MYL10 (myosin regulatory light chain 10; precursor lymphocyte-specific regulatory light chain, PLRLC) is a small EF-hand protein of the myosin regulatory light chain (RLC) family. Its conserved C-terminal light-chain core (about 150 residues) is nearly identical among horse, mouse, rat and human MYL10 and is most closely related to the cardiac ventricular light chain MYL2, while the N-terminal segment preceding the core is encoded by variable, species-specific exons. The core retains the canonical first EF-hand loop (DQNRDGFIDKED) that in RLCs forms the divalent-cation (Ca2+/Mg2+) site, so MYL10 is expected to bind calcium and to act as a soluble cytoplasmic light chain. In mouse, the gene is expressed in precursor lymphocytes, where it is induced by interleukin-7, and its loss in retinal ganglion cells enhances axon regeneration after optic nerve injury; the myosin heavy chain it associates with, its phosphorylation and its cellular mechanism are not established. A mitochondrial localization has been reported for an expressed human MYL10 fusion protein, but its physiological meaning is unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: Calcium binding through the conserved first EF-hand of the regulatory light chain fold; core molecular function. Reason: The PAINT node PTN000549442 places calcium ion binding at an ancestor of the regulatory light chains, seeded by the experimentally characterised ventricular light chain MYL2 (P10916). Horse MYL10 is inside that clade (it is a PTHR23049 member and its core is 84% identical to MYL2 and 98-99% identical to MYL10 of human, mouse and rat; neighbour-joining places the MYL10 clade as sister to MYL2), and it retains the canonical first EF-hand loop DQNRDGFIDKED with a PROSITE EF_HAND_1 calcium-binding site match, so there is no sign of loss. The RLC N-terminal site is a mixed Ca2+/Mg2+ site, and no direct binding measurement exists for any MYL10, so the term is kept at the general calcium ion binding level. Supporting Evidence: file:HORSE/MYL10/MYL10-uniprot.txt PROSITE; PS00018; EF_HAND_1; 1. file:HORSE/MYL10/MYL10-bioinformatics/RESULTS-rereview.md | P10916 | MLRV_HUMAN | 166 | 127/152 | 0.836 | 0 | file:HORSE/MYL10/MYL10-bioinformatics/RESULTS-rereview.md | A0A9L0TJE1_HORSE | 83 | file:HORSE/MYL10/MYL10-bioinformatics/RESULTS.md | BINDING | 97–97 | 83 | 1/1 | |
| GO:0005509 calcium ion binding | IEA GO_REF:0000120 | ACCEPT | Summary: Same calcium-binding claim as the IBA, from the EF-hand domain signature; consistent with the conserved first EF-hand loop. Reason: The EF-hand domain (IPR002048) and EF_HAND_1 calcium-binding-site signatures match the horse sequence, and the first EF-hand loop is conserved with the RLC paralogs and MYL10 orthologs. This row reinforces the IBA for the same term and receives the same action. Supporting Evidence: file:HORSE/MYL10/MYL10-uniprot.txt InterPro; IPR002048; EF_hand_dom. file:HORSE/MYL10/MYL10-uniprot.txt PROSITE; PS00018; EF_HAND_1; 1. file:HORSE/MYL10/MYL10-bioinformatics/RESULTS-rereview.md | A0A9L0TJE1_HORSE | 83 | |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasmic location inherited from a deep regulatory light chain ancestor; appropriate for a soluble light chain. Reason: PTN001495767 is a deep node supported by light chains from fungi, invertebrates and vertebrates, and horse MYL10 is a PTHR23049 regulatory light chain with an intact core and no transmembrane or signal features. Regulatory light chains function bound to myosin heavy chains in the cytoplasm, so cytoplasm is the expected location. The PAINT curators did not propagate a more specific myosin complex term to this node, and none is added here. It does not imply that MYL10 is exclusively cytoplasmic. Supporting Evidence: file:HORSE/MYL10/MYL10-uniprot.txt InterPro; IPR050403; Myosin_RLC. file:human/MYL10/MYL10-uniprot.txt Myosin is a hexamer of 2 heavy chains and 4 light chains. |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Mitochondrial location propagated from a single human expressed-fusion-protein observation; retained as non-core. Reason: The node PTN002746160 is grounded on human MYL10 (Q9BUA6), whose own mitochondrion annotation is IDA from expressed fusion proteins (GO_REF:0000054); human MYL10 appearing as the donor is normal grounding, not circularity, and horse MYL10 is in the MYL10 clade. The curator's placement is retained. Two caveats limit its weight. The observation is a single high-throughput fusion-protein localization, and the N-terminal segment that precedes the conserved core differs completely between human (MLLRLVSNSWPQ...) and horse (MTNSCKSMRKKS...), which is where any targeting signal would be expected; the conserved light-chain core itself carries no known mitochondrial targeting feature. No mitochondrial function is proposed. Supporting Evidence: file:HORSE/MYL10/MYL10-bioinformatics/RESULTS-rereview.md | A0A9L0TJE1 | 212 | 61 | `MTNSCKSMRKKSSRKIAKRPEHTFHTRRKNETHEYARTRSTSPRDQAPRRARKRAEGAAS` | True | |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara projection of the same human mitochondrion annotation; non-core, consistent with the IBA row. Reason: This is a one-to-one ortholog projection of the human fusion-protein localization and carries the same claim and caveats as the IBA row (single high-throughput observation; the variable N-terminal segment is not conserved between human and horse), so it receives the same action. Supporting Evidence: file:HORSE/MYL10/MYL10-bioinformatics/RESULTS-rereview.md | A0A9L0TJE1 | 212 | 61 | `MTNSCKSMRKKSSRKIAKRPEHTFHTRRKNETHEYARTRSTSPRDQAPRRARKRAEGAAS` | True | |
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Download this section (compressed HTML)Q: Which myosin heavy chain(s) does MYL10 associate with in vivo, and is it phosphorylated at the residues corresponding to the regulatory serine of MYL9/MYL12?
Q: Is the reported mitochondrial localization of human MYL10 a property of its human-specific N-terminal segment, or of the conserved light-chain core shared with other mammals?
Experiment: Co-immunoprecipitation and mass spectrometry of endogenous MYL10 from mouse pre-B cells or retinal ganglion cells to identify its myosin heavy chain partner, and test of divalent cation binding by the recombinant core.
Experiment: Compare localization of fluorescent-protein fusions of the human and horse MYL10 N-terminal variants and of the shared core alone in the same cell line.
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