RGRF1_RAT
ID RGRF1_RAT Reviewed; 1244 AA.
AC P28818;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=Ras-specific guanine nucleotide-releasing factor 1;
DE Short=Ras-GRF1;
DE AltName: Full=Guanine nucleotide-releasing protein;
DE Short=GNRP;
DE AltName: Full=P140 Ras-GRF;
GN Name=Rasgrf1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=1379346; DOI=10.1038/358351a0;
RA Shou C., Farusworth C.L., Neel B.G., Feig L.A.;
RT "Molecular cloning of cDNAs encoding a guanine-nucleotide-releasing factor
RT for Ras p21.";
RL Nature 358:351-354(1992).
RN [2]
RP FUNCTION, OLIGOMERIZATION, AND INTERACTION WITH RASGRF2.
RX PubMed=10373510; DOI=10.1128/mcb.19.7.4611;
RA Anborgh P.H., Qian X., Papageorge A.G., Vass W.C., DeClue J.E., Lowy D.R.;
RT "Ras-specific exchange factor GRF: oligomerization through its Dbl homology
RT domain and calcium-dependent activation of Raf.";
RL Mol. Cell. Biol. 19:4611-4622(1999).
RN [3]
RP PHOSPHORYLATION AT SER-71; SER-575; SER-611; SER-760; SER-781 AND SER-854,
RP UBIQUITINATION, AND MUTAGENESIS OF SER-71 AND SER-575.
RX PubMed=21382555; DOI=10.1016/j.neuron.2011.02.004;
RA Lee K.J., Lee Y., Rozeboom A., Lee J.Y., Udagawa N., Hoe H.S., Pak D.T.;
RT "Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic
RT structural plasticity, and memory.";
RL Neuron 69:957-973(2011).
CC -!- FUNCTION: Promotes the exchange of Ras-bound GDP by GTP.
CC {ECO:0000269|PubMed:10373510}.
CC -!- SUBUNIT: Homooligomer and heterooligomer with RASGRF2. Interacts with
CC USP8, thereby regulating its stability (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The DH (DBL-homology) domain mediates interaction with RASGRF2.
CC {ECO:0000250}.
CC -!- PTM: Phosphorylated by PLK2, leading to ubiquitination and degradation
CC by the proteasome. {ECO:0000269|PubMed:21382555}.
CC -!- PTM: Ubiquitinated and degraded following phosphorylation by PLK2.
CC {ECO:0000269|PubMed:21382555}.
CC -!- PTM: Phosphorylated by SRC and LCK. Phosphorylation by LCK increases
CC its capacity to stimulate the GDP/GTP exchange on Ras, whereas its
CC phosphorylation by SRC seems not to have an effect on stimulation
CC activity (By similarity). {ECO:0000250}.
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DR EMBL; X67241; CAA47666.1; -; mRNA.
DR PIR; S29083; S29083.
DR RefSeq; NP_001164002.1; NM_001170531.1.
DR AlphaFoldDB; P28818; -.
DR SMR; P28818; -.
DR BioGRID; 251354; 2.
DR STRING; 10116.ENSRNOP00000018794; -.
DR iPTMnet; P28818; -.
DR PhosphoSitePlus; P28818; -.
DR PaxDb; P28818; -.
DR PRIDE; P28818; -.
DR GeneID; 192213; -.
DR KEGG; rno:192213; -.
DR UCSC; RGD:620395; rat.
DR CTD; 5923; -.
DR RGD; 620395; Rasgrf1.
DR eggNOG; KOG3417; Eukaryota.
DR InParanoid; P28818; -.
DR OrthoDB; 70788at2759; -.
DR PhylomeDB; P28818; -.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR PRO; PR:P28818; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0097440; C:apical dendrite; IDA:RGD.
DR GO; GO:0016327; C:apicolateral plasma membrane; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:HGNC-UCL.
DR GO; GO:0030426; C:growth cone; ISS:HGNC-UCL.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0035254; F:glutamate receptor binding; ISO:RGD.
DR GO; GO:0005096; F:GTPase activator activity; TAS:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:RGD.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IPI:RGD.
DR GO; GO:0031267; F:small GTPase binding; IDA:RGD.
DR GO; GO:0090630; P:activation of GTPase activity; IMP:RGD.
DR GO; GO:0008283; P:cell population proliferation; ISO:RGD.
DR GO; GO:0071236; P:cellular response to antibiotic; IEP:RGD.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IEP:RGD.
DR GO; GO:0031175; P:neuron projection development; ISS:HGNC-UCL.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; IMP:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:RGD.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IDA:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; ISO:RGD.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; ISO:RGD.
DR GO; GO:0035020; P:regulation of Rac protein signal transduction; ISS:HGNC-UCL.
DR GO; GO:0046578; P:regulation of Ras protein signal transduction; ISS:HGNC-UCL.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IDA:UniProtKB.
