| Aspect | Key findings | Quantitative data (with values) | Evidence/source (paper + year + URL) | Citation ID |
|---|---|---|---|---|
| Identity/domains | Human TTC28 corresponds to UniProt Q96AY4 and is a very large tetratricopeptide repeat protein; literature describes ~270–271 kDa TTC28 with 28 TPR domains, consistent with the UniProt description. | ~270.9–271 kDa; 28 TPR domains; cloned protein reported at 2,365 aa in the 2024 study. | Freitas et al., 2014, *OMICS* — https://doi.org/10.1089/omi.2013.0133; Zhang et al., 2024, *PNAS* — https://doi.org/10.1073/pnas.2409447121 | (pqac-00000000, pqac-00000005, pqac-00000002) |
| Localization | TTC28 is mainly cytoplasmic with perinuclear enrichment; some nucleolar signal is reported; microscopy also places TTC28 at the midbody and overlapping with tubulin in interphase cells. | Perinuclear cytoplasmic localization observed in H1299/H661 cells; midbody localization shown in confocal imaging. | Zhang et al., 2024, *PNAS* — https://doi.org/10.1073/pnas.2409447121 | (pqac-00000001, pqac-00000003, pqac-00000021) |
| CMA/autophagy | TTC28 directly binds HSPA8 and is a substrate of HSPA8/LAMP2A-dependent chaperone-mediated autophagy (CMA)/microautophagy; HSPA8 stabilizes TTC28, while lysosome/CMA perturbation alters TTC28 abundance. | TTC28 contains 16 KFERQ-like motifs; TTC28 half-life increased to >12 h with siLAMP2A versus 4.6 h and 9.6 h in controls (cell-line dependent); TCGA/CCLE correlations reported for HSPA8-TTC28 expression (Spearman R = 0.43 in TCGA, 0.78 in CCLE). | Zhang et al., 2024, *PNAS* — https://doi.org/10.1073/pnas.2409447121 | (pqac-00000009, pqac-00000004, pqac-00000013) |
| Mitosis/cytokinesis | TTC28 interacts with microtubule/mitotic machinery, including TUBB and weakly AURKB, supporting a role in regulating mitosis and cytokinesis. | 222 TTC28-interacting protein candidates identified; TTC28 KO altered tubulin-related transcripts: TUBB6 +0.7 (adj-P = 5.98e-24), TUBA1A +0.62 (adj-P = 5.88e-16), TTL +0.55 (adj-P = 4.34e-11). | Zhang et al., 2024, *PNAS* — https://doi.org/10.1073/pnas.2409447121 | (pqac-00000008, pqac-00000009) |
| Genome stability assays | TTC28 is required for maintenance of chromosomal stability; loss of TTC28 increases micronuclei and DNA-damage markers, while rescue suppresses the phenotype. | Baseline FMN in TTC28-KO vs WT: 7.7% vs 2.3% (P = 4.86E−09); rescue: 11.9% vs 4.8% (P = 2.83E−11); siLAMP2A increased FMN in TTC28-WT cells 6.5% vs 13.0% (P = 5.26E−07) and 3.5% vs 9.3% (P = 5.30E−08); with cisplatin pretreatment, siTTC28 increased FMN 21.5% vs 17.9% (P = 4.36e−02). | Zhang et al., 2024, *PNAS* — https://doi.org/10.1073/pnas.2409447121 | (pqac-00000007, pqac-00000010, pqac-00000013, pqac-00000021) |
| Cancer genomic alterations | TTC28 is recurrently altered in cancer mainly via structural variation/CNV contexts rather than a well-established recurrent point-driver role; studies report downregulation, SV involvement in CRC, chr22q deletion context in mesothelioma, and a TTC28-MECOM fusion in esophageal carcinosarcoma. | TCGA transcriptome analysis across n = 10,071 cancers showed inverse association of TTC28 expression with mutation count (Spearman −0.29, P = 1.25E−186); in CRC cohort, 19.1% (138/723) of cancer-associated genes were SV-affected and TTC28 showed significant or near-significant mRNA decrease in SV-affected samples; chr22q deletion in mesothelioma reported at 59%; TTC28-MECOM observed in 1 of 2 esophageal carcinosarcoma cases. | Zhang et al., 2024, *PNAS* — https://doi.org/10.1073/pnas.2409447121; Tanaka et al., 2024, *Cell Reports* — https://doi.org/10.1016/j.celrep.2024.113810; Mangiante et al., 2023, *Nature Genetics* — https://doi.org/10.1038/s41588-023-01321-1; Inoue et al., 2024, *Surgical Case Reports* — https://doi.org/10.1186/s40792-024-01978-8 | (pqac-00000013, pqac-00000015, pqac-00000019, pqac-00000016, pqac-00000017) |
| Clinical/prognostic associations | Low TTC28 expression is linked to poorer survival in some cancers; TTC28 abundance may also modulate sensitivity to DNA-damaging and mitosis-targeting drugs in cell-line analyses. | Low TTC28 associated with worse overall survival in lung and ovarian cancer; high TTC28 expression reported to affect sensitivity to cisplatin, olaparib, and inhibitors targeting EGFR, ERBB2, and AURKA (direction not fully quantified in the excerpts). | Zhang et al., 2024, *PNAS* — https://doi.org/10.1073/pnas.2409447121 | (pqac-00000007, pqac-00000011) |
| Disease associations in OpenTargets | OpenTargets lists TTC28 associations across multiple diseases, but these are evidence-aggregated links rather than proof of causal function. | Reported association scores/evidence sizes: cancer 0.534 (5 evidences), breast carcinoma 0.479 (5), prostate carcinoma 0.472 (5), glaucoma 0.465 (5), polycystic ovary syndrome 0.449 (5). | Open Targets platform query for TTC28 — https://platform.opentargets.org/target/ENSG00000100154 | (pqac-00000006) |


*Table: This table summarizes the main functional annotation evidence for human TTC28 (UniProt Q96AY4), including experimentally supported roles in CMA, mitosis/cytokinesis, and genome stability, plus current cancer-genomic and disease-association evidence. It is useful as a compact evidence map linking each annotation aspect to quantitative findings and source citations.*