DTD2

Summary

DTD2 (D-aminoacyl-tRNA deacylase 2, HGNC:20277) is a protein-coding gene on chromosome 14q12, encoding D-aminoacyl-tRNA deacylase 2 (Q96FN9). Deacylates mischarged D-aminoacyl-tRNAs.

Enables Ala-tRNA(Thr) deacylase activity. Involved in aminoacyl-tRNA metabolism involved in translational fidelity. Predicted to be active in cytoplasm.

Source: NCBI Gene 112487 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 27 total — 1 pathogenic
• MANE Select transcript: NM_080664

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20277
Approved symbol	DTD2
Name	D-aminoacyl-tRNA deacylase 2
Location	14q12
Locus type	gene with protein product
Status	Approved
Aliases	MGC9912
Ensembl gene	ENSG00000129480
Ensembl biotype	protein_coding
Entrez	112487

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 1 protein_coding, 1 nonsense_mediated_decay

ENST00000310850, ENST00000549850

RefSeq mRNA: 1 — MANE Select: NM_080664 NM_080664

CCDS: CCDS9643

Canonical transcript exons

ENST00000310850 — 3 exons

Exon	Start	End
ENSE00001188825	31446036	31448454
ENSE00001353278	31457283	31457506
ENSE00003491807	31453275	31453344

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 93.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 3.9735 / max 54.2742, expressed in 1602 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142743	2.2489	1395
142744	1.2302	833
142745	0.4944	237

Top tissues by expression

253 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
oviduct epithelium	UBERON:0004804	93.45	gold quality
epithelial cell of pancreas	CL:0000083	90.72	silver quality
ventricular zone	UBERON:0003053	88.17	gold quality
cortical plate	UBERON:0005343	86.95	gold quality
endothelial cell	CL:0000115	86.43	silver quality
ganglionic eminence	UBERON:0004023	86.02	gold quality
ileal mucosa	UBERON:0000331	84.02	gold quality
pancreatic ductal cell	CL:0002079	83.68	silver quality
adrenal tissue	UBERON:0018303	83.59	gold quality
prefrontal cortex	UBERON:0000451	83.47	gold quality
gingival epithelium	UBERON:0001949	83.40	silver quality
gingiva	UBERON:0001828	83.37	gold quality
palpebral conjunctiva	UBERON:0001812	82.85	gold quality
medial globus pallidus	UBERON:0002477	82.14	gold quality
Brodmann (1909) area 46	UBERON:0006483	82.08	gold quality
fallopian tube	UBERON:0003889	81.91	gold quality
pigmented layer of retina	UBERON:0001782	81.70	gold quality
adipose tissue	UBERON:0001013	81.60	gold quality
esophagus squamous epithelium	UBERON:0006920	81.34	gold quality
parietal pleura	UBERON:0002400	81.14	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.96	gold quality
substantia nigra	UBERON:0002038	80.89	gold quality
monocyte	CL:0000576	80.79	gold quality
thoracic mammary gland	UBERON:0005200	80.69	gold quality
leukocyte	CL:0000738	80.66	gold quality
mammary gland	UBERON:0001911	80.61	gold quality
calcaneal tendon	UBERON:0003701	80.59	gold quality
visceral pleura	UBERON:0002401	80.53	gold quality
left adrenal gland	UBERON:0001234	80.51	gold quality
stromal cell of endometrium	CL:0002255	80.42	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

153 targeting DTD2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-23A-3P	99.95	74.24	3163

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	dtd2	ENSDARG00000036775
mus_musculus	Dtd2	ENSMUSG00000020956
rattus_norvegicus	Dtd2	ENSRNOG00000006727

Paralogs (1): DTD1 (ENSG00000125821)

Protein

Protein identifiers

D-aminoacyl-tRNA deacylase 2 — Q96FN9 (reviewed: Q96FN9)

Alternative names: Animalia-specific tRNA deacylase, D-tyrosyl-tRNA(Tyr) deacylase 2, L-alanyl-tRNA deacylase

