UNC119B (A6NIH7) curation notes

Deep research status

just deep-research-falcon human UNC119B first failed (falcon timed out at 600 s; perplexity-lite fallback unavailable in this environment). Re-run with --timeout 2400 succeeded: see UNC119B-deep-research-falcon.md.

Summary of function

• UNC119B is a myristoyl-binding cargo carrier of the PDE6D/UNC119 family (Ig-like beta-sandwich pocket) PMID:22085962
• Pocket phenylalanines are required for myristate binding PMID:22085962.
• ARL3-GTP releases cargo PMID:22085962; only ARL3 (not ARL2) allosterically releases cargo, and UNC119B releases more readily than UNC119A PMID:22960633.
• Paralog specificity in cells: UNC119B, not UNC119A, is required for NPHP3 ciliary targeting, and the myristoyl pocket is required PMID:22085962. GPCR delivery is unaffected PMID:22085962.
• Localization: transition zone and proximal cilium PMID:22085962.
• Zebrafish morphant data indicate ciliary dysfunction (KV, body curvature, vision) for the UNC119B-like zebrafish gene PMID:22085962, but cilia still form in human knockdown cells; treated cilium assembly as non-core.

Key decisions

• protein binding rows: ARL3 row -> MODIFY to small GTPase binding (GO:0031267); cargo rows (NPHP3, cystin) -> REMOVE (captured by lipid binding GO:0008289); MACIR row -> REMOVE.
• GO:0031997 (N-terminal myristoylation domain binding) is obsolete (verified in OLS), so lipid binding is the MF used.
• NEW: protein localization to ciliary membrane (GO:1903441), IMP PMID:22085962; comparator PDE6D carries protein localization to cilium (GO:0061512).
• HPA sperm flagellum rows (midpiece/principal/end piece): KEEP_AS_NON_CORE.

HPA cilium atlas vs module role

• Module (primary_cilium_life_cycle, stage 5 membrane composition): "myristoylated cargo carrier", process protein localization to cilium.
• HPA v25 (member_evidence.md): no primary cilium / basal body / centrosome call; main locations Annulus; Cytokinetic bridge; Cytosol; Flagellar centriole; Mitotic spindle. GOA HPA rows are sperm midpiece, principal piece and end piece (GO_REF:0000052). The Hansen et al. 2025 cilium atlas PMID:41005307 did not report UNC119B at primary cilia in the HPA cell lines.
• Interpretation: absence of an HPA cilium call is not evidence against the module role. UNC119B is a soluble carrier that concentrates at the transition zone/proximal cilium only transiently when it delivers cargo, and tagged-protein localization in RPE cells did show a ciliary pool. The cytosol call fits a soluble carrier. core_functions agree with the module role (lipid binding / small GTPase binding; lipoprotein transport; protein localization to ciliary membrane, a child of the module's GO:0061512).

Additional points from deep research (falcon)

• A 2025 study (Horne et al., PNAS, doi:10.1073/pnas.2420961122; not cached) reports that purified UNC119B binds and allosterically activates the kinase PSKH1 independently of PSKH1 lipidation. Not used for annotation (no cached paper); noted as a possible second activity in suggested questions territory.
• Yelland et al. 2021 (Biochemistry) report UNC119B-myristoyl-LCK and UNC119B-ARL3 structures; Jaiswal et al. 2016 measured sub-nM affinities for NPHP3/cystin peptides. Deep research: "UNC119 proteins preferentially carry N-myristoylated cargo, whereas PDE6D is primarily a prenyl-cargo carrier."
• Zebrafish nomenclature caution: zebrafish unc119a is the ortholog of human UNC119B.