CTU2_HUMAN
ID CTU2_HUMAN Reviewed; 515 AA.
AC Q2VPK5; B2RXK0; Q0P511; Q66K78; Q6P4C8; Q86SV4;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 1.
DT 03-AUG-2022, entry version 129.
DE RecName: Full=Cytoplasmic tRNA 2-thiolation protein 2 {ECO:0000255|HAMAP-Rule:MF_03054};
DE AltName: Full=Cytosolic thiouridylase subunit 2;
GN Name=CTU2 {ECO:0000255|HAMAP-Rule:MF_03054};
GN Synonyms=C16orf84, NCS2 {ECO:0000255|HAMAP-Rule:MF_03054};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), NUCLEOTIDE
RP SEQUENCE [LARGE SCALE MRNA] OF 42-515 (ISOFORM 3), AND VARIANTS VAL-253 AND
RP ARG-416.
RC TISSUE=Brain, Choriocarcinoma, and Skin;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419 AND SER-508, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [5]
RP FUNCTION IN 2-THIOLATION OF TRNA, AND IDENTIFICATION IN A COMPLEX WITH URM1
RP AND CTU1.
RX PubMed=19017811; DOI=10.1073/pnas.0808756105;
RA Schlieker C.D., Van der Veen A.G., Damon J.R., Spooner E., Ploegh H.L.;
RT "A functional proteomics approach links the ubiquitin-related modifier Urm1
RT to a tRNA modification pathway.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:18255-18260(2008).
RN [6]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT CYS-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-415, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419 AND SER-435, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP INVOLVEMENT IN MFRG.
RX PubMed=26633546; DOI=10.1038/gim.2015.147;
RA Shaheen R., Patel N., Shamseldin H., Alzahrani F., Al-Yamany R.,
RA Almoisheer A., Ewida N., Anazi S., Alnemer M., Elsheikh M., Alfaleh K.,
RA Alshammari M., Alhashem A., Alangari A.A., Salih M.A., Kircher M.,
RA Daza R.M., Ibrahim N., Wakil S.M., Alaqeel A., Altowaijri I., Shendure J.,
RA Al-Habib A., Faqieh E., Alkuraya F.S.;
RT "Accelerating matchmaking of novel dysmorphology syndromes through clinical
RT and genomic characterization of a large cohort.";
RL Genet. Med. 18:686-695(2016).
CC -!- FUNCTION: Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA
CC wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). May act by
CC forming a heterodimer with CTU1/ATPBD3 that ligates sulfur from
CC thiocarboxylated URM1 onto the uridine of tRNAs at wobble position.
CC {ECO:0000255|HAMAP-Rule:MF_03054, ECO:0000269|PubMed:19017811}.
CC -!- PATHWAY: tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA
CC biosynthesis. {ECO:0000255|HAMAP-Rule:MF_03054}.
CC -!- SUBUNIT: Component of a complex at least composed of URM1, CTU2/NCS2
CC and CTU1/ATPBD3. {ECO:0000255|HAMAP-Rule:MF_03054,
CC ECO:0000269|PubMed:19017811}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q2VPK5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q2VPK5-3; Sequence=VSP_025950;
CC Name=3;
CC IsoId=Q2VPK5-5; Sequence=VSP_039378;
CC -!- DISEASE: Microcephaly, facial dysmorphism, renal agenesis, and
CC ambiguous genitalia syndrome (MFRG) [MIM:618142]: An autosomal dominant
CC syndrome characterized by primary microcephaly, ambiguous male
CC genitalia, dysmorphic facies, polydactyly, and unilateral renal
CC agenesis. Variable brain, cardiac, and skeletal anomalies are present,
CC including corpus callosum agenesis or dysgenesis, lissencephaly, atrial
CC and ventricular septal defects, patent ductus arteriosus, hypoplastic
CC right ventricle, and joint contractures. {ECO:0000269|PubMed:26633546}.
