ID   DRG2_HUMAN              Reviewed;         364 AA.
AC   P55039; B2R8G5; Q53Y50; Q9BWB2;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 191.
DE   RecName: Full=Developmentally-regulated GTP-binding protein 2;
DE            Short=DRG-2;
DE   AltName: Full=Translation factor GTPase DRG2;
DE            Short=TRAFAC GTPase DRG2;
DE            EC=3.6.5.- {ECO:0000305|PubMed:29915238};
GN   Name=DRG2 {ECO:0000303|PubMed:29915238, ECO:0000312|HGNC:HGNC:3030};
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=Lung;
RX   PubMed=7929244; DOI=10.1016/s0021-9258(18)47271-7;
RA   Schenker T., Lach C., Kessler B., Calderara S., Trueb B.;
RT   "A novel GTP-binding protein which is selectively repressed in SV40
RT   transformed fibroblasts.";
RL   J. Biol. Chem. 269:25447-25453(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-194.
RA   Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA   Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA   Phelan M., Farmer A.;
RT   "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL   Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Thymus;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT MET-194.
RC   TISSUE=Lung;
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   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [7]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA   Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA   Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA   Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT   "N-terminal acetylome analyses and functional insights of the N-terminal
RT   acetyltransferase NatB.";
RL   Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN   [8]
RP   FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-21, CATALYTIC ACTIVITY,
RP   INTERACTION WITH JMJD7, HYDROXYLATION AT LYS-21, AND COFACTOR.
RX   PubMed=29915238; DOI=10.1038/s41589-018-0071-y;
RA   Markolovic S., Zhuang Q., Wilkins S.E., Eaton C.D., Abboud M.I., Katz M.J.,
RA   McNeil H.E., Lesniak R.K., Hall C., Struwe W.B., Konietzny R., Davis S.,
RA   Yang M., Ge W., Benesch J.L.P., Kessler B.M., Ratcliffe P.J., Cockman M.E.,
RA   Fischer R., Wappner P., Chowdhury R., Coleman M.L., Schofield C.J.;
RT   "The Jumonji-C oxygenase JMJD7 catalyzes (3S)-lysyl hydroxylation of TRAFAC
RT   GTPases.";
RL   Nat. Chem. Biol. 14:688-695(2018).
CC   -!- FUNCTION: Catalyzes the conversion of GTP to GDP through hydrolysis of
CC       the gamma-phosphate bond in GTP. When hydroxylated at C-3 of 'Lys-21'
CC       by JMJD7, may bind to RNA and play a role in translation.
CC       {ECO:0000269|PubMed:29915238}.
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:0000269|PubMed:29915238};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19670;
CC         Evidence={ECO:0000269|PubMed:29915238};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000305|PubMed:29915238};
CC   -!- SUBUNIT: Interacts with RWDD1; this interaction confers protection to
CC       polyubiquitination and proteolytic degradation (By similarity).
CC       Interacts with JMJD7; this interaction is direct (PubMed:29915238).
CC       {ECO:0000250, ECO:0000250|UniProtKB:Q9QXB9,
CC       ECO:0000269|PubMed:29915238}.
CC   -!- INTERACTION:
CC       P55039; P38919: EIF4A3; NbExp=3; IntAct=EBI-750565, EBI-299104;
CC       P55039; P0C870: JMJD7; NbExp=3; IntAct=EBI-750565, EBI-9090173;
CC       P55039; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-750565, EBI-1055254;
CC       P55039; Q15742: NAB2; NbExp=3; IntAct=EBI-750565, EBI-8641936;
CC       P55039; Q9H446: RWDD1; NbExp=8; IntAct=EBI-750565, EBI-748952;
CC       P55039; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-750565, EBI-5235340;
CC       P55039; Q96PN8: TSSK3; NbExp=3; IntAct=EBI-750565, EBI-3918381;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29915238}. Cytoplasm
CC       {ECO:0000269|PubMed:29915238}.
CC   -!- TISSUE SPECIFICITY: Highest levels in skeletal muscle, heart and
CC       kidney. Low levels in colon, thymus, spleen, small intestine, lung and
CC       Leukocytes.
CC   -!- PTM: Hydroxylated (with S stereochemistry) at C-3 of Lys-21 by JMJD7;
CC       this modification hinders trypsin-catalyzed proteolysis in vitro.
CC       {ECO:0000269|PubMed:29915238}.
CC   -!- PTM: Polyubiquitinated. {ECO:0000250|UniProtKB:Q9QXB9}.
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; X80754; CAA56730.1; -; mRNA.
DR   EMBL; BT006976; AAP35622.1; -; mRNA.
DR   EMBL; AK313362; BAG36162.1; -; mRNA.
DR   EMBL; CH471196; EAW55669.1; -; Genomic_DNA.
DR   EMBL; BC000493; AAH00493.1; -; mRNA.
DR   CCDS; CCDS11191.1; -.
DR   PIR; A55014; A55014.
DR   RefSeq; NP_001379.1; NM_001388.4.
DR   AlphaFoldDB; P55039; -.
DR   SMR; P55039; -.
DR   BioGRID; 108153; 69.
DR   IntAct; P55039; 19.
DR   STRING; 9606.ENSP00000225729; -.
DR   GlyGen; P55039; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P55039; -.
DR   MetOSite; P55039; -.
DR   PhosphoSitePlus; P55039; -.
DR   BioMuta; DRG2; -.
DR   DMDM; 1706518; -.
