DTD2_MOUSE
ID DTD2_MOUSE Reviewed; 168 AA.
AC Q8BHA3; Q9D363; Q9D4Q5;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 130.
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 deacylase 2 {ECO:0000305};
DE AltName: Full=L-alanyl-tRNA deacylase {ECO:0000305|PubMed:29410408};
GN Name=Dtd2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Olfactory bulb, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 1-168, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, AND DOMAIN.
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. Also deacylates
CC mischarged glycyl-tRNA(Ala), protecting cells against glycine
CC mischarging by AlaRS. Probably acts by rejecting L-amino acids from its
CC binding site rather than specific recognition of D-amino acids.
CC Catalyzes the hydrolysis of D-tyrosyl-tRNA(Tyr), has no activity on
CC correctly charged L-tyrosyl-tRNA(Tyr). By recycling D-aminoacyl-tRNA to
CC D-amino acids and free tRNA molecules, this enzyme counteracts the
CC toxicity associated with the formation of D-aminoacyl-tRNA entities in
CC vivo and helps enforce protein L-homochirality. In contrast to DTD1,
CC deacylates L-Ala mischarged on tRNA(Thr)(G4.U69) by alanine-tRNA ligase
CC AARS. Can deacylate L-Ala due to a relaxed specificity for substrate
CC chirality caused by the trans conformation of the Gly-Pro motif in the
CC active site. Also hydrolyzes correctly charged, achiral, glycyl-
CC tRNA(Gly) in vitro, although in vivo EEF1A1/EF-Tu may protect cognate
CC achiral glycyl-tRNA(Gly) from DTD2-mediated deacetylation.
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:0000269|PubMed:29410408};
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:0000269|PubMed:29410408}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BHA3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BHA3-2; Sequence=VSP_021174;
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:0000269|PubMed:29410408}.
CC -!- SIMILARITY: Belongs to the DTD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB31157.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK016300; BAB30185.1; -; mRNA.
DR EMBL; AK018311; BAB31157.1; ALT_FRAME; mRNA.
DR EMBL; AK032228; BAC27771.1; -; mRNA.
DR EMBL; AK042771; BAC31360.1; -; mRNA.
DR EMBL; BC089589; AAH89589.1; -; mRNA.
DR CCDS; CCDS25903.1; -. [Q8BHA3-1]
DR CCDS; CCDS83962.1; -. [Q8BHA3-2]
DR RefSeq; NP_001334333.1; NM_001347404.1. [Q8BHA3-2]
DR RefSeq; NP_083821.1; NM_029545.3. [Q8BHA3-1]
DR PDB; 5XAQ; X-ray; 1.86 A; A/B=1-168.
DR PDBsum; 5XAQ; -.
DR AlphaFoldDB; Q8BHA3; -.
DR SMR; Q8BHA3; -.
DR IntAct; Q8BHA3; 1.
DR STRING; 10090.ENSMUSP00000021339; -.
DR iPTMnet; Q8BHA3; -.
DR PhosphoSitePlus; Q8BHA3; -.
DR EPD; Q8BHA3; -.
DR jPOST; Q8BHA3; -.
DR MaxQB; Q8BHA3; -.
DR PaxDb; Q8BHA3; -.
DR PeptideAtlas; Q8BHA3; -.
DR PRIDE; Q8BHA3; -.
DR ProteomicsDB; 277513; -. [Q8BHA3-1]
DR ProteomicsDB; 277514; -. [Q8BHA3-2]
DR Antibodypedia; 47252; 99 antibodies from 19 providers.
DR Ensembl; ENSMUST00000021339; ENSMUSP00000021339; ENSMUSG00000020956. [Q8BHA3-1]
DR Ensembl; ENSMUST00000085404; ENSMUSP00000082525; ENSMUSG00000020956. [Q8BHA3-2]
DR GeneID; 328092; -.
DR KEGG; mmu:328092; -.
DR UCSC; uc007nnd.1; mouse. [Q8BHA3-2]
DR UCSC; uc007nne.1; mouse. [Q8BHA3-1]
DR CTD; 112487; -.
DR MGI; MGI:1923485; Dtd2.
DR VEuPathDB; HostDB:ENSMUSG00000020956; -.
DR eggNOG; KOG3323; Eukaryota.
DR GeneTree; ENSGT00940000153431; -.
DR HOGENOM; CLU_076118_1_0_1; -.
DR InParanoid; Q8BHA3; -.
DR OMA; NAKCMEA; -.
DR OrthoDB; 1170114at2759; -.
DR PhylomeDB; Q8BHA3; -.
DR TreeFam; TF329119; -.
DR BioGRID-ORCS; 328092; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Dtd2; mouse.
DR PRO; PR:Q8BHA3; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8BHA3; protein.
DR Bgee; ENSMUSG00000020956; Expressed in intestinal villus and 133 other tissues.
DR Genevisible; Q8BHA3; MM.
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; IDA:UniProtKB.
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 3D-structure; Alternative splicing; Cytoplasm; Hydrolase;
KW Reference proteome; RNA-binding; tRNA-binding.
FT CHAIN 1..168
FT /note="D-aminoacyl-tRNA deacylase 2"
FT /id="PRO_0000254050"
FT MOTIF 160..161
FT /note="Gly-transPro motif, allows the protein to recognize
FT chirality of D-amino acids"
FT /evidence="ECO:0000269|PubMed:29410408"
FT VAR_SEQ 152..168
FT /note="QVLKLDTNGPYTHLIEF -> WSHTQKELQTLLTAF (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_021174"
FT STRAND 10..25
FT /evidence="ECO:0007829|PDB:5XAQ"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:5XAQ"
FT STRAND 40..51
FT /evidence="ECO:0007829|PDB:5XAQ"
FT HELIX 56..66
FT /evidence="ECO:0007829|PDB:5XAQ"
FT TURN 80..84
FT /evidence="ECO:0007829|PDB:5XAQ"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:5XAQ"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:5XAQ"
FT STRAND 98..100
FT /evidence="ECO:0007829|PDB:5XAQ"
FT STRAND 103..105
FT /evidence="ECO:0007829|PDB:5XAQ"
FT HELIX 112..131
FT /evidence="ECO:0007829|PDB:5XAQ"
FT HELIX 134..139
FT /evidence="ECO:0007829|PDB:5XAQ"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:5XAQ"
FT STRAND 154..157
FT /evidence="ECO:0007829|PDB:5XAQ"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:5XAQ"
SQ SEQUENCE 168 AA; 18236 MW; 3CE2A5393043A5A4 CRC64;
MADGGRVAQA RALLQQCLHA RLQVRPADGD AAAQWVEIRR GLVIYVCFFK GADTDLLPKM
VNTLLNVKLS ETETGKHVSI LDLPGDVLII PQATLGGRVK GRSMQYHSNS GKEEGSELYS
QFVSLCEKAV ANNTKSVEAG VAVAHGTYGN RQVLKLDTNG PYTHLIEF
