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Protein

Ras-specific guanine nucleotide-releasing factor 2

Gene

Rasgrf2

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 4 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

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi69413. Rasgrf2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11901190Ras-specific guanine nucleotide-releasing factor 2PRO_0000312865Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei725 – 7251PhosphoserineBy similarity
Modified residuei726 – 7261PhosphoserineBy similarity
Modified residuei736 – 7361Phosphoserine; by CDK5By similarity
Modified residuei745 – 7451PhosphoserineBy similarity
Modified residuei749 – 7491PhosphoserineBy similarity
Modified residuei801 – 8011PhosphoserineBy similarity
Modified residuei805 – 8051PhosphoserineBy similarity
Modified residuei925 – 9251PhosphoserineBy similarity

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.
PhosphoSiteiQ99JE4.

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

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000019087.

Structurei

3D structure databases

ProteinModelPortaliQ99JE4.
SMRiQ99JE4. Positions 955-1187.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini22 – 133112PH 1PROSITE-ProRule annotationAdd
BLAST
Domaini205 – 23430IQPROSITE-ProRule annotationAdd
BLAST
Domaini243 – 429187DHPROSITE-ProRule annotationAdd
BLAST
Domaini470 – 588119PH 2PROSITE-ProRule annotationAdd
BLAST
Domaini635 – 755121N-terminal Ras-GEFPROSITE-ProRule annotationAdd
BLAST
Domaini955 – 1187233Ras-GEFPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni743 – 7519Regulates proteasomal degradationBy similarity
Regioni1052 – 108130Responsible of the affinity for farnesylated versus geranylgeranylated RasBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili155 – 19339Sequence analysisAdd
BLAST

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

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

eggNOGiENOG410KD3D. Eukaryota.
ENOG410XPWA. LUCA.
HOGENOMiHOG000046000.
HOVERGENiHBG005208.
InParanoidiQ99JE4.
KOiK12326.
PhylomeDBiQ99JE4.

Family and domain databases

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.

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliQ99JE4.
SMRiQ99JE4. Positions 955-1187.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000019087.

PTM databases

iPTMnetiQ99JE4.
PhosphoSiteiQ99JE4.

Proteomic databases

PaxDbiQ99JE4.
PRIDEiQ99JE4.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi114513.
KEGGirno:114513.
UCSCiRGD:69413. rat.

Organism-specific databases

CTDi5924.
RGDi69413. Rasgrf2.

Phylogenomic databases

eggNOGiENOG410KD3D. Eukaryota.
ENOG410XPWA. LUCA.
HOGENOMiHOG000046000.
HOVERGENiHBG005208.
InParanoidiQ99JE4.
KOiK12326.
PhylomeDBiQ99JE4.

Miscellaneous databases

PROiQ99JE4.

Family and domain databases

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...

Publicationsi

  1. "Analysis of candidate genes included in the mammary cancer susceptibility 1 (Mcs1) region."
    Laes J.-F., Quan X., Ravoet M., van Vooren P., van Reeth T., Szpirer J., Szpirer C.
    Mamm. Genome 12:199-206(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. "Cloning and characterization of Ras-GRF2, a novel guanine nucleotide exchange factor for Ras."
    Fam N.P., Fan W.-T., Wang Z., Zhang L.-J., Chen H., Moran M.F.
    Mol. Cell. Biol. 17:1396-1406(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  3. "Ras-specific exchange factor GRF: oligomerization through its Dbl homology domain and calcium-dependent activation of Raf."
    Anborgh P.H., Qian X., Papageorge A.G., Vass W.C., DeClue J.E., Lowy D.R.
    Mol. Cell. Biol. 19:4611-4622(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: OLIGOMERIZATION, INTERACTION WITH RASGRF1.
  4. "p35/cyclin-dependent kinase 5 phosphorylation of ras guanine nucleotide releasing factor 2 (RasGRF2) mediates Rac-dependent extracellular signal-regulated kinase 1/2 activity, altering RasGRF2 and microtubule-associated protein 1b distribution in neurons."
    Kesavapany S., Amin N., Zheng Y.-L., Nijhara R., Jaffe H., Sihag R., Gutkind J.S., Takahashi S., Kulkarni A., Grant P., Pant H.C.
    J. Neurosci. 24:4421-4431(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDK5R1, PHOSPHORYLATION BY CDK5.

Entry informationi

Entry nameiRGRF2_RAT
AccessioniPrimary (citable) accession number: Q99JE4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: June 1, 2001
Last modified: June 8, 2016
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.