CC Note=The disease may be caused by variants affecting the gene
CC represented in this entry. A homozygous synonymous variant at codon 247
CC has been identified in 3 consanguineous families. This variant impairs
CC normal splicing, causing a frameshift resulting in a premature
CC termination codon. {ECO:0000269|PubMed:26633546}.
CC -!- MISCELLANEOUS: [Isoform 3]: Incomplete sequence. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the CTU2/NCS2 family. {ECO:0000255|HAMAP-
CC Rule:MF_03054}.
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DR EMBL; AC138028; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC021829; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC080540; AAH80540.1; -; mRNA.
DR EMBL; BC108659; AAI08660.1; -; mRNA.
DR EMBL; BC121805; AAI21806.1; -; mRNA.
DR EMBL; BC125269; AAI25270.1; -; mRNA.
DR EMBL; BC157881; AAI57882.1; -; mRNA.
DR CCDS; CCDS32506.1; -. [Q2VPK5-5]
DR CCDS; CCDS45545.1; -. [Q2VPK5-1]
DR RefSeq; NP_001012777.1; NM_001012759.2. [Q2VPK5-1]
DR RefSeq; NP_001012780.1; NM_001012762.2. [Q2VPK5-5]
DR RefSeq; NP_001305436.1; NM_001318507.1.
DR RefSeq; NP_001305442.1; NM_001318513.1. [Q2VPK5-3]
DR AlphaFoldDB; Q2VPK5; -.
DR BioGRID; 131513; 89.
DR DIP; DIP-48633N; -.
DR IntAct; Q2VPK5; 21.
DR STRING; 9606.ENSP00000388320; -.
DR GlyGen; Q2VPK5; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q2VPK5; -.
DR PhosphoSitePlus; Q2VPK5; -.
DR BioMuta; CTU2; -.
DR DMDM; 121941955; -.
DR EPD; Q2VPK5; -.
DR jPOST; Q2VPK5; -.
DR MassIVE; Q2VPK5; -.
DR MaxQB; Q2VPK5; -.
DR PaxDb; Q2VPK5; -.
DR PeptideAtlas; Q2VPK5; -.
DR PRIDE; Q2VPK5; -.
DR ProteomicsDB; 61520; -. [Q2VPK5-1]
DR ProteomicsDB; 61521; -. [Q2VPK5-3]
DR ProteomicsDB; 61522; -. [Q2VPK5-5]
DR Antibodypedia; 49625; 41 antibodies from 13 providers.
DR DNASU; 348180; -.
DR Ensembl; ENST00000312060.9; ENSP00000308617.5; ENSG00000174177.13. [Q2VPK5-5]
DR Ensembl; ENST00000453996.7; ENSP00000388320.2; ENSG00000174177.13. [Q2VPK5-1]
DR GeneID; 348180; -.
DR KEGG; hsa:348180; -.
DR MANE-Select; ENST00000453996.7; ENSP00000388320.2; NM_001012759.3; NP_001012777.1.
DR UCSC; uc002flm.4; human. [Q2VPK5-1]
DR CTD; 348180; -.
DR DisGeNET; 348180; -.
DR GeneCards; CTU2; -.
DR HGNC; HGNC:28005; CTU2.
DR HPA; ENSG00000174177; Low tissue specificity.
DR MalaCards; CTU2; -.
DR MIM; 617057; gene.
DR MIM; 618142; phenotype.
DR neXtProt; NX_Q2VPK5; -.
DR OpenTargets; ENSG00000174177; -.
DR PharmGKB; PA165449882; -.
DR VEuPathDB; HostDB:ENSG00000174177; -.
DR eggNOG; KOG2594; Eukaryota.
DR GeneTree; ENSGT00390000008797; -.
DR HOGENOM; CLU_024534_2_0_1; -.
DR InParanoid; Q2VPK5; -.
DR OMA; SCSMLRQ; -.
DR OrthoDB; 1442062at2759; -.
DR PhylomeDB; Q2VPK5; -.
DR TreeFam; TF313203; -.
DR BioCyc; MetaCyc:MON-20243; -.
