ID DRG1_MOUSE Reviewed; 367 AA.
AC P32233;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 24-JAN-2024, entry version 166.
DE RecName: Full=Developmentally-regulated GTP-binding protein 1;
DE Short=DRG-1;
DE AltName: Full=Neural precursor cell expressed developmentally down-regulated protein 3;
DE Short=NEDD-3;
DE AltName: Full=Translation factor GTPase DRG1;
DE Short=TRAFAC GTPase DRG1;
DE EC=3.6.5.- {ECO:0000250|UniProtKB:Q9Y295};
GN Name=Drg1; Synonyms=Drg, Nedd-3, Nedd3;
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].
RX PubMed=1449490; DOI=10.1016/0006-291x(92)91567-a;
RA Sazuka T., Tomooka Y., Ikawa Y., Noda M., Kumar S.;
RT "DRG: a novel developmentally regulated GTP-binding protein.";
RL Biochem. Biophys. Res. Commun. 189:363-370(1992).
RN [2]
RP DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=1280421; DOI=10.1016/0006-291x(92)91568-b;
RA Sazuka T., Kinoshita M., Tomooka Y., Ikawa Y., Noda M., Kumar S.;
RT "Expression of DRG during murine embryonic development.";
RL Biochem. Biophys. Res. Commun. 189:371-377(1992).
RN [3]
RP INTERACTION WITH ZC3H15, AND UBIQUITINATION.
RX PubMed=15676025; DOI=10.1111/j.1365-2443.2005.00825.x;
RA Ishikawa K., Azuma S., Ikawa S., Semba K., Inoue J.;
RT "Identification of DRG family regulatory proteins (DFRPs): specific
RT regulation of DRG1 and DRG2.";
RL Genes Cells 10:139-150(2005).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
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).
CC -!- FUNCTION: Catalyzes the conversion of GTP to GDP through hydrolysis of
CC the gamma-phosphate bond in GTP. Appears to have an intrinsic GTPase
CC activity that is stimulated by ZC3H15/DFRP1 binding likely by
CC increasing the affinity for the potassium ions. When hydroxylated at C-
CC 3 of 'Lys-22' by JMJD7, may bind to RNA and play a role in translation.
CC Binds to microtubules and promotes microtubule polymerization and
CC bundling that are required for mitotic spindle assembly during prophase
CC to anaphase transition. GTPase activity is not necessary for these
CC microtubule-related functions. {ECO:0000250|UniProtKB:Q9Y295}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000250|UniProtKB:Q9Y295};
CC -!- ACTIVITY REGULATION: The GTPase activity is enhanced by potassium ions
CC as well as by DFRP1 binding. {ECO:0000250|UniProtKB:Q9Y295}.
CC -!- SUBUNIT: Interacts (via its C-terminal) with TAL1 (By similarity).
CC Interacts with DFRP1/ZC3H15; this interaction prevents DRG1 poly-
CC ubiquitination and degradation by proteasome. DRG1-DFRP1/ZC3H15 complex
CC co-sediments with polysomes (By similarity) (PubMed:15676025).
CC Interacts with STK16. Interacts with JMJD7 (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y295, ECO:0000269|PubMed:15676025}.
CC -!- INTERACTION:
CC P32233; O75716: STK16; Xeno; NbExp=4; IntAct=EBI-8429215, EBI-749295;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9Y295}. Cytoplasm
CC {ECO:0000269|PubMed:1280421}. Note=The DRG1-DFRP2/ZC3H15 complex
CC associates with polysomes. {ECO:0000250|UniProtKB:Q9Y295}.
CC -!- TISSUE SPECIFICITY: Fairly high levels in liver, heart, kidney, testis
CC and brain. Very low levels in lung, spleen, and skeletal muscle.
CC {ECO:0000269|PubMed:1280421}.
CC -!- DEVELOPMENTAL STAGE: Predominantly expressed in the embryo and down-
CC regulated during development. {ECO:0000269|PubMed:1280421}.
CC -!- DOMAIN: Its C-terminal domain interacts with TAL1.
CC -!- DOMAIN: The ThrRS, GTPase, SpoT (TGS) domain is not necessary for GTP
CC binding nor for the GTPase activity. It appears to play a regulatory
CC role favoring GTP hydrolysis mediated by DFRP1/ZC3H15.
CC {ECO:0000250|UniProtKB:Q9Y295}.
CC -!- PTM: Polyubiquitinated; this modification induces proteolytic
CC degradation and is impaired by interaction with ZC3H15.
CC {ECO:0000305|PubMed:15676025}.
CC -!- PTM: Sumoylated by UBE2I in response to MEKK1-mediated stimuli.
CC {ECO:0000250|UniProtKB:Q9Y295}.
CC -!- PTM: Hydroxylated (with S stereochemistry) at C-3 of Lys-22 by JMJD7.
CC {ECO:0000250|UniProtKB:Q9Y295}.
CC -!- PTM: Phosphorylated at Thr-100 by STK16.
CC {ECO:0000250|UniProtKB:Q9Y295}.
CC -!- SIMILARITY: Belongs to the TRAFAC class OBG-HflX-like GTPase
CC superfamily. OBG GTPase family. {ECO:0000255|PROSITE-ProRule:PRU01047}.
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DR EMBL; D10715; BAA01555.1; -; mRNA.
DR CCDS; CCDS24355.1; -.
DR PIR; JC1349; JC1349.
DR RefSeq; NP_031905.1; NM_007879.1.
DR AlphaFoldDB; P32233; -.
DR BMRB; P32233; -.
DR SMR; P32233; -.
DR BioGRID; 199310; 31.
DR DIP; DIP-29599N; -.
