Rhp

Summary: Broad but defensible; the HR1 Rho-binding module places Rhp in Rho-family GTPase signalling as a downstream adaptor.

Reason: The InterPro2GO mapping derives from the HR1 Rho-binding domain (IPR011072), present in Rhp (REM-1 domain, residues 36-110). Vertebrate rhophilins bind RhoA through this region and act downstream of it, so participation in signal transduction is a sound family-level inference. A more specific term (e.g. Rho protein signal transduction) is not supported for the fly protein because no fly Rho1 interaction has been shown, so this general term is as precise as the evidence allows. It is not a claim of GTPase or GEF/GAP activity.

Summary: Sound phylogenetic inference; both vertebrate paralogs that descend from the same ancestral node limit Rho-dependent stress-fiber formation, and fly Rhp is their pre-duplication co-ortholog.

Reason: The PAINT node PTN001126281 was seeded with experimental evidence from both vertebrate paralogs, mouse Rhpn1 (MGI:1098783) and human RHPN2 (Q8IUC4), each with an IDA for this term from PMID:25071083, and RHPN2 was earlier shown to disassemble stress fibres in HeLa cells in a Bro1- and PDZ-dependent manner (PMID:12221077). Because the activity is shared by both products of the vertebrate duplication, placing it at the ancestral node is appropriate, and fly Rhp (PANTHER SF15, outside the RHPN1 SF6 and RHPN2 SF5 subfamilies, about 35% identical to each, see file:DROME/Rhp/Rhp-bioinformatics/RESULTS-rereview.md) descends from that node. There is no fly evidence of loss or divergence, and the HR1, BRO1 and PDZ domains that RHPN2 needs for this effect are all present. The only fly experiment, an S2-cell RNAi screen, found no effect on lamella formation, which is a Rac/Arp2/3 readout and does not test stress fibres, so it does not contradict the IBA. The mammalian evidence is from overexpression and podocyte knockout, so the fly role remains an inference.