| Category | Evidence summary | Key citations | Publication date & URL |
|---|---|---|---|
| Identity/domains | Human ANKZF1 corresponds to UniProt Q9H8Y5 and the literature synonym ZNF744; it is the mammalian ortholog of yeast Vms1 and contains ankyrin repeats, zinc-finger regions, a mitochondrial targeting domain (MTD), and a VCP/p97-interacting motif (VIM). The VIM consensus was defined as RX5AAX2R and is necessary/sufficient for p97 binding. | (pqac-00000008, pqac-00000010, pqac-00000000) | 2011-11-04, https://doi.org/10.1074/jbc.m111.274472; 2018-10-11, https://doi.org/10.1016/j.molcel.2018.08.022 |
| Enzymatic activity | ANKZF1 is experimentally supported as an RQC-associated tRNA-cleaving factor that releases stalled nascent chains from 60S complexes. In mammalian systems it cleaves the acceptor arm/CCA end of peptidyl-tRNA, although some reviews describe the overall outcome as peptidyl-tRNA hydrolysis; the mechanistic consensus is release of nascent chains by ANKZF1 at stalled 60S ribosomes. | (pqac-00000000, pqac-00000001, pqac-00000003, pqac-00000025) | 2018-10-11, https://doi.org/10.1016/j.molcel.2018.08.022; 2020-02-18, https://doi.org/10.1016/j.celrep.2020.01.082; 2020-01-27, https://doi.org/10.1093/nar/gkz1201 |
| Substrate & products | The substrate is peptidyl-tRNA on stalled 60S ribosome–nascent chain complexes in RQC. ANKZF1 removes CCA74-76, generating a tRNA with a 2',3'-cyclic phosphate at discriminator base N73, and released nascent chains remain attached to a short tRNA remnant reported as 3-4 terminal nucleotides depending on assay/context. | (pqac-00000001, pqac-00000007, pqac-00000034) | 2020-02-18, https://doi.org/10.1016/j.celrep.2020.01.082; 2018-10-11, https://doi.org/10.1016/j.molcel.2018.08.022; 2024-02-29, https://doi.org/10.1093/nar/gkae087 |
| Pathway context (RQC steps) | In canonical mammalian RQC, ribosome stalling/collision triggers ZNF598-mediated 40S ubiquitination and ASCC-dependent splitting; NEMF and Listerin act on the 60S nascent-chain complex, and ANKZF1 then releases the stalled nascent chain for downstream p97/VCP extraction and proteasomal degradation. Cleaved tRNAs are repaired by ELAC1 and then re-CCA-added by TRNT1. | (pqac-00000025, pqac-00000026, pqac-00000031, pqac-00000042) | 2020-01-27, https://doi.org/10.1093/nar/gkz1201; 2020-02-18, https://doi.org/10.1016/j.celrep.2020.01.082; 2024-02-29, https://doi.org/10.1093/nar/gkae087 |
| Key interactors | Key pathway partners include VCP/p97 (via the VIM), NEMF/Rqc2, Listerin/LTN1, UFD1/NPLOC4, ELAC1, and TRNT1. Evidence supports direct VIM-dependent p97 binding through the p97 N-domain and functional coupling of ANKZF1 to ubiquitinated 60S RQC substrates. | (pqac-00000008, pqac-00000011, pqac-00000001, pqac-00000025) | 2011-11-04, https://doi.org/10.1074/jbc.m111.274472; 2020-02-18, https://doi.org/10.1016/j.celrep.2020.01.082; 2020-01-27, https://doi.org/10.1093/nar/gkz1201 |
| Subcellular localization | Basally, human ANKZF1 is predominantly diffuse/cytosolic, but upon cellular or mitochondrial stress it relocalizes to mitochondria, often together with VCP. Loss-of-function alleles can impair this stress-induced mitochondrial translocation and are associated with reduced mitochondrial integrity/respiration. | (pqac-00000017, pqac-00000012, pqac-00000015) | 2017-05-12, https://doi.org/10.1074/jbc.m116.772038 |
| Recent 2023-2024 developments | In 2024, ANKZF1 was identified as a strong suppressor of toxic RAN translation from GC-rich repeats in reporter systems and C9ALS/FTD patient iPSC-derived neurons; loss of ANKZF1 had among the largest effects on RAN product accumulation. Other 2024 work placed ANKZF1 within mitochondrial-stress-responsive RQC and identified it as a HIF-1α target contributing to angiogenic phenotypes in human MSCs. | (pqac-00000020, pqac-00000021, pqac-00000038, pqac-00000032, pqac-00000041) | 2024-02-29, https://doi.org/10.1093/nar/gkae137; 2024-02-22, https://doi.org/10.1038/s41467-024-45525-3; 2024-05-08, https://doi.org/10.1093/procel/pwad027 |
| Disease/translational relevance | Biallelic ANKZF1 mutations are associated with infantile-onset inflammatory bowel disease with apoptosis and mitochondrial respiration defects in patient cells. High ANKZF1 expression is also associated with worse colon cancer outcomes, and platform-level evidence links ANKZF1 to neurodegenerative, lysosomal, Alzheimer, and Parkinson disease contexts. | (pqac-00000017, pqac-00000046, pqac-00000048, pqac-00000051) | 2017-05-12, https://doi.org/10.1074/jbc.m116.772038; 2019-06, https://doi.org/10.2217/fon-2018-0920; 2025, Open Targets Platform reference in Nucleic Acids Research |
| Key quantitative stats | Colon cancer studies reported high ANKZF1 expression associated with poorer overall survival and recurrence-free survival: HR 2.094 (95% CI 1.188-3.689; p=0.011) and HR 1.762 (95% CI 1.021-3.042; p=0.042); broader CRC analyses also reported OS HR 1.661 (95% CI 1.145-2.408; p=0.007) and RFS HR 1.969 (95% CI 1.299-2.984; p=0.001). Open Targets disease association scores included neurodegenerative disease 0.555, lysosomal storage disease 0.428, inflammatory bowel disease 0.374, Alzheimer disease 0.240, and Parkinson disease 0.233. | (pqac-00000045, pqac-00000047, pqac-00000048) | 2019-06, https://doi.org/10.2217/fon-2018-0920; 2025, Open Targets Platform reference in Nucleic Acids Research |


*Table: This table summarizes experimentally supported functions, pathway context, localization, interactors, and translational relevance for human ANKZF1/Q9H8Y5. It is designed as a compact evidence map for downstream functional annotation and report writing.*