DR GO; GO:0001975; P:response to amphetamine; IEP:RGD.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:RGD.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd00160; RhoGEF; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR Gene3D; 1.20.900.10; -; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR035899; DBL_dom_sf.
DR InterPro; IPR000219; DH-domain.
DR InterPro; IPR001331; GDS_CDC24_CS.
DR InterPro; IPR000048; IQ_motif_EF-hand-BS.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR008937; Ras-like_GEF.
DR InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR InterPro; IPR019804; Ras_G-nucl-exch_fac_CS.
DR InterPro; IPR023578; Ras_GEF_dom_sf.
DR InterPro; IPR001895; RASGEF_cat_dom.
DR InterPro; IPR036964; RASGEF_cat_dom_sf.
DR InterPro; IPR030745; RasGRF1.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR PANTHER; PTHR23113:SF193; PTHR23113:SF193; 1.
DR Pfam; PF00169; PH; 2.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR Pfam; PF00621; RhoGEF; 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; 1.
DR PROSITE; PS00741; DH_1; 1.
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 Guanine-nucleotide releasing factor; Phosphoprotein; Reference proteome;
KW Repeat; Ubl conjugation.
FT CHAIN 1..1244
FT /note="Ras-specific guanine nucleotide-releasing factor 1"
FT /id="PRO_0000068882"
FT DOMAIN 22..129
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 204..229
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 240..426
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 456..582
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 629..743
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 1009..1241
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 707..730
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 800..840
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 71
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 575
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 611
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 739
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P27671"
FT MOD_RES 760
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 781
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MOD_RES 854
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000269|PubMed:21382555"
FT MUTAGEN 71
FT /note="S->A: Abolishes degradation by the proteasome."
FT /evidence="ECO:0000269|PubMed:21382555"
FT MUTAGEN 575
FT /note="S->A: Abolishes degradation by the proteasome."
FT /evidence="ECO:0000269|PubMed:21382555"
SQ SEQUENCE 1244 AA; 142667 MW; 4B647879E842AF6B CRC64;
MQKAIRLNDG HVVSLGLLAQ RDGTRKGYLS KRSSDNPKWQ TKWFALLQNL LFYFESDSSS
RPSGLYLLEG SICKRMPSPK RGTSSKESDK QHHYFTVNFS NDSQKSLELR TDDSKDCDEW
VAAIARASYK ILATEHEALM QKYLHLLQVV ETEKTVAKQL RQQLEDGEVE IERLKAEIAN
LIKDNERIQS NQLVAPEDED SDIKKIKKVQ SFLRGWLCRR KWKNIIQDYI RSPHADSMRK
RNQVVFSMLE AEAEYVQQLH ILVNNFLRPL RMAASSKKPP ITHDDVSSIF LNSETIMFLH
QIFYQGLKAR IASWPTLVLA DLFDILLPML NIYQEFVRNH QYSLQILAHC KQNRDFDKLL
KQYEAKPDCE ERTLETFLTY PMFQIPRYIL TLHELLAHTP HEHVERNSLD YAKSKLEELS
RVMHDEVSET ENIRKNLAIE RMITEGCEIL LDTSQTFVRQ GSLIQVPMSE KGKINKGRLG
SLSLKKEGER QCFLFSKHLI ICTRGSGSKL HLTKNGVISL IDCTLLDDPE NMDDDGKGQE
VDHLDFKIWV EPKDSPPFTV ILVASSRQEK AAWTSDIIQC VDNIRCNGLM MNAFEENSKV
TVPQMIKSDA SLYCDDVDIR FSKTMNSCKV LQIRYASVER LLERLTDLRF LSIDFLNTFL
HSYRVFTDAV VVLDKLISIY KKPITAIPAR SLELLFSSSH NTKLLYGDAP KSPRASRKFS
SPPPLAIGTS SPVRRRKLSL NIPIITGGKA LELASLGCPS DGYTNIHSPI SPFGKTTLDT
SKLCVASSLT RTPEEIDMTT LEESSGFRKP TSDILKEESD DDQSDVDDTE VSPPTPKSFR
NRITQEFPLF NYNSGIMMTC RDLMDSNRSP LSATSAFAIA TAGANESPAN KEIYRRMSLA
NTGYSSDQRN IDKEFVIRRA ATNRVLNVLR HWVTKHSQDF ETDDLLKYKV ICFLEEVMHD
PDLLPQERKA AANIMRTLTQ EEITENHSML DELLLMTEGV KTEPFENHSA MEIAEQLTLL
DHLVFKSIPY EEFFGQGWMK ADKNERTPYI MKTTRHFNHI SNLIASEILR NEEVSARAST
IEKWVAVADI CRCLHNYNAV LEITSSINRS AIFRLKKTWL KVSKQTKSLF DKLQKLVSSD
GRFKNLRETL RNCDPPCVPY LGMYLTDLAF LEEGTPNYTE DGLVNFSKMR MISHIIREIR
QFQQTTYKIE PQPKVTQYLV DETFVLDDES LYEASLRIEP KLPT
