DRG2_HUMAN
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 03-AUG-2022, entry version 182.
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; 51.
DR IntAct; P55039; 17.
DR STRING; 9606.ENSP00000225729; -.
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; P55039; -.
DR PeptideAtlas; P55039; -.
DR PRIDE; P55039; -.
DR ProteomicsDB; 56764; -.
DR Antibodypedia; 1408; 135 antibodies from 21 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 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; 754662at2759; -.
DR PhylomeDB; P55039; -.
DR TreeFam; TF105706; -.
DR PathwayCommons; P55039; -.
DR SignaLink; P55039; -.
DR BioGRID-ORCS; 1819; 21 hits in 1075 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 169 other tissues.
DR ExpressionAtlas; P55039; baseline and differential.
DR Genevisible; P55039; HS.
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 Gene3D; 3.10.20.30; -; 1.
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 PANTHER; PTHR43127; PTHR43127; 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; SSF52540; 1.
DR SUPFAM; SSF81271; SSF81271; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 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 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
