RGRF1_MOUSE
ID RGRF1_MOUSE Reviewed; 1262 AA.
AC P27671;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Ras-specific guanine nucleotide-releasing factor 1;
DE Short=Ras-GRF1;
DE AltName: Full=CDC25Mm;
DE AltName: Full=Guanine nucleotide-releasing protein;
DE Short=GNRP;
DE AltName: Full=Ras-specific nucleotide exchange factor CDC25;
GN Name=Rasgrf1; Synonyms=Cdc25, Grf1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ;
RX PubMed=1396590; DOI=10.1002/j.1460-2075.1992.tb05494.x;
RA Cen H., Lowy D.D.;
RT "Isolation of multiple mouse cDNAs with coding homology to Saccharomyces
RT cerevisiae CDC25: identification of a region related to Bcr, Vav, Dbl and
RT CDC24.";
RL EMBO J. 11:4007-4015(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 791-1262.
RC STRAIN=SWR/J; TISSUE=Brain;
RX PubMed=1376246; DOI=10.1002/j.1460-2075.1992.tb05274.x;
RA Martegani E., Vanoni M., Zippel R., Coccetti P., Brambilla R., Ferrari C.,
RA Sturani E.P., Alberghina L.;
RT "Cloning by functional complementation of a mouse cDNA encoding a homologue
RT of CDC25, a Saccharomyces cerevisiae RAS activator.";
RL EMBO J. 11:2151-2157(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1031-1226.
RX PubMed=1379731; DOI=10.1073/pnas.89.15.7100;
RA Wei W., Mosteller R.D., Sanyal P., Gonzales E., McKinney D., Dasgupta C.,
RA Li P., Liu B.-X., Broek D.;
RT "Identification of a mammalian gene structurally and functionally related
RT to the CDC25 gene of Saccharomyces cerevisiae.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:7100-7104(1992).
RN [4]
RP FUNCTION, OLIGOMERIZATION, INTERACTION WITH RASGRF2, AND MUTAGENESIS OF
RP LEU-263 AND 394-LEU--LEU-400.
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 [5]
RP UBIQUITINATION, AND INTERACTION WITH USP8.
RX PubMed=11500497; DOI=10.1074/jbc.m103454200;
RA Gnesutta N., Ceriani M., Innocenti M., Mauri I., Zippel R., Sturani E.,
RA Borgonovo B., Berruti G., Martegani E.;
RT "Cloning and characterization of mouse UBPy, a deubiquitinating enzyme that
RT interacts with the ras guanine nucleotide exchange factor CDC25(Mm)/Ras-
RT GRF1.";
RL J. Biol. Chem. 276:39448-39454(2001).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-745, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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. {ECO:0000269|PubMed:10373510,
CC ECO:0000269|PubMed:11500497}.
CC -!- INTERACTION:
CC P27671; P12023: App; NbExp=2; IntAct=EBI-645522, EBI-78814;
CC P27671; P01112: HRAS; Xeno; NbExp=2; IntAct=EBI-645522, EBI-350145;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DOMAIN: The DH (DBL-homology) domain mediates interaction with RASGRF2.
CC -!- PTM: Phosphorylated by PLK2, leading to ubiquitination and degradation
CC by the proteasome. {ECO:0000250}.
CC -!- PTM: Ubiquitinated and degraded following phosphorylation by PLK2.
CC {ECO:0000305|PubMed:11500497}.
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; L20899; AAA02741.1; -; mRNA.
DR EMBL; X59868; CAA42525.1; -; mRNA.
DR CCDS; CCDS40722.1; -.
DR PIR; S28407; S28407.
DR RefSeq; NP_035375.1; NM_011245.2.
DR PDB; 2IJE; X-ray; 2.20 A; S=1028-1262.
DR PDBsum; 2IJE; -.
DR AlphaFoldDB; P27671; -.
DR SMR; P27671; -.
DR BioGRID; 202600; 10.
DR CORUM; P27671; -.
DR DIP; DIP-41194N; -.
DR ELM; P27671; -.
DR IntAct; P27671; 4.
DR MINT; P27671; -.
DR STRING; 10090.ENSMUSP00000034912; -.
DR iPTMnet; P27671; -.
DR PhosphoSitePlus; P27671; -.
DR MaxQB; P27671; -.
DR PaxDb; P27671; -.
DR PRIDE; P27671; -.
DR ProteomicsDB; 254947; -.
DR Antibodypedia; 4170; 337 antibodies from 33 providers.
DR DNASU; 19417; -.
DR Ensembl; ENSMUST00000034912; ENSMUSP00000034912; ENSMUSG00000032356.
DR GeneID; 19417; -.
DR KEGG; mmu:19417; -.
DR UCSC; uc009qzt.1; mouse.
DR CTD; 5923; -.
DR MGI; MGI:99694; Rasgrf1.
DR VEuPathDB; HostDB:ENSMUSG00000032356; -.
DR eggNOG; KOG3417; Eukaryota.
DR GeneTree; ENSGT00940000157599; -.
DR HOGENOM; CLU_003405_0_1_1; -.
DR InParanoid; P27671; -.
DR OMA; HHYFTVN; -.
DR OrthoDB; 70788at2759; -.
DR PhylomeDB; P27671; -.
DR TreeFam; TF317296; -.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 19417; 0 hits in 73 CRISPR screens.
DR ChiTaRS; Rasgrf1; mouse.
DR EvolutionaryTrace; P27671; -.
DR PRO; PR:P27671; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P27671; protein.
DR Bgee; ENSMUSG00000032356; Expressed in pontine nuclear group and 133 other tissues.
DR ExpressionAtlas; P27671; baseline and differential.
DR Genevisible; P27671; MM.
