ID   GEFR_DICDI              Reviewed;        1721 AA.
AC   Q8SSQ0; Q555R4;
DT   22-SEP-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   25-MAY-2022, entry version 114.
DE   RecName: Full=Ras guanine nucleotide exchange factor R;
DE   AltName: Full=RasGEF domain-containing protein R;
GN   Name=gefR; Synonyms=rasGEFR; ORFNames=DDB_G0274605;
OS   Dictyostelium discoideum (Slime mold).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RC   STRAIN=AX4;
RX   PubMed=16086850; DOI=10.1186/gb-2005-6-8-r68;
RA   Wilkins A., Szafranski K., Fraser D.J., Bakthavatsalam D., Mueller R.,
RA   Fisher P.R., Gloeckner G., Eichinger L., Noegel A.A., Insall R.H.;
RT   "The Dictyostelium genome encodes numerous RasGEFs with multiple biological
RT   roles.";
RL   Genome Biol. 6:R68.1-R68.12(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=12097910; DOI=10.1038/nature00847;
RA   Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA   Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA   Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA   Noegel A.A.;
RT   "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL   Nature 418:79-85(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=15875012; DOI=10.1038/nature03481;
RA   Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA   Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA   Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA   Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA   Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA   Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA   Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA   Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA   Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA   Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA   Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA   Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA   Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA   Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA   Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA   Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA   Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT   "The genome of the social amoeba Dictyostelium discoideum.";
RL   Nature 435:43-57(2005).
RN   [4]
RP   NOMENCLATURE.
RC   STRAIN=AX3;
RX   PubMed=8793298; DOI=10.1016/s0960-9822(09)00453-9;
RA   Insall R.H., Borleis J., Devreotes P.N.;
RT   "The aimless RasGEF is required for processing of chemotactic signals
RT   through G-protein-coupled receptors in Dictyostelium.";
RL   Curr. Biol. 6:719-729(1996).
RN   [5]
RP   PHOSPHORYLATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=15352238; DOI=10.1002/pmic.200300788;
RA   Secko D.M., Insall R.H., Spiegelman G.B., Weeks G.;
RT   "The identification of Dictyostelium phosphoproteins altered in response to
RT   the activation of RasG.";
RL   Proteomics 4:2629-2639(2004).
RN   [6]
RP   FUNCTION.
RX   PubMed=17380187; DOI=10.1038/sj.embor.7400936;
RA   Kae H., Kortholt A., Rehmann H., Insall R.H., Van Haastert P.J.,
RA   Spiegelman G.B., Weeks G.;
RT   "Cyclic AMP signalling in Dictyostelium: G-proteins activate separate Ras
RT   pathways using specific RasGEFs.";
RL   EMBO Rep. 8:477-482(2007).
CC   -!- FUNCTION: Promotes the exchange of Ras-bound GDP by GTP. May also play
CC       a role in the activation of rasG. {ECO:0000269|PubMed:17380187}.
CC   -!- DEVELOPMENTAL STAGE: Expressed during development; especially between
CC       8-18 hours of development. Expressed (at protein level).
CC       {ECO:0000269|PubMed:16086850}.
CC   -!- PTM: Phosphorylated on threonine residues.
CC       {ECO:0000269|PubMed:15352238}.
CC   -!- DISRUPTION PHENOTYPE: Absence of the phosphoprotein gefR.
CC       {ECO:0000269|PubMed:15352238}.
CC   -!- CAUTION: Was originally (PubMed:8793298) named RasGEFA, as it was the
CC       second RasGEF, after aimless, to be identified there. When aimless,
CC       aleA, was renamed gefA to make the nomenclature consistent and
CC       systematic, RasGEFA was renamed gefR. {ECO:0000305|PubMed:8793298}.
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DR   EMBL; AY160106; AAN46886.1; -; Genomic_DNA.
DR   EMBL; AAFI02000012; EAL70195.1; -; Genomic_DNA.
DR   RefSeq; XP_643999.1; XM_638907.1.
DR   AlphaFoldDB; Q8SSQ0; -.
