TYW2_HUMAN
ID TYW2_HUMAN Reviewed; 448 AA.
AC Q53H54; Q6PKB9; Q96F21; Q9NWK6;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=tRNA wybutosine-synthesizing protein 2 homolog;
DE Short=tRNA-yW-synthesizing protein 2;
DE EC=2.5.1.114;
DE AltName: Full=tRNA(Phe) (4-demethylwyosine(37)-C(7)) aminocarboxypropyltransferase;
GN Name=TRMT12; Synonyms=TRM12, TYW2;
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].
RC TISSUE=Colon;
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 MRNA].
RC TISSUE=Colon;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ARG-28.
RC TISSUE=Ovary, 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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF LYS-225; TYR-242;
RP PHE-248; GLU-265 AND ASP-293.
RX PubMed=22761755; DOI=10.1371/journal.pone.0039297;
RA Rodriguez V., Vasudevan S., Noma A., Carlson B.A., Green J.E., Suzuki T.,
RA Chandrasekharappa S.C.;
RT "Structure-function analysis of human TYW2 enzyme required for the
RT biosynthesis of a highly modified Wybutosine (yW) base in phenylalanine-
RT tRNA.";
RL PLoS ONE 7:E39297-E39297(2012).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent transferase that acts as a
CC component of the wybutosine biosynthesis pathway. Wybutosine is a hyper
CC modified guanosine with a tricyclic base found at the 3'-position
CC adjacent to the anticodon of eukaryotic phenylalanine tRNA. Catalyzes
CC the transfer of the alpha-amino-alpha-carboxypropyl (acp) group from S-
CC adenosyl-L-methionine to the C-7 position of 4-demethylwyosine (imG-14)
CC to produce wybutosine-86. {ECO:0000269|PubMed:22761755}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4-demethylwyosine(37) in tRNA(Phe) + S-adenosyl-L-methionine =
CC 4-demethyl-7-[(3S)-3-amino-3-carboxypropyl]wyosine(37) in tRNA(Phe) +
CC H(+) + S-methyl-5'-thioadenosine; Xref=Rhea:RHEA:36355, Rhea:RHEA-
CC COMP:10164, Rhea:RHEA-COMP:10378, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17509, ChEBI:CHEBI:59789, ChEBI:CHEBI:64315,
CC ChEBI:CHEBI:73550; EC=2.5.1.114;
CC Evidence={ECO:0000269|PubMed:22761755};
CC -!- PATHWAY: tRNA modification; wybutosine-tRNA(Phe) biosynthesis.
CC {ECO:0000269|PubMed:22761755}.
CC -!- INTERACTION:
CC Q53H54; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-10242598, EBI-739832;
CC Q53H54; P36639-2: NUDT1; NbExp=3; IntAct=EBI-10242598, EBI-12380931;
CC Q53H54; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-10242598, EBI-11320284;
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. TRM5/TYW2 family. {ECO:0000255|PROSITE-ProRule:PRU01021}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH03057.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAH03057.2; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence starting in position 371.; Evidence={ECO:0000305};
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DR EMBL; AK000779; BAA91374.1; -; mRNA.
DR EMBL; AK222727; BAD96447.1; -; mRNA.
DR EMBL; BC003057; AAH03057.2; ALT_SEQ; mRNA.
DR EMBL; BC011713; AAH11713.1; -; mRNA.
DR CCDS; CCDS6349.1; -.
DR RefSeq; NP_060426.2; NM_017956.3.
DR AlphaFoldDB; Q53H54; -.
DR SMR; Q53H54; -.
DR BioGRID; 120368; 8.
DR IntAct; Q53H54; 7.
DR STRING; 9606.ENSP00000329858; -.
DR GlyGen; Q53H54; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q53H54; -.
DR PhosphoSitePlus; Q53H54; -.
DR BioMuta; TRMT12; -.
DR DMDM; 74726289; -.
DR EPD; Q53H54; -.
DR MassIVE; Q53H54; -.
DR MaxQB; Q53H54; -.
DR PaxDb; Q53H54; -.
DR PeptideAtlas; Q53H54; -.
DR PRIDE; Q53H54; -.
DR ProteomicsDB; 62495; -.
DR Antibodypedia; 13906; 102 antibodies from 19 providers.
DR DNASU; 55039; -.
DR Ensembl; ENST00000328599.4; ENSP00000329858.3; ENSG00000183665.5.
DR GeneID; 55039; -.
DR KEGG; hsa:55039; -.
DR MANE-Select; ENST00000328599.4; ENSP00000329858.3; NM_017956.4; NP_060426.2.
