RPGF5_HUMAN
ID RPGF5_HUMAN Reviewed; 580 AA.
AC Q92565; A4D140; Q8IXU5;
DT 20-JUN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Rap guanine nucleotide exchange factor 5;
DE AltName: Full=Guanine nucleotide exchange factor for Rap1;
DE AltName: Full=M-Ras-regulated Rap GEF;
DE Short=MR-GEF;
DE AltName: Full=Related to Epac;
DE Short=Repac;
GN Name=RAPGEF5; Synonyms=GFR, KIAA0277, MRGEF;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9039502; DOI=10.1093/dnares/3.5.321;
RA Nagase T., Seki N., Ishikawa K., Ohira M., Kawarabayasi Y., Ohara O.,
RA Tanaka A., Kotani H., Miyajima N., Nomura N.;
RT "Prediction of the coding sequences of unidentified human genes. VI. The
RT coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of
RT cDNA clones from cell line KG-1 and brain.";
RL DNA Res. 3:321-329(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
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 [4]
RP CHARACTERIZATION.
RX PubMed=10486569; DOI=10.1016/s0014-5793(99)01012-1;
RA Ichiba T., Hoshi Y., Eto Y., Tajima N., Kuraishi Y.;
RT "Characterization of GFR, a novel guanine nucleotide exchange factor for
RT Rap1.";
RL FEBS Lett. 457:85-89(1999).
RN [5]
RP FUNCTION.
RX PubMed=10777494; DOI=10.1074/jbc.m001113200;
RA de Rooij J., Rehmann H., van Triest M., Cool R.H., Wittinghofer A.,
RA Bos J.L.;
RT "Mechanism of regulation of the Epac family of cAMP-dependent RapGEFs.";
RL J. Biol. Chem. 275:20829-20836(2000).
RN [6]
RP FUNCTION AS A MRAS EFFECTOR.
RX PubMed=10934204; DOI=10.1074/jbc.m005327200;
RA Rebhun J.F., Castro A.F., Quilliam L.A.;
RT "Identification of guanine nucleotide exchange factors (GEFs) for the Rap1
RT GTPase. Regulation of MR-GEF by M-Ras-GTP interaction.";
RL J. Biol. Chem. 275:34901-34908(2000).
RN [7]
RP STRUCTURE BY NMR OF 241-331.
RG RIKEN structural genomics initiative (RSGI);
RT "RA domain of guanine nucleotide exchange factor for RAP1.";
RL Submitted (NOV-2004) to the PDB data bank.
CC -!- FUNCTION: Guanine nucleotide exchange factor (GEF) for RAP1A, RAP2A and
CC MRAS/M-Ras-GTP. Its association with MRAS inhibits Rap1 activation.
CC {ECO:0000269|PubMed:10777494, ECO:0000269|PubMed:10934204}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92565-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92565-2; Sequence=VSP_007616;
CC -!- TISSUE SPECIFICITY: Widely expressed with highest levels in brain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA13406.2; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D87467; BAA13406.2; ALT_INIT; mRNA.
DR EMBL; CH236948; EAL24270.1; -; Genomic_DNA.
DR EMBL; BC039203; AAH39203.1; -; mRNA.
DR RefSeq; NP_036426.3; NM_012294.3.
DR PDB; 1WGY; NMR; -; A=241-331.
DR PDBsum; 1WGY; -.
DR AlphaFoldDB; Q92565; -.
DR BMRB; Q92565; -.
DR SMR; Q92565; -.
DR BioGRID; 115116; 40.
DR IntAct; Q92565; 25.
DR STRING; 9606.ENSP00000343656; -.
DR iPTMnet; Q92565; -.
DR PhosphoSitePlus; Q92565; -.
DR BioMuta; RAPGEF5; -.
DR DMDM; 32171396; -.
DR jPOST; Q92565; -.
DR MassIVE; Q92565; -.
DR MaxQB; Q92565; -.
DR PaxDb; Q92565; -.
DR PeptideAtlas; Q92565; -.
DR PRIDE; Q92565; -.
DR ProteomicsDB; 75322; -. [Q92565-1]
DR ProteomicsDB; 75323; -. [Q92565-2]
DR Antibodypedia; 25491; 245 antibodies from 29 providers.
DR DNASU; 9771; -.
DR Ensembl; ENST00000401957.6; ENSP00000384044.1; ENSG00000136237.19. [Q92565-1]
DR Ensembl; ENST00000620335.4; ENSP00000479340.1; ENSG00000136237.19. [Q92565-2]
DR GeneID; 9771; -.
DR KEGG; hsa:9771; -.
