Source of all eleven IBA rows on ACTL8. Ten of them originate from two PANTHER nodes (PTN002631586, PTN007551913) whose only human member below 90.7 per cent identity to beta-actin is ACTL8 itself, at 33.8 per cent; the eleventh, GO:0015629, comes from a deeper node whose clade genuinely spans the divergent actin-like proteins.

Source of the GO:0005856 cytoskeleton IEA. Traces to a UniProt SUBCELLULAR LOCATION line carrying ECO:0000250 with no source entry cited, so the annotation re-encodes a by-similarity statement rather than adding evidence.

Source of the GO:0098974 IEA, generated from ACTL8's own GO:0098973 IBA. A propagation from a propagation, with no independent evidence about ACTL8.

Two-dimensional gel comparison of proliferating and differentiated Caco-2 cells found 53 differentially regulated spots, 34 of them identified by MALDI-TOF. This is the sole basis for the GO:0030855 IEP annotation on ACTL8.

Proteome-scale yeast two-hybrid map (HI-II-14) from the CCSB pipeline; source of the first ACTL8-CERT1 protein binding IPI row.

HuRI, the CCSB reference binary interactome, built with three yeast two-hybrid assay versions on an expanded search space that supersedes HI-II-14. Source of the second ACTL8-CERT1 IPI row, on isoform Q9Y5P4-2.

Massively parallel signature sequencing across 32 normal human tissues identified 1,056 testis-predominant genes, 202 of them candidate cancer/testis antigens. This is the source UniProt cites with ECO:0000269 for ACTL8's testis and pancreas expression, and the origin of the CT57 synonym.

siRNA knockdown of ACTL8 in MDA-MB-231 and BT-549 triple-negative breast cancer cells reduced EdU incorporation and colony formation.

Knockdown reduced migration and invasion in transwell assays.

Knockdown lowered phospho-PI3K, phospho-AKT and phospho-mTOR without changing total protein levels. No direct interaction with any pathway component was tested, so the relation is correlative.

shRNA knockdown of ACTL8 in A549 and NCI-H1975 lung adenocarcinoma cells affected proliferation, cell-cycle progression, apoptosis, migration, invasion, angiogenesis and EMT markers.

Knockdown also suppressed A549 tumour growth in nude-mouse xenografts, the only in vivo evidence for ACTL8.

ACTL8 knockdown reduced gastric cancer cell proliferation, migration and invasion.

Overexpression raised PI3K/AKT/mTOR phosphorylation and pathway inhibitors reversed the effect, replicating the breast-cancer result in a second tissue.

ACTL8 knockdown inhibited growth and motility, arrested the cell cycle and promoted apoptosis in TCA-83 and CAL27 oral squamous carcinoma cells, with reduced CDK1, cyclin E1, cyclin B2 and c-Myc.

ACTL8 knockdown inhibited A549 proliferation and altered 504 genes, with cyclin and cell-cycle-regulation pathways inhibited and cell-death pathways activated.

Anti-ACTL8 immunohistochemistry on head-and-neck squamous carcinoma tissue gave moderate focal cytoplasmic staining, the only protein-level localisation reported for ACTL8.

ACTL8 is classified as a testis-selective rather than strictly testis-restricted cancer-testis antigen, and is highly expressed in de novo HNSCC tumours.

The abstract explicitly reports ACTL8 knockdown effects on MYC and metabolic enzymes, partial MYC rescue, and direct Momordin Ic binding measured by SPR and TSA. Detailed assay controls and endogenous mechanism require the full article.

RETRACTED. The cached PubMed record carries the publication type "Retracted Publication" and a retraction notice in Biosci Biotechnol Biochem 2022;86(3):423. Its reported findings - that ACTL8 knockdown in KLE and Ishikawa endometrial cancer cells reduced proliferation, migration and invasion and altered p21, E-cadherin, cyclin A, MMP-9 and N-cadherin - are not used anywhere in this review.

Machine-generated literature summary that surfaced the entire tumour-biology literature for ACTL8, none of which is represented in GOA. Its self-evaluation reports a faithfulness score of 85.7 per cent and no pairwise score, and all eight of its citations are numeric PMIDs.

Used only as a lead. Every claim taken from it was re-read against the cached PMID, and no mechanistic assertion is sourced from its prose. Doing that check is what revealed that one of its eight cited papers, PMID:32125225, has been retracted.

PANTHER nodes PTN002631586 and PTN007551913 each donate to nine human genes; eight are at least 90.7 per cent identical to beta-actin over their aligned actin block, and ACTL8 is the ninth at 33.8 per cent.

Of 19 residues within 4.0 angstrom of ATP or its divalent cation in PDB 2BTF chain A, ACTL8 retains 11 identical and 3 conservatively substituted, with 5 non-conservative substitutions (D157, K213, E214, T303, K336). The four conventional actins score 19 of 19 compatible.

Of 38 residues within 4.0 angstrom of a neighbouring protomer in PDB 6DJO F-actin, ACTL8 retains only 8 identical and 3 conservative, with 24 non-conservative substitutions and 3 deletions; 8 of the 10 D-loop contacts are non-conservative. Both tallies are unchanged under a second substitution matrix and gap model.

The analyzed experimental source annotations are grounded in curated experiments; whether each ancestral assertion transfers to ACTL8 is unresolved rather than settled by source counts or identity.

Ranked across the panel, ACTL8's 11 of 38 compatible interface positions sits in a band with ACTL7A (14), ACTL7B and ACTL9 (16) and ACTRT1 (21), and human Arp3/ACTR3 scores 8 - below ACTL8 - while Arp2 scores 22. Since both Arps occupy protomer positions at an Arp2/3 branch, the metric bounds canonical two-stranded protomer incorporation, not filament association in general.

Of the eight divergent human actin-like / actin-related-T proteins, ACTL8 is the only one that receives an IBA from either narrow beta-actin node, and it carries 11 IBA rows against a median of 2 across the other seven.

Of 32 human PTHR11937 members, only 7 have an experimentally supported molecular function once bare GO:0005515 protein binding is excluded, and among the eight divergent actin-like and actin-related-T members (ACTL7A, ACTL7B, ACTL8, ACTL9, ACTL10, ACTRT1, ACTRT2, ACTRT3) only ACTRT1 does. Most but not all of that set is testis-restricted - UniProt describes ACTRT3 as ubiquitously expressed - so it is grouped here by sequence divergence, not by tissue.