CAPSL (calcyphosin-like) is a small EF-hand protein of the calcyphosin family (PANTHER PTHR34524, subfamily SF5 calcyphosin-like protein), which it shares with human CAPSL; the paralogous calcyphosin CAPS sits in a different subfamily (SF2). Horse CAPSL is 97% identical to human CAPSL across its full length, and its EF-hand pairs retain the residues that coordinate calcium, so it is expected to bind calcium. No experiments have been done on the horse protein. In other mammals, human CAPSL is found in the cytoplasm and the nucleus. Its depletion in human retinal endothelial cells impairs proliferation and migration, endothelial Capsl loss in mice disrupts retinal angiogenesis, and the gene has been linked to adipocyte differentiation. A 2026 cryo-electron tomography preprint on bovine tracheal cilia identifies CAPSL as a microtubule inner protein in the lumen of the ciliary transition-zone doublet, where it forms a pseudo-helical spiral. Recombinant human CAPSL stabilises microtubules in vitro. In horse, CAPSL is expressed in bronchial epithelium, which fits a role in multiciliated cells. Its most likely primary role is a structural one inside ciliary microtubules, but this rests on one unrefereed study, and whether calcium binding regulates it is unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005509 calcium ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: The EF-hand calcium-binding loops are conserved, which supports calcium ion binding for horse CAPSL. Reason: Horse CAPSL carries EF-hand domains (PROSITE PS50222, three matched; PS00018 calcium-binding-site motif, two matched) and the four-EF-hand architecture of the calcyphosin family. It is a member of the same PANTHER subfamily (PTHR34524:SF5) as human CAPSL Q8WWF8. In the human sequence, PROSITE-ProRule assigns calcium-coordinating positions in EF-hands 1 and 2. Of the ten mapped positions, nine are identical in horse. The one change, Asp to Asn at human position 54 (horse 71), is a conservative substitution that EF-hand loops tolerate. Calcium binding is a family-level property, and Ca2+-loaded structures of the paralog CAPS (PTHR34524:SF2) support it. The family review leaves the scope for the whole family unresolved because EF-hand integrity varies across distant members. For a mammalian SF5 ortholog with intact loops, the inference is sound. No direct measurement of calcium binding by CAPSL has been made. Supporting Evidence: file:human/CAPSL/CAPSL-uniprot.txt /note="EF-hand 1" file:human/CAPSL/CAPSL-uniprot.txt /ligand="Ca(2+)" file:HORSE/CAPSL/CAPSL-bioinformatics/RESULTS.md 202/208 identical paired residues (97.1%) file:HORSE/CAPSL/CAPSL-uniprot.txt PANTHER; PTHR34524:SF5; CALCYPHOSIN-LIKE PROTEIN; 1. |
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Download this section (compressed HTML)Q: If the transition-zone MIP assignment of the Cai et al. 2026 preprint holds up after peer review, should microtubule binding and a ciliary transition zone location be annotated to CAPSL across mammalian SF5 orthologs?
Q: Do the cytoplasmic and nuclear CAPSL pools seen in endothelial cells reflect functions separate from the ciliary pool, or a soluble pool in non-ciliated cells?
Q: Is the 17-residue N-terminal extension (MQERASIVASLSNWWQQ) of the horse Ensembl model supported by transcript evidence, or does it come from an upstream in-frame start codon that gene-model prediction chose instead of the conserved MAGTAR start?
Experiment: Measure calcium binding of recombinant CAPSL and EF-hand loop mutants by ITC. Compare microtubule co-sedimentation and stabilisation assays with and without calcium.
Hypothesis: CAPSL EF-hands bind calcium, and calcium occupancy modulates its binding to the microtubule lumen.
Type: binding assay
Experiment: Knock out CAPSL in primary airway multiciliated cultures, then assess transition-zone ultrastructure by cryo-ET, ciliary beating and the transition-zone barrier.
Hypothesis: CAPSL is required for transition-zone doublet integrity in motile cilia.
Type: genetic perturbation with ultrastructure
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: It is not known whether CAPSL is a constitutive microtubule inner protein of the ciliary transition zone in vivo across mammals. It is also not known whether its EF-hands bind calcium with physiologically relevant affinity, or whether calcium changes how it binds or stabilises tubulin.
BIOLOGY
What is known: What is established is the conserved EF-hand architecture, a single cryo-ET preprint placing CAPSL in the lumen of bovine transition-zone doublets, and perturbation phenotypes in human and mouse endothelial and adipogenic cells. No calcium affinity has been measured, and no ciliary loss-of-function phenotype has been reported.
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