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Protein

Rap guanine nucleotide exchange factor 3

Gene

Rapgef3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi245 – 363cAMPAdd BLAST119

GO - Molecular functioni

  • cAMP 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
  • 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 potassium:proton exchanging ATPase activity 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 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 functionGuanine-nucleotide releasing factor
Biological processAngiogenesis
LigandcAMP, cAMP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Rap guanine nucleotide exchange factor 3
Alternative 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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621869 Rapgef3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000688691 – 926Rap guanine nucleotide exchange factor 3Add BLAST926

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei79PhosphoserineBy similarity1
Modified residuei531PhosphoserineBy similarity1
Modified residuei867PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Z1C8
PRIDEiQ9Z1C8

PTM databases

iPTMnetiQ9Z1C8
PhosphoSitePlusiQ9Z1C8

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

Protein-protein interaction databases

BioGridi248769, 1 interactor
STRINGi10116.ENSRNOP00000061597

Structurei

3D structure databases

ProteinModelPortaliQ9Z1C8
SMRiQ9Z1C8
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini110 – 186DEPPROSITE-ProRule annotationAdd BLAST77
Domaini384 – 521N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST138
Domaini665 – 892Ras-GEFPROSITE-ProRule annotationAdd BLAST228

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni218 – 242Interaction with PDE3BBy similarityAdd BLAST25
Regioni398 – 422Interaction with PDE3BBy similarityAdd BLAST25

Domaini

The DEP domain is involved in membrane localization independent from regulation by cAMP.By similarity

Phylogenomic databases

eggNOGiKOG2378 Eukaryota
ENOG410XPX9 LUCA
HOGENOMiHOG000230545
HOVERGENiHBG056985
InParanoidiQ9Z1C8
KOiK08014
PhylomeDBiQ9Z1C8

Family and domain databases

CDDicd00038 CAP_ED, 1 hit
cd00155 RasGEF, 1 hit
cd06224 REM, 1 hit
Gene3Di1.10.10.10, 1 hit
1.10.840.10, 1 hit
2.60.120.10, 1 hit
InterProiView protein in InterPro
IPR018490 cNMP-bd-like
IPR000595 cNMP-bd_dom
IPR000591 DEP_dom
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
PfamiView protein in Pfam
PF00027 cNMP_binding, 1 hit
PF00610 DEP, 1 hit
PF00617 RasGEF, 1 hit
PF00618 RasGEF_N, 1 hit
SMARTiView protein in SMART
SM00100 cNMP, 1 hit
SM00049 DEP, 1 hit
SM00147 RasGEF, 1 hit
SM00229 RasGEFN, 1 hit
SUPFAMiSSF46785 SSF46785, 1 hit
SSF48366 SSF48366, 3 hits
SSF51206 SSF51206, 1 hit
SSF54236 SSF54236, 1 hit
PROSITEiView 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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Z1C8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        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
Length:926
Mass (Da):104,559
Last modified:July 1, 2008 - v2
Checksum:iB5D250C580883BF7
GO
Isoform 2 (identifier: Q9Z1C8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: Missing.

Show »
Length:884
Mass (Da):100,257
Checksum:iB082AAE3125AC933
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0343671 – 42Missing in isoform 2. 1 PublicationAdd BLAST42

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
RefSeqiNP_067722.1, NM_021690.1 [Q9Z1C8-2]
UniGeneiRn.42899

Genome annotation databases

GeneIDi59326
KEGGirno:59326
UCSCiRGD:621869 rat [Q9Z1C8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiRPGF3_RAT
AccessioniPrimary (citable) accession number: Q9Z1C8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: July 1, 2008
Last modified: May 23, 2018
This is version 127 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health