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   24-JAN-2024, entry version 120.
DE   RecName: Full=tRNA wybutosine-synthesizing protein 5 {ECO:0000305|PubMed:20739293};
DE            Short=hTYW5;
DE            Short=tRNA yW-synthesizing protein 5;
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; 15.
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; 9606-ENSP00000346627; -.
DR   PeptideAtlas; A2RUC4; -.
DR   ProteomicsDB; 511; -. [A2RUC4-1]
DR   ProteomicsDB; 512; -. [A2RUC4-2]
DR   Pumba; A2RUC4; -.
DR   Antibodypedia; 34079; 108 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   AGR; HGNC:26754; -.
DR   CTD; 129450; -.
DR   GeneCards; TYW5; -.
DR   HGNC; HGNC:26754; TYW5.
DR   HPA; ENSG00000162971; Low tissue specificity.
DR   MIM; 619882; gene.
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; LYDDRPV; -.
DR   OrthoDB; 9938at2759; -.
DR   PhylomeDB; A2RUC4; -.
DR   TreeFam; TF332364; -.
DR   BioCyc; MetaCyc:ENSG00000162971-MONOMER; -.
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; 9 hits in 1155 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 140 other cell types or tissues.
DR   ExpressionAtlas; A2RUC4; baseline and differential.
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:tRNA(Phe) (7-(3-amino-3-carboxypropyl)wyosine37-C2)-hydroxylase activity; IDA:UniProtKB.
DR   GO; GO:0031591; P:wybutosine biosynthetic process; IDA:UniProtKB.
DR   Gene3D; 6.10.140.1470; -; 1.
DR   Gene3D; 2.60.120.650; Cupin; 1.
DR   InterPro; IPR041667; Cupin_8.
DR   InterPro; IPR003347; JmjC_dom.
DR   PANTHER; PTHR12461:SF97; BIFUNCTIONAL PEPTIDASE AND (3S)-LYSYL HYDROXYLASE JMJD7-RELATED; 1.
DR   PANTHER; PTHR12461; HYPOXIA-INDUCIBLE FACTOR 1 ALPHA INHIBITOR-RELATED; 1.
DR   Pfam; PF13621; Cupin_8; 1.
DR   SMART; SM00558; JmjC; 1.
DR   SUPFAM; SSF51197; Clavaminate synthase-like; 1.
DR   PROSITE; PS51184; JMJC; 1.
DR   Genevisible; A2RUC4; HS.
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
//