DR UCSC; uc011jym.2; human. [Q92565-1]
DR CTD; 9771; -.
DR DisGeNET; 9771; -.
DR GeneCards; RAPGEF5; -.
DR HGNC; HGNC:16862; RAPGEF5.
DR HPA; ENSG00000136237; Group enriched (brain, parathyroid gland).
DR MIM; 609527; gene.
DR neXtProt; NX_Q92565; -.
DR OpenTargets; ENSG00000136237; -.
DR PharmGKB; PA134902361; -.
DR VEuPathDB; HostDB:ENSG00000136237; -.
DR eggNOG; KOG2378; Eukaryota.
DR GeneTree; ENSGT00940000155137; -.
DR HOGENOM; CLU_028002_1_0_1; -.
DR InParanoid; Q92565; -.
DR OrthoDB; 143470at2759; -.
DR PhylomeDB; Q92565; -.
DR PathwayCommons; Q92565; -.
DR SignaLink; Q92565; -.
DR SIGNOR; Q92565; -.
DR BioGRID-ORCS; 9771; 6 hits in 1036 CRISPR screens.
DR ChiTaRS; RAPGEF5; human.
DR EvolutionaryTrace; Q92565; -.
DR GeneWiki; RAPGEF5; -.
DR GenomeRNAi; 9771; -.
DR Pharos; Q92565; Tbio.
DR PRO; PR:Q92565; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q92565; protein.
DR Bgee; ENSG00000136237; Expressed in inferior vagus X ganglion and 196 other tissues.
DR ExpressionAtlas; Q92565; baseline and differential.
DR Genevisible; Q92565; HS.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0030742; F:GTP-dependent protein binding; IPI:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0007399; P:nervous system development; NAS:UniProtKB.
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:0007264; P:small GTPase mediated signal transduction; NAS:UniProtKB.
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; 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 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 SUPFAM; SSF54236; SSF54236; 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 3D-structure; Alternative splicing; Guanine-nucleotide releasing factor;
KW Nucleus; Reference proteome.
FT CHAIN 1..580
FT /note="Rap guanine nucleotide exchange factor 5"
FT /id="PRO_0000068873"
FT DOMAIN 68..201
FT /note="N-terminal Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00135"
FT DOMAIN 345..579
FT /note="Ras-GEF"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00168"
FT VAR_SEQ 270..405
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_007616"
FT CONFLICT 497
FT /note="M -> V (in Ref. 3; AAH39203)"
FT /evidence="ECO:0000305"
FT STRAND 245..248
FT /evidence="ECO:0007829|PDB:1WGY"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:1WGY"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:1WGY"
FT HELIX 266..276
FT /evidence="ECO:0007829|PDB:1WGY"
FT HELIX 280..282
FT /evidence="ECO:0007829|PDB:1WGY"
FT STRAND 283..288
FT /evidence="ECO:0007829|PDB:1WGY"
FT STRAND 301..304
FT /evidence="ECO:0007829|PDB:1WGY"
FT STRAND 313..318
FT /evidence="ECO:0007829|PDB:1WGY"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:1WGY"
SQ SEQUENCE 580 AA; 67733 MW; 732FB7AA11DFDA1C CRC64;
MGSSRLRVFD PHLERKDSAA ALSDRELPLP TFDVPYFKYI DEEDEDDEWS SRSQSSTEDD
SVDSLLSDRY VVVSGTPEKI LEHLLNDLHL EEVQDKETET LLDDFLLTYT VFMTTDDLCQ
ALLRHYSAKK YQGKEENSDV PRRKRKVLHL VSQWIALYKD WLPEDEHSKM FLKTIYRNVL
DDVYEYPILE KELKEFQKIL GMHRRHTVDE YSPQKKNKAL FHQFSLKENW LQHRGTVTET
EEIFCHVYIT EHSYVSVKAK VSSIAQEILK VVAEKIQYAE EDLALVAITF SGEKHELQPN
DLVISKSLEA SGRIYVYRKD LADTLNPFAE NEESQQRSMR ILGMNTWDLA LELMNFDWSL
FNSIHEQELI YFTFSRQGSG EHTANLSLLL QRCNEVQLWV ATEILLCSQL GKRVQLVKKF
IKIAAHCKAQ RNLNSFFAIV MGLNTASVSR LSQTWEKIPG KFKKLFSELE SLTDPSLNHK
AYRDAFKKMK PPKIPFMPLL LKDVTFIHEG NKTFLDNLVN FEKLHMIADT VRTLRHCRTN
QFGDLSPKEH QELKSYVNHL YVIDSQQALF ELSHRIEPRV
