ID RGRF2_RAT Reviewed; 1190 AA.
AC Q99JE4;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 29-MAY-2013, entry version 90.
DE RecName: Full=Ras-specific guanine nucleotide-releasing factor 2;
DE Short=Ras-GRF2;
DE AltName: Full=Ras guanine nucleotide exchange factor 2;
GN Name=Rasgrf2; Synonyms=Grf2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi;
OC Muroidea; Muridae; Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=11252168; DOI=10.1007/s003350010268;
RA Laes J.-F., Quan X., Ravoet M., van Vooren P., van Reeth T.,
RA Szpirer J., Szpirer C.;
RT "Analysis of candidate genes included in the mammary cancer
RT susceptibility 1 (Mcs1) region.";
RL Mamm. Genome 12:199-206(2001).
RN [2]
RP TISSUE SPECIFICITY.
RX PubMed=9032266;
RA Fam N.P., Fan W.-T., Wang Z., Zhang L.-J., Chen H., Moran M.F.;
RT "Cloning and characterization of Ras-GRF2, a novel guanine nucleotide
RT exchange factor for Ras.";
RL Mol. Cell. Biol. 17:1396-1406(1997).
RN [3]
RP OLIGOMERIZATION, AND INTERACTION WITH RASGRF1.
RX PubMed=10373510;
RA Anborgh P.H., Qian X., Papageorge A.G., Vass W.C., DeClue J.E.,
RA Lowy D.R.;
RT "Ras-specific exchange factor GRF: oligomerization through its Dbl
RT homology domain and calcium-dependent activation of Raf.";
RL Mol. Cell. Biol. 19:4611-4622(1999).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDK5R1, AND
RP PHOSPHORYLATION BY CDK5.
RX PubMed=15128856; DOI=10.1523/JNEUROSCI.0690-04.2004;
RA Kesavapany S., Amin N., Zheng Y.-L., Nijhara R., Jaffe H., Sihag R.,
RA Gutkind J.S., Takahashi S., Kulkarni A., Grant P., Pant H.C.;
RT "p35/cyclin-dependent kinase 5 phosphorylation of ras guanine
RT nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent
RT extracellular signal-regulated kinase 1/2 activity, altering RasGRF2
RT and microtubule-associated protein 1b distribution in neurons.";
RL J. Neurosci. 24:4421-4431(2004).
CC -!- FUNCTION: Functions as a calcium-regulated nucleotide exchange
CC factor activating both Ras and RAC1 through the exchange of bound
CC GDP for GTP. Preferentially activates HRAS in vivo compared to
CC RRAS based on their different types of prenylation. Functions in
CC synaptic plasticity by contributing to the induction of long term
CC potentiation.
CC -!- SUBUNIT: Homooligomer and heterooligomer with RASGRF1. Interacts
CC with Ras and RAC1 (By similarity). Interacts in a calcium-
CC dependent manner with calmodulin (By similarity). Interacts with
CC CDK5R1 and probably EPB49. Interacts with the AMPA receptor
CC through GRIA1 (By similarity). Interacts with microtubules (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral
CC membrane protein. Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Note=Translocates to membranes when activated
CC (By similarity). Found both at cell periphery and along the axon
CC of neurons.
CC -!- TISSUE SPECIFICITY: Widely expressed. Detected in brain, lung,
CC spleen, pancreas, kidney, liver, heart, mammary gland and skeletal
CC muscle.
CC -!- DOMAIN: The Ras-GEF domain and the N-terminal Ras-GEF domain form
CC a Ras-binding site and mediate Ras activation (By similarity).
CC -!- DOMAIN: The IQ domain mediates the calcium-dependent interaction
CC with calmodulin but is dispensable for the Ras-GEF activity (By
CC similarity).
CC -!- DOMAIN: The DH (DBL-homology) domain mediates interaction with
CC RASGRF1 and EPB49 and is required for RAC1 activation (By
CC similarity).
CC -!- PTM: Phosphorylated by CDK5; down-regulates RASGRF2-mediated RAC1
CC activation.
CC -!- PTM: Ubiquitinated upon interaction with Ras. Ubiquitination leads
CC to degradation through the 26S proteasome (By similarity).
CC -!- SIMILARITY: Contains 1 DH (DBL-homology) domain.
CC -!- SIMILARITY: Contains 1 IQ domain.
CC -!- SIMILARITY: Contains 1 N-terminal Ras-GEF domain.
CC -!- SIMILARITY: Contains 2 PH domains.
CC -!- SIMILARITY: Contains 1 Ras-GEF domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AJ276774; CAC37407.1; -; mRNA.
DR IPI; IPI00195067; -.
DR RefSeq; NP_446173.1; NM_053721.1.
DR UniGene; Rn.210995; -.
DR ProteinModelPortal; Q99JE4; -.
DR SMR; Q99JE4; 955-1187.
DR STRING; 10116.ENSRNOP00000019087; -.
DR PhosphoSite; Q99JE4; -.
DR PRIDE; Q99JE4; -.
DR GeneID; 114513; -.
DR KEGG; rno:114513; -.
DR UCSC; RGD:69413; rat.
DR CTD; 5924; -.
DR RGD; 69413; Rasgrf2.
DR eggNOG; NOG257844; -.
DR HOGENOM; HOG000046000; -.
DR HOVERGEN; HBG005208; -.
DR InParanoid; Q99JE4; -.
DR KO; K12326; -.