All UniProt accessions (2): Q96FN9, F8VVE1

UniProt curated annotations — full annotation on UniProt →

Function. Deacylates mischarged D-aminoacyl-tRNAs. Also deacylates mischarged glycyl-tRNA(Ala), protecting cells against glycine mischarging by AlaRS. Probably acts by rejecting L-amino acids from its binding site rather than specific recognition of D-amino acids. Catalyzes the hydrolysis of D-tyrosyl-tRNA(Tyr), has no activity on correctly charged L-tyrosyl-tRNA(Tyr). By recycling D-aminoacyl-tRNA to D-amino acids and free tRNA molecules, this enzyme counteracts the toxicity associated with the formation of D-aminoacyl-tRNA entities in vivo and helps enforce protein L-homochirality. In contrast to DTD1, deacylates L-Ala mischarged on tRNA(Thr)(G4.U69) by alanine-tRNA ligase AARS. Can deacylate L-Ala due to a relaxed specificity for substrate chirality caused by the trans conformation of the Gly-Pro motif in the active site. Also hydrolyzes correctly charged, achiral, glycyl-tRNA(Gly) in vitro, although in vivo EEF1A1/EF-Tu may protect cognate achiral glycyl-tRNA(Gly) from DTD2-mediated deacetylation.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm.

Domain organisation. A Gly-transPro motif from one monomer fits into the active site of the other monomer to allow specific chiral rejection of most L-amino acids except L-Ala. The trans conformation of the motif is maintained by Arg-151.

Similarity. Belongs to the DTD family.

RefSeq proteins (1): NP_542395* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003732	Daa-tRNA_deacyls_DTD	Family
IPR023509	DTD-like_sf	Homologous_superfamily

Pfam: PF02580

Catalyzed reactions (Rhea), 4 shown:

• a D-aminoacyl-tRNA + H2O = a tRNA + a D-alpha-amino acid + H(+) (RHEA:13953)
• L-alanyl-tRNA(Thr) + H2O = tRNA(Thr) + L-alanine + H(+) (RHEA:17793)
• D-tyrosyl-tRNA(Tyr) + H2O = D-tyrosine + tRNA(Tyr) (RHEA:25347)
• glycyl-tRNA(Ala) + H2O = tRNA(Ala) + glycine + H(+) (RHEA:53744)

UniProt features (3 total): chain 1, short sequence motif 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96FN9-F1	96.31	0.96

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 109 (showing top): FXR_IR1_Q6, WANG_CLIM2_TARGETS_UP, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, LFA1_Q6, GOBP_TRNA_METABOLIC_PROCESS, chr14q12, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM5, TGACATY_UNKNOWN, GOBP_REGULATION_OF_TRANSLATIONAL_FIDELITY, CDPCR3HD_01, GOMF_TRNA_BINDING, GOMF_HYDROLASE_ACTIVITY_ACTING_ON_ESTER_BONDS, GOMF_AMINOACYL_TRNA_DEACYLASE_ACTIVITY, GOMF_CARBOXYLIC_ESTER_HYDROLASE_ACTIVITY, KRIGE_RESPONSE_TO_TOSEDOSTAT_6HR_DN

GO Biological Process (2): tRNA metabolic process (GO:0006399), aminoacyl-tRNA metabolism involved in translational fidelity (GO:0106074)

GO Molecular Function (9): tRNA binding (GO:0000049), D-tyrosyl-tRNA(Tyr) deacylase activity (GO:0051500), Gly-tRNA(Ala) deacylase activity (GO:0106026), Ala-tRNA(Thr) deacylase activity (GO:0106105), aminoacyl-tRNA deacylase activity (GO:0002161), RNA binding (GO:0003723), protein binding (GO:0005515), hydrolase activity (GO:0016787), D-aminoacyl-tRNA deacylase activity (GO:0051499)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
aminoacyl-tRNA deacylase activity	3
RNA metabolic process	1
tRNA metabolic process	1
regulation of translational fidelity	1
RNA binding	1
D-aminoacyl-tRNA deacylase activity	1
carboxylic ester hydrolase activity	1
aminoacyl-tRNA metabolism involved in translational fidelity	1
catalytic activity, acting on a tRNA	1
deacylase activity	1
nucleic acid binding	1
binding	1
catalytic activity	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DTD2	DTD1	Q8TEA8	792
DTD2	HEATR5A	Q86XA9	591
DTD2	GPR33	Q49SQ1	570
DTD2	YARS1	P54577	566
DTD2	RBM42	Q9BTD8	530
DTD2	NUBPL	Q8TB37	508
DTD2	A0A3B3IRQ3	A0A3B3IRQ3	507
DTD2	YARS2	Q9Y2Z4	495
DTD2	G2E3	Q7L622	488
DTD2	TARS1	P26639	470
DTD2	TARS3	A2RTX5	465
DTD2	AARS1	P49588	452
DTD2	TARS2	Q9BW92	435
DTD2	SLC35G6	P0C7Q6	432
DTD2	KRTAP4-8	Q9BYQ9	431

