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Database: UniProt
Entry: Q99JE4
LinkDB: Q99JE4
Original site: Q99JE4 
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   03-SEP-2014, entry version 98.
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.
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DR   EMBL; AJ276774; CAC37407.1; -; mRNA.
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   PhylomeDB; Q99JE4; -.
DR   NextBio; 618627; -.
DR   PRO; PR: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:0005089; F:Rho guanyl-nucleotide exchange factor activity; 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; IPR001849; PH_domain.
DR   InterPro; IPR011993; PH_like_dom.
DR   InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR   InterPro; IPR019804; Ras_G-nucl-exch_fac_CS.
DR   InterPro; IPR023578; Ras_GEF_dom.
DR   InterPro; IPR001895; RasGRF_CDC25.
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; SSF48065; 1.
DR   SUPFAM; SSF48366; SSF48366; 2.
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
//
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