DR UCSC; uc003yra.5; human.
DR CTD; 55039; -.
DR DisGeNET; 55039; -.
DR GeneCards; TRMT12; -.
DR HGNC; HGNC:26091; TRMT12.
DR HPA; ENSG00000183665; Low tissue specificity.
DR MIM; 611244; gene.
DR neXtProt; NX_Q53H54; -.
DR OpenTargets; ENSG00000183665; -.
DR PharmGKB; PA142670700; -.
DR VEuPathDB; HostDB:ENSG00000183665; -.
DR eggNOG; KOG1227; Eukaryota.
DR GeneTree; ENSGT00940000153304; -.
DR HOGENOM; CLU_022610_1_0_1; -.
DR InParanoid; Q53H54; -.
DR OMA; WQRHGNL; -.
DR OrthoDB; 736943at2759; -.
DR PhylomeDB; Q53H54; -.
DR TreeFam; TF314137; -.
DR BRENDA; 2.5.1.114; 2681.
DR PathwayCommons; Q53H54; -.
DR Reactome; R-HSA-6782861; Synthesis of wybutosine at G37 of tRNA(Phe).
DR SignaLink; Q53H54; -.
DR UniPathway; UPA00375; -.
DR BioGRID-ORCS; 55039; 25 hits in 1078 CRISPR screens.
DR ChiTaRS; TRMT12; human.
DR GeneWiki; TRMT12; -.
DR GenomeRNAi; 55039; -.
DR Pharos; Q53H54; Tbio.
DR PRO; PR:Q53H54; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q53H54; protein.
DR Bgee; ENSG00000183665; Expressed in sperm and 159 other tissues.
DR ExpressionAtlas; Q53H54; baseline and differential.
DR Genevisible; Q53H54; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0102522; F:tRNA 4-demethylwyosine alpha-amino-alpha-carboxypropyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0008175; F:tRNA methyltransferase activity; IBA:GO_Central.
DR GO; GO:0030488; P:tRNA methylation; IBA:GO_Central.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR030382; MeTrfase_TRM5/TYW2.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF02475; Met_10; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51684; SAM_MT_TRM5_TYW2; 1.
PE 1: Evidence at protein level;
KW Reference proteome; S-adenosyl-L-methionine; Transferase; tRNA processing.
FT CHAIN 1..448
FT /note="tRNA wybutosine-synthesizing protein 2 homolog"
FT /id="PRO_0000281836"
FT BINDING 218
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01021"
FT BINDING 225
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01021"
FT BINDING 265
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01021"
FT BINDING 293..294
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01021"
FT VARIANT 28
FT /note="W -> R (in dbSNP:rs3812475)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_031291"
FT MUTAGEN 225
FT /note="K->A: Lack of activity."
FT /evidence="ECO:0000269|PubMed:22761755"
FT MUTAGEN 242
FT /note="Y->A: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:22761755"
FT MUTAGEN 248
FT /note="F->A: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:22761755"
FT MUTAGEN 265
FT /note="E->A: Lack of activity."
FT /evidence="ECO:0000269|PubMed:22761755"
FT MUTAGEN 293
FT /note="D->A: Does not affect activity."
FT /evidence="ECO:0000269|PubMed:22761755"
FT CONFLICT 342
FT /note="F -> S (in Ref. 1; BAA91374)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 448 AA; 50236 MW; 5E66C20AF26C4B5F CRC64;
MRENVVVSNM ERESGKPVAV VAVVTEPWFT QRYREYLQRQ KLFDTQHRVE KMPDGSVALP
VLGETLPEQH LQELRNRVAP GSPCMLTQLP DPVPSKRAQG CSPAQKLCLE VSRWVEGRGV
KWSAELEADL PRSWQRHGNL LLLSEDCFQA KQWKNLGPEL WETVALALGV QRLAKRGRVS
PDGTRTPAVT LLLGDHGWVE HVDNGIRYKF DVTQCMFSFG NITEKLRVAS LSCAGEVLVD
LYAGIGYFTL PFLVHAGAAF VHACEWNPHA VVALRNNLEI NGVADRCQIH FGDNRKLKLS
NIADRVILGL IPSSEEGWPI ACQVLRQDAG GILHIHQNVE SFPGKNLQAL GVSKVEKEHW
LYPQQITTNQ WKNGATRDSR GKMLSPATKP EWQRWAESAE TRIATLLQQV HGKPWKTQIL
HIQPVKSYAP HVDHIVLDLE CCPCPSVG
