MYL10 (myosin regulatory light chain 10; also called PLRLC, precursor lymphocyte-specific regulatory light chain) is a non-enzymatic, calmodulin-like EF-hand protein of the myosin regulatory light chain (RLC) family. It belongs to the MYL10 subfamily of the RLC family, which sits in the sarcomeric-type lineage that also contains the cardiac and skeletal RLCs MYL2, MYL7 and MYLPF, rather than with the nonmuscle/smooth-muscle RLCs MYL9 and MYL12A/B. The human protein (226 aa) carries a unique N-terminal extension of about 60 residues ahead of the conserved RLC core; the core contains a canonical calcium-coordinating loop in the first EF hand and three predicted EF-hand domains. By family membership MYL10 is expected to bind the neck (lever-arm) region of a myosin heavy chain and to modulate actomyosin mechanics, but its endogenous heavy-chain partner, regulatory phosphorylation and calcium affinity have not been measured. The mouse ortholog was first described as a gene expressed in precursor B and T lymphocytes and induced by interleukin-7. The protein is soluble and cytoplasmic; an expressed GFP-fusion of human MYL10 and a mouse mitochondrial proteome both place a pool in mitochondria, whose function is unknown.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005509 calcium ion binding | IBA GO_REF:0000033 | ACCEPT | Summary: Calcium ion binding is the conserved molecular function placed by PAINT at the sarcomeric-type RLC node and supported by the canonical first EF-hand loop in human MYL10. Reason: The IBA derives from PAINT node PTN000549442, the node shared by MYL2, MYL7, MYLPF and MYL10 (human MYL2, P10916, is the experimental donor); MYL10 falls inside that clade (PANTHER subfamily PTHR23049:SF36) and has no sequence evidence of loss. Human MYL10 residues 97-108 (DQNRDGFIDKED) form a canonical 12-residue EF-hand calcium-binding loop with D/N/D/D at positions 1, 3, 5 and 9 and Glu at position 12, matching the PROSITE EF_HAND_1 pattern and the ProRule binding-site features in the UniProt record. The InterPro2GO row (IPR002048) is consistent sequence-level support. No direct calcium affinity measurement exists for MYL10, so the assertion rests on phylogeny and conserved coordinating residues; in RLCs this first-EF-hand site is the divalent-cation (Ca/Mg) site, not a calmodulin-like trigger. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt This chain binds calcium. file:human/MYL10/MYL10-uniprot.txt /ligand="Ca(2+)" |
| GO:0005509 calcium ion binding | IEA GO_REF:0000002 | ACCEPT | Summary: Calcium ion binding is the conserved molecular function placed by PAINT at the sarcomeric-type RLC node and supported by the canonical first EF-hand loop in human MYL10. Reason: The IBA derives from PAINT node PTN000549442, the node shared by MYL2, MYL7, MYLPF and MYL10 (human MYL2, P10916, is the experimental donor); MYL10 falls inside that clade (PANTHER subfamily PTHR23049:SF36) and has no sequence evidence of loss. Human MYL10 residues 97-108 (DQNRDGFIDKED) form a canonical 12-residue EF-hand calcium-binding loop with D/N/D/D at positions 1, 3, 5 and 9 and Glu at position 12, matching the PROSITE EF_HAND_1 pattern and the ProRule binding-site features in the UniProt record. The InterPro2GO row (IPR002048) is consistent sequence-level support. No direct calcium affinity measurement exists for MYL10, so the assertion rests on phylogeny and conserved coordinating residues; in RLCs this first-EF-hand site is the divalent-cation (Ca/Mg) site, not a calmodulin-like trigger. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt This chain binds calcium. file:human/MYL10/MYL10-uniprot.txt /ligand="Ca(2+)" |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Binary interactome hit with ZNF76; generic protein binding is uninformative and is removed under the protein-binding policy. Reason: The IPI comes from the HuRI binary interactome screen (PMID:32296183), and UniProt lists the Q9BUA6-P36508 (ZNF76) pair with three experiments. The interaction may well be real, but GO:0005515 says nothing about what MYL10 does: ZNF76 is a nuclear zinc-finger transcription factor with no established link to myosin light-chain function, and no informative molecular-function term can be derived from a yeast two-hybrid hit alone. Removal follows the repository policy for bare protein binding and does not assert that the interaction is false. