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Q8VCC8 (RPGF3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Rapgef3
Synonyms:Epac, Epac1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length918 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Subcellular location

Cytoplasm. Membrane; Peripheral membrane protein By similarity.

Domain

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

Sequence similarities

Contains 1 cyclic nucleotide-binding domain.

Contains 1 DEP domain.

Contains 1 N-terminal Ras-GEF domain.

Contains 1 Ras-GEF domain.

Caution

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

Sequence caution

The sequence AAH20532.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processAngiogenesis
   Cellular componentCytoplasm
Membrane
   Coding sequence diversityAlternative splicing
   LigandcAMP
cAMP-binding
Nucleotide-binding
   Molecular functionGuanine-nucleotide releasing factor
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRap protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to cAMP

Inferred from sequence or structural similarity. Source: UniProtKB

establishment of endothelial barrier

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of Rap GTPase activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of stress fiber assembly

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of actin cytoskeleton reorganization

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcAMP-dependent protein kinase complex

Inferred from electronic annotation. Source: InterPro

cytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionRap guanyl-nucleotide exchange factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

cAMP binding

Inferred from electronic annotation. Source: UniProtKB-KW

cAMP-dependent protein kinase regulator activity

Inferred from electronic annotation. Source: InterPro

guanyl-nucleotide exchange factor activity

Inferred from direct assay PubMed 14712229. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8VCC8-1)

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.
Note: No experimental confirmation available.
Isoform 2 (identifier: Q8VCC8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     688-689: QE → ELIHYVLGPQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 918918Rap guanine nucleotide exchange factor 3
PRO_0000068868

Regions

Domain110 – 18677DEP
Domain384 – 521138N-terminal Ras-GEF
Domain665 – 884220Ras-GEF
Nucleotide binding245 – 363119cAMP
Region218 – 24225Interaction with PDE3B By similarity
Region398 – 42225Interaction with PDE3B By similarity

Natural variations

Alternative sequence688 – 6892QE → ELIHYVLGPQ in isoform 2.
VSP_007610

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 1, 2008. Version 2.
Checksum: DB774BBF7CB4428E

FASTA918103,533
        10         20         30         40         50         60 
MKVSWPGENH WQVGPAVVES PAVGAPQVGG LPDVVPEGTL LNMVLKRMHR PRCCSYQLVF 

        70         80         90        100        110        120 
EHRRPSCIQG LRWTPLTNSE DSLDFRVSLE QATTEHVHKA GKLLHRHLLA TYPTLIRDRK 

       130        140        150        160        170        180 
YHLRLYRHCC SGRELVDGIL ALGLGVHSRS QAVGICQVLL DEGALCHVKH DWTFQDRDAQ 

       190        200        210        220        230        240 
FYRFPGPEPE PTGTQDVEEE LVEAMALLSQ RGPDALLTVA LRKPPGQRTD EELDLIFEEL 

       250        260        270        280        290        300 
LHIKAVAHLS NSVKRELAAV LLFEPHSKAG TVLFSQGDKG TSWYIIWKGS VNVVTHGKGL 

       310        320        330        340        350        360 
VTTLHEGDDF GQLALVNDAP RAATIILREN NCHFLRVDKQ DFNRIIKDVE AKTMRLEEHG 

       370        380        390        400        410        420 
KVVLVLERTS QGAGPSRPPT PGRNRYTVMS GTPEKILELL LEAMRPDSSA HDPTETFLSD 

       430        440        450        460        470        480 
FLLTHSVFMP STQLFTALLH HFHVEPADPA GGSEQEHSTY ICNKRQQILR LVGRWVALYS 

       490        500        510        520        530        540 
PMLHSDPVAT SFLQKLSDLV SRDARLSNLL REQYPERRRH HRLENGCGNV SPQTKARNAP 

       550        560        570        580        590        600 
VWLPNQEEPL PSSAGAIRVG DKVPYDICRP DHSVLTLHLP VTASVREVMA ALAHEDHWTK 

       610        620        630        640        650        660 
GQVLVKVNSA GDVVGLQPDA RGVATSLGLN ERLFVVDPQE VHELTPHPEQ LGPTLGSSEM 

