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Protein

Ras-specific guanine nucleotide-releasing factor 2

Gene

Rasgrf2

Organism
Rattus norvegicus (Rat)
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

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69413 Rasgrf2

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003128651 – 1190Ras-specific guanine nucleotide-releasing factor 2Add BLAST1190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei725PhosphoserineBy similarity1
Modified residuei726PhosphoserineBy similarity1
Modified residuei736Phosphoserine; by CDK5By similarity1
Modified residuei745PhosphoserineBy similarity1
Modified residuei749PhosphoserineBy similarity1
Modified residuei801PhosphoserineBy similarity1
Modified residuei805PhosphoserineBy similarity1
Modified residuei925PhosphoserineBy 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

PaxDbiQ99JE4
PRIDEiQ99JE4

PTM databases

iPTMnetiQ99JE4
PhosphoSitePlusiQ99JE4

Expressioni

Tissue specificityi

Widely expressed. Detected in brain, lung, spleen, pancreas, kidney, liver, heart, mammary gland and skeletal muscle.1 Publication

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000019087

Structurei

3D structure databases

ProteinModelPortaliQ99JE4
SMRiQ99JE4
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 – 755N-terminal Ras-GEFPROSITE-ProRule annotationAdd BLAST121
Domaini955 – 1187Ras-GEFPROSITE-ProRule annotationAdd BLAST233

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni743 – 751Regulates proteasomal degradationBy similarity9
Regioni1052 – 1081Responsible 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.By similarity

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

eggNOGiENOG410KD3D Eukaryota
ENOG410XPWA LUCA
HOGENOMiHOG000046000
HOVERGENiHBG005208
InParanoidiQ99JE4
KOiK12326
PhylomeDBiQ99JE4

Family and domain databases

CDDicd00155 RasGEF, 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, 2 hits
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.

Q99JE4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQKSVRYNEG HALYLAFLAR KEGTKRGFLS KKAAEASRWH EKWFALYQNV
60 70 80 90 100
LFYFEGEQSG RPAGMYLLEG CSCERTPAPP RTNAGPAGAR DALDKQYYFT
110 120 130 140 150
VLFGHEGQKP LELRCEEEQA GKEWMEAIHQ ASYADILIER EVLMQKYIHL
160 170 180 190 200
VQIVETEKIA ANQLRHQLED QDTEIERLKS EIVALNKTKE RMRPYHTHQE
210 220 230 240 250
EEDPDIKKIK KVQSFMRGWL CRRKWKTIVQ DYICSPHAES MRKRNQIVFT
260 270 280 290 300
MVEAESEYVH QLYILVNGFL RPLRMAASSK KPPISHDDVS SIFLNSETIM
310 320 330 340 350
FLHEIFHQGL KARLANWPTL VLADLFDILL PMLNIYQEFV RNHQYSLQVL
360 370 380 390 400
ANCKQNRDFD KLLKQYEGNP 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 VLSLIQCTLI EEPDTSDDDT KGPGHMFGHL
560 570 580 590 600
DFKIVVEPPD AAPFTVVLLA 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
FFATSQNNRE HLVDGKSPRL CRKFSSPPPL AVSRTSSPVR ARKLSLTSSL
760 770 780 790 800
NSRIGALDLT TSSSSSSPTT TVHSPAASPP PHTAVPESAP ADRAGDSTDM
810 820 830 840 850
SPCRSPSTTP RHLRYRQPGG QVADSTHCAV SPASAFAIAT AAAGHGSPPG
860 870 880 890 900
FNNERTCDKE FIIRRTATNR VLNVLRHWVS KHSQDFELNN ELKMNVLNLL
910 920 930 940 950
EEVLRDPDLL PQERKATANI LRALSQDDQD DIHLKLEDII QMTDCPKAEC
960 970 980 990 1000
FETLSAMELA EQITLLDHIV FRSIPYEEFL GQGWMKLDKN ERTPYIMKTS
1010 1020 1030 1040 1050
QHFNEMSNLV ASQIMNYADI SSRANAIEKW VAVADICRCL HNYNGVLEIT
1060 1070 1080 1090 1100
SALNRSAIYR LKKTWTKVSK QTKALMDKLQ KTVSSEGRFK NLRETLKNCN
1110 1120 1130 1140 1150
PPAVPYLGMY LTDLAFIEEG TPNFTEEGLV NFSKMRMISH IIREIRQFQQ
1160 1170 1180 1190
TAYRIDQQPK VIQYLLDKAL VIDEDTLYEL SLKIEPRLPA
Length:1,190
Mass (Da):135,827
Last modified:June 1, 2001 - v1
Checksum:i5A2A2C6C8AABBC2F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ276774 mRNA Translation: CAC37407.1
RefSeqiNP_446173.1, NM_053721.1
UniGeneiRn.210995

Genome annotation databases

GeneIDi114513
KEGGirno:114513
UCSCiRGD:69413 rat

Similar proteinsi

Entry informationi

Entry nameiRGRF2_RAT
AccessioniPrimary (citable) accession number: Q99JE4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: June 1, 2001
Last modified: March 28, 2018
This is version 121 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health