSVKRELAAV LLFEPHSKAG TVLFSQGDKG TSWYIIWKGS VNVVTRGKGL
VTTLHEGDDF GQLALVNDAP RAATIILREN NCHFLRVDKQ DFNRIIKDVE AKTMRLEEHG
KVVLVLERTS QGAGPSRPPT PGRNRYTVMS GTPEKILELL LEAMRPDSSA HDPTETFLSD
FLLTHSVFMP CTQLFAALLH HFHVEPSEPA GGSEQERSTY ICNKRQQILR LVSRWVALYS
PMLRSDPVAT SFLQKLSDLV SRDTRLSNLL REQYPERRRH HRLENGCGNV SPQTKARNAP
VWFPNHEEPL PSSAGAIRVG DKVPYDICRP DHSVLTLHLP VTASVREVMA ALAHEDHWTK
GQVLVKVNSA GDVVGLQPDA RGVATSLGLN ERIFVVDPQE VHELTPHPEQ LGPTLGSSEM
LDLVSAKDLA GQLTEHDWNL FNRIHQVELI HYVLGPQHLR DVTTANLERF MRRFNELQYW
VATELCLCPV PGPRAQLLRK FIKLAAHLKE QKNLNSFFAV MFGLSNSAIS RLAHTWERLP
HKVRKLYSAL ERLLDPSWNH RVYRLALTKL SPPVIPFMPL LLKDMTFIHE GNHTLVENLI
NFEKMRMMAR AVRMLHHCRS HSTAPLSPLR SRVSHIHEDS QASRISTCSE QSLSTRSPAS
TWAYVQQLKV IDNQRELSRL SRELEP
