ACTL8: does the actin fold come with actin's residues, and do its IBA sources transfer?

Generated by uv run python analyze_actl8.py. Every number below is computed at run
time from the UniProt REST API, RCSB coordinate files, QuickGO, and the repository's
cached PANTHER family listing. Nothing is hard-coded from a previous run.

1. Is actin's nucleotide site still present in ACTL8?

Contacts were computed from PDB 2BTF chain A (beta-actin with bound ATP, SR), taking every residue with a heavy atom within 4.0 Å of the nucleotide or its divalent cation. 19 residues qualify. The structure chain's own observed sequence (residues 2–375) was then aligned to each panel sequence, so the residue reported for each protein is the aligned residue, not the residue at the same number.

~ = conservative substitution, ** = non-conservative substitution.

Column key: Q9H568 = ACTL8 (human actin-like 8); P60709 = ACTB (human beta-actin; IBA donor); Q9Y615 = ACTL7A (human actin-like 7A); Q8TDG2 = ACTRT1 (human actin-related protein T1); P61160 = ACTR2 (human Arp2); P45891 = Arp53D (Drosophila actin-like 53D; IBA donor)

Per-protein tally over the same contact set:

Residues that enter only the 5.0 Å shell (second shell, water-mediated in this structure): D11, D154, G74, N12, R183, R210, S155, T186.

2. Is the filament protomer interface still present?

PDB 6DJO contains 4 F-actin protomers (A, B, C, D). Chain C has the most inter-protomer contacts and was used. Interface residues are every residue within 4.0 Å of any other chain: 38 residues.

What this metric does and does not bound

Ranking the whole panel by chemically compatible positions (identical + conservative) out of
38:

The ordering carries an important caveat, and it is one this analysis produces against itself.
Arp3 (ACTR3) scores below ACTL8, and Arp2 only a little above, yet Arp2 and Arp3 form the
first protomer pair of a daughter filament at an Arp2/3 branch - they do make actin-like
protomer contacts. A low score on this metric therefore bounds canonical protomer
incorporation into a conventional two-stranded filament; it does not show that a protein
cannot occupy any position in an actin-containing structure. ACTL8 sits in a band with the
other divergent actin-likes and Arp3, not uniquely below them, and any argument built on the
tally should be stated at that strength.

Per-residue detail for ACTL8 and two reference points:

Alignment sensitivity

ACTL8 is far enough from actin that gap placement could in principle drive the tallies,
so both residue sets were re-scored under a second matrix and gap model. If the
counts below move only marginally, the conservation call is not an artefact of one
alignment.

3. What evidence do the IBA WITH/FROM sources carry for the term they donated?

• WITH/FROM tokens across all rows (parsed from ACTL8-goa.tsv, not by hand): 62
• resolved to protein entries: 47
• distinct reviewed (Swiss-Prot) source proteins: 25
• sources carrying their own experimental-code annotation for the donated term: 47
• non-protein sources (PANTHER tree nodes, GO ids): 13
• unresolved: 0

GO:0015629 actin cytoskeleton (cellular_component, IBA, is_active_in)

GO:0045202 synapse (cellular_component, IBA, is_active_in)

GO:0005737 cytoplasm (cellular_component, IBA, is_active_in)

GO:0016020 membrane (cellular_component, IBA, is_active_in)

GO:0030424 axon (cellular_component, IBA, is_active_in)

GO:0098973 structural constituent of postsynaptic actin cytoskeleton (molecular_function, IBA, enables)

GO:0005884 actin filament (cellular_component, IBA, is_active_in)

GO:0007409 axonogenesis (biological_process, IBA, involved_in)

GO:0019901 protein kinase binding (molecular_function, IBA, enables)

GO:0035267 NuA4 histone acetyltransferase complex (cellular_component, IBA, part_of)

GO:0048870 cell motility (biological_process, IBA, involved_in)

GO:0005856 cytoskeleton (cellular_component, IEA, located_in)

GO:0098974 postsynaptic actin cytoskeleton organization (biological_process, IEA, involved_in)

4. Which clade does each donating PANTHER node actually cover?

For every PANTHER ancestral node cited in an ACTL8 WITH/FROM field, QuickGO was asked
which human genes that node donates to. Each of those genes was then aligned locally to
human beta-actin (P60709), so that a multidomain protein is compared over its actin block
rather than over its full length.

PANTHER:PTN002631484

Donates to human genes: GO:0015629 (18 human annotations).

PANTHER:PTN002631586

Donates to human genes: GO:0005884, GO:0098973 (18 human annotations).

PANTHER:PTN007551913

Donates to human genes: GO:0005737, GO:0007409, GO:0016020, GO:0019901, GO:0030424, GO:0035267, GO:0045202, GO:0048870 (71 human annotations).

ACTL8 is 33.8% identical to beta-actin over its aligned block. In the narrow nodes the lowest identity to beta-actin among the other human members is: PTN002631586 90.7%; PTN007551913 90.7%.

5. Do ACTL8's own closest relatives sit under the same PANTHER nodes?

For each divergent human actin-like / actin-related-T protein, QuickGO was asked which PANTHER
nodes appear in the WITH/FROM field of its own IBA annotations. If ACTL8's membership of the
cytoplasmic-actin subfamily were normal for this group, its relatives would be there too.

Narrow (beta-actin subfamily) nodes: PTN002631586, PTN007551913. Of the 8 relatives examined, the ones other than ACTL8 that sit under a narrow node are: none. ACTL8 carries 11 IBA rows against a median of 2 for its relatives.

6. How common is experimental molecular function in this family?

Human members of PANTHER PTHR11937 (ACTIN) listed in the repository's cached InterPro entry table: 32. Of these, 24 carry at least one experimental-code molecular-function annotation in QuickGO, 31 carry an experimental annotation in any aspect, and 1 have none at all. Once bare GO:0005515 protein binding is excluded — which nearly every human protein has from interactome screens, so counting it would make this survey uninformative — 7 members retain an experimentally supported, informative molecular function.

Experimental codes counted: EXP, HDA, HEP, HGI, HMP, HTP, IDA, IEP, IGI, IMP, IPI.