IntAct

0 interactions, top by confidence:

BioGRID (8): DTD2 (Affinity Capture-RNA), DTD2 (Co-fractionation), DTD2 (Co-fractionation), DTD2 (Co-fractionation), PDLIM7 (Co-fractionation), DTD2 (Affinity Capture-RNA), APP (Reconstituted Complex), HDHD2 (Co-fractionation)

ESM2 similar proteins: A0RH40, A1T099, A3MA28, A4FVW2, A6TG77, A7GR01, A9VPT9, B0VP57, B4RYB0, B7HCD1, B7HKJ2, B7ISJ3, B7JI81, B8G1X0, B9IUH1, C0QLA8, C1EN94, C3L981, C3P4M3, H8ZW44, O83606, O98453, P02658, P27356, P39431, P43395, P45625, P58532, P76157, P80502, P80638, Q01ZT9, Q2RCH0, Q38SQ2, Q3J6Q0, Q3KJC8, Q3V4T2, Q4KJL5, Q4Q1E7, Q5ZY48

Diamond homologs: C0QT00, E1C762, O66742, P84066, Q68EL2, Q8BHA3, Q96FN9, A8ZUJ9, Q2NG79, A6LTN7, A9KK74, C4Z1C2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

27 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	19
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
929501	NUBPL, 240-KB DEL AND 130-KB DUP	Pathogenic

SpliceAI

501 predictions. Top by Δscore:

Variant	Effect	Δscore
14:31448333:T:TA	donor_gain	1.0000
14:31453343:ACC:A	acceptor_loss	1.0000
14:31453344:CCTA:C	acceptor_loss	1.0000
14:31453345:C:T	acceptor_loss	1.0000
14:31453346:T:A	acceptor_loss	1.0000
14:31453270:CATA:C	donor_loss	0.9900
14:31453271:ATACC:A	donor_loss	0.9900
14:31453272:TAC:T	donor_loss	0.9900
14:31453272:TACCC:T	donor_loss	0.9900
14:31453273:A:AC	donor_gain	0.9900
14:31453273:A:T	donor_loss	0.9900
14:31453273:AC:A	donor_gain	0.9900
14:31453274:C:A	donor_loss	0.9900
14:31453274:C:CC	donor_gain	0.9900
14:31453274:CC:C	donor_gain	0.9900
14:31454289:CAGG:C	donor_gain	0.9900
14:31457284:TCC:T	donor_gain	0.9900
14:31448455:C:CC	acceptor_gain	0.9800
14:31453268:CACAT:C	donor_loss	0.9800
14:31453269:ACATA:A	donor_loss	0.9800
14:31453345:C:CC	acceptor_gain	0.9800
14:31448250:T:TA	donor_gain	0.9700
14:31453304:C:CA	donor_gain	0.9700
14:31457209:CGAG:C	donor_gain	0.9700
14:31457284:T:TA	donor_gain	0.9700
14:31457291:A:AC	donor_gain	0.9700
14:31457292:C:CC	donor_gain	0.9700
14:31448345:T:TA	donor_gain	0.9600
14:31448451:TTAA:T	acceptor_gain	0.9600
14:31457061:T:TA	donor_gain	0.9600

