GNDS_MOUSE
ID GNDS_MOUSE Reviewed; 852 AA.
AC Q03385; Q8R077;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Ral guanine nucleotide dissociation stimulator;
DE Short=RalGDS;
DE AltName: Full=Ral guanine nucleotide exchange factor;
DE Short=RalGEF;
GN Name=Ralgds; Synonyms=Rgds;
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 TISSUE=Fibroblast;
RX PubMed=8094051; DOI=10.1002/j.1460-2075.1993.tb05662.x;
RA Albright C.F., Giddings B.W., Liu J., Vito M., Weinberg R.A.;
RT "Characterization of a guanine nucleotide dissociation stimulator for a
RT ras-related GTPase.";
RL EMBO J. 12:339-347(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH OOG1, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=16580637; DOI=10.1016/j.bbrc.2006.03.063;
RA Tsukamoto S., Ihara R., Aizawa A., Kishida S., Kikuchi A., Imai H.,
RA Minami N.;
RT "Oog1, an oocyte-specific protein, interacts with Ras and Ras-signaling
RT proteins during early embryogenesis.";
RL Biochem. Biophys. Res. Commun. 343:1105-1112(2006).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
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).
RN [7]
RP FUNCTION, PHOSPHORYLATION AT TYR-752, AND INTERACTION WITH HRAS.
RX PubMed=27773821; DOI=10.1016/j.bbrc.2016.10.074;
RA Wong R., Feig L.A.;
RT "Tyrosine phosphorylation of RalGDS by c-Met receptor blocks its
RT interaction with Ras.";
RL Biochem. Biophys. Res. Commun. 480:468-473(2016).
CC -!- FUNCTION: Functions as a guanine nucleotide exchange factor (GEF)
CC activating either RalA or RalB GTPases and plays an important role in
CC intracellular transport. Interacts and acts as an effector molecule for
CC R-Ras, H-Ras, K-Ras, and Rap (PubMed:27773821). During bacterial
CC clearance, recognizes 'Lys-33'-linked polyubiquitinated TRAF3 and
CC subsequently mediates assembly of the exocyst complex (By similarity).
CC {ECO:0000250|UniProtKB:Q12967, ECO:0000269|PubMed:27773821}.
CC -!- SUBUNIT: Interacts with RIT1 and RIT2 (By similarity). Interacts with
CC OOG1 (PubMed:16580637). Interacts with TRAF3 (By similarity). Interacts
CC with HRAS (PubMed:27773821). {ECO:0000250|UniProtKB:Q12967,
CC ECO:0000269|PubMed:27773821}.
CC -!- INTERACTION:
CC Q03385; E9Q5G7: Oog1; NbExp=5; IntAct=EBI-923705, EBI-923698;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16580637}. Nucleus
CC {ECO:0000269|PubMed:16580637}. Note=Localizes mainly in the peripheral
CC region of the cytoplasmic membrane in oocytes and in preimplantation
CC embryos until the 8-cell stage. Between the late 1-cell and the early
CC 2-cell stages, nuclear localization becomes stronger. After the 4-cell
CC stage, not detected in the nucleus. {ECO:0000269|PubMed:16580637}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the ovarian oocytes from the primary
CC follicle stage to the antral follicle stage (at protein level).
CC Expressed in preimplantation embryos until the early 2-cell stage,
CC decreasing thereafter. {ECO:0000269|PubMed:16580637}.
CC -!- DOMAIN: The Ras-associating domain interacts with Ras. {ECO:0000250}.
CC -!- PTM: Phosphorylation of Tyr-752 by MET blocks HRAS binding.
CC {ECO:0000269|PubMed:27773821}.
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DR EMBL; L07924; AAA37714.1; -; mRNA.
DR EMBL; AL772249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466542; EDL08385.1; -; Genomic_DNA.
DR EMBL; BC027225; AAH27225.1; -; mRNA.
DR CCDS; CCDS15840.1; -.
DR PIR; S28415; S28415.
DR RefSeq; NP_033084.2; NM_009058.2.
DR AlphaFoldDB; Q03385; -.
DR SMR; Q03385; -.
DR BioGRID; 202878; 1.
DR IntAct; Q03385; 2.
DR STRING; 10090.ENSMUSP00000097812; -.
DR iPTMnet; Q03385; -.
DR PhosphoSitePlus; Q03385; -.
DR MaxQB; Q03385; -.
DR PaxDb; Q03385; -.
DR PRIDE; Q03385; -.
DR ProteomicsDB; 267737; -.
DR DNASU; 19730; -.
DR Ensembl; ENSMUST00000028170; ENSMUSP00000028170; ENSMUSG00000026821.
DR GeneID; 19730; -.
