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Protein

Ras-specific guanine nucleotide-releasing factor 2

Gene

Rasgrf2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 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.8 Publications

Miscellaneous

Preferentially activates HRAS in vivo compared to R-RAS based on their different types of prenylation.

GO - Molecular functioni

GO - Biological processi

  • long-term synaptic potentiation Source: MGI
  • regulation of NMDA receptor activity Source: MGI
  • regulation of Rho protein signal transduction Source: InterPro
  • small GTPase mediated signal transduction Source: InterPro

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:109137. 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

Pathology & Biotechi

Disruption phenotypei

Mice do not display overt phenotype.2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1022R → E: Loss of interaction with Ras. Loss of Ras activation. Loss of ubiquitination. 1 Publication1
Mutagenesisi1092R → E: Partial loss of interaction with Ras. Partial loss of Ras activation. Partial loss of ubiquitination. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003128641 – 1189Ras-specific guanine nucleotide-releasing factor 2Add BLAST1189

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei725PhosphoserineCombined sources1
Modified residuei726PhosphoserineCombined sources1
Modified residuei736Phosphoserine; by CDK5By similarity1
Modified residuei745PhosphoserineCombined sources1
Modified residuei749PhosphoserineCombined sources1
Modified residuei801PhosphoserineCombined sources1
Modified residuei805PhosphoserineCombined sources1
Modified residuei924PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by CDK5; down-regulates RASGRF2-mediated RAC1 activation.2 Publications
Ubiquitinated upon interaction with Ras. Ubiquitination leads to degradation through the 26S proteasome.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP70392.
PeptideAtlasiP70392.
PRIDEiP70392.

PTM databases

iPTMnetiP70392.
PhosphoSitePlusiP70392.

Expressioni

Tissue specificityi

Expressed in brain in the nucleus of the solitary tract. Not observed in the hippocampus (at protein level).1 Publication

Developmental stagei

Expression increases in the cortex from birth to adulthood.1 Publication

Interactioni

Subunit structurei

Homooligomer and heterooligomer with RASGRF1. Interacts with Ras and RAC1. Interacts in a calcium-dependent manner with calmodulin. Interacts with EPB49 and probably CDK5R1. Interacts with the AMPA receptor through GRIA1. Interacts with microtubules.6 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi202601. 1 interactor.
IntActiP70392. 4 interactors.
MINTiMINT-1753415.

Structurei

3D structure databases

ProteinModelPortaliP70392.
SMRiP70392.
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
Domaini954 – 1186Ras-GEFPROSITE-ProRule annotationAdd BLAST233

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni743 – 751Regulates proteasomal degradation9
Regioni1051 – 1080Responsible of the affinity for farnesylated versus geranylgeranylated RasAdd BLAST30

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili158 – 193Sequence analysisAdd BLAST36

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.
The DH (DBL-homology) domain mediates interaction with RASGRF1 and probably EPB49 and is required for RAC1 activation.

Keywords - Domaini

Coiled coil, Repeat

Phylogenomic databases

HOVERGENiHBG005208.
InParanoidiP70392.
KOiK12326.
PhylomeDBiP70392.

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_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.
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.
SSF50729. SSF50729. 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.

P70392-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQKSVRYNEG HALYLAMLAR KEGTKRGFLS KKAAEASRWH EKWFALYQNV
60 70 80 90 100
LFYFEGEQSG RPAGMYLLEG CSCERTPAPP RTNAGPAGAR DALDKQYYFT
110 120 130 140 150
VLFGHDGQKP LELRCEEEQA GKEWMEAIHQ ASYADILIER EVLMQKYIHL
160 170 180 190 200
VQIVETEKIA TNQLRHQLED QDTEIERLKS EIVALNKTKE RMRPYHVHQE
210 220 230 240 250
EEDPDIKKIK KVQSFMRGWL CRRKWKTIVQ DYICSPHAES MRKRNQIVFT
260 270 280 290 300
MVEAETEYVH QLYILVNGFL RPLRMAASSK KPPINHDDVS SIFLNSETIM
310 320 330 340 350
FLHEIFHQGL KARLANWPTL VLADLFDILL 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 VLSLIQCTLI EEPDGSDDDP KGSGHMFGHL
560 570 580 590 600
DFKIVVEPPD AASFTVVLLA PSRQEKAAWM SDISQCVDNI RCNGLMTIVF
610 620 630 640 650
EENSKVTVPH MIKSDARLHK DDTDICFSKT LNSCKVPQIR YASVERLLER
660 670 680 690 700
LTDLRFLSID FLNTFLHTYR IFTTATVVLA KLSDIYKRPF TSIPVRSLEL
710 720 730 740 750
FFATSQNNRE HLVDGKSPRL CRKFSSPPPL AVSRTSSPVR ARKLSLTSSL
760 770 780 790 800
NSRIGALDLT NSSSSSSPTT TTHSPAASPP PHTAVLESAP ADKAGDSADM
810 820 830 840 850
SPCRSPTTPR HLRYRQPGGQ VADSAHCSVS PASAFAIATA AAGHGSPPGF
860 870 880 890 900
NNERTCDKEF IIRRTATNRV LNVLRHWVSK HAQDFELNNE LKMNVLNLLE
910 920 930 940 950
EVLRDPDLLP QERKATANIL RALSQDDQDD IHLKLEDIIQ MTDCPKAECF
960 970 980 990 1000
ETLSAMELAE QITLLDHIVF RSIPYEEFLG QGWMKLDKNE RTPYIMKTSQ
1010 1020 1030 1040 1050
HFNEMSNLVA SQIMNYADIS SRANAIEKWV AVADICRCLH NYNGVLEITS
1060 1070 1080 1090 1100
ALNRSAIYRL KKTWAKVSKQ TKALMDKLQK TVSSEGRFKN LRETLKNCNP
1110 1120 1130 1140 1150
PAVPYLGMYL TDLAFIEEGT PNFTEEGLVN FSKMRMISHI IREIRQFQQT
1160 1170 1180
AYRIDQQPKV IQYLLDKALV IDEDSLYELS LKIEPRLPA
Length:1,189
Mass (Da):135,668
Last modified:May 1, 2000 - v2
Checksum:i42E346B623F18E59
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1023A → P in AAF18297 (PubMed:11909944).Curated1
Sequence conflicti1056A → P in AAF18297 (PubMed:11909944).Curated1
Sequence conflicti1061K → R in BAE34529 (PubMed:16141072).Curated1
Sequence conflicti1076D → N in BAE34529 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67326 mRNA. Translation: AAC53058.2.
AK158472 mRNA. Translation: BAE34529.1.
AH008805 Genomic DNA. Translation: AAF18297.1.
PIRiT42726.
RefSeqiNP_033053.2. NM_009027.3.
UniGeneiMm.248630.

Genome annotation databases

GeneIDi19418.
KEGGimmu:19418.
UCSCiuc029sco.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiRGRF2_MOUSE
AccessioniPrimary (citable) accession number: P70392
Secondary accession number(s): Q3TYN3, Q9QX51
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: May 1, 2000
Last modified: October 25, 2017
This is version 137 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot