Affinage mechanistic annotation for ARHGAP23 (human) Affinage Affinage (Claude Sonnet reading pass + Opus synthesis pass) 3 citations

Affinage mechanistic annotation for ARHGAP23 (human)

Current model (mechanistic narrative)

ARHGAP23 is a multidomain RhoGAP-family protein that functions as a cytoplasmic suppressor of RhoA activity at cell-cell junctions PMID:38970683. At adherens junctions in keratinocytes, association of plakophilin 4 (PKP4) with ARHGAP23 reduces its binding to RhoA, thereby restraining cytoplasmic RhoA activation and stress fiber formation; this PKP4 scaffolding spatially restricts where ARHGAP23 acts on RhoA PMID:38970683. ARHGAP23 is also a component of the core VE-cadherin interactome in endothelial cells, binding VE-cadherin independently of intracellular-domain tyrosine phosphorylation PMID:42006337. Beyond these junction-associated roles, the enzymatic GAP activity and domain functions of ARHGAP23 have not been experimentally characterized in the available corpus.

Affinage mechanism profile (Affinage's own GO/Reactome grounding)

Dated findings (citation-anchored)

Year Confidence Finding PMIDs Journal
2004 Low ARHGAP23 (KIAA1501) was identified as a RhoGAP-domain-containing protein with a domain structure consisting of PDZ, Pleckstrin homology (PH), and RhoGAP domains, shared with ARHGAP21 and Xenopus rGAP. Two protein isoforms (1491-aa isoform 1 and 1144-aa isoform 2) arise from alternative splicing involving a 23-bp exon 23 that causes a frameshift and C-terminal truncation in isoform 2. PMID:15254754 International journal of oncology
2024 Medium ARHGAP23 acts as a Rho suppressor at adherens junctions: association of PKP4 (plakophilin 4) with ARHGAP23 reduced ARHGAP23 binding to RhoA, thereby preventing RhoA activation in the cytoplasm and stress fiber formation. This places ARHGAP23 as a cytoplasmic inhibitor of RhoA activity whose function is spatially regulated by PKP4 scaffolding. PMID:38970683 Cellular and molecular life sciences : CMLS
2026 Low ARHGAP23 was identified as a component of the core VE-cadherin interactome in endothelial cells, binding VE-cadherin even when its intracellular domain is not tyrosine-phosphorylated, as detected by mass spectrometry-based proteomics. PMID:42006337 iScience

Citations