Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Rap guanine nucleotide exchange factor 1

Gene

RAPGEF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

EuPathDBiHostDB:ENSG00000107263.18
HGNCiHGNC:4568 RAPGEF1
MIMi600303 gene
neXtProtiNX_Q13905

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

EPDiQ13905
MaxQBiQ13905
PaxDbiQ13905
PeptideAtlasiQ13905
PRIDEiQ13905
ProteomicsDBi59720
59721 [Q13905-2]
59722 [Q13905-3]

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 Expressed in 196 organ(s), highest expression level in gastrocnemius
CleanExiHS_RAPGEF1
ExpressionAtlasiQ13905 baseline and differential
GenevisibleiQ13905 HS

Organism-specific databases

HPAiHPA006426

Interactioni

Subunit structurei

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

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109146, 20 interactors
CORUMiQ13905
DIPiDIP-29392N
ELMiQ13905
IntActiQ13905, 17 interactors
MINTiQ13905
STRINGi9606.ENSP00000361264

Structurei

3D structure databases

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
GeneTreeiENSGT00910000143985
HOGENOMiHOG000048190
HOVERGENiHBG058477
InParanoidiQ13905
KOiK06277
OMAiPVHQSQS
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
IPR008937 Ras-like_GEF
IPR000651 Ras-like_Gua-exchang_fac_N
IPR019804 Ras_G-nucl-exch_fac_CS
IPR023578 Ras_GEF_dom_sf
IPR001895 RASGEF_cat_dom
IPR036964 RASGEF_cat_dom_sf
PANTHERiPTHR23113 PTHR23113, 1 hit
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

This entry has 4 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y6R4H0Y6R4_HUMAN
Rap guanine nucleotide exchange fac...
RAPGEF1
319Annotation score:
Q5JUE9Q5JUE9_HUMAN
Rap guanine nucleotide exchange fac...
RAPGEF1
158Annotation score:
H0Y4V2H0Y4V2_HUMAN
Rap guanine nucleotide exchange fac...
RAPGEF1
228Annotation score:

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 Genomic DNA No translation available.
AL160276 Genomic DNA No translation available.
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

Similar proteinsi

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 Genomic DNA No translation available.
AL160276 Genomic DNA No translation available.
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, 20 interactors
CORUMiQ13905
DIPiDIP-29392N
ELMiQ13905
IntActiQ13905, 17 interactors
MINTiQ13905
STRINGi9606.ENSP00000361264

PTM databases

iPTMnetiQ13905
PhosphoSitePlusiQ13905

Polymorphism and mutation databases

BioMutaiRAPGEF1
DMDMi143811452

Proteomic databases

EPDiQ13905
MaxQBiQ13905
PaxDbiQ13905
PeptideAtlasiQ13905
PRIDEiQ13905
ProteomicsDBi59720
59721 [Q13905-2]
59722 [Q13905-3]

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
EuPathDBiHostDB:ENSG00000107263.18
GeneCardsiRAPGEF1
HGNCiHGNC:4568 RAPGEF1
HPAiHPA006426
MIMi600303 gene
neXtProtiNX_Q13905
OpenTargetsiENSG00000107263
PharmGKBiPA28964
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQ6P Eukaryota
ENOG410XP7D LUCA
GeneTreeiENSGT00910000143985
HOGENOMiHOG000048190
HOVERGENiHBG058477
InParanoidiQ13905
KOiK06277
OMAiPVHQSQS
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 Expressed in 196 organ(s), highest expression level in gastrocnemius
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
IPR008937 Ras-like_GEF
IPR000651 Ras-like_Gua-exchang_fac_N
IPR019804 Ras_G-nucl-exch_fac_CS
IPR023578 Ras_GEF_dom_sf
IPR001895 RASGEF_cat_dom
IPR036964 RASGEF_cat_dom_sf
PANTHERiPTHR23113 PTHR23113, 1 hit
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: November 7, 2018
This is version 177 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again