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Q8VCC8

- RPGF3_MOUSE

UniProt

Q8VCC8 - RPGF3_MOUSE

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Protein

Rap guanine nucleotide exchange factor 3

Gene

Rapgef3

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. cAMP binding Source: UniProtKB-KW
  2. cAMP-dependent protein kinase regulator activity Source: InterPro
  3. guanyl-nucleotide exchange factor activity Source: MGI
  4. Rap guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

  1. angiogenesis Source: UniProtKB-KW
  2. cellular response to cAMP Source: UniProtKB
  3. establishment of endothelial barrier Source: UniProtKB
  4. positive regulation of angiogenesis Source: UniProtKB
  5. positive regulation of Rap GTPase activity Source: UniProtKB
  6. positive regulation of stress fiber assembly Source: UniProtKB
  7. Rap protein signal transduction Source: UniProtKB
  8. regulation of actin cytoskeleton reorganization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Biological processi

Angiogenesis

Keywords - Ligandi

cAMP, cAMP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiREACT_237855. Rap1 signalling.
REACT_246176. Integrin alphaIIb beta3 signaling.
REACT_248547. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
REACT_263148. 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 15

Organism-specific databases

MGIiMGI:2441741. Rapgef3.

Subcellular locationi

Cytoplasm. Membrane By similarity; Peripheral membrane protein By similarity

GO - Cellular componenti

  1. cAMP-dependent protein kinase complex Source: InterPro
  2. cytoplasm Source: UniProtKB-KW
  3. extracellular vesicular exosome Source: Ensembl
  4. membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 918918Rap guanine nucleotide exchange factor 3PRO_0000068868Add
BLAST

Proteomic databases

MaxQBiQ8VCC8.
PaxDbiQ8VCC8.
PRIDEiQ8VCC8.

PTM databases

PhosphoSiteiQ8VCC8.

Expressioni

Gene expression databases

BgeeiQ8VCC8.
CleanExiMM_RAPGEF3.
ExpressionAtlasiQ8VCC8. baseline and differential.
GenevestigatoriQ8VCC8.

Interactioni

Protein-protein interaction databases

BioGridi230205. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ8VCC8.
SMRiQ8VCC8. Positions 89-918.
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 – 884220Ras-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

eggNOGiNOG236726.
GeneTreeiENSGT00770000120448.
HOGENOMiHOG000230545.
HOVERGENiHBG056985.
InParanoidiQ8VCC8.
KOiK08014.
OMAiNSFFAVM.
OrthoDBiEOG7ZD1TF.
PhylomeDBiQ8VCC8.
TreeFamiTF313184.

Family and domain databases

Gene3Di1.10.10.10. 1 hit.
1.10.840.10. 1 hit.
2.60.120.10. 1 hit.
InterProiIPR002373. 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. 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]
PRINTSiPR00103. CAMPKINASE.
SMARTiSM00100. cNMP. 1 hit.
SM00049. DEP. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMiSSF48366. 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. Align

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 AAH20532.1 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei688 – 6892QE → ELIHYVLGPQ in isoform 2. 2 PublicationsVSP_007610

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]
XP_006520940.1. XM_006520877.1. [Q8VCC8-2]
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

Cross-referencesi

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 .
CCDSi CCDS37187.2. [Q8VCC8-1 ]
CCDS49714.1. [Q8VCC8-2 ]
RefSeqi NP_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 ]
UniGenei Mm.24028.

3D structure databases

ProteinModelPortali Q8VCC8.
SMRi Q8VCC8. Positions 89-918.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 230205. 1 interaction.

PTM databases

PhosphoSitei Q8VCC8.

Proteomic databases

MaxQBi Q8VCC8.
PaxDbi Q8VCC8.
PRIDEi Q8VCC8.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000126854 ; ENSMUSP00000116426 ; ENSMUSG00000022469 . [Q8VCC8-2 ]
ENSMUST00000129223 ; ENSMUSP00000118148 ; ENSMUSG00000022469 . [Q8VCC8-1 ]
GeneIDi 223864.
KEGGi mmu:223864.
UCSCi uc007xkz.2. mouse. [Q8VCC8-2 ]
uc007xla.2. mouse. [Q8VCC8-1 ]

Organism-specific databases

CTDi 10411.
MGIi MGI:2441741. Rapgef3.

Phylogenomic databases

eggNOGi NOG236726.
GeneTreei ENSGT00770000120448.
HOGENOMi HOG000230545.
HOVERGENi HBG056985.
InParanoidi Q8VCC8.
KOi K08014.
OMAi NSFFAVM.
OrthoDBi EOG7ZD1TF.
PhylomeDBi Q8VCC8.
TreeFami TF313184.

Enzyme and pathway databases

Reactomei REACT_237855. Rap1 signalling.
REACT_246176. Integrin alphaIIb beta3 signaling.
REACT_248547. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
REACT_263148. Regulation of insulin secretion.

Miscellaneous databases

ChiTaRSi Rapgef3. mouse.
NextBioi 376937.
PROi Q8VCC8.
SOURCEi Search...

Gene expression databases

Bgeei Q8VCC8.
CleanExi MM_RAPGEF3.
ExpressionAtlasi Q8VCC8. baseline and differential.
Genevestigatori Q8VCC8.

Family and domain databases

Gene3Di 1.10.10.10. 1 hit.
1.10.840.10. 1 hit.
2.60.120.10. 1 hit.
InterProi IPR002373. 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. RASGEF_cat_dom.
IPR014710. RmlC-like_jellyroll.
IPR029071. Ubiquitin-rel_dom.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view ]
Pfami PF00027. cNMP_binding. 1 hit.
PF00610. DEP. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view ]
PRINTSi PR00103. CAMPKINASE.
SMARTi SM00100. cNMP. 1 hit.
SM00049. DEP. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view ]
SUPFAMi SSF48366. SSF48366. 3 hits.
SSF51206. SSF51206. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEi PS50042. 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 ]
ProtoNeti Search...

Publicationsi

  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.
    , 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.

Entry informationi

Entry nameiRPGF3_MOUSE
AccessioniPrimary (citable) accession number: Q8VCC8
Secondary accession number(s): Q8BZK9, Q8R1R1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: July 1, 2008
Last modified: November 26, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3