RAD_HUMAN
ID RAD_HUMAN Reviewed; 308 AA.
AC P55042; Q96F39;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2003, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=GTP-binding protein RAD;
DE AltName: Full=RAD1;
DE AltName: Full=Ras associated with diabetes;
GN Name=RRAD; Synonyms=RAD;
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 [MRNA].
RC TISSUE=Skeletal muscle;
RX PubMed=8248782; DOI=10.1126/science.8248782;
RA Reynet C., Kahn C.R.;
RT "Rad: a member of the Ras family overexpressed in muscle of type II
RT diabetic humans.";
RL Science 262:1441-1444(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Placenta, and Retina;
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 [3]
RP INTERACTION WITH CALMODULIN.
RX PubMed=9115241; DOI=10.1074/jbc.272.18.11832;
RA Moyers J.S., Bilan P.J., Zhu J., Kahn C.R.;
RT "Rad and Rad-related GTPases interact with calmodulin and calmodulin-
RT dependent protein kinase II.";
RL J. Biol. Chem. 272:11832-11839(1997).
RN [4]
RP FUNCTION, INDUCTION, TISSUE SPECIFICITY, AND INTERACTION WITH CAMK2D AND
RP CALMODULIN.
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).
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 (By similarity). Inhibits cardiac hypertrophy
CC through the calmodulin-dependent kinase II (CaMKII) pathway. Inhibits
CC phosphorylation and activation of CAMK2D. {ECO:0000250,
CC ECO:0000269|PubMed:18056528}.
CC -!- SUBUNIT: Interacts with calmodulin preferentially in the inactive, GDP-
CC bound form. Binds CAMKII which is capable of phosphorylating RAD in
CC vitro. Interacts with CAMK2D and CACNB2. Interaction with CACNB2
CC regulates the trafficking of CACNA1C to the cell membrane (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P55042; O95273: CCNDBP1; NbExp=5; IntAct=EBI-3911502, EBI-748961;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Most abundantly expressed in the heart. Also found
CC in the skeletal muscle and lung. Lesser amounts in placenta and kidney.
CC Also detected in adipose tissue. Overexpressed in muscle of type II
CC diabetic humans. {ECO:0000269|PubMed:18056528}.
CC -!- INDUCTION: Down-regulated in failing hearts.
CC {ECO:0000269|PubMed:18056528}.
CC -!- SIMILARITY: Belongs to the small GTPase superfamily. RGK family.
CC {ECO:0000305}.
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DR EMBL; L24564; AAA36540.1; -; mRNA.
DR EMBL; BC011645; AAH11645.1; -; mRNA.
DR EMBL; BC057815; AAH57815.1; -; mRNA.
DR CCDS; CCDS10824.1; -.
DR PIR; A49334; A49334.
DR RefSeq; NP_001122322.1; NM_001128850.1.
DR RefSeq; NP_004156.1; NM_004165.2.
DR PDB; 2DPX; X-ray; 1.80 A; A/B=87-258.
DR PDB; 2GJS; X-ray; 1.90 A; A/B=87-260.
DR PDB; 3Q72; X-ray; 1.66 A; A/B=90-255.
DR PDB; 3Q7P; X-ray; 2.50 A; A/B=90-255.
DR PDB; 3Q7Q; X-ray; 2.30 A; A/B=90-255.
DR PDBsum; 2DPX; -.
DR PDBsum; 2GJS; -.
DR PDBsum; 3Q72; -.
DR PDBsum; 3Q7P; -.
DR PDBsum; 3Q7Q; -.
DR AlphaFoldDB; P55042; -.
DR SMR; P55042; -.
DR BioGRID; 112150; 27.
DR IntAct; P55042; 4.
DR STRING; 9606.ENSP00000299759; -.
DR iPTMnet; P55042; -.
DR PhosphoSitePlus; P55042; -.
DR BioMuta; RRAD; -.
DR DMDM; 38258885; -.
DR jPOST; P55042; -.
DR MassIVE; P55042; -.
DR MaxQB; P55042; -.
DR PaxDb; P55042; -.
DR PeptideAtlas; P55042; -.
DR PRIDE; P55042; -.
DR ProteomicsDB; 56766; -.
DR TopDownProteomics; P55042; -.
DR Antibodypedia; 44221; 171 antibodies from 31 providers.
DR DNASU; 6236; -.
DR Ensembl; ENST00000299759.11; ENSP00000299759.6; ENSG00000166592.12.
