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Q13905 (RPGF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 134. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rap guanine nucleotide exchange factor 1
Alternative name(s):
CRK SH3-binding GNRP
Guanine nucleotide-releasing factor 2
Protein C3G
Gene names
Name:RAPGEF1
Synonyms:GRF2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1077 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Guanine nucleotide-releasing protein that binds to SH3 domain of CRK and GRB2/ASH. Transduces signals from CRK to activate RAS. Plays a role in the establishment of basal endothelial barrier function. Plays a role in nerve growth factor (NGF)-induced sustained activation of Rap1 and neurite outgrowth. Ref.2 Ref.8 Ref.11

Subunit structure

Interacts with CRK via its SH3-binding sites. Ref.5 Ref.6

Subcellular location

Early endosome Ref.8.

Tissue specificity

Ubiquitously expressed in adult and fetus. Expression is high in adult skeletal muscle and placenta and in fetal brain and heart. Low levels of expression in adult and fetal liver.

Post-translational modification

Phosphorylation at Tyr-504 enhances activity as Rap guanine nucleotide exchange factor.

Sequence similarities

Contains 1 N-terminal Ras-GEF domain.

Contains 1 Ras-GEF domain.

Ontologies

Keywords
   Biological processNeurogenesis
   Cellular componentEndosome
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH3-binding
   Molecular functionGuanine-nucleotide releasing factor
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processRap protein signal transduction

Inferred from mutant phenotype Ref.11. Source: UniProtKB

activation of MAPKK activity

Traceable author statement. Source: Reactome

blood vessel development

Inferred from electronic annotation. Source: Ensembl

cellular response to cAMP

Inferred from direct assay Ref.11. Source: UniProtKB

cellular response to nerve growth factor stimulus

Inferred from direct assay Ref.8. Source: UniProtKB

establishment of endothelial barrier

Inferred from mutant phenotype Ref.11. Source: UniProtKB

nerve growth factor signaling pathway

Inferred from direct assay Ref.8. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

platelet-derived growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of Rap GTPase activity

Inferred from direct assay PubMed 10548487. Source: UniProtKB

positive regulation of neuron projection development

Inferred from mutant phenotype Ref.8. Source: UniProtKB

regulation of cell junction assembly

Inferred from mutant phenotype Ref.11. Source: UniProtKB

signal transduction

Non-traceable author statement Ref.1. Source: ProtInc

single organismal cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

transmembrane receptor protein tyrosine kinase signaling pathway

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentcytosol

Traceable author statement. Source: Reactome

early endosome

Inferred from direct assay Ref.8. Source: UniProtKB

endosome

Traceable author statement. Source: Reactome

   Molecular_functionRap guanyl-nucleotide exchange factor activity

Inferred from direct assay PubMed 10548487. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 9748234. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: Q13905-1)

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.
Isoform Short (identifier: Q13905-2)

The sequence of this isoform differs from the canonical sequence as follows:
     50-88: Missing.
Isoform 3 (identifier: Q13905-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MDT → MGNAIEKQKPLKRSHLYPWKQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10771077Rap guanine nucleotide exchange factor 1
PRO_0000068864

Regions

Domain688 – 810123N-terminal Ras-GEF
Domain840 – 1064225Ras-GEF
Motif281 – 29212SH3-binding
Motif451 – 46212SH3-binding
Motif538 – 54912SH3-binding
Motif606 – 61712SH3-binding
Compositional bias963 – 9664Poly-Ser

Amino acid modifications

Modified residue2931Phosphoserine Ref.12
Modified residue3601Phosphoserine Ref.9
Modified residue5041Phosphotyrosine; by HCK Ref.6

Natural variations

Alternative sequence1 – 33MDT → MGNAIEKQKPLKRSHLYPWK Q in isoform 3.
VSP_042052
Alternative sequence50 – 8839Missing in isoform Short.
VSP_001822
Natural variant10121R → Q Found in a patient with mental retardation, frontal epilepsy and mild facial dysmorphism. Ref.13
VAR_069375

Experimental info

Mutagenesis5041Y → F: Abolishes phosphorylation by HCK. Ref.6
Sequence conflict1371P → R Ref.2
Sequence conflict1831E → G Ref.2
Sequence conflict2171S → C Ref.2
Sequence conflict2541T → S Ref.2
Sequence conflict2871P → T in BAA04770. Ref.1
Sequence conflict3551G → D in BAA04770. Ref.1
Sequence conflict6361G → V Ref.2
Sequence conflict6981D → N Ref.2
Sequence conflict846 – 8472EQ → DE Ref.2