DR IntAct; P32233; 2.
DR STRING; 10090.ENSMUSP00000020741; -.
DR GlyGen; P32233; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P32233; -.
DR PhosphoSitePlus; P32233; -.
DR SwissPalm; P32233; -.
DR EPD; P32233; -.
DR jPOST; P32233; -.
DR PaxDb; 10090-ENSMUSP00000020741; -.
DR PeptideAtlas; P32233; -.
DR ProteomicsDB; 279580; -.
DR Pumba; P32233; -.
DR Antibodypedia; 238; 263 antibodies from 28 providers.
DR DNASU; 13494; -.
DR Ensembl; ENSMUST00000020741.12; ENSMUSP00000020741.6; ENSMUSG00000020457.14.
DR GeneID; 13494; -.
DR KEGG; mmu:13494; -.
DR UCSC; uc007hsh.1; mouse.
DR AGR; MGI:1343297; -.
DR CTD; 4733; -.
DR MGI; MGI:1343297; Drg1.
DR VEuPathDB; HostDB:ENSMUSG00000020457; -.
DR eggNOG; KOG1487; Eukaryota.
DR GeneTree; ENSGT00940000153340; -.
DR HOGENOM; CLU_044997_0_0_1; -.
DR InParanoid; P32233; -.
DR OMA; SAKHPGQ; -.
DR OrthoDB; 146471at2759; -.
DR PhylomeDB; P32233; -.
DR TreeFam; TF105677; -.
DR Reactome; R-MMU-9629569; Protein hydroxylation.
DR BioGRID-ORCS; 13494; 7 hits in 79 CRISPR screens.
DR ChiTaRS; Drg1; mouse.
DR PRO; PR:P32233; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; P32233; Protein.
DR Bgee; ENSMUSG00000020457; Expressed in floor plate of midbrain and 280 other cell types or tissues.
DR ExpressionAtlas; P32233; baseline and differential.
DR Genevisible; P32233; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005844; C:polysome; ISO:MGI.
DR GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR GO; GO:0003924; F:GTPase activity; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0030955; F:potassium ion binding; ISO:MGI.
DR GO; GO:0002181; P:cytoplasmic translation; IBA:GO_Central.
DR GO; GO:0031116; P:positive regulation of microtubule polymerization; ISS:UniProtKB.
DR GO; GO:1901673; P:regulation of mitotic spindle assembly; ISS:UniProtKB.
DR CDD; cd01896; DRG; 1.
DR CDD; cd17230; TGS_DRG1; 1.
DR Gene3D; 3.10.20.30; -; 1.
DR Gene3D; 6.10.140.1070; -; 2.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR InterPro; IPR045001; DRG.
DR InterPro; IPR031167; G_OBG.
DR InterPro; IPR006073; GTP-bd.
DR InterPro; IPR031662; GTP-binding_2.
DR InterPro; IPR006074; GTP1-OBG_CS.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR004095; TGS.
DR InterPro; IPR012676; TGS-like.
DR NCBIfam; TIGR00231; small_GTP; 1.
DR PANTHER; PTHR43127:SF1; DEVELOPMENTALLY-REGULATED GTP-BINDING PROTEIN 1; 1.
DR PANTHER; PTHR43127; DEVELOPMENTALLY-REGULATED GTP-BINDING PROTEIN 2; 1.
DR Pfam; PF01926; MMR_HSR1; 1.
DR Pfam; PF16897; MMR_HSR1_Xtn; 1.
DR Pfam; PF02824; TGS; 1.
DR PRINTS; PR00326; GTP1OBG.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
DR SUPFAM; SSF81271; TGS-like; 1.
DR PROSITE; PS51710; G_OBG; 1.
DR PROSITE; PS00905; GTP1_OBG; 1.
DR PROSITE; PS51880; TGS; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; GTP-binding; Hydrolase; Hydroxylation; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q9Y295"
FT CHAIN 2..367
FT /note="Developmentally-regulated GTP-binding protein 1"
FT /id="PRO_0000205425"
FT DOMAIN 65..290
FT /note="OBG-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT DOMAIN 290..366
FT /note="TGS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01228"
FT REGION 2..16
FT /note="Required for interaction with STK16"
FT /evidence="ECO:0000250|UniProtKB:Q9Y295"
FT BINDING 71..78
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT BINDING 78
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT BINDING 96..100
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT BINDING 98
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT BINDING 117..120
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT BINDING 248..251
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT BINDING 271..273
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y295"
FT MOD_RES 22
FT /note="(3S)-3-hydroxylysine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y295"
FT MOD_RES 100
FT /note="Phosphothreonine; by STK16"
FT /evidence="ECO:0000250|UniProtKB:Q9Y295"
SQ SEQUENCE 367 AA; 40512 MW; 87D77767CA0E89E2 CRC64;
MSGTLAKIAE IEAEMARTQK NKATAHHLGL LKARLAKLRR ELITPKGGGG GGPGEGFDVA
KTGDARIGFV GFPSVGKSTL LSNLAGVYSE VAAYEFTTLT TVPGVIRYKG AKIQLLDLPG
IIEGAKDGKG RGRQVIAVAR TCNLILIVLD VLKPLGHKKI IENELEGFGI RLNSKPPNIG
FKKKDKGGIN LTATCPQSEL DAETVKSILA EYKIHNADVT LRSDATADDL IDVVEGNRVY
IPCIYVLNKI DQISIEELDI IYKVPHCVPI SAHHRWNFDD LLEKIWDYLK LVRIYTKPKG
QLPDYTSPVV LPYSRTTVED FCMKIHKNLI KEFKYALVWG LSVKHNPQKV GKDHTLEDED
VIQIVKK
//