DR GO; GO:0097440; C:apical dendrite; ISO:MGI.
DR GO; GO:0016327; C:apicolateral plasma membrane; ISO:MGI.
DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:HGNC-UCL.
DR GO; GO:0030426; C:growth cone; IDA:HGNC-UCL.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0035254; F:glutamate receptor binding; IPI:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; ISO:MGI.
DR GO; GO:0031267; F:small GTPase binding; ISO:MGI.
DR GO; GO:0090630; P:activation of GTPase activity; IDA:HGNC-UCL.
DR GO; GO:0031175; P:neuron projection development; IDA:HGNC-UCL.
DR GO; GO:0048146; P:positive regulation of fibroblast proliferation; ISO:MGI.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:HGNC-UCL.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:MGI.
DR GO; GO:2000310; P:regulation of NMDA receptor activity; IGI:MGI.
DR GO; GO:0035020; P:regulation of Rac protein signal transduction; IDA:HGNC-UCL.
DR GO; GO:0046578; P:regulation of Ras protein signal transduction; IDA:HGNC-UCL.
DR GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; ISO:MGI.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; IMP:MGI.
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 3D-structure; Guanine-nucleotide releasing factor; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..1262
FT /note="Ras-specific guanine nucleotide-releasing factor 1"
FT /id="PRO_0000068881"
FT DOMAIN 22..130
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 208..233
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 244..430
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 460..588
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 635..749
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 1027..1259
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT REGION 714..738
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 800..854
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 814..832
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 71
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:P28818"
FT MOD_RES 581
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:P28818"
FT MOD_RES 617
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:P28818"
FT MOD_RES 745
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 766
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:P28818"
FT MUTAGEN 263
FT /note="L->Q: Loss of function and oligomerization."
FT /evidence="ECO:0000269|PubMed:10373510"
FT MUTAGEN 394..400
FT /note="LTLHELL->IIIRDII: Partial loss of function. No
FT effect on oligomerization."
FT /evidence="ECO:0000269|PubMed:10373510"
FT CONFLICT 1033
FT /note="E -> D (in Ref. 3)"
FT /evidence="ECO:0000305"
FT HELIX 1028..1044
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1048..1057
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1061..1064
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1066..1087
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1092..1111
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1115..1125
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1128..1131
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1134..1138
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1142..1154
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1158..1169
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1179..1192
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1204..1222
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1231..1238
FT /evidence="ECO:0007829|PDB:2IJE"
FT HELIX 1246..1256
FT /evidence="ECO:0007829|PDB:2IJE"
SQ SEQUENCE 1262 AA; 144102 MW; 38BFE68F7C228DC8 CRC64;
MQKAIRLNDG HVVTLGLLAQ KDGTRKGYLS KRSADNPKWQ TKWFALLQNL LFYFESDSSP
RPSGLYLLEG SICKRAPSPK RGTSSKESGE KQQHYFTVNF SNDSQKTLEL RTEDAKDCDE
WVAAIARASY KILATEHEAL MQKYLHLLQV VETEKTVAKQ LRQQLEDGEV EIERLKTEVT
ITNLIKDNDR IQSSNKAGSA DDEDSDIKKI KKVQSFLRGW LCRRKWKNII QDYIRSPHAD
SMRKRNQVVF SMLEAEAEYV QQLHILVNNF LRPLRMAASS KKPPITHDDV SSIFLNSETI
MFLHQIFYQG LKARISSWPT LVLADLFDIL LPMLNIYQEF VRNHQYSLQI LAHCKQNRDF
DKLLKQYEAK PDCEERTLET FLTYPMFQIP RYILTLHELL AHTPHEHVER NSLDYAKSKL
EELSRIMHDE VSETENIRKN LAIERMITEG CEILLDTSQT FVRQGSLMQM SLSEKSKSSR
GRLGSLSTKK EGERQCFLFS KHLIICTRGS GGKLHLTKNG VISLIDCTLL DEPENLDDEA
KGAGPEIEHL EFKIGVEPKD SLPFTVILVA STRQEKAAWT SDIIQCVDNI RCNGLMMNAF
EENSKVTVPQ MIKSDASLYC DDVDIRFSKT MNSCKVLQIR YASVERLLER LTDLRFLSID
FLNTFLHSYR VFTNAMVVLD KLINIYRKPM SAIPARSLEL LFSSSHNAKL LYGDAPKSPR
ASRKFSSPPP LAIGTSSPSR RRKLSLNIPI ITGGKALELA SLGCSSDSYA NIHSPISPFG
KTTLDTGKLC MASSLPKTPE EIDVPATIPE KPGELSASRK HSSDVLKEES EDDQNHSDED
NTEVSPVKSP PTPKSFLNRT ITEFPFFNYN NGILMTTCRD LVDNNRSTLS ATSAFAIATA
GANEGPSNKE VFRRMSLANT GFSSDQRNID KEFVIRRAAT NRVLNVLRHW VTKHTQDFDT
DDTLKYRVIC FLEEVMHDPD LLTQERKAAA NIIRTLTLEE TTEQHSMLEE VILMTEGVKT
EPFENHPALE IAEQLTLLDH LVFKSIPYEE FFGQGWMKAE KYERTPYIMK TTKHFNHVSN
FIASEIIRNE DISARASAIE KWVAVADICR CLHNYNAVLE ITSSINRSAI FRLKKTWLKV
SKQTKSLLDK LQKLVSSDGR FKNLRESLRN CDPPCVPYLG MYLTDLVFIE EGTPNYTEDG
LVNFSKMRMI SHIIREIRQF QQTTYKIDPQ PKVIQYLLDE SFMLDEESLY ESSLLIEPKL
PT