DR Ensembl; ENST00000420652.5; ENSP00000388744.1; ENSG00000166592.12.
DR GeneID; 6236; -.
DR KEGG; hsa:6236; -.
DR MANE-Select; ENST00000299759.11; ENSP00000299759.6; NM_004165.3; NP_004156.1.
DR UCSC; uc002eqn.2; human.
DR CTD; 6236; -.
DR DisGeNET; 6236; -.
DR GeneCards; RRAD; -.
DR HGNC; HGNC:10446; RRAD.
DR HPA; ENSG00000166592; Group enriched (heart muscle, skeletal muscle).
DR MIM; 179503; gene.
DR neXtProt; NX_P55042; -.
DR OpenTargets; ENSG00000166592; -.
DR PharmGKB; PA34860; -.
DR VEuPathDB; HostDB:ENSG00000166592; -.
DR eggNOG; KOG0395; Eukaryota.
DR GeneTree; ENSGT00940000159836; -.
DR HOGENOM; CLU_041217_3_2_1; -.
DR InParanoid; P55042; -.
DR OMA; MPQTGQT; -.
DR OrthoDB; 679855at2759; -.
DR PhylomeDB; P55042; -.
DR TreeFam; TF314379; -.
DR PathwayCommons; P55042; -.
DR Reactome; R-HSA-9031628; NGF-stimulated transcription.
DR SignaLink; P55042; -.
DR SIGNOR; P55042; -.
DR BioGRID-ORCS; 6236; 24 hits in 1082 CRISPR screens.
DR EvolutionaryTrace; P55042; -.
DR GeneWiki; RRAD; -.
DR GenomeRNAi; 6236; -.
DR Pharos; P55042; Tbio.
DR PRO; PR:P55042; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P55042; protein.
DR Bgee; ENSG00000166592; Expressed in olfactory segment of nasal mucosa and 147 other tissues.
DR ExpressionAtlas; P55042; baseline and differential.
DR Genevisible; P55042; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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; TAS:ProtInc.
DR GO; GO:1901842; P:negative regulation of high voltage-gated calcium channel activity; IEA:InterPro.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:ProtInc.
DR DisProt; DP02572; -.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR028869; RAD.
DR InterPro; IPR017358; RGK.
DR InterPro; IPR005225; Small_GTP-bd_dom.
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 TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS51421; RAS; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calmodulin-binding; Cell membrane; GTP-binding; Membrane;
KW Methylation; Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..308
FT /note="GTP-binding protein RAD"
FT /id="PRO_0000122478"
FT REGION 1..88
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..297
FT /note="Calmodulin-binding"
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:0000250|UniProtKB:O88667"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88667"
FT VARIANT 66
FT /note="Q -> P (in dbSNP:rs7198458)"
FT /id="VAR_049497"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:3Q72"
FT HELIX 104..111
FT /evidence="ECO:0007829|PDB:3Q72"
FT STRAND 126..133
FT /evidence="ECO:0007829|PDB:3Q72"
FT STRAND 136..144
FT /evidence="ECO:0007829|PDB:3Q72"
FT HELIX 155..159
FT /evidence="ECO:0007829|PDB:2DPX"
FT STRAND 164..170
FT /evidence="ECO:0007829|PDB:3Q72"
FT HELIX 174..189
FT /evidence="ECO:0007829|PDB:3Q72"
FT STRAND 198..203
FT /evidence="ECO:0007829|PDB:3Q72"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:2GJS"
FT HELIX 215..224
FT /evidence="ECO:0007829|PDB:3Q72"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:3Q72"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:3Q72"
FT HELIX 240..254
FT /evidence="ECO:0007829|PDB:3Q72"
SQ SEQUENCE 308 AA; 33245 MW; EF098960A371D2C4 CRC64;
MTLNGGGSGA GGSRGGGQER ERRRGSTPWG PAPPLHRRSM PVDERDLQAA LTPGALTAAA
AGTGTQGPRL DWPEDSEDSL SSGGSDSDES VYKVLLLGAP GVGKSALARI FGGVEDGPEA
EAAGHTYDRS IVVDGEEASL MVYDIWEQDG GRWLPGHCMA MGDAYVIVYS VTDKGSFEKA
SELRVQLRRA RQTDDVPIIL VGNKSDLVRS REVSVDEGRA CAVVFDCKFI ETSAALHHNV
QALFEGVVRQ IRLRRDSKEA NARRQAGTRR RESLGKKAKR FLGRIVARNS RKMAFRAKSK
SCHDLSVL
