E1BL04 (bovine XIRP2) notes

2026-10-20 — Full re-review, independent of the ProtNLM2 predictions

ProtNLM2 prediction files were not opened or used.

The deep-research file E1BL04-deep-research-falcon.md failed. It contains "no contexts were retrieved" / "System error" and has no usable content, so it was not used.
Cached via just fetch-pmid: PMID:17046827, 25772365, 37294664, 20360251, 17766470. PMID:15454575 was already cached.
QuickGO (2026-10-20) was used to identify the experimental donors behind the IEA/IBA rows: human XIRP2 A4UGR9 and mouse Xirp2 Q4U4S6.

E1BL04 is an unreviewed 3561-aa product, PANTHER PTHR22591:SF1 (XIRP2). It aligns over 99% of human XIRP2 A4UGR9 (3374 aa) at 80.5% identity, against 36-38% for XIRP1 (E1BL04-bioinformatics/RESULTS.md).
It is not a fragment. It lacks the C-terminal LIM domain/CTD present in mouse Xirp2 isoform 1 (Q4U4S6-1, LIM 3255-3315) and in the short stereocilia isoform (XEPLIN, isoform 3), so it is the LIM-less long isoform class (like human canonical A4UGR9).
There are two other unreviewed bovine XIRP2 entries, A0AAA9SWG7 (936 aa) and A0AAA9SUE1 (957 aa), which may be short-isoform models.

PAINT node PTN000502290 is family-level, spanning SF1 and SF2. Its seeds are A4UGR9 (human XIRP2) and Q702N8 (human XIRP1). The earlier review wrongly called Q702N8 "mouse Xirp2". The IBD for actin filament organization (GO:0007015) is seeded by XIRP1 only. It is accepted because XIRP2-specific evidence agrees: the Xin-repeat properties are identical PMID:15454575, and the knockout disorganizes stereocilia actin PMID:25772365.
Ensembl Compara donors are mouse Xirp2 (Z disc and alpha-actinin binding, IDA, PMID:17046827; cell-cell junction, IDA, PMID:37294664; regulation of actin filament organization, IMP, PMID:25772365; positive regulation of protein localization, IMP, PMID:37294664) and human XIRP2 (stress fiber, focal adhesion and actin filament binding, IMP, PMID:15454575).
PMID:37294664 assigns gamma-actin recruitment to stereocilia gaps to the short-isoform LIM/CTD PMID:37294664. That region is absent from E1BL04, so GO:1903829 is marked as over-annotated (domain-architecture mismatch).
Mouse knockout phenotypes (cardiac development, ventricular septum, conduction) were not proposed as process annotations, because they are necessity evidence.

actin binding, actin cytoskeleton organization, cell junction and anchoring junction: changed from MARK_AS_OVER_ANNOTATED/KEEP_AS_NON_CORE to MODIFY, refined to actin filament binding, actin filament organization and cell-cell junction.
positive regulation of protein localization: kept as MARK_AS_OVER_ANNOTATED, with a domain-architecture reason added.
NEW: intercalated disc (GO:0014704), a location supported by the mouse ortholog PMID:20360251.
Added PMID references and the bioinformatics comparison. The description was rewritten without claims of bovine-specific experiments.

interpro/panther/PTHR22591/PTHR22591-review.yaml places E1BL04 in SF1, which agrees. There is no subfamily disagreement.

No module in modules/ covers Xin proteins, sarcomere/Z disc, intercalated disc or stereocilia.