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Protein

Rap guanine nucleotide exchange factor 3

Gene

Rapgef3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi245 – 363119cAMPAdd
BLAST

GO - Molecular functioni

  • cAMP binding Source: RGD
  • ion channel 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 hydrogen:potassium-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 from RNA polymerase II promoter 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
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Angiogenesis

Keywords - Ligandi

cAMP, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621869. Rapgef3.

Subcellular locationi

GO - Cellular componenti

  • apical part of cell Source: RGD
  • axon terminus Source: RGD
  • basal plasma membrane Source: RGD
  • basolateral part of cell Source: RGD
  • brush border membrane 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
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 926926Rap guanine nucleotide exchange factor 3PRO_0000068869Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei79 – 791PhosphoserineBy similarity
Modified residuei531 – 5311PhosphoserineBy similarity
Modified residuei867 – 8671PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9Z1C8.

PTM databases

iPTMnetiQ9Z1C8.

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

  • ion channel binding Source: RGD

Protein-protein interaction databases

BioGridi248769. 1 interaction.
STRINGi10116.ENSRNOP00000061597.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1C8.
SMRiQ9Z1C8. Positions 96-351.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini110 – 18677DEPPROSITE-ProRule annotationAdd
BLAST
Domaini384 – 521138N-terminal Ras-GEFPROSITE-ProRule annotationAdd
BLAST
Domaini665 – 892228Ras-GEFPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni218 – 24225Interaction with PDE3BBy similarityAdd
BLAST
Regioni398 – 42225Interaction with PDE3BBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation
Contains 1 DEP domain.PROSITE-ProRule annotation
Contains 1 N-terminal Ras-GEF domain.PROSITE-ProRule annotation
Contains 1 Ras-GEF domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG2378. Eukaryota.
ENOG410XPX9. LUCA.
HOGENOMiHOG000230545.
HOVERGENiHBG056985.
InParanoidiQ9Z1C8.
KOiK08014.
PhylomeDBiQ9Z1C8.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
1.10.840.10. 1 hit.
2.60.120.10. 1 hit.
InterProiIPR018490. 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.
IPR001895. RASGEF_cat_dom.
IPR014710. RmlC-like_jellyroll.
IPR029071. Ubiquitin-rel_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00610. DEP. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
SMARTiSM00100. cNMP. 1 hit.
SM00049. DEP. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF48366. SSF48366. 3 hits.
SSF51206. SSF51206. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
PS50186. DEP. 1 hit.
PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 4242Missing in isoform 2. 1 PublicationVSP_034367Add
BLAST

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

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

3D structure databases

ProteinModelPortaliQ9Z1C8.
SMRiQ9Z1C8. Positions 96-351.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248769. 1 interaction.
STRINGi10116.ENSRNOP00000061597.

PTM databases

iPTMnetiQ9Z1C8.

Proteomic databases

PaxDbiQ9Z1C8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi10411.
RGDi621869. Rapgef3.

Phylogenomic databases

eggNOGiKOG2378. Eukaryota.
ENOG410XPX9. LUCA.
HOGENOMiHOG000230545.
HOVERGENiHBG056985.
InParanoidiQ9Z1C8.
KOiK08014.
PhylomeDBiQ9Z1C8.

Miscellaneous databases

PROiQ9Z1C8.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
1.10.840.10. 1 hit.
2.60.120.10. 1 hit.
InterProiIPR018490. 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.
IPR001895. RASGEF_cat_dom.
IPR014710. RmlC-like_jellyroll.
IPR029071. Ubiquitin-rel_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamiPF00027. cNMP_binding. 1 hit.
PF00610. DEP. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
SMARTiSM00100. cNMP. 1 hit.
SM00049. DEP. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMiSSF46785. SSF46785. 1 hit.
SSF48366. SSF48366. 3 hits.
SSF51206. SSF51206. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
PS50186. DEP. 1 hit.
PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.

Entry informationi

Entry nameiRPGF3_RAT
AccessioniPrimary (citable) accession number: Q9Z1C8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: July 1, 2008
Last modified: June 8, 2016
This is version 117 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

It is uncertain whether Met-1 or Met-43 is the initiator.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.