TYW5_HUMAN
ID TYW5_HUMAN Reviewed; 315 AA.
AC A2RUC4; B2RNE3; Q8N1R2;
DT 13-NOV-2007, integrated into UniProtKB/Swiss-Prot.
DT 06-MAR-2007, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=tRNA wybutosine-synthesizing protein 5 {ECO:0000305|PubMed:20739293};
DE Short=hTYW5;
DE EC=1.14.11.42 {ECO:0000269|PubMed:20739293, ECO:0000269|PubMed:20972222};
DE AltName: Full=tRNA(Phe) (7-(3-amino-3-carboxypropyl)wyosine(37)-C(2))-hydroxylase;
GN Name=TYW5; Synonyms=C2orf60;
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 MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Tongue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Retinoblastoma;
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=20739293; DOI=10.1074/jbc.m110.156398;
RA Noma A., Ishitani R., Kato M., Nagao A., Nureki O., Suzuki T.;
RT "Expanding role of the jumonji C domain as an RNA hydroxylase.";
RL J. Biol. Chem. 285:34503-34507(2010).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 4-311 IN COMPLEX WITH
RP 2-OXOGLUTARATE AND NICKEL ION, FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP COFACTOR, SUBUNIT, AND MUTAGENESIS OF ARG-108 AND ARG-149.
RX PubMed=20972222; DOI=10.1093/nar/gkq919;
RA Kato M., Araiso Y., Noma A., Nagao A., Suzuki T., Ishitani R., Nureki O.;
RT "Crystal structure of a novel JmjC-domain-containing protein, TYW5,
RT involved in tRNA modification.";
RL Nucleic Acids Res. 39:1576-1585(2011).
CC -!- FUNCTION: tRNA hydroxylase that acts as a component of the wybutosine
CC biosynthesis pathway. Wybutosine is a hyper modified guanosine with a
CC tricyclic base found at the 3'-position adjacent to the anticodon of
CC eukaryotic phenylalanine tRNA. Catalyzes the hydroxylation of 7-(a-
CC amino-a-carboxypropyl)wyosine (yW-72) into undermodified
CC hydroxywybutosine (OHyW*). OHyW* being further transformed into
CC hydroxywybutosine (OHyW) by LCMT2/TYW4. OHyW is a derivative of
CC wybutosine found in higher eukaryotes. {ECO:0000269|PubMed:20739293,
CC ECO:0000269|PubMed:20972222}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + 7-[(3S)-3-amino-3-carboxypropyl]wyosine(37)
CC in tRNA(Phe) + O2 = 7-(2-hydroxy-3-amino-3-carboxypropyl)wyosine(37)
CC in tRNA(Phe) + CO2 + succinate; Xref=Rhea:RHEA:37899, Rhea:RHEA-
CC COMP:10379, Rhea:RHEA-COMP:11848, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:16810, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:73543, ChEBI:CHEBI:73603; EC=1.14.11.42;
CC Evidence={ECO:0000269|PubMed:20739293, ECO:0000269|PubMed:20972222};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37900;
CC Evidence={ECO:0000269|PubMed:20739293};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000269|PubMed:20972222};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000269|PubMed:20972222};
CC -!- PATHWAY: tRNA modification; wybutosine-tRNA(Phe) biosynthesis.
CC {ECO:0000269|PubMed:20739293, ECO:0000269|PubMed:20972222}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:20972222}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A2RUC4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A2RUC4-2; Sequence=VSP_029106;
CC -!- SIMILARITY: Belongs to the TYW5 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH63502.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK095272; BAC04517.1; -; mRNA.
DR EMBL; AK298977; BAG61071.1; -; mRNA.
DR EMBL; AC097717; AAY24162.1; -; Genomic_DNA.
DR EMBL; CH471063; EAW70191.1; -; Genomic_DNA.
DR EMBL; BC063502; AAH63502.1; ALT_INIT; mRNA.
DR EMBL; BC132835; AAI32836.1; -; mRNA.
DR EMBL; BC136837; AAI36838.1; -; mRNA.
DR CCDS; CCDS42795.1; -. [A2RUC4-1]
DR RefSeq; NP_001034782.1; NM_001039693.2. [A2RUC4-1]
DR PDB; 3AL5; X-ray; 2.50 A; A/B/C/D=1-315.
DR PDB; 3AL6; X-ray; 2.80 A; A/B/C/D=1-315.
DR PDBsum; 3AL5; -.
DR PDBsum; 3AL6; -.
DR AlphaFoldDB; A2RUC4; -.
DR SMR; A2RUC4; -.
DR BioGRID; 126193; 14.
DR IntAct; A2RUC4; 8.
DR STRING; 9606.ENSP00000346627; -.
DR iPTMnet; A2RUC4; -.
DR PhosphoSitePlus; A2RUC4; -.
DR BioMuta; TYW5; -.
DR EPD; A2RUC4; -.
DR jPOST; A2RUC4; -.
DR MassIVE; A2RUC4; -.
DR MaxQB; A2RUC4; -.
DR PaxDb; A2RUC4; -.
DR PeptideAtlas; A2RUC4; -.
DR PRIDE; A2RUC4; -.
DR ProteomicsDB; 511; -. [A2RUC4-1]
DR ProteomicsDB; 512; -. [A2RUC4-2]
DR Antibodypedia; 34079; 91 antibodies from 19 providers.
DR DNASU; 129450; -.