DR   EPD; P55039; -.
DR   jPOST; P55039; -.
DR   MassIVE; P55039; -.
DR   MaxQB; P55039; -.
DR   PaxDb; 9606-ENSP00000225729; -.
DR   PeptideAtlas; P55039; -.
DR   ProteomicsDB; 56764; -.
DR   Pumba; P55039; -.
DR   Antibodypedia; 1408; 161 antibodies from 23 providers.
DR   DNASU; 1819; -.
DR   Ensembl; ENST00000225729.8; ENSP00000225729.3; ENSG00000108591.10.
DR   GeneID; 1819; -.
DR   KEGG; hsa:1819; -.
DR   MANE-Select; ENST00000225729.8; ENSP00000225729.3; NM_001388.5; NP_001379.1.
DR   UCSC; uc002gsh.3; human.
DR   AGR; HGNC:3030; -.
DR   CTD; 1819; -.
DR   DisGeNET; 1819; -.
DR   GeneCards; DRG2; -.
DR   HGNC; HGNC:3030; DRG2.
DR   HPA; ENSG00000108591; Low tissue specificity.
DR   MIM; 602986; gene.
DR   neXtProt; NX_P55039; -.
DR   OpenTargets; ENSG00000108591; -.
DR   PharmGKB; PA27484; -.
DR   VEuPathDB; HostDB:ENSG00000108591; -.
DR   eggNOG; KOG1486; Eukaryota.
DR   GeneTree; ENSGT00940000153340; -.
DR   HOGENOM; CLU_044997_0_0_1; -.
DR   InParanoid; P55039; -.
DR   OMA; VCDQVHR; -.
DR   OrthoDB; 146471at2759; -.
DR   PhylomeDB; P55039; -.
DR   TreeFam; TF105706; -.
DR   PathwayCommons; P55039; -.
DR   Reactome; R-HSA-9629569; Protein hydroxylation.
DR   SignaLink; P55039; -.
DR   BioGRID-ORCS; 1819; 24 hits in 1153 CRISPR screens.
DR   ChiTaRS; DRG2; human.
DR   GeneWiki; DRG2; -.
DR   GenomeRNAi; 1819; -.
DR   Pharos; P55039; Tbio.
DR   PRO; PR:P55039; -.
DR   Proteomes; UP000005640; Chromosome 17.
DR   RNAct; P55039; Protein.
DR   Bgee; ENSG00000108591; Expressed in granulocyte and 171 other cell types or tissues.
DR   ExpressionAtlas; P55039; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0005525; F:GTP binding; IBA:GO_Central.
DR   GO; GO:0003924; F:GTPase activity; IDA:UniProtKB.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR   GO; GO:0002181; P:cytoplasmic translation; IBA:GO_Central.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   CDD; cd01896; DRG; 1.
DR   CDD; cd17231; TGS_DRG2; 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; DEVELOPMENTALLY-REGULATED GTP-BINDING PROTEIN 2; 1.
DR   PANTHER; PTHR43127:SF2; 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.
DR   Genevisible; P55039; HS.
PE   1: Evidence at protein level;
KW   Cytoplasm; GTP-binding; Hydrolase; Hydroxylation; Magnesium; Metal-binding;
KW   Nucleotide-binding; Nucleus; Reference proteome; Ubl conjugation.
FT   CHAIN           1..364
FT                   /note="Developmentally-regulated GTP-binding protein 2"
FT                   /id="PRO_0000205427"
FT   DOMAIN          63..288
FT                   /note="OBG-type G"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT   DOMAIN          288..363
FT                   /note="TGS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01228"
FT   BINDING         69..76
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT   BINDING         76
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT   BINDING         94..98
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT   BINDING         96
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT   BINDING         115..118
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT   BINDING         246..249
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT   BINDING         269..271
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01047"
FT   MOD_RES         21
FT                   /note="(3S)-3-hydroxylysine"
FT                   /evidence="ECO:0000269|PubMed:29915238"
FT   VARIANT         194
FT                   /note="T -> M (in dbSNP:rs17855350)"
FT                   /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.2"
FT                   /id="VAR_067452"
FT   VARIANT         224
FT                   /note="S -> T (in dbSNP:rs61256737)"
FT                   /id="VAR_067453"
FT   MUTAGEN         21
FT                   /note="K->A: Impairs JMJD7-mediated hydroxylation and
FT                   ribonucleic acid binding."
FT                   /evidence="ECO:0000269|PubMed:29915238"
SQ   SEQUENCE   364 AA;  40746 MW;  D1754BEB02671F85 CRC64;
     MGILEKISEI EKEIARTQKN KATEYHLGLL KAKLAKYRAQ LLEPSKSASS KGEGFDVMKS
     GDARVALIGF PSVGKSTFLS LMTSTASEAA SYEFTTLTCI PGVIEYKGAN IQLLDLPGII
     EGAAQGKGRG RQVIAVARTA DVIIMMLDAT KGEVQRSLLE KELESVGIRL NKHKPNIYFK
     PKKGGGISFN STVTLTQCSE KLVQLILHEY KIFNAEVLFR EDCSPDEFID VIVGNRVYMP
     CLYVYNKIDQ ISMEEVDRLA RKPNSVVISC GMKLNLDYLL EMLWEYLALT CIYTKKRGQR
     PDFTDAIILR KGASVEHVCH RIHRSLASQF KYALVWGTST KYSPQRVGLT HTMEHEDVIQ
     IVKK
//