DTD2_HUMAN
ID DTD2_HUMAN Reviewed; 168 AA.
AC Q96FN9; D3DS87;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=D-aminoacyl-tRNA deacylase 2 {ECO:0000305};
DE EC=3.1.1.96 {ECO:0000269|PubMed:29410408};
DE AltName: Full=Animalia-specific tRNA deacylase {ECO:0000303|PubMed:29410408};
DE Short=ATD {ECO:0000303|PubMed:29410408};
DE AltName: Full=D-tyrosyl-tRNA(Tyr) deacylase 2 {ECO:0000305};
DE AltName: Full=L-alanyl-tRNA deacylase {ECO:0000305|PubMed:29410408};
GN Name=DTD2; Synonyms=C14orf126;
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 GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [2]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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, AND CATALYTIC ACTIVITY.
RX PubMed=29410408; DOI=10.1038/s41467-017-02204-w;
RA Kuncha S.K., Mazeed M., Singh R., Kattula B., Routh S.B.,
RA Sankaranarayanan R.;
RT "A chiral selectivity relaxed paralog of DTD for proofreading tRNA
RT mischarging in Animalia.";
RL Nat. Commun. 9:511-511(2018).
CC -!- FUNCTION: Deacylates mischarged D-aminoacyl-tRNAs (By similarity). Also
CC deacylates mischarged glycyl-tRNA(Ala), protecting cells against
CC glycine mischarging by AlaRS (By similarity). Probably acts by
CC rejecting L-amino acids from its binding site rather than specific
CC recognition of D-amino acids (By similarity). Catalyzes the hydrolysis
CC of D-tyrosyl-tRNA(Tyr), has no activity on correctly charged L-tyrosyl-
CC tRNA(Tyr) (By similarity). By recycling D-aminoacyl-tRNA to D-amino
CC acids and free tRNA molecules, this enzyme counteracts the toxicity
CC associated with the formation of D-aminoacyl-tRNA entities in vivo and
CC helps enforce protein L-homochirality. In contrast to DTD1, deacylates
CC L-Ala mischarged on tRNA(Thr)(G4.U69) by alanine-tRNA ligase AARS
CC (PubMed:29410408). Can deacylate L-Ala due to a relaxed specificity for
CC substrate chirality caused by the trans conformation of the Gly-Pro
CC motif in the active site (PubMed:29410408). Also hydrolyzes correctly
CC charged, achiral, glycyl-tRNA(Gly) in vitro, although in vivo
CC EEF1A1/EF-Tu may protect cognate achiral glycyl-tRNA(Gly) from DTD2-
CC mediated deacetylation (By similarity). {ECO:0000250|UniProtKB:Q8BHA3,
CC ECO:0000269|PubMed:29410408}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a D-aminoacyl-tRNA + H2O = a D-alpha-amino acid + a tRNA +
CC H(+); Xref=Rhea:RHEA:13953, Rhea:RHEA-COMP:10123, Rhea:RHEA-
CC COMP:10124, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:59871,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:79333; EC=3.1.1.96;
CC Evidence={ECO:0000269|PubMed:29410408};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=glycyl-tRNA(Ala) + H2O = glycine + H(+) + tRNA(Ala);
CC Xref=Rhea:RHEA:53744, Rhea:RHEA-COMP:9657, Rhea:RHEA-COMP:13640,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78522; EC=3.1.1.96;
CC Evidence={ECO:0000269|PubMed:29410408};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=D-tyrosyl-tRNA(Tyr) + H2O = D-tyrosine + tRNA(Tyr);
CC Xref=Rhea:RHEA:25347, Rhea:RHEA-COMP:9707, Rhea:RHEA-COMP:9872,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:58570, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78723; Evidence={ECO:0000250|UniProtKB:Q8BHA3};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-alanyl-tRNA(Thr) = H(+) + L-alanine + tRNA(Thr);
CC Xref=Rhea:RHEA:17793, Rhea:RHEA-COMP:9670, Rhea:RHEA-COMP:14576,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57972,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78497;
CC Evidence={ECO:0000269|PubMed:29410408};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q8BHA3}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- DOMAIN: A Gly-transPro motif from one monomer fits into the active site
CC of the other monomer to allow specific chiral rejection of most L-amino
CC acids except L-Ala. The trans conformation of the motif is maintained
CC by Arg-151. {ECO:0000250|UniProtKB:Q8BHA3}.
CC -!- SIMILARITY: Belongs to the DTD family. {ECO:0000305}.
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DR EMBL; AL139353; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL163973; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65944.1; -; Genomic_DNA.
DR EMBL; CH471078; EAW65945.1; -; Genomic_DNA.
DR EMBL; BC010618; AAH10618.1; -; mRNA.
