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Protein

Ras-specific guanine nucleotide-releasing factor 2

Gene

RASGRF2

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

Functioni

Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP. Preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation. Functions in synaptic plasticity by contributing to the induction of long term potentiation.1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Keywords - Ligandi

Calcium, Calmodulin-binding

Enzyme and pathway databases

ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-HSA-5673001. RAF/MAP kinase cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Ras-specific guanine nucleotide-releasing factor 2
Short name:
Ras-GRF2
Alternative name(s):
Ras guanine nucleotide exchange factor 2
Gene namesi
Name:RASGRF2
Synonyms:GRF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:9876. RASGRF2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi737S → A: Loss of phosphorylation by CDK5. 1 Publication1

Organism-specific databases

DisGeNETi5924.
OpenTargetsiENSG00000113319.
PharmGKBiPA34239.

Polymorphism and mutation databases

BioMutaiRASGRF2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003128631 – 1237Ras-specific guanine nucleotide-releasing factor 2Add BLAST1237

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei726PhosphoserineBy similarity1
Modified residuei727PhosphoserineBy similarity1
Modified residuei737Phosphoserine; by CDK51 Publication1
Modified residuei746PhosphoserineCombined sources1
Modified residuei848PhosphoserineBy similarity1
Modified residuei852PhosphoserineBy similarity1
Modified residuei972PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated by CDK5; down-regulates RASGRF2-mediated RAC1 activation.1 Publication
Ubiquitinated upon interaction with Ras. Ubiquitination leads to degradation through the 26S proteasome (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO14827.
PaxDbiO14827.
PeptideAtlasiO14827.
PRIDEiO14827.

PTM databases

iPTMnetiO14827.
PhosphoSitePlusiO14827.

Expressioni

Tissue specificityi

Widely expressed with higher expression in brain, followed by heart, lung, pancreas and kidney. Detected in placenta. Expressed in brain and lung (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000113319.
CleanExiHS_RASGRF2.
ExpressionAtlasiO14827. baseline and differential.
GenevisibleiO14827. HS.

Organism-specific databases

HPAiHPA018679.

Interactioni

Subunit structurei

Homooligomer and heterooligomer with RASGRF1. Interacts with Ras and RAC1. Interacts in a calcium-dependent manner with calmodulin (By similarity). Interacts with CDK5R1 and EPB49. Interacts with the AMPA receptor through GRIA1 (By similarity). Interacts with microtubules (By similarity).By similarity

Protein-protein interaction databases

BioGridi111859. 5 interactors.
IntActiO14827. 2 interactors.
STRINGi9606.ENSP00000265080.

Structurei

3D structure databases

ProteinModelPortaliO14827.
SMRiO14827.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini22 – 133PH 1PROSITE-ProRule annotationAdd BLAST112
Domaini205 – 234IQPROSITE-ProRule annotationAdd BLAST30
Domaini243 – 429DHPROSITE-ProRule annotationAdd BLAST187
Domaini470 – 588PH 2PROSITE-ProRule annotationAdd BLAST119
Domaini635 – 756N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST122
Domaini1002 – 1234Ras-GEFPROSITE-ProRule annotationAdd BLAST233

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni744 – 752Regulates proteasomal degradationBy similarity9
Regioni1099 – 1128Responsible of the affinity for farnesylated versus geranylgeranylated RasBy similarityAdd BLAST30

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili155 – 193Sequence analysisAdd BLAST39

Domaini

The Ras-GEF domain and the N-terminal Ras-GEF domain form a Ras-binding site and mediate Ras activation.By similarity
The IQ domain mediates the calcium-dependent interaction with calmodulin but is dispensable for the Ras-GEF activity.By similarity
The DH (DBL-homology) domain mediates interaction with RASGRF1 and EPB49 and is required for RAC1 activation.

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 IQ domain.PROSITE-ProRule annotation
Contains 1 N-terminal Ras-GEF domain.PROSITE-ProRule annotation
Contains 2 PH domains.PROSITE-ProRule annotation
Contains 1 Ras-GEF domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410IQ6Q. Eukaryota.
ENOG410XPWA. LUCA.
GeneTreeiENSGT00860000133664.
HOGENOMiHOG000046000.
HOVERGENiHBG005208.
InParanoidiO14827.
KOiK12326.
OMAiIIQLTDC.
OrthoDBiEOG091G09V6.
PhylomeDBiO14827.
TreeFamiTF317296.