DR   SMR; Q8SSQ0; -.
DR   STRING; 44689.DDB0185198; -.
DR   PaxDb; Q8SSQ0; -.
DR   PRIDE; Q8SSQ0; -.
DR   EnsemblProtists; EAL70195; EAL70195; DDB_G0274605.
DR   GeneID; 8619425; -.
DR   KEGG; ddi:DDB_G0274605; -.
DR   dictyBase; DDB_G0274605; gefR.
DR   eggNOG; KOG3417; Eukaryota.
DR   HOGENOM; CLU_240268_0_0_1; -.
DR   InParanoid; Q8SSQ0; -.
DR   OMA; QKRELIC; -.
DR   Reactome; R-DDI-1169092; Activation of RAS in B cells.
DR   Reactome; R-DDI-171007; p38MAPK events.
DR   Reactome; R-DDI-193648; NRAGE signals death through JNK.
DR   Reactome; R-DDI-354192; Integrin signaling.
DR   Reactome; R-DDI-381676; Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
DR   Reactome; R-DDI-392517; Rap1 signalling.
DR   Reactome; R-DDI-5673001; RAF/MAP kinase cascade.
DR   Reactome; R-DDI-9013148; CDC42 GTPase cycle.
DR   Reactome; R-DDI-9013149; RAC1 GTPase cycle.
DR   PRO; PR:Q8SSQ0; -.
DR   Proteomes; UP000002195; Chromosome 2.
DR   GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR   GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:dictyBase.
DR   GO; GO:0043547; P:positive regulation of GTPase activity; IBA:GO_Central.
DR   GO; GO:0007265; P:Ras protein signal transduction; IDA:dictyBase.
DR   GO; GO:1903013; P:response to differentiation-inducing factor 1; HDA:dictyBase.
DR   CDD; cd00155; RasGEF; 1.
DR   CDD; cd06224; REM; 1.
DR   Gene3D; 1.10.840.10; -; 1.
DR   InterPro; IPR008937; Ras-like_GEF.
DR   InterPro; IPR000651; Ras-like_Gua-exchang_fac_N.
DR   InterPro; IPR023578; Ras_GEF_dom_sf.
DR   InterPro; IPR001895; RASGEF_cat_dom.
DR   InterPro; IPR036964; RASGEF_cat_dom_sf.
DR   PANTHER; PTHR23113; PTHR23113; 1.
DR   Pfam; PF00617; RasGEF; 1.
DR   Pfam; PF00618; RasGEF_N; 1.
DR   SMART; SM00147; RasGEF; 1.
DR   SMART; SM00229; RasGEFN; 1.
DR   SUPFAM; SSF48366; SSF48366; 1.
DR   PROSITE; PS50009; RASGEF_CAT; 1.
DR   PROSITE; PS50212; RASGEF_NTER; 1.
