RAD_MOUSE
ID RAD_MOUSE Reviewed; 308 AA.
AC O88667;
DT 07-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 131.
DE RecName: Full=GTP-binding protein RAD;
GN Name=Rrad;
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].
RA Finlin B.S., Andres D.A.;
RT "Cloning of the mouse Rad gene.";
RL Submitted (AUG-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18056528; DOI=10.1161/circulationaha.107.707257;
RA Chang L., Zhang J., Tseng Y.-H., Xie C.-Q., Ilany J., Bruning J.C., Sun Z.,
RA Zhu X., Cui T., Youker K.A., Yang Q., Day S.M., Kahn C.R., Chen Y.E.;
RT "Rad GTPase deficiency leads to cardiac hypertrophy.";
RL Circulation 116:2976-2983(2007).
RN [3]
RP FUNCTION, INTERACTION WITH CACNB2, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP SER-105.
RX PubMed=17525370; DOI=10.1161/circresaha.106.146399;
RA Yada H., Murata M., Shimoda K., Yuasa S., Kawaguchi H., Ieda M., Adachi T.,
RA Murata M., Ogawa S., Fukuda K.;
RT "Dominant negative suppression of Rad leads to QT prolongation and causes
RT ventricular arrhythmias via modulation of L-type Ca2+ channels in the
RT heart.";
RL Circ. Res. 101:69-77(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart;
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 [5]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-24, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: May play an important role in cardiac antiarrhythmia via the
CC strong suppression of voltage-gated L-type Ca(2+) currents. Regulates
CC voltage-dependent L-type calcium channel subunit alpha-1C trafficking
CC to the cell membrane. Inhibits cardiac hypertrophy through the
CC calmodulin-dependent kinase II (CaMKII) pathway. Inhibits
CC phosphorylation and activation of CAMK2D. {ECO:0000269|PubMed:17525370,
CC ECO:0000269|PubMed:18056528}.
CC -!- SUBUNIT: Interacts with Calmodulin preferentially in the inactive, GDP-
CC bound form. Interacts with CAMK2D (By similarity). Interacts with
CC CACNB2. Interaction with CACNB2 regulates the trafficking of CACNA1C to
CC the cell membrane. {ECO:0000250, ECO:0000269|PubMed:17525370}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17525370}.
CC -!- DISRUPTION PHENOTYPE: Mice show increased susceptibility to thoracic
CC transverse aortic constriction (TAC)-induced cardiac hypertrophy. TAC-
CC induced CAMKII phosphorylation in the heart is also significantly
CC increased. {ECO:0000269|PubMed:18056528}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. RGK family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF084466; AAC33133.1; -; mRNA.
DR AlphaFoldDB; O88667; -.
DR SMR; O88667; -.
DR IntAct; O88667; 1.
DR MINT; O88667; -.
DR STRING; 10090.ENSMUSP00000034351; -.
DR iPTMnet; O88667; -.
DR PhosphoSitePlus; O88667; -.
DR EPD; O88667; -.
DR MaxQB; O88667; -.
DR PaxDb; O88667; -.
DR PRIDE; O88667; -.
DR ProteomicsDB; 255075; -.
DR MGI; MGI:1930943; Rrad.
DR eggNOG; KOG0395; Eukaryota.
DR InParanoid; O88667; -.
DR PhylomeDB; O88667; -.
DR PRO; PR:O88667; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O88667; protein.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005246; F:calcium channel regulator activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; IEA:InterPro.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:1901842; P:negative regulation of high voltage-gated calcium channel activity; IEA:InterPro.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR028869; RAD.
DR InterPro; IPR017358; RGK.
DR InterPro; IPR001806; Small_GTPase.
DR PANTHER; PTHR45775:SF3; PTHR45775:SF3; 1.
DR Pfam; PF00071; Ras; 1.
DR PIRSF; PIRSF038017; GTP-binding_GEM; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW Calmodulin-binding; Cell membrane; GTP-binding; Membrane; Methylation;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..308
FT /note="GTP-binding protein RAD"
FT /id="PRO_0000122479"
FT REGION 1..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..297
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 58..86
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 98..105
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 203..206
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT MOD_RES 24
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MUTAGEN 105
FT /note="S->A: Loss of interaction with CACNB2. QT
FT prolongation and ventricular arrhythmias, caused by the
FT augmentation of L-type Ca(2+) channels in the heart."
FT /evidence="ECO:0000269|PubMed:17525370"
SQ SEQUENCE 308 AA; 33279 MW; 698F0A3BCE605D53 CRC64;
MTLNGGSGAS GSRGAGGRER DRRRGSTPWG PAPPLHRRSM PVDERDLQAA LAPGSLATTA
AGTRTQGQRL DWPEGSSDSL SSGGSGSEEG VYKVLLLGAP GVGKSALARI FGGIEDGPEA
EAAGHTYDRS ITVDGEEASL LVYDIWEEDG GCWLPGHCMA MGDAYVIVYS ITDKGSFEKA
SELRVQLRRA RQTDDVPIIL VGNKSDLVRS REVSVDEGRA CAVVFDCKFI ETSAALHHNV
QALFEGVVRQ IRLRRDSKED NARRQAGTRR RESLGKKAKR FLGRIVARNS RKMAFRAKSK
SCHDLSVL
