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Protein

Rap guanine nucleotide exchange factor 3

Gene

Rapgef3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein 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

GO - Biological processi

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
Biological processAngiogenesis
LigandcAMP, cAMP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-354192 Integrin alphaIIb beta3 signaling
R-MMU-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-MMU-392517 Rap1 signalling
R-MMU-422356 Regulation of insulin secretion

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 15

Organism-specific databases

MGIiMGI:2441741 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_00000688681 – 918Rap guanine nucleotide exchange factor 3Add BLAST918

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei79PhosphoserineCombined sources1
Modified residuei531PhosphoserineCombined sources1
Modified residuei859PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8VCC8
PRIDEiQ8VCC8

PTM databases

iPTMnetiQ8VCC8
PhosphoSitePlusiQ8VCC8

Expressioni

Gene expression databases

BgeeiENSMUSG00000022469
CleanExiMM_RAPGEF3
ExpressionAtlasiQ8VCC8 baseline and differential
GenevisibleiQ8VCC8 MM

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
Akap6E9Q9K82EBI-6902706,EBI-6902745

GO - Molecular functioni

Protein-protein interaction databases

BioGridi230205, 1 interactor
IntActiQ8VCC8, 1 interactor
STRINGi10090.ENSMUSP00000116426

Structurei

3D structure databases

ProteinModelPortaliQ8VCC8
SMRiQ8VCC8
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 – 884Ras-GEFPROSITE-ProRule annotationAdd BLAST220

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
GeneTreeiENSGT00880000137870
HOGENOMiHOG000230545
HOVERGENiHBG056985
InParanoidiQ8VCC8
KOiK08014
OMAiWVATELC
OrthoDBiEOG091G0HKG
PhylomeDBiQ8VCC8
TreeFamiTF313184

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: Q8VCC8-1) [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 DSLDFRVSLE QATTEHVHKA
110 120 130 140 150
GKLLHRHLLA TYPTLIRDRK YHLRLYRHCC SGRELVDGIL ALGLGVHSRS
160 170 180 190 200
QAVGICQVLL DEGALCHVKH DWTFQDRDAQ FYRFPGPEPE PTGTQDVEEE
210 220 230 240 250
LVEAMALLSQ RGPDALLTVA LRKPPGQRTD EELDLIFEEL LHIKAVAHLS
260 270 280 290 300
NSVKRELAAV LLFEPHSKAG TVLFSQGDKG TSWYIIWKGS VNVVTHGKGL
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 STQLFTALLH HFHVEPADPA
460 470 480 490 500
GGSEQEHSTY ICNKRQQILR LVGRWVALYS PMLHSDPVAT SFLQKLSDLV
510 520 530 540 550
SRDARLSNLL REQYPERRRH HRLENGCGNV SPQTKARNAP VWLPNQEEPL
560 570 580 590 600
PSSAGAIRVG DKVPYDICRP DHSVLTLHLP VTASVREVMA ALAHEDHWTK
610 620 630 640 650
GQVLVKVNSA GDVVGLQPDA RGVATSLGLN ERLFVVDPQE VHELTPHPEQ
660 670 680 690 700
LGPTLGSSEM LDLVSAKDLA GQLTDHDWNL FNRIHQVQEH LRDVTTANLE
710 720 730 740 750
RFMRRFNELQ YWVATELCLC PVPGSRAQLL RKFIKLAAHL KEQKNLNSFF
760 770 780 790 800
AVMFGLSNSA ISRLAHTWER LPHKVRKLYS ALERLLDPSW NHRVYRLALT
810 820 830 840 850
KLSPPVIPFM PLLLKDVTFI HEGNHTLVEN LINFEKMRMM ARAVRMLHHC
860 870 880 890 900
RSHSTAPLSP LRSRVSHIHE DSQGSRISTC SEQSLSTRSP ASTWAYVQQL
910
KVIDNQRELS RLSRELEP
Note: No experimental confirmation available.
Length:918
Mass (Da):103,533
Last modified:July 1, 2008 - v2
Checksum:iDB774BBF7CB4428E
GO
Isoform 2 (identifier: Q8VCC8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     688-689: QE → ELIHYVLGPQ

Note: No experimental confirmation available.
Show »
Length:926
Mass (Da):104,426
Checksum:iA8140C76937E5A95
GO

Sequence cautioni

The sequence AAH20532 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_007610688 – 689QE → ELIHYVLGPQ in isoform 2. 2 Publications2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC020532 mRNA Translation: AAH20532.1 Different initiation.
BC020311 mRNA Translation: AAH20311.1
AK034265 mRNA Translation: BAC28653.1
CCDSiCCDS37187.2 [Q8VCC8-1]
CCDS49714.1 [Q8VCC8-2]
RefSeqiNP_001171281.1, NM_001177810.1 [Q8VCC8-2]
NP_001171282.1, NM_001177811.1
NP_659099.2, NM_144850.2 [Q8VCC8-1]
UniGeneiMm.24028

Genome annotation databases

EnsembliENSMUST00000126854; ENSMUSP00000116426; ENSMUSG00000022469 [Q8VCC8-2]
ENSMUST00000129223; ENSMUSP00000118148; ENSMUSG00000022469 [Q8VCC8-1]
GeneIDi223864
KEGGimmu:223864
UCSCiuc007xkz.2 mouse [Q8VCC8-2]
uc007xla.2 mouse [Q8VCC8-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiRPGF3_MOUSE
AccessioniPrimary (citable) accession number: Q8VCC8
Secondary accession number(s): Q8BZK9, Q8R1R1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: July 1, 2008
Last modified: March 28, 2018
This is version 135 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

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