TYW4_HUMAN
ID TYW4_HUMAN Reviewed; 686 AA.
AC O60294; Q4JFT6; Q96B55; Q9NR10;
DT 24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2004, sequence version 3.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=tRNA wybutosine-synthesizing protein 4;
DE Short=tRNA yW-synthesizing protein 4;
DE EC=2.1.1.290;
DE EC=2.3.1.231;
DE AltName: Full=Leucine carboxyl methyltransferase 2;
DE AltName: Full=tRNA(Phe) (7-(3-amino-3-(methoxycarbonyl)propyl)wyosine(37)-N)-methoxycarbonyltransferase;
DE AltName: Full=tRNA(Phe) (7-(3-amino-3-carboxypropyl)wyosine(37)-O)-methyltransferase;
GN Name=LCMT2; Synonyms=KIAA0547, TYW4;
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=Brain;
RX PubMed=9628581; DOI=10.1093/dnares/5.1.31;
RA Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N.,
RA Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. IX. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:31-39(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-67; SER-141; TYR-149
RP AND ALA-518.
RG NIEHS SNPs program;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=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 NUCLEOTIDE SEQUENCE [MRNA] OF 126-686.
RA Li S., Zhang B., Li X.;
RT "Isolation of genes coding for p21WAF1/CIP1 promoter-interacting proteins
RT using the yeast one-hybrid system.";
RL Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP INTERACTION WITH RNF144B.
RX PubMed=12853982; DOI=10.1038/sj.onc.1206586;
RA Ng C.-C., Arakawa H., Fukuda S., Kondoh H., Nakamura Y.;
RT "p53RFP, a p53-inducible RING-finger protein, regulates the stability of
RT p21WAF1.";
RL Oncogene 22:4449-4458(2003).
CC -!- FUNCTION: Probable S-adenosyl-L-methionine-dependent methyltransferase
CC that acts as a 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 (By similarity). May methylate the carboxyl group of leucine
CC residues to form alpha-leucine ester residues. {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-[(3S)-3-amino-3-carboxypropyl]wyosine(37) in tRNA(Phe) + S-
CC adenosyl-L-methionine = 7-[(3S)-(3-amino-3-
CC methoxycarbonyl)propyl]wyosine(37) in tRNA(Phe) + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:36903, Rhea:RHEA-COMP:10379, Rhea:RHEA-
CC COMP:11844, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:73543,
CC ChEBI:CHEBI:74275; EC=2.1.1.290;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-[(3S)-(3-amino-3-methoxycarbonyl)propyl]wyosine(37) in
CC tRNA(Phe) + CO2 + S-adenosyl-L-methionine = 2 H(+) + S-adenosyl-L-
CC homocysteine + wybutosine(37) in tRNA(Phe); Xref=Rhea:RHEA:37119,
CC Rhea:RHEA-COMP:11844, Rhea:RHEA-COMP:11847, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:73544, ChEBI:CHEBI:74275; EC=2.3.1.231;
CC -!- PATHWAY: tRNA modification; wybutosine-tRNA(Phe) biosynthesis.
CC -!- SUBUNIT: Interacts with RNF144B/IBRDC2. {ECO:0000269|PubMed:12853982}.
CC -!- INTERACTION:
CC O60294; O43707: ACTN4; NbExp=3; IntAct=EBI-11023122, EBI-351526;
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily. LCMT family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA25473.2; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/lcmt2/";
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DR EMBL; AB011119; BAA25473.2; ALT_INIT; mRNA.
DR EMBL; DQ102852; AAY88744.1; -; Genomic_DNA.
DR EMBL; BC015949; AAH15949.1; -; mRNA.
DR EMBL; AF265443; AAF75774.1; -; mRNA.
DR CCDS; CCDS10094.1; -.
DR RefSeq; NP_055608.2; NM_014793.4.
DR AlphaFoldDB; O60294; -.
DR SMR; O60294; -.
DR BioGRID; 115173; 34.
DR IntAct; O60294; 12.
DR STRING; 9606.ENSP00000307214; -.
DR DrugBank; DB00149; Leucine.
DR iPTMnet; O60294; -.
DR PhosphoSitePlus; O60294; -.
DR BioMuta; LCMT2; -.
DR EPD; O60294; -.
DR jPOST; O60294; -.
DR MassIVE; O60294; -.
DR MaxQB; O60294; -.
DR PaxDb; O60294; -.
DR PeptideAtlas; O60294; -.
DR PRIDE; O60294; -.
DR ProteomicsDB; 49327; -.
DR TopDownProteomics; O60294; -.
DR Antibodypedia; 11180; 105 antibodies from 23 providers.
DR DNASU; 9836; -.
DR Ensembl; ENST00000305641.7; ENSP00000307214.5; ENSG00000168806.8.
DR GeneID; 9836; -.
DR KEGG; hsa:9836; -.
DR MANE-Select; ENST00000305641.7; ENSP00000307214.5; NM_014793.5; NP_055608.2.