DR CCDS; CCDS9643.1; -.
DR RefSeq; NP_542395.1; NM_080664.2.
DR AlphaFoldDB; Q96FN9; -.
DR SMR; Q96FN9; -.
DR BioGRID; 125191; 3.
DR STRING; 9606.ENSP00000312224; -.
DR iPTMnet; Q96FN9; -.
DR PhosphoSitePlus; Q96FN9; -.
DR BioMuta; DTD2; -.
DR DMDM; 74731729; -.
DR EPD; Q96FN9; -.
DR MassIVE; Q96FN9; -.
DR MaxQB; Q96FN9; -.
DR PaxDb; Q96FN9; -.
DR PeptideAtlas; Q96FN9; -.
DR PRIDE; Q96FN9; -.
DR ProteomicsDB; 76548; -.
DR Antibodypedia; 47252; 99 antibodies from 19 providers.
DR DNASU; 112487; -.
DR Ensembl; ENST00000310850.9; ENSP00000312224.4; ENSG00000129480.13.
DR Ensembl; ENST00000356180.4; ENSP00000348503.4; ENSG00000129480.13.
DR GeneID; 112487; -.
DR KEGG; hsa:112487; -.
DR MANE-Select; ENST00000310850.9; ENSP00000312224.4; NM_080664.3; NP_542395.1.
DR UCSC; uc001wrj.5; human.
DR CTD; 112487; -.
DR GeneCards; DTD2; -.
DR HGNC; HGNC:20277; DTD2.
DR HPA; ENSG00000129480; Low tissue specificity.
DR neXtProt; NX_Q96FN9; -.
DR OpenTargets; ENSG00000129480; -.
DR PharmGKB; PA134963117; -.
DR VEuPathDB; HostDB:ENSG00000129480; -.
DR eggNOG; KOG3323; Eukaryota.
DR GeneTree; ENSGT00940000153431; -.
DR HOGENOM; CLU_076118_1_0_1; -.
DR InParanoid; Q96FN9; -.
DR OMA; NAKCMEA; -.
DR OrthoDB; 1170114at2759; -.
DR PhylomeDB; Q96FN9; -.
DR TreeFam; TF329119; -.
DR PathwayCommons; Q96FN9; -.
DR SignaLink; Q96FN9; -.
DR BioGRID-ORCS; 112487; 31 hits in 1078 CRISPR screens.
DR ChiTaRS; DTD2; human.
DR GenomeRNAi; 112487; -.
DR Pharos; Q96FN9; Tbio.
DR PRO; PR:Q96FN9; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q96FN9; protein.
DR Bgee; ENSG00000129480; Expressed in oviduct epithelium and 177 other tissues.
DR ExpressionAtlas; Q96FN9; baseline and differential.
DR Genevisible; Q96FN9; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0106105; F:Ala-tRNA(Thr) hydrolase activity; IDA:UniProtKB.
DR GO; GO:0051500; F:D-tyrosyl-tRNA(Tyr) deacylase activity; IBA:GO_Central.
DR GO; GO:0000049; F:tRNA binding; IEA:UniProtKB-KW.
DR GO; GO:0106074; P:aminoacyl-tRNA metabolism involved in translational fidelity; IDA:UniProtKB.
DR GO; GO:0006399; P:tRNA metabolic process; IBA:GO_Central.
DR Gene3D; 3.50.80.10; -; 1.
DR InterPro; IPR003732; Daa-tRNA_deacyls_DTD.
DR InterPro; IPR023509; DTD-like_sf.
DR PANTHER; PTHR10472; PTHR10472; 1.
DR Pfam; PF02580; Tyr_Deacylase; 1.
DR SUPFAM; SSF69500; SSF69500; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Reference proteome; RNA-binding; tRNA-binding.
FT CHAIN 1..168
FT /note="D-aminoacyl-tRNA deacylase 2"
FT /id="PRO_0000254049"
FT MOTIF 160..161
FT /note="Gly-transPro motif, allows the protein to recognize
FT chirality of D-amino acids"
FT /evidence="ECO:0000250|UniProtKB:Q8BHA3"
FT VARIANT 6
FT /note="R -> W (in dbSNP:rs17097904)"
FT /id="VAR_028802"
SQ SEQUENCE 168 AA; 18660 MW; F74D05F238C8D0A9 CRC64;
MAEGSRIPQA RALLQQCLHA RLQIRPADGD VAAQWVEVQR GLVIYVCFFK GADKELLPKM
VNTLLNVKLS ETENGKHVSI LDLPGNILII PQATLGGRLK GRNMQYHSNS GKEEGFELYS
QFVTLCEKEV AANSKCAEAR VVVEHGTYGN RQVLKLDTNG PFTHLIEF
