UniProtKB - Q9Z1C8 (RPGF3_RAT)
Protein
Rap guanine nucleotide exchange factor 3
Gene
Rapgef3
Organism
Rattus norvegicus (Rat)
Status
Functioni
Guanine nucleotide exchange factor (GEF) for RAP1A and RAP2A small GTPases that is activated by binding cAMP. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which it activates the PI3K gamma complex and which is involved in angiogenesis. Plays a role in the modulation of the cAMP-induced dynamic control of endothelial barrier function through a pathway that is independent on Rho-mediated signaling. Required for the actin rearrangement at cell-cell junctions, such as stress fibers and junctional actin (By similarity).By similarity
Caution
It is uncertain whether Met-1 or Met-43 is the initiator.Curated
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 245 – 363 | cAMPAdd BLAST | 119 |
GO - Molecular functioni
- cAMP binding Source: RGD
- guanyl-nucleotide exchange factor activity Source: RGD
- ion channel binding Source: RGD
- protein domain specific binding Source: RGD
- Rap guanyl-nucleotide exchange factor activity Source: UniProtKB
GO - Biological processi
- angiogenesis Source: UniProtKB-KW
- artery development Source: RGD
- brain development Source: RGD
- cellular response to cAMP Source: UniProtKB
- cellular response to drug Source: RGD
- cellular response to L-dopa Source: RGD
- cellular response to organic cyclic compound Source: RGD
- cellular response to transforming growth factor beta stimulus Source: RGD
- dorsal root ganglion development Source: RGD
- establishment of endothelial barrier Source: UniProtKB
- liver regeneration Source: RGD
- negative regulation of cardiac muscle cell apoptotic process Source: RGD
- negative regulation of collagen biosynthetic process Source: RGD
- negative regulation of syncytium formation by plasma membrane fusion Source: RGD
- positive regulation of actin cytoskeleton reorganization Source: RGD
- positive regulation of angiogenesis Source: UniProtKB
- positive regulation of calcium ion transmembrane transport Source: RGD
- positive regulation of cell size Source: RGD
- positive regulation of GTPase activity Source: UniProtKB
- positive regulation of GTP binding Source: RGD
- positive regulation of peptidyl-serine phosphorylation Source: RGD
- positive regulation of potassium:proton exchanging ATPase activity Source: RGD
- positive regulation of protein acetylation Source: RGD
- positive regulation of protein export from nucleus Source: RGD
- positive regulation of protein phosphorylation Source: RGD
- positive regulation of smooth muscle cell migration Source: RGD
- positive regulation of stress fiber assembly Source: UniProtKB
- positive regulation of syncytium formation by plasma membrane fusion Source: RGD
- positive regulation of transcription by RNA polymerase II Source: RGD
- Rap protein signal transduction Source: UniProtKB
- regulation of actin cytoskeleton reorganization Source: UniProtKB
- response to nicotine Source: RGD
- spinal cord development Source: RGD
Keywordsi
Molecular function | Guanine-nucleotide releasing factor |
Biological process | Angiogenesis |
Ligand | cAMP, cAMP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-RNO-354192, Integrin signaling R-RNO-381676, Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-RNO-392517, Rap1 signalling R-RNO-422356, Regulation of insulin secretion |
Names & Taxonomyi
Protein namesi | Recommended name: Rap guanine nucleotide exchange factor 3Alternative name(s): Exchange factor directly activated by cAMP 1 Exchange protein directly activated by cAMP 1 Short name: EPAC 1 cAMP-regulated guanine nucleotide exchange factor I Short name: cAMP-GEFI |
Gene namesi | Name:Rapgef3 Synonyms:Epac, Epac1 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 621869, Rapgef3 |
Subcellular locationi
Other locations
- Cytoplasm
- Membrane By similarity; Peripheral membrane protein By similarity
Plasma Membrane
- basal plasma membrane Source: RGD
- brush border membrane Source: RGD
Other locations
- apical part of cell Source: RGD