DR UCSC; uc001zrg.4; human.
DR CTD; 9836; -.
DR DisGeNET; 9836; -.
DR GeneCards; LCMT2; -.
DR HGNC; HGNC:17558; LCMT2.
DR HPA; ENSG00000168806; Low tissue specificity.
DR MIM; 611246; gene.
DR neXtProt; NX_O60294; -.
DR OpenTargets; ENSG00000168806; -.
DR PharmGKB; PA134878443; -.
DR VEuPathDB; HostDB:ENSG00000168806; -.
DR eggNOG; KOG2918; Eukaryota.
DR GeneTree; ENSGT00940000162599; -.
DR HOGENOM; CLU_002761_2_0_1; -.
DR InParanoid; O60294; -.
DR OMA; WEVDFPD; -.
DR OrthoDB; 1094856at2759; -.
DR PhylomeDB; O60294; -.
DR TreeFam; TF315087; -.
DR PathwayCommons; O60294; -.
DR Reactome; R-HSA-6782861; Synthesis of wybutosine at G37 of tRNA(Phe).
DR SignaLink; O60294; -.
DR UniPathway; UPA00375; -.
DR BioGRID-ORCS; 9836; 21 hits in 1073 CRISPR screens.
DR GeneWiki; LCMT2; -.
DR GenomeRNAi; 9836; -.
DR Pharos; O60294; Tbio.
DR PRO; PR:O60294; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; O60294; protein.
DR Bgee; ENSG00000168806; Expressed in hair follicle and 188 other tissues.
DR ExpressionAtlas; O60294; baseline and differential.
DR Genevisible; O60294; HS.
DR GO; GO:0005737; C:cytoplasm; TAS:Reactome.
DR GO; GO:0008175; F:tRNA methyltransferase activity; IBA:GO_Central.
DR GO; GO:0030488; P:tRNA methylation; IBA:GO_Central.
DR GO; GO:0006400; P:tRNA modification; TAS:Reactome.
DR GO; GO:0031591; P:wybutosine biosynthetic process; IBA:GO_Central.
DR Gene3D; 2.120.10.80; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR015915; Kelch-typ_b-propeller.
DR InterPro; IPR007213; Ppm1/Ppm2/Tcmp.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF04072; LCM; 1.
DR SUPFAM; SSF117281; SSF117281; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase; tRNA processing.
FT CHAIN 1..686
FT /note="tRNA wybutosine-synthesizing protein 4"
FT /id="PRO_0000204423"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 59
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 89
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 161..162
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 188
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT VARIANT 67
FT /note="V -> L (in dbSNP:rs45552436)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023378"
FT VARIANT 141
FT /note="R -> S (in dbSNP:rs3742970)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_022081"
FT VARIANT 149
FT /note="C -> Y (in dbSNP:rs45593931)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023379"
FT VARIANT 518
FT /note="T -> A (in dbSNP:rs45530831)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_023380"
FT CONFLICT 164..165
FT /note="QL -> HV (in Ref. 4; AAF75774)"
FT /evidence="ECO:0000305"
FT CONFLICT 202
FT /note="L -> F (in Ref. 4; AAF75774)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="M -> I (in Ref. 1; BAA25473)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 686 AA; 75602 MW; 146F1C44F541059F CRC64;
MGPRSRERRA GAVQNTNDSS ALSKRSLAAR GYVQDPFAAL LVPGAARRAP LIHRGYYVRA
RAVRHCVRAF LEQIGAPQAA LRAQILSLGA GFDSLYFRLK TAGRLARAAV WEVDFPDVAR
RKAERIGETP ELCALTGPFE RGEPASALCF ESADYCILGL DLRQLQRVEE ALGAAGLDAA
SPTLLLAEAV LTYLEPESAA ALIAWAAQRF PNALFVVYEQ MRPQDAFGQF MLQHFRQLNS
PLHGLERFPD VEAQRRRFLQ AGWTACGAVD MNEFYHCFLP AEERRRVENI EPFDEFEEWH
LKCAHYFILA ASRGDTLSHT LVFPSSEAFP RVNPASPSGV FPASVVSSEG QVPNLKRYGH
ASVFLSPDVI LSAGGFGEQE GRHCRVSQFH LLSRDCDSEW KGSQIGSCGT GVQWDGRLYH
TMTRLSESRV LVLGGRLSPV SPALGVLQLH FFKSEDNNTE DLKVTITKAG RKDDSTLCCW
RHSTTEVSCQ NQEYLFVYGG RSVVEPVLSD WHFLHVGTMA WVRIPVEGEV PEARHSHSAC
TWQGGALIAG GLGASEEPLN SVLFLRPISC GFLWESVDIQ PPITPRYSHT AHVLNGKLLL
VGGIWIHSSS FPGVTVINLT TGLSSEYQID TTYVPWPLML HNHTSILLPE EQQLLLLGGG
GNCFSFGTYF NPHTVTLDLS SLSAGQ
