RGRF2_DANRE
ID RGRF2_DANRE Reviewed; 1244 AA.
AC A2CEA7; B0S6A1;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-FEB-2007, sequence version 1.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Ras-specific guanine nucleotide-releasing factor 2;
DE Short=Ras-GRF2;
DE AltName: Full=Ras guanine nucleotide exchange factor 2;
GN Name=rasgrf2; ORFNames=si:ch211-194b21.1, si:dkey-56d12.3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
CC -!- FUNCTION: Functions as a calcium-regulated nucleotide exchange factor
CC activating both Ras and rac1 through the exchange of bound GDP for GTP.
CC May function in synaptic plasticity.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Endoplasmic
CC reticulum membrane {ECO:0000250}; Peripheral membrane protein
CC {ECO:0000250}.
CC -!- DOMAIN: The Ras-GEF domain and the N-terminal Ras-GEF domain mediate
CC Ras activation. {ECO:0000250}.
CC -!- DOMAIN: The IQ domain is dispensable for the Ras-GEF activity.
CC {ECO:0000250}.
CC -!- DOMAIN: The DH (DBL-homology) domain is required for rac1 activation.
CC {ECO:0000250}.
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DR EMBL; BX470070; CAQ13408.1; -; Genomic_DNA.
DR EMBL; CR848716; CAQ13408.1; JOINED; Genomic_DNA.
DR EMBL; CR388055; CAM16158.1; -; Genomic_DNA.
DR RefSeq; NP_001121705.1; NM_001128233.1.
DR AlphaFoldDB; A2CEA7; -.
DR SMR; A2CEA7; -.
DR STRING; 7955.ENSDARP00000077785; -.
DR PaxDb; A2CEA7; -.
DR PRIDE; A2CEA7; -.
DR Ensembl; ENSDART00000083350; ENSDARP00000077785; ENSDARG00000002816.
DR GeneID; 553520; -.
DR KEGG; dre:553520; -.
DR CTD; 553520; -.
DR ZFIN; ZDB-GENE-060504-1; rasgrf2b.
DR eggNOG; KOG3417; Eukaryota.
DR GeneTree; ENSGT00940000155679; -.
DR HOGENOM; CLU_003405_0_1_1; -.
DR InParanoid; A2CEA7; -.
DR OMA; WMKVDKM; -.
DR OrthoDB; 70788at2759; -.
DR PhylomeDB; A2CEA7; -.
DR TreeFam; TF317296; -.
DR Reactome; R-DRE-193648; NRAGE signals death through JNK.
DR Reactome; R-DRE-416482; G alpha (12/13) signalling events.
DR Reactome; R-DRE-5673001; RAF/MAP kinase cascade.
DR Reactome; R-DRE-8980692; RHOA GTPase cycle.
DR Reactome; R-DRE-9013148; CDC42 GTPase cycle.
DR Reactome; R-DRE-9013149; RAC1 GTPase cycle.
DR PRO; PR:A2CEA7; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 5.
DR Bgee; ENSDARG00000002816; Expressed in retina and 3 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
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 GO; GO:0035023; P:regulation of Rho protein signal transduction; IEA:InterPro.
DR CDD; cd00155; RasGEF; 1.
DR CDD; cd06224; REM; 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; 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; IPR030744; RasGRF2.
DR PANTHER; PTHR23113; PTHR23113; 1.
DR PANTHER; PTHR23113:SF187; PTHR23113:SF187; 1.
DR Pfam; PF00169; PH; 1.
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; 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 3: Inferred from homology;
KW Calcium; Calmodulin-binding; Cell membrane; Coiled coil; Cytoplasm;
KW Endoplasmic reticulum; Guanine-nucleotide releasing factor; Membrane;
KW Reference proteome; Repeat.
FT CHAIN 1..1244
FT /note="Ras-specific guanine nucleotide-releasing factor 2"
FT /id="PRO_0000312866"
FT DOMAIN 22..129
FT /note="PH 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 201..230
FT /note="IQ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00116"
FT DOMAIN 239..425
FT /note="DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00062"
FT DOMAIN 466..584
FT /note="PH 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 631..745
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 704..743
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 759..814
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 843..879
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 147..189
FT /evidence="ECO:0000255"
FT COMPBIAS 724..743
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 759..806
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 864..879
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 1244 AA; 141587 MW; 7C69A7FBFF358C71 CRC64;
MQKSVRYNEG HALFLSVIAR KEGTKRGYLS KKTTENSKWH EKFFALYQNV LFYFDTDQSA
RPSGIYLLEG CTCERVPALK VSTVGKDALD KLQYFLVVFG HDGQKPLELR TEEESDCDEW
VEAIQQASYS DIIIEREVLM QKYIHLVQIV ETEKVAANQL RTQLEDQDTE IERLKAEIIA
LNKTKERMRP YHVFQEEEDP DIKKIKKVQS FMRGWLCRRK WKIIVQDYIC SPHAESMRKR
NQIVFNMVEA ETEYVHQLSI LVNCFLRPLR MAASSKKPPI SHDDVSSIFL NSETIMFLHE
IFHQGLKARI ANWPTLVLAD LFDILLPMLN IYQEFVRNHQ YSLQVLANCK QNRDFDKLLK
QYESNAACEG RMLETFLTYP MFQIPRYIIT LHELLAHTPH EHVERKSLEF AKSKLEELSR
VMHDEVSDTE NIRKNLAIER MIVEGCDILL DTSQTFVRQG SLIQLPSVER GKLSKVRLGS
LSLKKEGERQ CFLFTKHFLI CTRSSGGKLH LLKQGGVLSL IECTLIEEPD ANDEDAKNSG
QVFGHLDFKI VVEPSDAPAF TVVLLAPSRQ EKAAWTSDIS QCIDNIRCNG LMTSVFEENS
KVTVPHMIKS DARLHKDDVD ICFSKTLNSC KVPQIRYASV ERLLERLTDL RFLSIDFLNT
FLHTYRIFTT ATVVMEKLAD IYKKPFTSIP VRSLELFFAT NQNNRSGDHV NDKSPRLCRK
FSSPPPLSIS SRTSSPVRTR KLSLNSPIGS KVGILDLSTT SSSAASSPTS ANPTISPPPS
NNNNNSKPPL DLSRGQSPSS PEQSPGALDD NAEVPRIDAL CGKLRRSIRR AVLESVSLDK
FIPESPQASE PGEISPCRSP STPRHLRYRQ SGVQTAENSR CSVSPASAFA IATAAAGHSS
PPVFNNSERT CDKEFIIRRA ATNRVLNVLR HWVSKHSQDF EMNGELKMGV ICLLEEVLRD
PDLLPQERKA TANILSALSQ DDQDDAQLKI EDILQMAECP KAECFESLSA MEIAEQITLL
DHIVFRSIPY EEFLGQGWMK TDKTERTPYI MKTSQHFNDM SNLVASQIMS HTDVGSRAGS
IEKWVAVADI CRCLNNYNGV LEITSALNRS AIYRLKKTWA KVCKQTKALM DKLQKTVSSE
GRFKNLRETL KNCNPPCVPY LGMYLTDLAF IEEGTPNFTE EGLVNFSKMR MISHIIREIR
QFQQTPYRIE HQPKVTQYLL DKTLIMDEDT LYDLSLKIEP RLPA