DR PathwayCommons; Q2VPK5; -.
DR Reactome; R-HSA-6782315; tRNA modification in the nucleus and cytosol.
DR SignaLink; Q2VPK5; -.
DR UniPathway; UPA00988; -.
DR BioGRID-ORCS; 348180; 527 hits in 1062 CRISPR screens.
DR ChiTaRS; CTU2; human.
DR GeneWiki; C16orf84; -.
DR GenomeRNAi; 348180; -.
DR Pharos; Q2VPK5; Tdark.
DR PRO; PR:Q2VPK5; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; Q2VPK5; protein.
DR Bgee; ENSG00000174177; Expressed in oocyte and 125 other tissues.
DR ExpressionAtlas; Q2VPK5; baseline and differential.
DR Genevisible; Q2VPK5; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0016779; F:nucleotidyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0016783; F:sulfurtransferase activity; IBA:GO_Central.
DR GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR GO; GO:0032447; P:protein urmylation; IEA:UniProtKB-UniRule.
DR GO; GO:0034227; P:tRNA thio-modification; NAS:UniProtKB.
DR GO; GO:0002143; P:tRNA wobble position uridine thiolation; IBA:GO_Central.
DR GO; GO:0002098; P:tRNA wobble uridine modification; NAS:UniProtKB.
DR Gene3D; 3.40.50.620; -; 1.
DR HAMAP; MF_03054; CTU2; 1.
DR InterPro; IPR019407; CTU2.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR20882; PTHR20882; 1.
DR Pfam; PF10288; CTU2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Cytoplasm; Phosphoprotein;
KW Primary microcephaly; Reference proteome; tRNA processing.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330"
FT CHAIN 2..515
FT /note="Cytoplasmic tRNA 2-thiolation protein 2"
FT /id="PRO_0000289175"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 188..217
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..214
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylcysteine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 415
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 419
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 435
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 508
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..87
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_025950"
FT VAR_SEQ 474..515
FT /note="PSLDPLPPYILAEAQLRTQRAWGLQEIRDCLIEDSDDEAGQS -> GLGLAG
FT DPGLSD (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039378"
FT VARIANT 186
FT /note="H -> Y (in dbSNP:rs2290895)"
FT /id="VAR_062244"
FT VARIANT 253
FT /note="M -> V (in dbSNP:rs11549837)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032595"
FT VARIANT 332
FT /note="V -> I (in dbSNP:rs4782321)"
FT /id="VAR_032596"
FT VARIANT 416
FT /note="Q -> R (in dbSNP:rs8059048)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_032597"
FT CONFLICT 297
FT /note="R -> W (in Ref. 1; AAH80540)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 515 AA; 56107 MW; 200CE7129FC89E65 CRC64;
MCQVGEDYGE PAPEEPPPAP RPSREQKCVK CKEAQPVVVI RAGDAFCRDC FKAFYVHKFR
AMLGKNRLIF PGEKVLLAWS GGPSSSSMVW QVLEGLSQDS AKRLRFVAGV IFVDEGAACG
QSLEERSKTL AEVKPILQAT GFPWHVVALE EVFSLPPSVL WCSAQELVGS EGAYKAAVDS
FLQQQHVLGA GGGPGPTQGE EQPPQPPLDP QNLARPPAPA QTEALSQLFC SVRTLTAKEE
LLQTLRTHLI LHMARAHGYS KVMTGDSCTR LAIKLMTNLA LGRGAFLAWD TGFSDERHGD
VVVVRPMRDH TLKEVAFYNR LFSVPSVFTP AVDTKAPEKA SIHRLMEAFI LRLQTQFPST
VSTVYRTSEK LVKGPRDGPA AGDSGPRCLL CMCALDVDAA DSATAFGAQT SSRLSQMQSP
IPLTETRTPP GPCCSPGVGW AQRCGQGACR REDPQACIEE QLCYSCRVNM KDLPSLDPLP
PYILAEAQLR TQRAWGLQEI RDCLIEDSDD EAGQS