AlphaMissense

1089 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:31453315:G:C	C47W	0.992
14:31453317:A:G	C47R	0.991
14:31457335:G:T	A20D	0.987
14:31448199:C:T	G146D	0.986
14:31448373:A:G	L88P	0.986
14:31448175:A:G	L154S	0.985
14:31457329:A:G	L22P	0.985
14:31448349:C:T	G96E	0.984
14:31453316:C:T	C47Y	0.984
14:31453334:C:T	G41E	0.984
14:31448132:A:C	F168L	0.983
14:31448132:A:T	F168L	0.983
14:31448134:A:G	F168L	0.983
14:31448180:C:A	Q152H	0.983
14:31448180:C:G	Q152H	0.983
14:31453312:A:C	F48L	0.983
14:31453312:A:T	F48L	0.983
14:31453314:A:G	F48L	0.983
14:31457343:G:C	C17W	0.983
14:31448148:G:T	T163K	0.982
14:31448157:C:T	G160E	0.982
14:31448158:C:G	G160R	0.982
14:31448158:C:T	G160R	0.982
14:31453335:C:G	G41R	0.981
14:31453335:C:T	G41R	0.981
14:31448146:G:C	H164D	0.980
14:31448352:A:T	L95H	0.980
14:31448367:A:T	I90N	0.979
14:31448199:C:A	G146V	0.978
14:31448320:A:G	Y106H	0.978

dbSNP variants (sampled 300 via entrez): RS1000332163 (14:31454871 G>T), RS1000620550 (14:31454997 A>C), RS1000933653 (14:31448008 C>T), RS1001344961 (14:31449041 G>A), RS1002191878 (14:31457957 G>A), RS1002349467 (14:31447389 G>A,C), RS1002377378 (14:31447152 T>C), RS1002436280 (14:31451754 A>G), RS1002732802 (14:31458365 A>G), RS1003316228 (14:31452627 T>C), RS1003352582 (14:31445989 T>C,G), RS1004133494 (14:31459037 T>A), RS1004269798 (14:31458778 T>C), RS1004346672 (14:31448803 T>C), RS1004777656 (14:31451594 A>G)

Disease associations

OMIM: gene `` | disease phenotypes: MIM:168600, MIM:618242

GenCC curated gene-disease

Mondo (2): late-onset Parkinson disease (MONDO:0008199), mitochondrial complex I deficiency, nuclear type 21 (MONDO:0032625)

Orphanet (1): Hereditary late-onset Parkinson disease (Orphanet:411602)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

31 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, affects cotreatment, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Air Pollutants	decreases expression, increases abundance	2
Arsenic	affects methylation, affects cotreatment, increases abundance, increases expression	2
Smoke	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
epigallocatechin gallate	decreases expression, affects cotreatment	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
MT19c compound	increases expression	1
Vorinostat	increases expression, affects cotreatment	1
Benzo(a)pyrene	increases methylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Phthalic Acids	increases methylation	1
Quercetin	decreases expression	1
Thiram	decreases expression	1
Tretinoin	decreases expression	1
Urethane	decreases expression	1
Copper Sulfate	decreases expression	1

Clinical trials (associated diseases)

12 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00455143	PHASE4	TERMINATED	Cognitive Protection - Dexmedetomidine and Cognitive Reserve
NCT00561678	PHASE4	COMPLETED	Perioperative Cognitive Function - Dexmedetomidine and Cognitive Reserve
NCT01807481	PHASE4	UNKNOWN	Phase IV Study to Evaluate the Efficacy and Safety of Mircera in PD
NCT07015671	PHASE3	COMPLETED	Bioavailability and Bioequivalence Study of ER Torsemide and Spironolactone FDC Tablet in Healthy Subjects
NCT03942458	PHASE1	COMPLETED	Pharmacokinetics and Pharmacodynamics of Vicagrel in Healthy Adult Subjects of Different CYP2C19
NCT07195825	PHASE1	RECRUITING	A Clinical Study to Evaluate the Safety, and Tolerability of BBM-P002 in the Treatment of Parkinson’s Disease
NCT04093349	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Gene Transfer Study for Late-Onset Pompe Disease (RESOLUTE)
NCT07282847	PHASE1/PHASE2	RECRUITING	A Study to Evaluate Safety, Tolerability, and Efficacy of AB-1009 Gene Therapy (GAA Gene) in Adult Participants With Late Onset Pompe Disease (PROGRESS-GT LOPD)
NCT00105131	Not specified	COMPLETED	Genetic Characterization of Parkinson’s Disease
NCT03021408	Not specified	UNKNOWN	Effectiveness of Different Approaches for the Rehabilitation of Gait in Patients With Parkinson’s Disease
NCT03893240	Not specified	COMPLETED	Neutralizing Antibody Seroprevalence Study With a Retrospective Component in Participants With Late-Onset Pompe Disease
NCT05810454	Not specified	NOT_YET_RECRUITING	iPACES v3 MCI NIA Protocol Copied for iPACES v4 PD NINDS