TYW1_HUMAN
ID TYW1_HUMAN Reviewed; 732 AA.
AC Q9NV66; Q6PJG8; Q75MG8; Q75MN3; Q86V12; Q8IVS7; Q9H9C4;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=S-adenosyl-L-methionine-dependent tRNA 4-demethylwyosine synthase TYW1;
DE EC=4.1.3.44;
DE AltName: Full=Radical S-adenosyl methionine and flavodoxin domain-containing protein 1;
DE AltName: Full=tRNA wybutosine-synthesizing protein 1 homolog;
DE AltName: Full=tRNA-yW-synthesizing protein;
GN Name=TYW1; Synonyms=RSAFD1;
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] (ISOFORM 1), AND VARIANTS ARG-632
RP AND ASN-671.
RC TISSUE=Teratocarcinoma;
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=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Colon, Placenta, and Uterus;
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).
CC -!- FUNCTION: Probable component of the wybutosine biosynthesis pathway.
CC Wybutosine is a hyper modified guanosine with a tricyclic base found at
CC the 3'-position adjacent to the anticodon of eukaryotic phenylalanine
CC tRNA. Catalyzes the condensation of N-methylguanine with 2 carbon atoms
CC from pyruvate to form the tricyclic 4-demethylwyosine, an intermediate
CC in wybutosine biosynthesis (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(1)-methylguanosine(37) in tRNA(Phe) + pyruvate + S-adenosyl-
CC L-methionine = 4-demethylwyosine(37) in tRNA(Phe) + 5'-deoxyadenosine
CC + CO2 + H2O + L-methionine; Xref=Rhea:RHEA:36347, Rhea:RHEA-
CC COMP:10164, Rhea:RHEA-COMP:10165, ChEBI:CHEBI:15361,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:16526, ChEBI:CHEBI:17319,
CC ChEBI:CHEBI:57844, ChEBI:CHEBI:59789, ChEBI:CHEBI:64315,
CC ChEBI:CHEBI:73542; EC=4.1.3.44;
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 1 [4Fe-4S] cluster. The cluster is coordinated with 3
CC cysteines and an exchangeable S-adenosyl-L-methionine. {ECO:0000250};
CC -!- PATHWAY: tRNA modification; wybutosine-tRNA(Phe) biosynthesis.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NV66-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NV66-2; Sequence=VSP_024066, VSP_024067;
CC -!- SIMILARITY: Belongs to the TYW1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH15591.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAB14307.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK001762; BAA91891.1; -; mRNA.
DR EMBL; AK022917; BAB14307.1; ALT_INIT; mRNA.
DR EMBL; AC079920; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC006480; AAS07568.1; -; Genomic_DNA.
DR EMBL; AC073089; AAS07520.1; -; Genomic_DNA.
DR EMBL; BC015591; AAH15591.1; ALT_FRAME; mRNA.
DR EMBL; BC042156; AAH42156.1; ALT_TERM; mRNA.
DR EMBL; BC051888; AAH51888.1; -; mRNA.
DR CCDS; CCDS5538.1; -. [Q9NV66-1]
DR RefSeq; NP_060734.2; NM_018264.3. [Q9NV66-1]
DR AlphaFoldDB; Q9NV66; -.
DR SMR; Q9NV66; -.
DR BioGRID; 120544; 126.
DR IntAct; Q9NV66; 33.
DR STRING; 9606.ENSP00000352645; -.
DR iPTMnet; Q9NV66; -.
DR PhosphoSitePlus; Q9NV66; -.
DR BioMuta; TYW1; -.
DR DMDM; 143678193; -.
DR EPD; Q9NV66; -.
DR jPOST; Q9NV66; -.
DR MassIVE; Q9NV66; -.
DR MaxQB; Q9NV66; -.
DR PaxDb; Q9NV66; -.
DR PeptideAtlas; Q9NV66; -.
DR PRIDE; Q9NV66; -.
DR ProteomicsDB; 82752; -. [Q9NV66-1]
DR ProteomicsDB; 82753; -. [Q9NV66-2]
DR Antibodypedia; 2749; 72 antibodies from 21 providers.
DR DNASU; 55253; -.
DR Ensembl; ENST00000359626.10; ENSP00000352645.5; ENSG00000198874.14. [Q9NV66-1]
DR Ensembl; ENST00000361660.8; ENSP00000354795.4; ENSG00000198874.14. [Q9NV66-2]
DR GeneID; 55253; -.
DR KEGG; hsa:55253; -.
DR MANE-Select; ENST00000359626.10; ENSP00000352645.5; NM_018264.4; NP_060734.2.
DR UCSC; uc003tvn.5; human. [Q9NV66-1]
DR CTD; 55253; -.
DR DisGeNET; 55253; -.
DR GeneCards; TYW1; -.
DR HGNC; HGNC:25598; TYW1.
DR HPA; ENSG00000198874; Low tissue specificity.
DR MIM; 611243; gene.
DR neXtProt; NX_Q9NV66; -.
DR OpenTargets; ENSG00000198874; -.
DR PharmGKB; PA134940167; -.
DR VEuPathDB; HostDB:ENSG00000198874; -.
DR eggNOG; KOG1160; Eukaryota.
DR GeneTree; ENSGT00510000047059; -.
DR HOGENOM; CLU_007952_2_0_1; -.
DR InParanoid; Q9NV66; -.
DR OMA; WMLGARR; -.
DR OrthoDB; 731783at2759; -.
DR PhylomeDB; Q9NV66; -.
DR TreeFam; TF300773; -.
DR PathwayCommons; Q9NV66; -.