       670        680        690        700        710        720 
LDLVSAKDLA GQLTDHDWNL FNRIHQVQEH LRDVTTANLE RFMRRFNELQ YWVATELCLC 

       730        740        750        760        770        780 
PVPGSRAQLL RKFIKLAAHL KEQKNLNSFF AVMFGLSNSA ISRLAHTWER LPHKVRKLYS 

       790        800        810        820        830        840 
ALERLLDPSW NHRVYRLALT KLSPPVIPFM PLLLKDVTFI HEGNHTLVEN LINFEKMRMM 

       850        860        870        880        890        900 
ARAVRMLHHC RSHSTAPLSP LRSRVSHIHE DSQGSRISTC SEQSLSTRSP ASTWAYVQQL 

       910 
KVIDNQRELS RLSRELEP 

« Hide

Isoform 2 [UniParc].

Checksum: A8140C76937E5A95
Show »

FASTA926104,426

References

[1]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 640-918 (ISOFORM 2).
Tissue: Kidney.
[2]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 466-918 (ISOFORM 2).
Strain: C57BL/6J.
Tissue: Diencephalon.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC020532 mRNA. Translation: AAH20532.1. Different initiation.
BC020311 mRNA. Translation: AAH20311.1.
AK034265 mRNA. Translation: BAC28653.1.
CCDSCCDS37187.2. [Q8VCC8-1]
CCDS49714.1. [Q8VCC8-2]
RefSeqNP_001171281.1. NM_001177810.1. [Q8VCC8-2]
NP_001171282.1. NM_001177811.1.
NP_659099.2. NM_144850.2. [Q8VCC8-1]
XP_006520940.1. XM_006520877.1. [Q8VCC8-2]
UniGeneMm.24028.

3D structure databases

ProteinModelPortalQ8VCC8.
SMRQ8VCC8. Positions 89-918.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid230205. 1 interaction.

PTM databases

PhosphoSiteQ8VCC8.

Proteomic databases

PaxDbQ8VCC8.
PRIDEQ8VCC8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000126854; ENSMUSP00000116426; ENSMUSG00000022469. [Q8VCC8-2]
ENSMUST00000129223; ENSMUSP00000118148; ENSMUSG00000022469. [Q8VCC8-1]
GeneID223864.
KEGGmmu:223864.
UCSCuc007xkz.2. mouse. [Q8VCC8-2]
uc007xla.2. mouse. [Q8VCC8-1]

Organism-specific databases

CTD10411.
MGIMGI:2441741. Rapgef3.

Phylogenomic databases

eggNOGNOG236726.
GeneTreeENSGT00750000117452.
HOGENOMHOG000230545.
HOVERGENHBG056985.
InParanoidQ8VCC8.
KOK08014.
OMANSFFAVM.
OrthoDBEOG7ZD1TF.
PhylomeDBQ8VCC8.
TreeFamTF313184.

Gene expression databases

ArrayExpressQ8VCC8.
BgeeQ8VCC8.
CleanExMM_RAPGEF3.
GenevestigatorQ8VCC8.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
1.10.840.10. 1 hit.
2.60.120.10. 1 hit.
InterProIPR002373. cAMP/cGMP_kin.
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.
IPR001895. RasGRF_CDC25.
IPR014710. RmlC-like_jellyroll.
IPR029071. Ubiquitin-rel_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00027. cNMP_binding. 1 hit.
PF00610. DEP. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
PRINTSPR00103. CAMPKINASE.
SMARTSM00100. cNMP. 1 hit.
SM00049. DEP. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMSSF48366. SSF48366. 3 hits.
SSF51206. SSF51206. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEPS50042. 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]
ProtoNetSearch...

Other

ChiTaRSRAPGEF3. mouse.
NextBio376937.
PROQ8VCC8.
SOURCESearch...

Entry information

Entry nameRPGF3_MOUSE
AccessionPrimary (citable) accession number: Q8VCC8
Secondary accession number(s): Q8BZK9, Q8R1R1
Entry history
Integrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: July 1, 2008
Last modified: July 9, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot