MAK (P20794) curation notes

Deep research status

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

Summary of function

• RCK kinase; testis-enriched expression PMID:2183027 (expression-based inference only).
• Photoreceptor cilium length control in mouse [PMID:21148103 "Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization."; "Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells."; "In the Mak -null retina, photoreceptors exhibit elongated cilia and progressive degeneration."]. IFT88/IFT57 accumulate in mutant axonemes; Mak phosphorylates RP1 N-terminus. Respiratory (motile) cilia length unaffected.
• Human RP: homozygous Alu insertion in exon 9 PMID:21825139; human IHC: inner segments, cell bodies and axons, little distal to connecting cilium.
• Activation by TDY dual phosphorylation, autophosphorylation and CCRK PMID:21986944; prostate cancer cell observations: AR coactivator PMID:16951154, CDH1 phosphorylation, spindle/centrosome/midbody localization PMID:21986944.

Key decisions

• Kinase activity rows ACCEPT; AR protein binding MODIFY -> nuclear androgen receptor binding (GO:0050681); CDK20 and FZR1 binding REMOVE.
• Transcription coactivator / positive regulation of transcription KEEP_AS_NON_CORE (cancer cell lines).
• Spermatogenesis NAS MARK_AS_OVER_ANNOTATED (expression-based).
• cilium assembly IBA KEEP_AS_NON_CORE (MAK restricts length, not required for assembly).
• NEW negative regulation of non-motile cilium assembly (GO:1902856), ISS from mouse Mak (PMID:21148103; mouse ortholog already carries IMP/IDA/IGI).

HPA cilium atlas vs module role

• Module (stage 6 length control): RCK kinase restricting length at the ciliary tip (protein serine/threonine kinase activity; regulation of cilium assembly; ciliary tip).
• HPA v25: Basal body (Approved); main locations Basal body; Connecting piece; Cytosol; Nucleoplasm. GOA HPA rows: nucleoplasm, nucleolus.
• Interpretation: partial agreement. HPA places MAK at the basal body (and sperm connecting piece) in cultured cells, whereas the module assigns it to the ciliary tip. Mouse photoreceptor and cultured-cell data (Chaya et al. 2024, PMID:39293864) do place Mak at ciliary tips, so I keep ciliary tip in core_functions (as a NEW ISS location) together with the photoreceptor connecting cilium and axoneme. The HPA basal-body call may reflect a base pool or cell-type differences; human retina immunostaining placed MAK mainly in inner segments. The length-control role is supported (GO:1902856, a descendant of the module's GO:1902017), but the evidence is essentially photoreceptor-specific, and in non-retinal cells CILK1 is the better-supported length-control kinase.

Additional points from deep research (falcon) and follow-up

• Chaya et al. 2024 (PMID:39293864, cached full text) show that mouse Mak localizes to ciliary tips and regulates IFT together with Ick PMID:39293864; Mak/Ick double loss abolishes photoreceptor axonemes, and Ccrk (CDK20) activates both. IFT components concentrate at connecting-cilium tips in Mak-/- retina.
• Added NEW ciliary tip (ISS) and ciliary tip in core_functions based on this paper.