Sequences

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

Last modified April 3, 2007. Version 3.
Checksum: E700631A0EE76CA1

FASTA1,077120,548
        10         20         30         40         50         60 
MDTDSQRSHL SSFTMKLMDK FHSPKIKRTP SKKGKPAEVS VKIPEKPVNK EATDRFLPEG 

        70         80         90        100        110        120 
YPLPLDLEQQ AVEFMSTSAV ASRSQRQKNL SWLEEKEKEV VSALRYFKTI VDKMAIDKKV 

       130        140        150        160        170        180 
LEMLPGSASK VLEAILPLVQ NDPRIQHSSA LSSCYSRVYQ SLANLIRWSD QVMLEGVNSE 

       190        200        210        220        230        240 
DKEMVTTVKG VIKAVLDGVK ELVRLTIEKQ GRPSPTSPVK PSSPASKPDG PAELPLTDRE 

       250        260        270        280        290        300 
VEILNKTTGM SQSTELLPDA TDEEVAPPKP PLPGIRVVDN SPPPALPPKK RQSAPSPTRV 

       310        320        330        340        350        360 
AVVAPMSRAT SGSSLPVGIN RQDFDVDCYA QRRLSGGSHS YGGESPRLSP CSSIGKLSKS 

       370        380        390        400        410        420 
DEQLSSLDRD SGQCSRNTSC ETLDHYDPDY EFLQQDLSNA DQIPQQTAWN LSPLPESLGE 

       430        440        450        460        470        480 
SGSPFLGPPF QLPLGGHPQP DGPLAPGQQT DTPPALPEKK RRSAASQTAD GSGCRVSYER 

       490        500        510        520        530        540 
HPSQYDNISG EDLQSTAPIP SVPYAPFAAI LPFQHGGSSA PVEFVGDFTA PESTGDPEKP 

       550        560        570        580        590        600 
PPLPEKKNKH MLAYMQLLED YSEPQPSMFY QTPQNEHIYQ QKNKLLMEVY GFSDSFSGVD 

       610        620        630        640        650        660 
SVQELAPPPA LPPKQRQLEP PAGKDGHPRD PSAVSGVPGK DSRDGSERAP KSPDALESAQ 

       670        680        690        700        710        720 
SEEEVDELSL IDHNEIMSRL TLKQEGDDGP DVRGGSGDIL LVHATETDRK DLVLYCEAFL 

       730        740        750        760        770        780 
TTYRTFISPE ELIKKLQYRY EKFSPFADTF KKRVSKNTFF VLVRVVDELC LVELTEEILK 

       790        800        810        820        830        840 
LLMELVFRLV CNGELSLARV LRKNILDKVD QKKLLRCATS SQPLAARGVA ARPGTLHDFH 

       850        860        870        880        890        900 
SHEIAEQLTL LDAELFYKIE IPEVLLWAKE QNEEKSPNLT QFTEHFNNMS YWVRSIIMLQ 

       910        920        930        940        950        960 
EKAQDRERLL LKFIKIMKHL RKLNNFNSYL AILSALDSAP IRRLEWQKQT SEGLAEYCTL 

       970        980        990       1000       1010       1020 
IDSSSSFRAY RAALSEVEPP CIPYLGLILQ DLTFVHLGNP DYIDGKVNFS KRWQQFNILD 

      1030       1040       1050       1060       1070 
SMRCFQQAHY DMRRNDDIIN FFNDFSDHLA EEALWELSLK IKPRNITRRK TDREEKT 

« Hide

Isoform Short [UniParc].

Checksum: 34F0A1BD9C8B0732
Show »

FASTA1,038116,141
Isoform 3 [UniParc].