DR KEGG; mmu:19730; -.
DR UCSC; uc008iym.2; mouse.
DR CTD; 5900; -.
DR MGI; MGI:107485; Ralgds.
DR VEuPathDB; HostDB:ENSMUSG00000026821; -.
DR eggNOG; KOG3629; Eukaryota.
DR GeneTree; ENSGT00940000153181; -.
DR HOGENOM; CLU_010252_0_1_1; -.
DR InParanoid; Q03385; -.
DR OMA; EEHFVAW; -.
DR OrthoDB; 940219at2759; -.
DR Reactome; R-MMU-171007; p38MAPK events.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR BioGRID-ORCS; 19730; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Ralgds; mouse.
DR PRO; PR:Q03385; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q03385; protein.
DR Bgee; ENSMUSG00000026821; Expressed in thoracic mammary gland and 236 other tissues.
DR ExpressionAtlas; Q03385; baseline and differential.
DR Genevisible; Q03385; MM.
DR GO; GO:0005903; C:brush border; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030695; F:GTPase regulator activity; ISO:MGI.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 1.
DR Gene3D; 1.10.840.10; -; 1.
DR InterPro; IPR000159; RA_dom.
DR InterPro; IPR015758; RalGDS.
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; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR PANTHER; PTHR23113:SF35; PTHR23113:SF35; 1.
DR Pfam; PF00788; RA; 1.
DR Pfam; PF00617; RasGEF; 1.
DR Pfam; PF00618; RasGEF_N; 1.
DR SMART; SM00314; RA; 1.
DR SMART; SM00147; RasGEF; 1.
DR SMART; SM00229; RasGEFN; 1.
DR SUPFAM; SSF48366; SSF48366; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50200; RA; 1.
DR PROSITE; PS00720; RASGEF; 1.
DR PROSITE; PS50009; RASGEF_CAT; 1.
DR PROSITE; PS50212; RASGEF_NTER; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Guanine-nucleotide releasing factor; Nucleus; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..852
FT /note="Ral guanine nucleotide dissociation stimulator"
FT /id="PRO_0000068878"
FT DOMAIN 57..194
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 324..586
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT DOMAIN 736..823
FT /note="Ras-associating"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00166"
FT REGION 606..627
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 665..711
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 675..711
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 752
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q12967"
FT CONFLICT 357
FT /note="D -> A (in Ref. 1; AAA37714)"
FT /evidence="ECO:0000305"
FT CONFLICT 691
FT /note="S -> T (in Ref. 1; AAA37714)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 852 AA; 94202 MW; 5C6731F7BF3B07B8 CRC64;
MMVDCQSSTQ EIGEELINGV IYSISLRKVQ LHQGATKGQR WLGCENESAL NLYETCKVRT
VKAGTLEKLV EHLVPAFQGS DLSYVTVFLC TYRAFTTTQQ VLDLLFKRYG RCDALTASSR
YGCILPYSSE DGGPQDQLKN AISSILGTWL DQYSEDFCQP PDFPCLKQLV AYVQLNMPGS
DLERRAHLLL AQLEDLEPSE AESEALSPAP VLSLKPASQL EPALLLTPSQ VVTSTPVREP
AAAPVPVLAS SPVVAPAPEL EPVPEPPQEP EPSLALAPEL EPAVSQSLEL ESAPVPTPAL
EPSWSLPEAT ENGLTEKPHL LLFPPDLVAE QFTLMDAELF KKVVPYHCLG SIWSQRDKKG
KEHLAPTIRA TVAQFNNVAN CVITTCLGDQ SMKAPDRARV VEHWIEVARE CRALKNFSSL
YAILSALQSN AIHRLKKTWE EVSRDSFRVF QKLSEIFSDE NNYSLSRELL IKEGTSKFAT
LEMNPRRAQR RQKETGVIQG TVPYLGTFLT DLVMLDTAMK DYLYGRLINF EKRRKEFEVI
AQIKLLQSAC NNYSIAPEEH FGTWFRAMER LSEAESYTLS CELEPPSESA SNTLRSKKST
AIVKRWSDRQ APSTELSTSS SAHSKSCDQL RCSPYLGSGD ITDALSVHSA GSSSSDVEEI
NMSFVPESPD GQEKKFWESA SQSSPETSGI SSASSSTSSS SASTTPVSTT RTHKRSVSGV
CSYSSSLPLY NQQVGDCCII RVSLDVDNGN MYKSILVTSQ DKAPTVIRKA MDKHNLDEDE
PEDYELVQII SEDHKLKIPE NANVFYAMNS TANYDFILKK RTFTKGAKVK HGASSTLPRM
KQKGLRIAKG IF