PE   1: Evidence at protein level;
KW   Coiled coil; Guanine-nucleotide releasing factor; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..1721
FT                   /note="Ras guanine nucleotide exchange factor R"
FT                   /id="PRO_0000384476"
FT   DOMAIN          1291..1411
FT                   /note="N-terminal Ras-GEF"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT   DOMAIN          1447..1676
FT                   /note="Ras-GEF"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT   REGION          213..232
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          445..515
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          551..701
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          716..766
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          797..837
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          929..981
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COILED          148..279
FT                   /evidence="ECO:0000255"
FT   COILED          802..831
FT                   /evidence="ECO:0000255"
FT   COMPBIAS        215..232
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        451..515
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        551..582
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        583..599
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        604..691
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        720..766
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        929..980
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   1721 AA;  193133 MW;  68EA5A422CAFC8EC CRC64;
     MKEEEIANLG PQEYFNYLEG INKKIIIELK TVANIDTAKD TDNLQNILIE SSLALEHNIR
     NLLYFVDKCP ISYDQIVHYH SHFKEVVKIF FQVCQDLIKA AQALILNSCD YLTTSNFAKC
     RGEAIKTIKN TMATCSNFEK LYYNPDLQLE DEVDLVHQQQ QKEQEQQQKE QEQYEQEQLI
     LKQLKEQELK KQQEQQQQQQ QQQQQQQQQQ QQQQQKHQEE KEKNDQKEKE EKLKKQLLAE
     QQKQKQEELE RQQQQLQQQQ QLLQQQQQLL QQQQQQQRSD PIIIPPITLK TSQSDLLSGG
     LSPKVNSPGS PNLGKFTESA ERVANFDRGT ANIILNMNKI KEISLSGDSE QAPEIVTAAR
     IISENIAIIS KELRYKTLGT NLSEHFVSVV QVARLAIKNK SDQFYQDQLE LAIEKFNDTM
     RKIIYSVKSI SKSSMNLRQF GVDESSLGRS PVVSPEKSIS PSFTSSTSER ILSHEIKNHN
     NNNNNYNNSS TNNLQTSFST PSLSSNHSQQ PNQQPLQSPL LINQLQSTSS SSSSSSSNLS
     NSLNSIQLPQ ATTTTTTATS PSTSTSTSTS TSPNSSSLSI SDQDKQLKRK EKQHQIVIPK
     DVKDSVANQQ QQQQQQQNGT TSPRNNESSV TAATTTTTST TASITTNVNT IPNFPPNKQL
     PATPTTGTPS TSTPTPQTPT STSQNDKQNE NNNKENFVDK QKTLGKLFSK FVHKKRTPLP
     GFDSSNSSSP SNNSNTTNSS SHSSTNSSPM ETSPGVESPK ITKSPSQNNI LVDSLDIGSD
     NQQQQQDKLT TTTSTTTITI NNNNNNNNNN NNNNNNNNNN IQQQQQQQQQ IPTTPNKLSN
     SIAMNSSNRL MTPKKERSFT IGLVSGKHSC VVVETPKSKK LFQHESAKQI LSIISMNFPS
     FEKEFQMQNS EVISNIIEQI GNVIKNYHDE VSESSSSSSS STTSPNNINT PSDCSPILNS
     ENSKDSHNLS SINNSSYDPV SPALRKMYEN GSYDSKEHSR SSIQSKITRK LGTIRKKGPS
     PFNMLLNSST GSLSSLYLDQ LNGGNGDSSS SSSSSYNLVG GSGISGYDNQ NEIDASEHLV
     STSSLFTEEA IELVSKCFEA SIIVNHSGGT SSEIKALFSS TLDHLESMLQ SSVNFGKIDP
     SSFCMTFLKN IRQHIPTMKS KGGKCDPTLV TAATKLFRHT ILSNLDKSIH SLCHSVRVLA
     IQMTIIVISI SAKPWDISSQ LQLFASAKSF IDSLVSLLDA VENKIYISTN TNIQDDVEVP
     TIDDTEDTNI WEEADSPLTF GWISDEGSKT GRYVPKAGTL NKLISALTQD NKHDISRYTK
     TFLLTYQSFT NPWKLMEKLI QRYNVPLDEK PDVRATTQLR VVSFMQTWIE RNFNDFDDQL
     IGQLKEFRTR LLMDNNNDLA VILGGLIKKK EAERSLSKER STNHLTFPEL MIPDGQKSPT
     ALFLLLNESE IARQLTLIDF NIFSKIQPTE LLDQSWNKDS LKFKSPNVIE MINRANKFSF
     WVSSQILWQE DIEERVKVFE KFILISKYLR EMNNFNTLLA IFTGLNTAPI LRLKKTFALL
     SPNSLSIYNS LEKLMNSSGS YKNYRSVSKN PPLLPYLPVI LSDLTFMEDG NPDKINNLIN
     FQKRELICRV ISEVQQCQQQ TKYEFPVVEP IHTLLTELPS STPSELYQLS LIREPRETNQ
     SNANSSISSG SNFLSNSSNH NIGNNNGFDT LKKYYKSSNN N