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Protein

Rap guanine nucleotide exchange factor 1

Gene

RAPGEF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.3 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGuanine-nucleotide releasing factor
Biological processNeurogenesis

Enzyme and pathway databases

ReactomeiR-HSA-170968. Frs2-mediated activation.
R-HSA-186763. Downstream signal transduction.
R-HSA-8875555. MET activates RAP1 and RAC1.
R-HSA-912631. Regulation of signaling by CBL.
SIGNORiQ13905.

Names & Taxonomyi

Protein namesi
Recommended name:
Rap guanine nucleotide exchange factor 1
Alternative name(s):
CRK SH3-binding GNRP
Guanine nucleotide-releasing factor 2
Protein C3G
Gene namesi
Name:RAPGEF1
Synonyms:GRF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:4568. RAPGEF1.

Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

Endosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi504Y → F: Abolishes phosphorylation by HCK. 1 Publication1

Organism-specific databases

DisGeNETi2889.
OpenTargetsiENSG00000107263.
PharmGKBiPA28964.

Polymorphism and mutation databases

BioMutaiRAPGEF1.
DMDMi143811452.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000688641 – 1077Rap guanine nucleotide exchange factor 1Add BLAST1077

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei281PhosphoserineCombined sources1
Modified residuei293PhosphoserineCombined sources1
Modified residuei314PhosphoserineCombined sources1
Modified residuei335PhosphoserineCombined sources1
Modified residuei360PhosphoserineCombined sources1
Modified residuei504Phosphotyrosine; by HCK1 Publication1
Isoform Short (identifier: Q13905-2)
Cross-linki57Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Phosphorylation at Tyr-504 enhances activity as Rap guanine nucleotide exchange factor.1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ13905.
PaxDbiQ13905.
PeptideAtlasiQ13905.
PRIDEiQ13905.

PTM databases

iPTMnetiQ13905.
PhosphoSitePlusiQ13905.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000107263.
CleanExiHS_RAPGEF1.
ExpressionAtlasiQ13905. baseline and differential.
GenevisibleiQ13905. HS.

Organism-specific databases

HPAiHPA006426.
HPA075984.

Interactioni

Subunit structurei

Interacts with CRK via its SH3-binding sites.2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109146. 17 interactors.
DIPiDIP-29392N.
IntActiQ13905. 16 interactors.
MINTiMINT-107377.
STRINGi9606.ENSP00000361264.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5L23X-ray1.77B279-293[»]
ProteinModelPortaliQ13905.
SMRiQ13905.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini688 – 810N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST123
Domaini840 – 1064Ras-GEFPROSITE-ProRule annotationAdd BLAST225

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi281 – 292SH3-bindingAdd BLAST12
Motifi451 – 462SH3-bindingAdd BLAST12
Motifi538 – 549SH3-bindingAdd BLAST12
Motifi606 – 617SH3-bindingAdd BLAST12

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi963 – 966Poly-Ser4

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiENOG410IQ6P. Eukaryota.
ENOG410XP7D. LUCA.
GeneTreeiENSGT00860000133664.
HOGENOMiHOG000048190.
HOVERGENiHBG058477.
InParanoidiQ13905.
KOiK06277.
OMAiGQQTDTP.
OrthoDBiEOG091G03MV.
PhylomeDBiQ13905.
TreeFamiTF317296.