- axon terminus Source: RGD
- basolateral part of cell Source: RGD
- cell periphery Source: RGD
- filopodium Source: UniProtKB
- growth cone Source: RGD
- lamellipodium Source: UniProtKB
- microvillus Source: UniProtKB
- neuronal cell body Source: RGD
- organelle membrane Source: RGD
- perinuclear region of cytoplasm Source: RGD
- photoreceptor cell terminal bouton Source: RGD
- ribbon synapse Source: RGD
- rod bipolar cell terminal bouton Source: RGD
Keywords - Cellular componenti
Cytoplasm, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000068869 | 1 – 926 | Rap guanine nucleotide exchange factor 3Add BLAST | 926 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 79 | PhosphoserineBy similarity | 1 | |
Modified residuei | 531 | PhosphoserineBy similarity | 1 | |
Modified residuei | 867 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q9Z1C8 |
PRIDEi | Q9Z1C8 |
PTM databases
iPTMneti | Q9Z1C8 |
PhosphoSitePlusi | Q9Z1C8 |
Expressioni
Tissue specificityi
Expressed at low levels in adult brain. Strongly expressed in parts of the neonatal brain, including the septum and the thalamus.1 Publication
Interactioni
GO - Molecular functioni
- guanyl-nucleotide exchange factor activity Source: RGD
- ion channel binding Source: RGD
- protein domain specific binding Source: RGD
- Rap guanyl-nucleotide exchange factor activity Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 248769, 1 interactor |
STRINGi | 10116.ENSRNOP00000061597 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 110 – 186 | DEPPROSITE-ProRule annotationAdd BLAST | 77 | |
Domaini | 384 – 521 | N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST | 138 | |
Domaini | 665 – 892 | Ras-GEFPROSITE-ProRule annotationAdd BLAST | 228 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 218 – 242 | Interaction with PDE3BBy similarityAdd BLAST | 25 | |
Regioni | 398 – 422 | Interaction with PDE3BBy similarityAdd BLAST | 25 |
Domaini
The DEP domain is involved in membrane localization independent from regulation by cAMP.By similarity
Phylogenomic databases
eggNOGi | KOG2378, Eukaryota |
InParanoidi | Q9Z1C8 |
OrthoDBi | 143470at2759 |
PhylomeDBi | Q9Z1C8 |
Family and domain databases
CDDi | cd00038, CAP_ED, 1 hit cd00155, RasGEF, 1 hit cd06224, REM, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 1.10.840.10, 1 hit 2.60.120.10, 1 hit |
InterProi | View protein in InterPro IPR018490, cNMP-bd-like IPR000595, cNMP-bd_dom IPR000591, DEP_dom IPR008937, Ras-like_GEF IPR000651, Ras-like_Gua-exchang_fac_N IPR019804, Ras_G-nucl-exch_fac_CS IPR023578, Ras_GEF_dom_sf IPR001895, RASGEF_cat_dom IPR036964, RASGEF_cat_dom_sf IPR014710, RmlC-like_jellyroll IPR029071, Ubiquitin-like_domsf IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR23113, PTHR23113, 1 hit |
Pfami | View protein in Pfam PF00027, cNMP_binding, 1 hit PF00610, DEP, 1 hit PF00617, RasGEF, 1 hit PF00618, RasGEF_N, 1 hit |
SMARTi | View protein in SMART SM00100, cNMP, 1 hit SM00049, DEP, 1 hit SM00147, RasGEF, 1 hit SM00229, RasGEFN, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF48366, SSF48366, 1 hit SSF51206, SSF51206, 1 hit SSF54236, SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS50042, CNMP_BINDING_3, 1 hit PS50186, DEP, 1 hit PS00720, RASGEF, 1 hit PS50009, RASGEF_CAT, 1 hit PS50212, RASGEF_NTER, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q9Z1C8-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MKVSWPGENH WQVGPAVVES PAVGAPQVGG LPDVVPEGTL LNMVLKRMHR
60 70 80 90 100
PRCCSYQLVF EHRRPSCIQG LRWTPLTNSE GSLDFRVSLE QATTEHVHKA
110 120 130 140 150
GKLLYRHLLA TYPTLIRDRK YHLRLHRQCC SGRELVDGIL ALGLGVHSRS
160 170 180 190 200
QAVGICQVLL DEGALCHVKH DWTFQDRDAQ FYRFPGPEPQ PAGTHDVEEE
210 220 230 240 250
LVEAMALLSQ RGPDALLTVA LRKSPGQRTD EELDLIFEEL VHIKAVAHLS
260 270 280 290 300
NSVKRELAAV LLFEPHSKAG TVLFSQGDKG TSWYIIWKGS VNVVTRGKGL
310 320 330 340 350
VTTLHEGDDF GQLALVNDAP RAATIILREN NCHFLRVDKQ DFNRIIKDVE
360 370 380 390 400
AKTMRLEEHG KVVLVLERTS QGAGPSRPPT PGRNRYTVMS GTPEKILELL
410 420 430 440 450
