DTD1 encodes D-aminoacyl-tRNA deacylase 1 (also called DUE-B), a member of the DTD family (PANTHER PTHR10472:SF5) of dimeric trans-acting tRNA editing enzymes. The canonical 209-residue product (UniProt Q8TEA8) hydrolyses D-aminoacyl-tRNAs and mischarged Gly-tRNA(Ala); chiral selection depends on a Gly-cisPro dipeptide that one subunit donates to the active site of the other at the dimer interface. The human protein also carries a disordered, vertebrate-specific C-terminal extension that is needed for DNA binding and has been linked to replication-origin binding and Cdc45 loading. A0A2R8YCT7 is a 127-residue protein predicted from an Ensembl nonsense-mediated-decay transcript (ENST00000647441) that includes an extra 47-nt cassette exon. It is identical to canonical residues 1-124, then ends with a frameshifted Thr-Leu-Phe tail. It therefore lacks the final core beta-strand (residues 131-146), the NxGP(V/F)T motif carrying the Gly139-Pro140 chiral-selection dipeptide, and the whole C-terminal DNA-binding extension. No activity, localization or stable expression has been shown for this product specifically.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002161 aminoacyl-tRNA deacylase activity | IEA GO_REF:0000002 | REMOVE | Summary: InterPro2GO transfer from the DTD domain signature (IPR003732). The DTD1 gene clearly encodes an aminoacyl-tRNA deacylase. This product, though, is a truncated NMD-transcript translation that lacks the part of the fold the editing site needs. Reason: PANTHER places DTD1 in SF5 (D-aminoacyl-tRNA deacylase 1), and deacylase activity is an ancestral property of the DTD family. The truncation is specific to this product, which is the only reason the transfer fails here. In the DTD dimer the two active sites sit at the subunit interface, and each subunit donates an invariant Gly-cisPro dipeptide to its partner's pocket (PMID:24302572). In human DTD1 that dipeptide is Gly139-Pro140, inside the NxGP(V/F)T motif (QNDGPVT, 136-142) and the final core beta-strand (131-146) seen in the 2OKV structure of the active N-terminal core (PMID:17264083). A0A2R8YCT7 diverges after residue 124 and has none of these elements (file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md). The product therefore cannot form the deacylase active site. The activity belongs to the canonical product Q8TEA8, not to this one. The general term is removed for the same reason as its child GO:0051499, so the two rows are consistent. Supporting Evidence: PMID:24302572 The ligand binds in the two active sites located at the dimer interface. PMID:24302572 'cross-subunit' Gly-cisPro dipeptide to capture the chiral centre of incoming file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md | Gly-cisPro motif (ECO:0000250 Q8IIS0) | 139-140 | no (after divergence) | file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md | Beta strand 131-146 (PDB:2OKV) | 131-146 | no (after divergence) | |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | UNDECIDED | Summary: The cytoplasm assignment comes from a family-level rule. For the canonical human protein, cytoplasm is itself only by similarity, and nuclear and chromatin localization have been shown experimentally. Reason: No localization data exist for A0A2R8YCT7. Its transcript is annotated as an NMD target (file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md), so the protein may never accumulate. If it were made, a soluble 14.5 kDa N-terminal fragment without the human C-terminal extension could occupy both cytoplasm and nucleus. Canonical DUE-B was reported as primarily nuclear (PMID:15653697). Nothing here contradicts the term, and nothing establishes it for this product, so the row stays undecided rather than removed. Supporting Evidence: PMID:15653697 the human protein is approximately 60 amino file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md ### ENST00000647441 (nonsense_mediated_decay, Ensembl canonical=False) |