Family and domain databases

CDDicd00155. RasGEF. 1 hit.
cd06224. REM. 1 hit.
Gene3Di1.10.840.10. 1 hit.
1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
InterProiIPR000219. DH-domain.
IPR000048. IQ_motif_EF-hand-BS.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR019804. Ras_G-nucl-exch_fac_CS.
IPR023578. Ras_GEF_dom.
IPR001895. RASGEF_cat_dom.
IPR030744. RasGRF2.
[Graphical view]
PANTHERiPTHR23113:SF187. PTHR23113:SF187. 3 hits.
PfamiPF00169. PH. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 2 hits.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF48366. SSF48366. 2 hits.
SSF50729. SSF50729. 2 hits.
PROSITEiPS50010. DH_2. 1 hit.
PS50096. IQ. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O14827-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQKSVRYNEG HALYLAFLAR KEGTKRGFLS KKTAEASRWH EKWFALYQNV
60 70 80 90 100
LFYFEGEQSC RPAGMYLLEG CSCERTPAPP RAGAGQGGVR DALDKQYYFT
110 120 130 140 150
VLFGHEGQKP LELRCEEEQD GKEWMEAIHQ ASYADILIER EVLMQKYIHL
160 170 180 190 200
VQIVETEKIA ANQLRHQLED QDTEIERLKS EIIALNKTKE RMRPYQSNQE
210 220 230 240 250
DEDPDIKKIK KVQSFMRGWL CRRKWKTIVQ DYICSPHAES MRKRNQIVFT
260 270 280 290 300
MVEAESEYVH QLYILVNGFL RPLRMAASSK KPPISHDDVS SIFLNSETIM
310 320 330 340 350
FLHEIFHQGL KARIANWPTL ILADLFDILL PMLNIYQEFV RNHQYSLQVL
360 370 380 390 400
ANCKQNRDFD KLLKQYEANP ACEGRMLETF LTYPMFQIPR YIITLHELLA
410 420 430 440 450
HTPHEHVERK SLEFAKSKLE ELSRVMHDEV SDTENIRKNL AIERMIVEGC
460 470 480 490 500
DILLDTSQTF IRQGSLIQVP SVERGKLSKV RLGSLSLKKE GERQCFLFTK
510 520 530 540 550
HFLICTRSSG GKLHLLKTGG VLSLIDCTLI EEPDASDDDS KGSGQVFGHL
560 570 580 590 600
DFKIVVEPPD AAAFTVVLLA PSRQEKAAWM SDISQCVDNI RCNGLMTIVF
610 620 630 640 650
EENSKVTVPH MIKSDARLHK DDTDICFSKT LNSCKVPQIR YASVERLLER
660 670 680 690 700
LTDLRFLSID FLNTFLHTYR IFTTAAVVLG KLSDIYKRPF TSIPVRSLEL
710 720 730 740 750
FFATSQNNRG EHLVDGKSPR LCRKFSSPPP LAVSRTSSPV RARKLSLTSP
760 770 780 790 800
LNSKIGALDL TTSSSPTTTT QSPAASPPPH TGQIPLDLSR GLSSPEQSPG
810 820 830 840 850
TVEENVDNPR VDLCNKLKRS IQKAVLESAP ADRAGVESSP AADTTELSPC
860 870 880 890 900
RSPSTPRHLR YRQPGGQTAD NAHCSVSPAS AFAIATAAAG HGSPPGFNNT
910 920 930 940 950
ERTCDKEFII RRTATNRVLN VLRHWVSKHA QDFELNNELK MNVLNLLEEV
960 970 980 990 1000
LRDPDLLPQE RKAAANILRA LSQDDQDDIH LKLEDIIQMT DCMKAECFES
1010 1020 1030 1040 1050
LSAMELAEQI TLLDHVIFRS IPYEEFLGQG WMKLDKNERT PYIMKTSQHF
1060 1070 1080 1090 1100
NDMSNLVASQ IMNYADVSSR ANAIEKWVAV ADICRCLHNY NGVLEITSAL
1110 1120 1130 1140 1150
NRSAIYRLKK TWAKVSKQTK ALMDKLQKTV SSEGRFKNLR ETLKNCNPPA
1160 1170 1180 1190 1200
VPYLGMYLTD LAFIEEGTPN FTEEGLVNFS KMRMISHIIR EIRQFQQTSY
1210 1220 1230
RIDHQPKVAQ YLLDKDLIID EDTLYELSLK IEPRLPA
Length:1,237
Mass (Da):140,764
Last modified:December 4, 2007 - v2
Checksum:iA136CF4FA111FDD9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti561A → R in AAB80953 (PubMed:10373510).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037595114R → H in a colorectal cancer sample; somatic mutation. 1 PublicationCorresponds to variant rs779986744dbSNPEnsembl.1
Natural variantiVAR_037596538D → N in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_037597713L → W.Corresponds to variant rs16878472dbSNPEnsembl.1
Natural variantiVAR_0375981216D → E in a breast cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF023130 mRNA. Translation: AAB80953.1.
AF181250 mRNA. Translation: AAD55268.1.
CH471084 mRNA. Translation: EAW95863.1.
BC126112 mRNA. Translation: AAI26113.1.
BC136296 mRNA. Translation: AAI36297.1.
CCDSiCCDS4052.1.
RefSeqiNP_008840.1. NM_006909.2.
UniGeneiHs.162129.
Hs.684592.

