FAM111B has a supported serine endopeptidase activity and a predominantly nuclear pool. The one catalytic core records those properties. Controlled self-cleavage is experimentally established; the physiological trans-substrate and the reaction linking proteolysis to nuclear or telomere phenotypes remain unresolved. The positive nuclear-lamina annotation is retained as a non-core spatial region, not a lamin complex or a separately demonstrated catalytic site. The smaller cytoplasmic pool remains positive and non-core.
All eighteen imported contexts are reviewed: three ACCEPT, two MODIFY, ten KEEP_AS_NON_CORE and three UNDECIDED. The imported source objects are preserved; the feedback revision qualifies four reviews and removes a speculative DNM2 aside. Seven positive generic interaction contexts remain non-core under the campaign curation instructions; no partner activity is assigned to FAM111B. No new publication quotations are added. One NEW annotation records directly measured protein autoprocessing; it is also included in the existing catalytic core.
Hoffmann et al., PMID:32776417, Results Human FAM111A and FAM111B are active proteases, Figure 1H and EV1E/G, and Purification of recombinant FAM111 proteins, directly test full-length human FLAG-FAM111B expressed in yeast JEL-1. Internal cleavage fragments, the D544N catalytic control and AEBSF inhibition support the specific serine-type endopeptidase activity term. Both lanes independently inspected Figure 1 and EV1 pixels qualitatively. Figure 1A depicts the 734-residue protein. Exact historical plasmid resequencing, cleavage-site sequencing and kinetic quantitation were not performed in these reviews.
The same paper distinguishes disease-mutant hyperactivity from wild-type cellular behavior. Its FAM111B Results and Figure EV5A report no recognizable PIP motif or replication-site enrichment. The main Results describing Appendix Figure S2 report basal replication, PCNA loading and proliferation dispensability for both FAM111A and FAM111B; this shared basal negative does not refute obstacle-dependent FAM111A activity. Only patient-associated FAM111B alleles, not wild type, produce the reported synthesis shutdown and toxicity. Mutant-induced loss of chromatin-associated RFC1/RPB1 does not establish those proteins as direct proteolytic substrates. The target-specific Results, Methods and relevant Figure 5 captions were read; Figure 5/EV5 pixels and other appendix data were not inspected. The F438 cleavage-site assignment in the later paper is inferred from homology and fragment size, unlike the sequenced FAM111A F334 site.
The literal natural products remain Q6SJ93-1, 734 residues, and Q6SJ93-2, 704 residues, lacking residues 1–30. A full-chain feature is not evidence of proteolytic processing. Tagged full-length constructs, catalytic mutants, patient variants and engineered fragments are separate experimental preparations. Neither antibody localization nor the purified full-length assay establishes equivalent activity or distribution of both natural products.
Kliszczak et al., PMID:37342232, Results 2.1–2.4, Figure 1–3 captions, selected telomere Results, Discussion and corresponding Methods, were independently read in both lanes. Endogenous human U2OS FAM111B is predominantly nuclear, with positive cytoplasmic and detergent-resistant peripheral pools. Spatial overlap with Lamin A/C supports the bounded lamina-region location. Affinity experiments identify nuclear-pore proteins rather than a lamin-containing FAM111B complex. No direct lamin binding or protease substrate is assigned from those associations.
Soluble/pellet fractionation can retain chromatin and membranes together. It is not a chromatin-specific assay, and nuclear-pore localization is not itself chromatin association. No Figure 1–3 pixels, movies or raw supplemental S1/S2 measurements were newly inspected. The retained reference notes and private ledgers preserve each lane's complete selected read scope.
Loss of FAM111B gives positive nuclear-shape, chromosome-instability and telomere phenotypes in human cell models. Wild-type versus protease-dead rescue of ultrafine bridges links controlled protease activity to that endpoint, without locating the rescuing reaction at the lamina or identifying a nuclear-pore substrate. Nuclear-pore catalysis is a Discussion working model. The drug-survival comparison uses MCF7 knockouts, 72-hour treatment and resazurin; U2OS knockout growth defects prevent the same comparison in U2OS. Lack of extra sensitivity under those conditions is not a universal absence-of-function test, a fork-restart measurement or a DNA–protein-adduct-removal assay.