| GO:0006399 tRNA metabolic process | IEA GO_REF:0000104 | MARK AS OVER ANNOTATED | Summary: The DTD1 gene takes part in tRNA metabolism through D-aminoacyl-tRNA editing, a process GO Central assigns to canonical DTD1 by IBA. This product cannot carry out the editing chemistry, so the process transfer goes beyond what it can do. Reason: The process annotation rests on the deacylase activity, which this truncated product lacks (see the GO:0002161 row). Because no deacylation step is possible, A0A2R8YCT7 does no part of the work of tRNA metabolism. A dominant-negative or heterodimer role has never been tested. The term is true of the gene and stays appropriate for Q8TEA8, but it is over-annotated on this gene model. Supporting Evidence: file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md - Identical N-terminal prefix: residues 1-124 PMID:24302572 The ligand binds in the two active sites located at the dimer interface. |
| GO:0051499 D-aminoacyl-tRNA deacylase activity | IEA GO_REF:0000120 | REMOVE | Summary: EC 3.1.1.96 / RHEA:13953 transfer for the DTD family. This is correct for canonical human DTD1, whose N-terminal core was shown to have D-aminoacyl-tRNA deacylase activity. It is not correct for this 127-residue NMD-transcript product. Reason: PMID:17264083 assayed the active N-terminal core, which is the dimeric domain resolved in the 2OKV structure and reaches beyond residue 140. A0A2R8YCT7 ends at canonical residue 124 plus a three-residue frameshift tail, so it lacks the last core strand and the cross-subunit Gly139-Pro140 motif that captures the D-aminoacyl substrate (PMID:24302572). Because family membership holds while the active site is lost, transferring the EC number to this product is demonstrably wrong. Supporting Evidence: PMID:17264083 The structure corresponds to a dimer of the N-terminal PMID:24302572 'cross-subunit' Gly-cisPro dipeptide to capture the chiral centre of incoming file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md | Gly-cisPro motif (ECO:0000250 Q8IIS0) | 139-140 | no (after divergence) | |
| GO:0106026 Gly-tRNA(Ala) deacylase activity | IEA GO_REF:0000116 | REMOVE | Summary: RHEA-based transfer of glycyl-tRNA(Ala) deacylation. In the DTD family this activity uses the same Gly-cisPro-dependent active site as D-aminoacyl-tRNA deacylation, and that site is incomplete in this product. Reason: Gly-tRNA(Ala) clearance by DTD uses the same dimer-interface pocket as D-aminoacyl-tRNA hydrolysis. Even for canonical human DTD1, UniProt asserts this activity by similarity to Plasmodium DTD (Q8IIS0). A0A2R8YCT7 lacks the Gly-cisPro-bearing strand (file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md), so the activity cannot be transferred to it. Supporting Evidence: PMID:24302572 The ligand binds in the two active sites located at the dimer interface. file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md | Gly-cisPro motif (ECO:0000250 Q8IIS0) | 139-140 | no (after divergence) | |
| GO:0106074 aminoacyl-tRNA metabolism involved in translational fidelity | IEA GO_REF:0000120 | MARK AS OVER ANNOTATED | Summary: This process term is derived from the three deacylase MF terms. It describes the canonical DTD1 proofreading role well, but this product cannot do it. Reason: The process is inferred directly from GO:0002161, GO:0051499 and GO:0106026, and all three are removed for this product because it lacks the cross-subunit editing site. With no deacylase activity, the truncated product contributes no step to translational proofreading. The term remains correct for the canonical product Q8TEA8. Supporting Evidence: PMID:24302572 'cross-subunit' Gly-cisPro dipeptide to capture the chiral centre of incoming file:human/DTD1/DTD1-bioinformatics/RESULTS-rereview.md | Gly-cisPro motif (ECO:0000250 Q8IIS0) | 139-140 | no (after divergence) | |
Loading supporting content…
Download this section (compressed HTML)Q: Is the ENST00000647441 transcript (extra 47-nt exon between canonical exons 3 and 4) translated at detectable levels, or is it efficiently removed by nonsense-mediated decay? Proteomics peptides mapped to A0A2R8YCT7 fall within residues shared with Q8TEA8, so they do not show that this product exists.
Q: Could a 1-124 DTD1 fragment heterodimerize with full-length DTD1 and act as a dominant-negative regulator of D-aminoacyl-tRNA editing?
Experiment: Use isoform-specific RT-qPCR with and without NMD inhibition (UPF1 knockdown or cycloheximide) to measure ENST00000647441, and use targeted proteomics for the unique C-terminal ...KDTLF peptide junction to test whether the product accumulates.
Experiment: Express the 1-124+TLF product recombinantly and test its folding, dimerization and D-Tyr-tRNA(Tyr) deacylation, with full-length DTD1 as positive control and alone or co-expressed with it.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)