DR OrthoDB; EOG4W6NV6; -.
DR NextBio; 618627; -.
DR ArrayExpress; Q99JE4; -.
DR Genevestigator; Q99JE4; -.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005543; F:phospholipid binding; IEA:InterPro.
DR GO; GO:0005089; F:Rho guanyl-nucleotide exchange factor activity; IEA:InterPro.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IEA:InterPro.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR011993; PH_like_dom.
DR InterPro; IPR001849; Pleckstrin_homology.
DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR InterPro; IPR019804; Ras_G-nucl-exch_fac_CS.
DR InterPro; IPR008937; Ras_GEF.
DR InterPro; IPR023578; Ras_GEF_dom.
DR InterPro; IPR001895; RasGRF_CDC25.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR Pfam; PF00621; RhoGEF; 1.
DR SMART; SM00015; IQ; 1.
DR SMART; SM00233; PH; 2.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 2.
DR SMART; SM00325; RhoGEF; 1.
DR SUPFAM; SSF48065; DH-domain; 1.
DR SUPFAM; SSF48366; Ras_GEF; 1.
DR PROSITE; PS00741; DH_1; FALSE_NEG.
DR PROSITE; PS50010; DH_2; 1.
DR PROSITE; PS50096; IQ; 1.
DR PROSITE; PS50003; PH_DOMAIN; 2.
DR PROSITE; PS00720; RASGEF; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
PE 1: Evidence at protein level;
KW Calcium; Calmodulin-binding; Cell membrane; Coiled coil;
KW Complete proteome; Cytoplasm; Endoplasmic reticulum;
KW Guanine-nucleotide releasing factor; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1 1190 Ras-specific guanine nucleotide-releasing
FT factor 2.
FT /FTId=PRO_0000312865.
FT DOMAIN 22 133 PH 1.
FT DOMAIN 205 234 IQ.
FT DOMAIN 243 429 DH.
FT DOMAIN 470 588 PH 2.
FT DOMAIN 635 755 N-terminal Ras-GEF.
FT DOMAIN 955 1187 Ras-GEF.
FT REGION 743 751 Regulates proteasomal degradation (By
FT similarity).
FT REGION 1052 1081 Responsible of the affinity for
FT farnesylated versus geranylgeranylated
FT Ras (By similarity).
FT COILED 155 193 Potential.
FT MOD_RES 736 736 Phosphoserine; by CDK5 (By similarity).
FT MOD_RES 745 745 Phosphoserine (By similarity).
SQ SEQUENCE 1190 AA; 135827 MW; 5A2A2C6C8AABBC2F CRC64;
MQKSVRYNEG HALYLAFLAR KEGTKRGFLS KKAAEASRWH EKWFALYQNV LFYFEGEQSG
RPAGMYLLEG CSCERTPAPP RTNAGPAGAR DALDKQYYFT VLFGHEGQKP LELRCEEEQA
GKEWMEAIHQ ASYADILIER EVLMQKYIHL VQIVETEKIA ANQLRHQLED QDTEIERLKS
EIVALNKTKE RMRPYHTHQE EEDPDIKKIK KVQSFMRGWL CRRKWKTIVQ DYICSPHAES
MRKRNQIVFT MVEAESEYVH QLYILVNGFL RPLRMAASSK KPPISHDDVS SIFLNSETIM
FLHEIFHQGL KARLANWPTL VLADLFDILL PMLNIYQEFV RNHQYSLQVL ANCKQNRDFD
KLLKQYEGNP ACEGRMLETF LTYPMFQIPR YIITLHELLA HTPHEHVERK SLEFAKSKLE
ELSRVMHDEV SDTENIRKNL AIERMIVEGC DILLDTSQTF IRQGSLIQVP SVERGKLSKV
RLGSLSLKKE GERQCFLFTK HFLICTRSSG GKLHLLKTGG VLSLIQCTLI EEPDTSDDDT
KGPGHMFGHL DFKIVVEPPD AAPFTVVLLA PSRQEKAAWM SDISQCVDNI RCNGLMTIVF
EENSKVTVPH MIKSDARLHK DDTDICFSKT LNSCKVPQIR YASVERLLER LTDLRFLSID
FLNTFLHTYR IFTTAAVVLG KLSDIYKRPF TSIPVRSLEL FFATSQNNRE HLVDGKSPRL
CRKFSSPPPL AVSRTSSPVR ARKLSLTSSL NSRIGALDLT TSSSSSSPTT TVHSPAASPP
PHTAVPESAP ADRAGDSTDM SPCRSPSTTP RHLRYRQPGG QVADSTHCAV SPASAFAIAT
AAAGHGSPPG FNNERTCDKE FIIRRTATNR VLNVLRHWVS KHSQDFELNN ELKMNVLNLL
EEVLRDPDLL PQERKATANI LRALSQDDQD DIHLKLEDII QMTDCPKAEC FETLSAMELA
EQITLLDHIV FRSIPYEEFL GQGWMKLDKN ERTPYIMKTS QHFNEMSNLV ASQIMNYADI
SSRANAIEKW VAVADICRCL HNYNGVLEIT SALNRSAIYR LKKTWTKVSK QTKALMDKLQ
KTVSSEGRFK NLRETLKNCN PPAVPYLGMY LTDLAFIEEG TPNFTEEGLV NFSKMRMISH
IIREIRQFQQ TAYRIDQQPK VIQYLLDKAL VIDEDTLYEL SLKIEPRLPA
//