LEAMRPDSSA HDPTETFLSD FLLTHSVFMP CTQLFAALLH HFHVEPSEPA
460 470 480 490 500
GGSEQERSTY ICNKRQQILR LVSRWVALYS PMLRSDPVAT SFLQKLSDLV
510 520 530 540 550
SRDTRLSNLL REQYPERRRH HRLENGCGNV SPQTKARNAP VWFPNHEEPL
560 570 580 590 600
PSSAGAIRVG DKVPYDICRP DHSVLTLHLP VTASVREVMA ALAHEDHWTK
610 620 630 640 650
GQVLVKVNSA GDVVGLQPDA RGVATSLGLN ERIFVVDPQE VHELTPHPEQ
660 670 680 690 700
LGPTLGSSEM LDLVSAKDLA GQLTEHDWNL FNRIHQVELI HYVLGPQHLR
710 720 730 740 750
DVTTANLERF MRRFNELQYW VATELCLCPV PGPRAQLLRK FIKLAAHLKE
760 770 780 790 800
QKNLNSFFAV MFGLSNSAIS RLAHTWERLP HKVRKLYSAL ERLLDPSWNH
810 820 830 840 850
RVYRLALTKL SPPVIPFMPL LLKDMTFIHE GNHTLVENLI NFEKMRMMAR
860 870 880 890 900
AVRMLHHCRS HSTAPLSPLR SRVSHIHEDS QASRISTCSE QSLSTRSPAS
910 920
TWAYVQQLKV IDNQRELSRL SRELEP
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0G2JWN8 | A0A0G2JWN8_RAT | Rap guanine nucleotide exchange fac... | Rapgef3 | 926 | Annotation score: | ||
Q3B7C8 | Q3B7C8_RAT | Rap guanine nucleotide exchange fac... | Rapgef3 rCG_50571 | 884 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_034367 | 1 – 42 | Missing in isoform 2. 1 PublicationAdd BLAST | 42 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AABR03056109 Genomic DNA No translation available. AABR03058672 Genomic DNA No translation available. U78167 mRNA Translation: AAD12739.1 |
RefSeqi | NP_067722.1, NM_021690.1 [Q9Z1C8-2] |
Genome annotation databases
GeneIDi | 59326 |
KEGGi | rno:59326 |
UCSCi | RGD:621869, rat [Q9Z1C8-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AABR03056109 Genomic DNA No translation available. AABR03058672 Genomic DNA No translation available. U78167 mRNA Translation: AAD12739.1 |
RefSeqi | NP_067722.1, NM_021690.1 [Q9Z1C8-2] |
3D structure databases
SMRi | Q9Z1C8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 248769, 1 interactor |
STRINGi | 10116.ENSRNOP00000061597 |
PTM databases
iPTMneti | Q9Z1C8 |
PhosphoSitePlusi | Q9Z1C8 |
Proteomic databases
PaxDbi | Q9Z1C8 |
PRIDEi | Q9Z1C8 |
Genome annotation databases
GeneIDi | 59326 |
KEGGi | rno:59326 |
UCSCi | RGD:621869, rat [Q9Z1C8-1] |
Organism-specific databases
CTDi | 10411 |
RGDi | 621869, Rapgef3 |
Phylogenomic databases
eggNOGi | KOG2378, Eukaryota |
InParanoidi | Q9Z1C8 |
OrthoDBi | 143470at2759 |
PhylomeDBi | Q9Z1C8 |
Enzyme and pathway databases
Reactomei | R-RNO-354192, Integrin signaling R-RNO-381676, Glucagon-like Peptide-1 (GLP1) regulates insulin secretion R-RNO-392517, Rap1 signalling R-RNO-422356, Regulation of insulin secretion |
Miscellaneous databases
PROi | PR:Q9Z1C8 |
Family and domain databases
CDDi | cd00038, CAP_ED, 1 hit cd00155, RasGEF, 1 hit cd06224, REM, 1 hit |
Gene3Di | 1.10.10.10, 1 hit 1.10.840.10, 1 hit 2.60.120.10, 1 hit |
InterProi | View protein in InterPro IPR018490, cNMP-bd-like IPR000595, cNMP-bd_dom IPR000591, DEP_dom IPR008937, Ras-like_GEF IPR000651, Ras-like_Gua-exchang_fac_N IPR019804, Ras_G-nucl-exch_fac_CS IPR023578, Ras_GEF_dom_sf IPR001895, RASGEF_cat_dom IPR036964, RASGEF_cat_dom_sf IPR014710, RmlC-like_jellyroll IPR029071, Ubiquitin-like_domsf IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
PANTHERi | PTHR23113, PTHR23113, 1 hit |
Pfami | View protein in Pfam PF00027, cNMP_binding, 1 hit PF00610, DEP, 1 hit PF00617, RasGEF, 1 hit PF00618, RasGEF_N, 1 hit |
SMARTi | View protein in SMART SM00100, cNMP, 1 hit SM00049, DEP, 1 hit SM00147, RasGEF, 1 hit SM00229, RasGEFN, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF48366, SSF48366, 1 hit SSF51206, SSF51206, 1 hit SSF54236, SSF54236, 1 hit |
PROSITEi | View protein in PROSITE PS50042, CNMP_BINDING_3, 1 hit PS50186, DEP, 1 hit PS00720, RASGEF, 1 hit PS50009, RASGEF_CAT, 1 hit PS50212, RASGEF_NTER, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | RPGF3_RAT | |
Accessioni | Q9Z1C8Primary (citable) accession number: Q9Z1C8 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 20, 2003 |
Last sequence update: | July 1, 2008 | |
Last modified: | December 2, 2020 | |
This is version 137 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |