Gene Ontology annotation through association of InterPro records with GO terms

InterPro identifies the Xin repeat domain (IPR012510) and the XIRP1/XIRP2 family (IPR030072), giving actin binding, actin cytoskeleton organization and cell junction mappings; all are correct but general.

Annotation inferences using phylogenetic trees

PAINT node PTN000502290 is a family-level Xin node seeded by human XIRP2 (A4UGR9) and human XIRP1 (Q702N8). The actin filament organization IBD is seeded by XIRP1 alone. (The earlier version of this review mislabelled Q702N8 as mouse Xirp2; it is human XIRP1, PANTHER SF2.)

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

The mapping of SL-0038 Cell junction gives anchoring junction. The bovine subcellular location statement is ARBA-derived.

GO_REF:0000107

Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara

These transfers are from human XIRP2 (A4UGR9) and mouse Xirp2 (Q4U4S6). They are the most informative annotations for this entry, but one, positive regulation of protein localization, derives from an isoform-specific (LIM/CTD) activity that E1BL04 lacks.

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

The combined IEA methods assign the general term actin binding, which is better refined to actin filament binding.

file:BOVIN/E1BL04/E1BL04-uniprot.txt

UniProt entry E1BL04

This is an unreviewed (PE 3) 3561-aa XIRP2 entry with 26 PROSITE Xin repeats and 18 Pfam Xin domains. It is placed in PANTHER PTHR22591:SF1 (XIRP2) and has no LIM domain.

file:BOVIN/E1BL04/E1BL04-bioinformatics/RESULTS.md

E1BL04 comparison with characterized Xin-family proteins

E1BL04 aligns over 99% of human XIRP2 at 80.5% identity, against 36-38% identity to XIRP1. It lacks the LIM/CTD region of mouse Xirp2 isoform 1 and the short isoform.

PMID:15454575

Xin repeats define a novel actin-binding motif.

Xin repeats bind actin filaments directly, stabilize them and arrange them into networks. Human XIRP2 repeats share these properties.

"they not only directly bind actin filaments, but also have the capability of arranging microfilaments into networks"

PMID:17046827

Myomaxin is a novel transcriptional target of MEF2A that encodes a Xin-related alpha-actinin-interacting protein.

Mouse Xirp2 (myomaxin) localizes to the Z-disc/costamere and interacts with alpha-actinin-2.

"interacts with the sarcomeric Z-disc protein, alpha-actinin-2"

PMID:20360251

Essential roles of an intercalated disc protein, mXinbeta, in postnatal heart growth and survival.

Mouse Xirp2 localizes to the intercalated disc and is required for intercalated disc maturation and for the localization of Xirp1 and N-cadherin there.

"Loss of mXinbeta resulted in the failure of forming mature intercalated discs and the mislocalization of mXinalpha and N-cadherin."

PMID:25772365

XIRP2, an actin-binding protein essential for inner ear hair-cell stereocilia.

Long XIRP2 isoforms with Xin repeats occur in stereocilia and cuticular plates. Loss of Xirp2 disorganizes the paracrystalline actin of stereocilia.

"XIRP2 is notable for its 28 Xin repeats, which bind and stabilize actin bundles"

PMID:37294664

Repair of noise-induced damage to stereocilia F-actin cores is facilitated by XIRP2 and its novel mechanosensor domain.

The repair of stereocilia gaps and the gamma-actin recruitment depend on the LIM/CTD of the short XIRP2 isoform. The long isoform is at the cuticular plate and cell junctions.

"The long isoform primarily localizes to the cuticular plate and cell junctions, while the short isoform is enriched in stereocilia"

PMID:17766470

Loss of mXinalpha, an intercalated disk protein, results in cardiac hypertrophy and cardiomyopathy with conduction defects.