Rhoda et al., PMID:36610347 remains operative-main-unread. Its positive abstract identifies human HT1080 nuclear expression and a patient Y621D context. Publisher HTML/PDF returned 403; the Elsevier HTTP200 response contained metadata only. No Methods, Results, figures or supplement were recovered. Independent PMID:37342232 evidence supports the retained locations without being misattributed to unseen methods in the older citation.
The actual PANTHER family tree response and alignment response, captured on 2026-10-25, identify version 19. The exact human FAM111B 734-residue sequence is leaf PTN002494619 beneath PTN002683271. Five term/source combinations match actual PAINT IBDs, and no NOT assertion occurs on the saved target path. The human FAM111A donor also descends from that node. The official GO_REF:0000033 method explains why a target can legitimately appear among its own experimental descendant sources. Neither donor count nor self-WITH is treated as weakness.
Alabert et al., PMID:24561620, the FAM111A nascent-chromatin/PCNA Results, NCC and construct/imaging Methods and Figure 6/7 captions, supply positive human donor chromatin evidence. Kojima et al., PMID:32165630, selected TOP1 cleavage-complex, stressed-fork, mutant-rescue and ssDNA-binding Results and corresponding Methods, supply positive donor fork and repair evidence. These are FAM111A experiments. The failed purified-protease preparation reported in that donor paper remains distinct from later positive preparations. Neither donor paper's new pixels nor supplements were inspected by this database review.
The current chromatin definition concerns the chromosome-forming DNA–protein complex; target nuclear/pellet evidence does not resolve that compartment. Replication fork processing concerns restoration of a stalled fork, and DNA–protein crosslink repair concerns removal of the covalent adduct. Target phenotypes do not establish these particular steps. The three assertions remain UNDECIDED while valid ancestry and sound donor experiments are preserved. No demonstrated evolutionary loss is alleged. The target negatives are considered alongside, rather than substituted for, the valid donor evidence. These uncertainties are why the catalytic core has no copied FAM111A ssDNA-binding, fork-processing or crosslink-repair facet. Genome/telomere findings remain in the biological description and focused experimental questions, without manufacturing a new process annotation.
Specific alternatives were assessed in the accepted direct lane. SET-domain binding is not SET-protein binding; SET, DNM2 or GRN contact does not transfer phosphatase inhibition, GTPase regulation or cytokine function to FAM111B. HTT fragment contacts do not establish polyglutamine-tract-specific recognition. Supported generic contacts are retained as non-core rather than assigned an invented mechanism.
The selected normal-cache full_text_available metadata governs reference full_text_unavailable flags. External complete-main availability and actual selected reading are recorded separately. Both donor caches and PMID:32814053 are abstract-only despite separately recovered originals. PMID:36610347 has no recovered operative main. PMID:25416956 and PMID:33961781 caches declare full text but contain only introductory/discussion material; separate actual primary captures supplied the operative reads. Failed or empty files are preserved in the evidence packets and are not credited as originals.
The two shared references retain both complete direct and database assessments with labels. Notes contain the intake checkpoint once, the two accepted lane appendices once, and the integration/core checkpoint. Historical PENDING statements are historical, while all eighteen reviews are now populated. Notes and this guide are agent-authored. No normal cache, source object or provider-branded file was rewritten; the normal delivery selection consists only of genuine cited records and machine provenance.
Protein autoprocessing (GO:0016540) is supported by the purified wild-type FAM111B, catalytic-mutant and AEBSF experiments in PMID:32776417 Figure 1H and EV1E/G. FAM111B performs the cleavage; this is not a process assigned merely because it consumes the protein. The term is an is_a child of protein processing and reaches proteolysis through typed ancestry. Current exact-term comparator records include human FAM111A and HTRA2; a bounded CAPN1 query returned none. These comparisons inform the convention but do not replace the target assay. The fixed published GO-CAM index contains no FAM111B entry, and no existing target process is an ancestor or descendant of this addition.
The core retains one enzyme activity and one directly measured self-processing facet. It does not assert physiological maturation, cis-only cleavage, an experimentally sequenced F438 site, or equivalent behavior of the 704-residue natural product. Nuclear pore (GO:0005643) denotes a protein complex; peripheral localization and SEC13/NUP42 coassociation do not by themselves establish FAM111B as a constituent. That optional NEW claim is therefore not added.