Family and domain databases

CDDicd00155. RasGEF. 1 hit.
cd06224. REM. 1 hit.
Gene3Di1.10.840.10. 1 hit.
InterProiView protein in InterPro
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR019804. Ras_G-nucl-exch_fac_CS.
IPR023578. Ras_GEF_dom.
IPR001895. RASGEF_cat_dom.
PfamiView protein in Pfam
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
SMARTiView protein in SMART
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
SUPFAMiSSF48366. SSF48366. 1 hit.
PROSITEiView protein in PROSITE
PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Long (identifier: Q13905-1) [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
MDTDSQRSHL SSFTMKLMDK FHSPKIKRTP SKKGKPAEVS VKIPEKPVNK
60 70 80 90 100
EATDRFLPEG YPLPLDLEQQ AVEFMSTSAV ASRSQRQKNL SWLEEKEKEV
110 120 130 140 150
VSALRYFKTI VDKMAIDKKV LEMLPGSASK VLEAILPLVQ NDPRIQHSSA
160 170 180 190 200
LSSCYSRVYQ SLANLIRWSD QVMLEGVNSE DKEMVTTVKG VIKAVLDGVK
210 220 230 240 250
ELVRLTIEKQ GRPSPTSPVK PSSPASKPDG PAELPLTDRE VEILNKTTGM
260 270 280 290 300
SQSTELLPDA TDEEVAPPKP PLPGIRVVDN SPPPALPPKK RQSAPSPTRV
310 320 330 340 350
AVVAPMSRAT SGSSLPVGIN RQDFDVDCYA QRRLSGGSHS YGGESPRLSP
360 370 380 390 400
CSSIGKLSKS DEQLSSLDRD SGQCSRNTSC ETLDHYDPDY EFLQQDLSNA
410 420 430 440 450
DQIPQQTAWN LSPLPESLGE SGSPFLGPPF QLPLGGHPQP DGPLAPGQQT
460 470 480 490 500
DTPPALPEKK RRSAASQTAD GSGCRVSYER HPSQYDNISG EDLQSTAPIP
510 520 530 540 550
SVPYAPFAAI LPFQHGGSSA PVEFVGDFTA PESTGDPEKP PPLPEKKNKH
560 570 580 590 600
MLAYMQLLED YSEPQPSMFY QTPQNEHIYQ QKNKLLMEVY GFSDSFSGVD
610 620 630 640 650
SVQELAPPPA LPPKQRQLEP PAGKDGHPRD PSAVSGVPGK DSRDGSERAP
660 670 680 690 700
KSPDALESAQ SEEEVDELSL IDHNEIMSRL TLKQEGDDGP DVRGGSGDIL
710 720 730 740 750
LVHATETDRK DLVLYCEAFL TTYRTFISPE ELIKKLQYRY EKFSPFADTF
760 770 780 790 800
KKRVSKNTFF VLVRVVDELC LVELTEEILK LLMELVFRLV CNGELSLARV
810 820 830 840 850
LRKNILDKVD QKKLLRCATS SQPLAARGVA ARPGTLHDFH SHEIAEQLTL
860 870 880 890 900
LDAELFYKIE IPEVLLWAKE QNEEKSPNLT QFTEHFNNMS YWVRSIIMLQ
910 920 930 940 950
EKAQDRERLL LKFIKIMKHL RKLNNFNSYL AILSALDSAP IRRLEWQKQT
960 970 980 990 1000
SEGLAEYCTL IDSSSSFRAY RAALSEVEPP CIPYLGLILQ DLTFVHLGNP
1010 1020 1030 1040 1050
DYIDGKVNFS KRWQQFNILD SMRCFQQAHY DMRRNDDIIN FFNDFSDHLA
1060 1070
EEALWELSLK IKPRNITRRK TDREEKT
Length:1,077
Mass (Da):120,548
Last modified:April 3, 2007 - v3
Checksum:iE700631A0EE76CA1
GO
Isoform Short (identifier: Q13905-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     50-88: Missing.

Show »
Length:1,038
Mass (Da):116,141
Checksum:i34F0A1BD9C8B0732
GO
Isoform 3 (identifier: Q13905-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MDT → MGNAIEKQKPLKRSHLYPWKQ

Note: No experimental confirmation available.
Show »
Length:1,095
Mass (Da):122,735
Checksum:i04C19860FF7F11E8
GO
Isoform 4 (identifier: Q13905-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-3: MDT → MSGGLGLRRSPEMSGKIEKA

Note: No experimental confirmation available.
Show »
Length:1,094
Mass (Da):122,287
Checksum:i00A95564C0B9974A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti137P → R (PubMed:7806500).Curated1
Sequence conflicti183E → G (PubMed:7806500).Curated1
Sequence conflicti217S → C (PubMed:7806500).Curated1
Sequence conflicti254T → S (PubMed:7806500).Curated1
Sequence conflicti287P → T in BAA04770 (PubMed:7512734).Curated1
Sequence conflicti355G → D in BAA04770 (PubMed:7512734).Curated1
Sequence conflicti636G → V (PubMed:7806500).Curated1
Sequence conflicti698D → N (PubMed:7806500).Curated1
Sequence conflicti846 – 847EQ → DE (PubMed:7806500).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0693751012R → Q Found in a patient with mental retardation, frontal epilepsy and mild facial dysmorphism. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0420521 – 3MDT → MGNAIEKQKPLKRSHLYPWK Q in isoform 3. 1 Publication3
Alternative sequenceiVSP_0574161 – 3MDT → MSGGLGLRRSPEMSGKIEKA in isoform 4. 1 Publication3
Alternative sequenceiVSP_00182250 – 88Missing in isoform Short. CuratedAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21239 mRNA. Translation: BAA04770.1.
CR749354 mRNA. Translation: CAH18207.1.
AL160271, AL160276 Genomic DNA. Translation: CAI13382.1.
AL160276, AL160271 Genomic DNA. Translation: CAI40646.1.
BC041710 mRNA. Translation: AAH41710.1.
CCDSiCCDS48047.1. [Q13905-1]
CCDS48048.1. [Q13905-3]
CCDS78450.1. [Q13905-4]
RefSeqiNP_001291204.1. NM_001304275.1. [Q13905-4]
NP_005303.2. NM_005312.3. [Q13905-1]
NP_941372.1. NM_198679.1. [Q13905-3]
UniGeneiHs.127897.