DR Ensembl; ENST00000354611.9; ENSP00000346627.4; ENSG00000162971.11. [A2RUC4-1]
DR GeneID; 129450; -.
DR KEGG; hsa:129450; -.
DR MANE-Select; ENST00000354611.9; ENSP00000346627.4; NM_001039693.3; NP_001034782.1.
DR UCSC; uc002uvi.5; human. [A2RUC4-1]
DR CTD; 129450; -.
DR GeneCards; TYW5; -.
DR HGNC; HGNC:26754; TYW5.
DR HPA; ENSG00000162971; Low tissue specificity.
DR neXtProt; NX_A2RUC4; -.
DR OpenTargets; ENSG00000162971; -.
DR PharmGKB; PA162379298; -.
DR VEuPathDB; HostDB:ENSG00000162971; -.
DR eggNOG; KOG2132; Eukaryota.
DR GeneTree; ENSGT00940000158493; -.
DR HOGENOM; CLU_016785_4_0_1; -.
DR InParanoid; A2RUC4; -.
DR OMA; PLYDDRP; -.
DR OrthoDB; 1385616at2759; -.
DR PhylomeDB; A2RUC4; -.
DR TreeFam; TF332364; -.
DR BioCyc; MetaCyc:ENSG00000162971-MON; -.
DR BRENDA; 1.14.11.42; 2681.
DR PathwayCommons; A2RUC4; -.
DR Reactome; R-HSA-6782861; Synthesis of wybutosine at G37 of tRNA(Phe).
DR SignaLink; A2RUC4; -.
DR UniPathway; UPA00375; -.
DR BioGRID-ORCS; 129450; 8 hits in 1077 CRISPR screens.
DR GenomeRNAi; 129450; -.
DR Pharos; A2RUC4; Tbio.
DR PRO; PR:A2RUC4; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; A2RUC4; protein.
DR Bgee; ENSG00000162971; Expressed in epithelial cell of pancreas and 139 other tissues.
DR ExpressionAtlas; A2RUC4; baseline and differential.
DR Genevisible; A2RUC4; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:Reactome.
DR GO; GO:0016706; F:2-oxoglutarate-dependent dioxygenase activity; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB.
DR GO; GO:0102524; F:tRNAPhe (7-(3-amino-3-carboxypropyl)wyosine37-C2)-hydroxylase activity; IDA:UniProtKB.
DR GO; GO:0031591; P:wybutosine biosynthetic process; IDA:UniProtKB.
DR InterPro; IPR041667; Cupin_8.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR029612; TYW5.
DR PANTHER; PTHR12461:SF50; PTHR12461:SF50; 1.
DR Pfam; PF13621; Cupin_8; 1.
DR SMART; SM00558; JmjC; 1.
DR PROSITE; PS51184; JMJC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Dioxygenase; Iron; Metal-binding;
KW Oxidoreductase; Reference proteome; tRNA processing.
FT CHAIN 1..315
FT /note="tRNA wybutosine-synthesizing protein 5"
FT /id="PRO_0000309274"
FT DOMAIN 102..267
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 106
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:20972222"
FT BINDING 160
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT BINDING 162
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT BINDING 166
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:20972222"
FT BINDING 175
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000269|PubMed:20972222"
FT BINDING 235
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT VAR_SEQ 1..163
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_029106"
FT VARIANT 50
FT /note="S -> G (in dbSNP:rs10497844)"
FT /id="VAR_036926"
FT MUTAGEN 108
FT /note="R->A: Abolishes enzyme activity and ability to bind
FT tRNA."
FT /evidence="ECO:0000269|PubMed:20972222"
FT MUTAGEN 149
FT /note="R->A: Abolishes enzyme activity and ability to bind
FT tRNA."
FT /evidence="ECO:0000269|PubMed:20972222"
FT STRAND 10..13
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 16..22
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 40..43
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 46..53
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 57..66
FT /evidence="ECO:0007829|PDB:3AL5"
FT TURN 70..72
FT /evidence="ECO:0007829|PDB:3AL6"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 82..90
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:3AL5"
FT TURN 114..116
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 121..124
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 126..129
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 140..142
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 143..151
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 156..160
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 163..170
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 175..180
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 182..188
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:3AL5"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 211..213
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 216..221
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 226..229
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 234..241
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 243..250
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:3AL5"
FT STRAND 263..265
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 270..286
FT /evidence="ECO:0007829|PDB:3AL5"
FT HELIX 291..308
FT /evidence="ECO:0007829|PDB:3AL5"
SQ SEQUENCE 315 AA; 36548 MW; F291C48E8CA729FE CRC64;
MAGQHLPVPR LEGVSREQFM QHLYPQRKPL VLEGIDLGPC TSKWTVDYLS QVGGKKEVKI
HVAAVAQMDF ISKNFVYRTL PFDQLVQRAA EEKHKEFFVS EDEKYYLRSL GEDPRKDVAD
IRKQFPLLKG DIKFPEFFKE EQFFSSVFRI SSPGLQLWTH YDVMDNLLIQ VTGKKRVVLF
SPRDAQYLYL KGTKSEVLNI DNPDLAKYPL FSKARRYECS LEAGDVLFIP ALWFHNVISE
EFGVGVNIFW KHLPSECYDK TDTYGNKDPT AASRAAQILD RALKTLAELP EEYRDFYARR
MVLHIQDKAY SKNSE