Checksum: 04C19860FF7F11E8
Show »

FASTA1,095122,735

References

« Hide 'large scale' references
[1]"C3G, a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins."
Tanaka S., Morishita T., Hashimoto Y., Hattori S., Nakamura S., Shibuya M., Matuoka K., Takenawa T., Kurata T., Nagashima K., Matsuda M.
Proc. Natl. Acad. Sci. U.S.A. 91:3443-3447(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), CHARACTERIZATION.
Tissue: Placenta and Spleen.
[2]"Four proline-rich sequences of the guanine-nucleotide exchange factor C3G bind with unique specificity to the first Src homology 3 domain of Crk."
Knudsen B., Feller S., Hanafusa H.
J. Biol. Chem. 269:32781-32787(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ALTERNATIVE SPLICING.
[3]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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 3).
Tissue: Skin.
[5]"Interaction between the amino-terminal SH3 domain of CRK and its natural target proteins."
Matsuda M., Ota S., Tanimura R., Nakamura H., Matuoka K., Takenawa T., Nagashima K., Kurata T.
J. Biol. Chem. 271:14468-14472(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRK.
[6]"Physical and functional interaction between Hck tyrosine kinase and guanine nucleotide exchange factor C3G results in apoptosis, which is independent of C3G catalytic domain."
Shivakrupa R., Radha V., Sudhakar C., Swarup G.
J. Biol. Chem. 278:52188-52194(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HCK, MUTAGENESIS OF TYR-504, PHOSPHORYLATION AT TYR-504.
[7]"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[8]"Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth."
Hisata S., Sakisaka T., Baba T., Yamada T., Aoki K., Matsuda M., Takai Y.
J. Cell Biol. 178:843-860(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-360, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control."
Pannekoek W.J., van Dijk J.J., Chan O.Y., Huveneers S., Linnemann J.R., Spanjaard E., Brouwer P.M., van der Meer A.J., Zwartkruis F.J., Rehmann H., de Rooij J., Bos J.L.
Cell. Signal. 23:2056-2064(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-293, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Diagnostic exome sequencing in persons with severe intellectual disability."
de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., Veltman J.A., Vissers L.E.
N. Engl. J. Med. 367:1921-1929(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLN-1012.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D21239 mRNA. Translation: BAA04770.1.
AL160271, AL160276 Genomic DNA. Translation: CAI13382.1.
AL160276, AL160271 Genomic DNA. Translation: CAI40646.1.
BC041710 mRNA. Translation: AAH41710.1.
CCDSCCDS48047.1. [Q13905-1]
CCDS48048.1. [Q13905-3]
RefSeqNP_005303.2. NM_005312.2. [Q13905-1]
NP_941372.1. NM_198679.1. [Q13905-3]
UniGeneHs.127897.

3D structure databases

ProteinModelPortalQ13905.
SMRQ13905. Positions 715-1065.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109146. 12 interactions.
DIPDIP-29392N.
IntActQ13905. 13 interactions.
MINTMINT-107377.
STRING9606.ENSP00000361264.

PTM databases

PhosphoSiteQ13905.

Polymorphism databases

DMDM143811452.

Proteomic databases

MaxQBQ13905.
PaxDbQ13905.
PRIDEQ13905.

Protocols and materials databases

DNASU2889.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372189; ENSP00000361263; ENSG00000107263. [Q13905-1]
ENST00000372190; ENSP00000361264; ENSG00000107263. [Q13905-3]
GeneID2889.
KEGGhsa:2889.
UCSCuc022bos.1. human. [Q13905-3]
uc022bot.1. human. [Q13905-1]

Organism-specific databases

CTD2889.
GeneCardsGC09M134452.
HGNCHGNC:4568. RAPGEF1.
HPAHPA006426.
MIM600303. gene.
neXtProtNX_Q13905.
PharmGKBPA28964.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG288712.
HOGENOMHOG000048190.
HOVERGENHBG058477.
KOK06277.
OMADHYDPDY.
OrthoDBEOG7SR4M9.
PhylomeDBQ13905.
TreeFamTF317296.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressQ13905.
BgeeQ13905.
CleanExHS_RAPGEF1.
GenevestigatorQ13905.

Family and domain databases

Gene3D1.10.840.10. 1 hit.
InterProIPR000651. Ras-like_Gua-exchang_fac_N.
IPR019804. Ras_G-nucl-exch_fac_CS.
IPR023578. Ras_GEF_dom.
IPR001895. RasGRF_CDC25.
[Graphical view]
PfamPF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
SMARTSM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMSSF48366. SSF48366. 1 hit.
PROSITEPS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRAPGEF1. human.
GeneWikiRAPGEF1.
GenomeRNAi2889.
NextBio11419.
PROQ13905.
SOURCESearch...

Entry information

Entry nameRPGF1_HUMAN
AccessionPrimary (citable) accession number: Q13905
Secondary accession number(s): Q5JUE4, Q8IV73
Entry history
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: April 3, 2007
Last modified: July 9, 2014
This is version 134 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 9

Human chromosome 9: entries, gene names and cross-references to MIM