DR Reactome; R-HSA-6782861; Synthesis of wybutosine at G37 of tRNA(Phe).
DR SignaLink; Q9NV66; -.
DR UniPathway; UPA00375; -.
DR BioGRID-ORCS; 55253; 14 hits in 1041 CRISPR screens.
DR ChiTaRS; TYW1; human.
DR GenomeRNAi; 55253; -.
DR Pharos; Q9NV66; Tbio.
DR PRO; PR:Q9NV66; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9NV66; protein.
DR Bgee; ENSG00000198874; Expressed in sural nerve and 100 other tissues.
DR ExpressionAtlas; Q9NV66; baseline and differential.
DR Genevisible; Q9NV66; HS.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0010181; F:FMN binding; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0102521; F:tRNA-4-demethylwyosine synthase activity; IEA:UniProtKB-EC.
DR GO; GO:0031591; P:wybutosine biosynthetic process; IBA:GO_Central.
DR Gene3D; 3.20.20.70; -; 1.
DR Gene3D; 3.40.50.360; -; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR001094; Flavdoxin-like.
DR InterPro; IPR008254; Flavodoxin/NO_synth.
DR InterPro; IPR029039; Flavoprotein-like_sf.
DR InterPro; IPR007197; rSAM.
DR InterPro; IPR013917; tRNA_wybutosine-synth.
DR InterPro; IPR034556; tRNA_wybutosine-synthase.
DR PANTHER; PTHR13930; PTHR13930; 1.
DR Pfam; PF00258; Flavodoxin_1; 1.
DR Pfam; PF04055; Radical_SAM; 1.
DR Pfam; PF08608; Wyosine_form; 1.
DR PRINTS; PR00369; FLAVODOXIN.
DR SFLD; SFLDS00029; Radical_SAM; 1.
DR SFLD; SFLDF00284; tRNA_wybutosine-synthesizing; 1.
DR SUPFAM; SSF52218; SSF52218; 1.
DR PROSITE; PS50902; FLAVODOXIN_LIKE; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 2: Evidence at transcript level;
KW 4Fe-4S; Alternative splicing; Iron; Iron-sulfur; Lyase; Metal-binding;
KW Nucleotide-binding; Reference proteome; S-adenosyl-L-methionine;
KW tRNA processing.
FT CHAIN 1..732
FT /note="S-adenosyl-L-methionine-dependent tRNA 4-
FT demethylwyosine synthase TYW1"
FT /id="PRO_0000281826"
FT DOMAIN 79..237
FT /note="Flavodoxin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT DOMAIN 400..644
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 248..314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 256..290
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 85..89
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 176..208
FT /ligand="FMN"
FT /ligand_id="ChEBI:CHEBI:58210"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00088"
FT BINDING 416
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255"
FT BINDING 420
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255"
FT BINDING 423
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000255"
FT VAR_SEQ 368..384
FT /note="GYQLIGSHSGVKLCRWT -> VHAPRERRLLQTHILWN (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_024066"
FT VAR_SEQ 385..732
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_024067"
FT VARIANT 462
FT /note="G -> V (in dbSNP:rs2261015)"
FT /id="VAR_031288"
FT VARIANT 632
FT /note="H -> R (in dbSNP:rs2949097)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_031289"
FT VARIANT 671
FT /note="D -> N (in dbSNP:rs28450001)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_031290"
FT CONFLICT 382
FT /note="R -> M (in Ref. 1; BAB14307)"
FT /evidence="ECO:0000305"
FT CONFLICT 388
FT /note="L -> F (in Ref. 1; BAB14307)"
FT /evidence="ECO:0000305"
FT CONFLICT 416
FT /note="C -> Y (in Ref. 1; BAB14307)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="K -> R (in Ref. 1; BAB14307)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 732 AA; 83702 MW; 95E8E5C3F88ADD23 CRC64;
MDPSADTWDL FSPLISLWIN RFYIYLGFAV SISLWICVQI VIKTQGKNLQ EKSVPKAAQD
LMTNGYVSLQ EKDIFVSGVK IFYGSQTGTA KGFATVLAEA VTSLDLPVAI INLKEYDPDD
HLIEEVTSKN VCVFLVATYT DGLPTESAEW FCKWLEEASI DFRFGKTYLK GMRYAVFGLG
NSAYASHFNK VGKNVDKWLW MLGAHRVMSR GEGDCDVVKS KHGSIEADFR AWKTKFISQL
QALQKGERKK SCGGHCKKGK CESHQHGSEE REEGSHEQDE LHHRDTEEEE PFESSSEEEF
GGEDHQSLNS IVDVEDLGKI MDHVKKEKRE KEQQEEKSGL FRNMGRNEDG ERRAMITPAL
REALTKQGYQ LIGSHSGVKL CRWTKSMLRG RGGCYKHTFY GIESHRCMET TPSLACANKC
VFCWRHHTNP VGTEWRWKMD QPEMILKEAI ENHQNMIKQF KGVPGVKAER FEEGMTVKHC
ALSLVGEPIM YPEINRFLKL LHQCKISSFL VTNAQFPAEI RNLEPVTQLY VSVDASTKDS
LKKIDRPLFK DFWQRFLDSL KALAVKQQRT VYRLTLVKAW NVDELQAYAQ LVSLGNPDFI
EVKGVTYCGE SSASSLTMAH VPWHEEVVQF VHELVDLIPE YEIACEHEHS NCLLIAHRKF
KIGGEWWTWI DYNRFQELIQ EYEDSGGSKT FSAKDYMART PHWALFGASE RGFDPKDTRH
QRKNKSKAIS GC