Genome annotation databases

EnsembliENST00000265080; ENSP00000265080; ENSG00000113319.
GeneIDi5924.
KEGGihsa:5924.
UCSCiuc003kha.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF023130 mRNA. Translation: AAB80953.1.
AF181250 mRNA. Translation: AAD55268.1.
CH471084 mRNA. Translation: EAW95863.1.
BC126112 mRNA. Translation: AAI26113.1.
BC136296 mRNA. Translation: AAI36297.1.
CCDSiCCDS4052.1.
RefSeqiNP_008840.1. NM_006909.2.
UniGeneiHs.162129.
Hs.684592.

3D structure databases

ProteinModelPortaliO14827.
SMRiO14827.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111859. 5 interactors.
IntActiO14827. 2 interactors.
STRINGi9606.ENSP00000265080.

PTM databases

iPTMnetiO14827.
PhosphoSitePlusiO14827.

Polymorphism and mutation databases

BioMutaiRASGRF2.

Proteomic databases

EPDiO14827.
PaxDbiO14827.
PeptideAtlasiO14827.
PRIDEiO14827.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265080; ENSP00000265080; ENSG00000113319.
GeneIDi5924.
KEGGihsa:5924.
UCSCiuc003kha.3. human.

Organism-specific databases

CTDi5924.
DisGeNETi5924.
GeneCardsiRASGRF2.
HGNCiHGNC:9876. RASGRF2.
HPAiHPA018679.
MIMi606614. gene.
neXtProtiNX_O14827.
OpenTargetsiENSG00000113319.
PharmGKBiPA34239.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQ6Q. Eukaryota.
ENOG410XPWA. LUCA.
GeneTreeiENSGT00860000133664.
HOGENOMiHOG000046000.
HOVERGENiHBG005208.
InParanoidiO14827.
KOiK12326.
OMAiIIQLTDC.
OrthoDBiEOG091G09V6.
PhylomeDBiO14827.
TreeFamiTF317296.

Enzyme and pathway databases

ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-442982. Ras activation uopn Ca2+ infux through NMDA receptor.
R-HSA-5673001. RAF/MAP kinase cascade.

Miscellaneous databases

ChiTaRSiRASGRF2. human.
GeneWikiiRASGRF2.
GenomeRNAii5924.
PROiO14827.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113319.
CleanExiHS_RASGRF2.
ExpressionAtlasiO14827. baseline and differential.
GenevisibleiO14827. HS.

Family and domain databases

CDDicd00155. RasGEF. 1 hit.
cd06224. REM. 1 hit.
Gene3Di1.10.840.10. 1 hit.
1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
InterProiIPR000219. DH-domain.
IPR000048. IQ_motif_EF-hand-BS.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR019804. Ras_G-nucl-exch_fac_CS.
IPR023578. Ras_GEF_dom.
IPR001895. RASGEF_cat_dom.
IPR030744. RasGRF2.
[Graphical view]
PANTHERiPTHR23113:SF187. PTHR23113:SF187. 3 hits.
PfamiPF00169. PH. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 2 hits.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF48366. SSF48366. 2 hits.
SSF50729. SSF50729. 2 hits.
PROSITEiPS50010. DH_2. 1 hit.
PS50096. IQ. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRGRF2_HUMAN
AccessioniPrimary (citable) accession number: O14827
Secondary accession number(s): B9EG89, Q9UK56
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: December 4, 2007
Last modified: November 30, 2016
This is version 141 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: 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. SIMILARITY comments
    Index of protein domains and families

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.