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Protein

Ras-specific guanine nucleotide-releasing factor 2

Gene

RASGRF2

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

Keywordsi

Molecular functionCalmodulin-binding, Guanine-nucleotide releasing factor
LigandCalcium

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 upon Ca2+ influx 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

EuPathDBiHostDB:ENSG00000113319.11
HGNCiHGNC:9876 RASGRF2
MIMi606614 gene
neXtProtiNX_O14827

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

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

GO - Molecular functioni

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.

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410IQ6Q Eukaryota
ENOG410XPWA LUCA
GeneTreeiENSGT00910000143985
HOGENOMiHOG000046000
HOVERGENiHBG005208
InParanoidiO14827
KOiK12326
OMAiQNNRGEH
OrthoDBiEOG091G09V6
PhylomeDBiO14827
TreeFamiTF317296

Family and domain databases

CDDicd00155 RasGEF, 1 hit
cd06224 REM, 1 hit
cd00160 RhoGEF, 1 hit
Gene3Di1.10.840.10, 1 hit
1.20.900.10, 1 hit
2.30.29.30, 2 hits
InterProiView protein in InterPro
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR000048 IQ_motif_EF-hand-BS
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
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
IPR030744 RasGRF2
PANTHERiPTHR23113:SF187 PTHR23113:SF187, 1 hit
PfamiView protein in Pfam
PF00169 PH, 1 hit
PF00617 RasGEF, 1 hit
PF00618 RasGEF_N, 1 hit
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00233 PH, 2 hits
SM00147 RasGEF, 1 hit
SM00229 RasGEFN, 2 hits
SM00325 RhoGEF, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
SSF48366 SSF48366, 2 hits
PROSITEiView protein in PROSITE
PS50010 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

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 dbSNP:rs779986744Ensembl.1
Natural variantiVAR_037596538D → N in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_037597713L → W. Corresponds to variant dbSNP:rs16878472Ensembl.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

Similar proteinsi

Entry informationi

Entry nameiRGRF2_HUMAN
AccessioniPrimary (citable) accession number: O14827
Secondary accession number(s): B9EG89, Q9UK56
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: December 4, 2007
Last modified: May 23, 2018
This is version 152 of the entry and version 2 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

Complete proteome, Reference proteome

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