Genome annotation databases

EnsembliENST00000372189; ENSP00000361263; ENSG00000107263. [Q13905-1]
ENST00000372190; ENSP00000361264; ENSG00000107263. [Q13905-3]
ENST00000372195; ENSP00000361269; ENSG00000107263. [Q13905-4]
GeneIDi2889.
KEGGihsa:2889.
UCSCiuc064wrk.1. human. [Q13905-1]
uc064wrl.1. human.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D21239 mRNA. Translation: BAA04770.1.
CR749354 mRNA. Translation: CAH18207.1.
AL160271, AL160276 Genomic DNA. Translation: CAI13382.1.
AL160276, AL160271 Genomic DNA. Translation: CAI40646.1.
BC041710 mRNA. Translation: AAH41710.1.
CCDSiCCDS48047.1. [Q13905-1]
CCDS48048.1. [Q13905-3]
CCDS78450.1. [Q13905-4]
RefSeqiNP_001291204.1. NM_001304275.1. [Q13905-4]
NP_005303.2. NM_005312.3. [Q13905-1]
NP_941372.1. NM_198679.1. [Q13905-3]
UniGeneiHs.127897.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5L23X-ray1.77B279-293[»]
ProteinModelPortaliQ13905.
SMRiQ13905.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109146. 17 interactors.
DIPiDIP-29392N.
IntActiQ13905. 16 interactors.
MINTiMINT-107377.
STRINGi9606.ENSP00000361264.

PTM databases

iPTMnetiQ13905.
PhosphoSitePlusiQ13905.

Polymorphism and mutation databases

BioMutaiRAPGEF1.
DMDMi143811452.

Proteomic databases

MaxQBiQ13905.
PaxDbiQ13905.
PeptideAtlasiQ13905.
PRIDEiQ13905.

Protocols and materials databases

DNASUi2889.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372189; ENSP00000361263; ENSG00000107263. [Q13905-1]
ENST00000372190; ENSP00000361264; ENSG00000107263. [Q13905-3]
ENST00000372195; ENSP00000361269; ENSG00000107263. [Q13905-4]
GeneIDi2889.
KEGGihsa:2889.
UCSCiuc064wrk.1. human. [Q13905-1]
uc064wrl.1. human.

Organism-specific databases

CTDi2889.
DisGeNETi2889.
GeneCardsiRAPGEF1.
HGNCiHGNC:4568. RAPGEF1.
HPAiHPA006426.
HPA075984.
MIMi600303. gene.
neXtProtiNX_Q13905.
OpenTargetsiENSG00000107263.
PharmGKBiPA28964.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQ6P. Eukaryota.
ENOG410XP7D. LUCA.
GeneTreeiENSGT00860000133664.
HOGENOMiHOG000048190.
HOVERGENiHBG058477.
InParanoidiQ13905.
KOiK06277.
OMAiGQQTDTP.
OrthoDBiEOG091G03MV.
PhylomeDBiQ13905.
TreeFamiTF317296.

Enzyme and pathway databases

ReactomeiR-HSA-170968. Frs2-mediated activation.
R-HSA-186763. Downstream signal transduction.
R-HSA-8875555. MET activates RAP1 and RAC1.
R-HSA-912631. Regulation of signaling by CBL.
SIGNORiQ13905.

Miscellaneous databases

ChiTaRSiRAPGEF1. human.
GeneWikiiRAPGEF1.
GenomeRNAii2889.
PROiPR:Q13905.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107263.
CleanExiHS_RAPGEF1.
ExpressionAtlasiQ13905. baseline and differential.
GenevisibleiQ13905. HS.

Family and domain databases

CDDicd00155. RasGEF. 1 hit.
cd06224. REM. 1 hit.
Gene3Di1.10.840.10. 1 hit.
InterProiView protein in InterPro
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR019804. Ras_G-nucl-exch_fac_CS.
IPR023578. Ras_GEF_dom.
IPR001895. RASGEF_cat_dom.
PfamiView protein in Pfam
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
SMARTiView protein in SMART
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
SUPFAMiSSF48366. SSF48366. 1 hit.
PROSITEiView protein in PROSITE
PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiRPGF1_HUMAN
AccessioniPrimary (citable) accession number: Q13905
Secondary accession number(s): Q5JUE4, Q68DL3, Q8IV73
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: April 3, 2007
Last modified: March 15, 2017
This is version 162 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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.