Q13905 (RPGF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 122.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: Rap guanine nucleotide exchange factor 1 Alternative name(s): CRK SH3-binding GNRP Guanine nucleotide-releasing factor 2 Protein C3G | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1077 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence 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. Ref.2 |
| Subunit structure | |
| 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
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CRK | P46108 | 3 | EBI-976876,EBI-886 | |
| FYN | P06241 | 2 | EBI-976876,EBI-515315 | |
| NCK1 | P16333 | 2 | EBI-976876,EBI-389883 | |
| PIK3R1 | P27986 | 2 | EBI-976876,EBI-79464 | |
| SRC | P12931 | 2 | EBI-976876,EBI-621482 |
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 key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1077 | 1077 | Rap guanine nucleotide exchange factor 1 | PRO_0000068864 | |||||
Regions | |||||||||
| Domain | 688 – 810 | 123 | N-terminal Ras-GEF | ||||||
| Domain | 840 – 1064 | 225 | Ras-GEF | ||||||
| Motif | 281 – 292 | 12 | SH3-binding | ||||||
| Motif | 451 – 462 | 12 | SH3-binding | ||||||
| Motif | 538 – 549 | 12 | SH3-binding | ||||||
| Motif | 606 – 617 | 12 | SH3-binding | ||||||
| Compositional bias | 963 – 966 | 4 | Poly-Ser | ||||||
Amino acid modifications | |||||||||
| Modified residue | 293 | 1 | Phosphoserine Ref.10 | ||||||
| Modified residue | 360 | 1 | Phosphoserine Ref.8 | ||||||
| Modified residue | 504 | 1 | Phosphotyrosine; by HCK Ref.6 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 3 | 3 | MDT → MGNAIEKQKPLKRSHLYPWK Q in isoform 3. | VSP_042052 | |||||
| Alternative sequence | 50 – 88 | 39 | Missing in isoform Short. | VSP_001822 | |||||
Experimental info | |||||||||
| Mutagenesis | 504 | 1 | Y → F: Abolishes phosphorylation by HCK. Ref.6 | ||||||
| Sequence conflict | 137 | 1 | P → R Ref.2 | ||||||
| Sequence conflict | 183 | 1 | E → G Ref.2 | ||||||
| Sequence conflict | 217 | 1 | S → C Ref.2 | ||||||
| Sequence conflict | 254 | 1 | T → S Ref.2 | ||||||
| Sequence conflict | 287 | 1 | P → T in BAA04770. Ref.1 | ||||||
| Sequence conflict | 355 | 1 | G → D in BAA04770. Ref.1 | ||||||
| Sequence conflict | 636 | 1 | G → V Ref.2 | ||||||
| Sequence conflict | 698 | 1 | D → N Ref.2 | ||||||
| Sequence conflict | 846 – 847 | 2 | EQ → DE Ref.2 | ||||||
Sequences
| ||||||||||||||||||||||||||||||
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. 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] | "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, MASS SPECTROMETRY. Tissue: Leukemic T-cell. |
| [9] | "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]. |
| [10] | "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, MASS SPECTROMETRY. |
| + | 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. |
| IPI | IPI00332841. IPI00394743. |
| RefSeq | NP_005303.2. NM_005312.2. NP_941372.1. NM_198679.1. |
| UniGene | Hs.127897. |
3D structure databases | |
| ProteinModelPortal | Q13905. |
| ModBase | Search... |
Protein-protein interaction databases | |
| DIP | DIP-29392N. |
| IntAct | Q13905. 12 interactions. |
| MINT | MINT-107377. |
| STRING | 9606.ENSP00000361264. |
PTM databases | |
| PhosphoSite | Q13905. |
Polymorphism databases | |
| DMDM | 143811452. |
Proteomic databases | |
| PaxDb | Q13905. |
| PRIDE | Q13905. |
Protocols and materials databases | |
| DNASU | 2889. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000266110; ENSP00000266110; ENSG00000107263. ENST00000372189; ENSP00000361263; ENSG00000107263. ENST00000372190; ENSP00000361264; ENSG00000107263. |
| GeneID | 2889. |
| KEGG | hsa:2889. |
| UCSC | uc022bot.1. human. |
Organism-specific databases | |
| CTD | 2889. |
| GeneCards | GC09M134452. |
| HGNC | HGNC:4568. RAPGEF1. |
| HPA | HPA006426. |
| MIM | 600303. gene. |
| neXtProt | NX_Q13905. |
| PharmGKB | PA28964. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG288712. |
| HOGENOM | HOG000048190. |
| HOVERGEN | HBG058477. |
| KO | K06277. |
| OMA | RRNDDII. |
| OrthoDB | EOG4HX509. |
Enzyme and pathway databases | |
| Pathway_Interaction_DB | epopathway. EPO signaling pathway. ifngpathway. IFN-gamma pathway. insulin_pathway. Insulin Pathway. trkrpathway. Neurotrophic factor-mediated Trk receptor signaling. pdgfrapathway. PDGFR-alpha signaling pathway. reelinpathway. Reelin signaling pathway. met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met). |
| Reactome | REACT_111102. Signal Transduction. REACT_6900. Immune System. |
Gene expression databases | |
| ArrayExpress | Q13905. |
| Bgee | Q13905. |
| CleanEx | HS_RAPGEF1. |
| Genevestigator | Q13905. |
| GermOnline | ENSG00000107263. Homo sapiens. |
Family and domain databases | |
| Gene3D | 1.10.840.10. 1 hit. |
| InterPro | IPR000651. Ras-like_Gua-exchang_fac_N. IPR019804. Ras_G-nucl-exch_fac_CS. IPR008937. Ras_GEF. IPR023578. Ras_GEF_dom. IPR001895. RasGRF_CDC25. [Graphical view] |
| PANTHER | PTHR23113. PTHR23113. 1 hit. |
| Pfam | PF00617. RasGEF. 1 hit. PF00618. RasGEF_N. 1 hit. [Graphical view] |
| SMART | SM00147. RasGEF. 1 hit. SM00229. RasGEFN. 1 hit. [Graphical view] |
| SUPFAM | SSF48366. Ras_GEF. 1 hit. |
| PROSITE | PS00720. RASGEF. 1 hit. PS50009. RASGEF_CAT. 1 hit. PS50212. RASGEF_NTER. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| ChiTaRS | RAPGEF1. human. |
| GenomeRNAi | 2889. |
| NextBio | 11419. |
| SOURCE | Search... |
Entry information
| Entry name | RPGF1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q13905 Secondary accession number(s): Q5JUE4, Q8IV73 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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
| Human chromosome 9 Human chromosome 9: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