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt Q9BUA6; P36508: ZNF76; NbExp=3; |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm is the appropriate location for a soluble myosin light chain. Reason: This IBA is placed at PTN001495767, a deep node of the RLC family whose experimentally characterised descendants (including human MYL2, MYL9 and MYL12A and fly, worm and yeast RLCs) are cytoplasmic or actomyosin-associated. MYL10 is inside that clade and is a soluble EF-hand protein without a signal peptide or transmembrane segment, so the inherited location holds. The more specific sarcomere/myofibril terms that PAINT placed on the MYL2 branch (node PTN002746142) were not propagated to the MYL10 branch, and they are not added here. Supporting Evidence: 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: A mitochondrial pool is reported by a human GFP-fusion localization and propagated within the MYL10 subfamily; retained as a non-core location. Reason: The IDA row is a LIFEdb localization of an expressed fusion protein (GO_REF:0000054), and the IBA (PTN002746160, the MYL10-subfamily node) is grounded on that human observation; human Q9BUA6 appearing as its own source is the expected marker of experimental grounding, not circularity. The mouse ortholog Myl10 (Q62082, same PANTHER subfamily SF36) independently carries a mitochondrion HDA annotation from the MitoCarta mouse tissue proteome (PMID:18614015), so two independent methods in two species agree. The location is therefore kept, but as non-core: no mitochondrial targeting signal is annotated, the 60-residue N-terminal extension has not been tested as one, and no mitochondrial activity or partner of MYL10 is known. ORGANELLES check (2026-11-03). The IBA WITH/FROM names only PTN002746160 and Q9BUA6 itself, so the node rests on the human LIFEdb fusion (no PAINT table for PTHR23049 is cached to list further seeds); the mouse Myl10 HDA from MitoCarta is an independent line. The record has no transit peptide or transmembrane segment and no sub-mitochondrial assay exists, so the rows stay at the root. The is_active_in qualifier is not borne out by this review: no MYL10 activity has been shown in mitochondria, so the row joins the ORGANELLES is_active_in worklist. |
| GO:0005739 mitochondrion | IDA GO_REF:0000054 | KEEP AS NON CORE | Summary: A mitochondrial pool is reported by a human GFP-fusion localization and propagated within the MYL10 subfamily; retained as a non-core location. Reason: The IDA row is a LIFEdb localization of an expressed fusion protein (GO_REF:0000054), and the IBA (PTN002746160, the MYL10-subfamily node) is grounded on that human observation; human Q9BUA6 appearing as its own source is the expected marker of experimental grounding, not circularity. The mouse ortholog Myl10 (Q62082, same PANTHER subfamily SF36) independently carries a mitochondrion HDA annotation from the MitoCarta mouse tissue proteome (PMID:18614015), so two independent methods in two species agree. The location is therefore kept, but as non-core: no mitochondrial targeting signal is annotated, the 60-residue N-terminal extension has not been tested as one, and no mitochondrial activity or partner of MYL10 is known. ORGANELLES check (2026-11-03). A GFP-fusion localization is an organelle-level assay that cannot resolve a sub-compartment, and the record has no transit peptide or transmembrane segment, so the row stays at the root and stays non-core. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: Cytosol is a correct location for a soluble myosin regulatory light chain. Reason: MYL10 is a soluble RLC-family protein, and the IBA to cytoplasm (above) establishes the compartment; cytosol is the specific soluble compartment where non-filament-bound light chains and cytoplasmic myosin II reside. The Reactome rows place MYL10 among the light chains in smooth-muscle contraction reactions; those reactions are curated for the RLC family generically and do not show that MYL10 itself acts in smooth muscle (its closest relatives are sarcomeric RLCs, and the mouse gene is expressed in precursor lymphocytes), but the location claim stands on its own. The ARBA row is a machine-learned prediction that agrees with this, not independent evidence. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt Myosin is a hexamer of 2 heavy chains and 4 light chains. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445699 | ACCEPT | Summary: Cytosol is a correct location for a soluble myosin regulatory light chain. Reason: MYL10 is a soluble RLC-family protein, and the IBA to cytoplasm (above) establishes the compartment; cytosol is the specific soluble compartment where non-filament-bound light chains and cytoplasmic myosin II reside. The Reactome rows place MYL10 among the light chains in smooth-muscle contraction reactions; those reactions are curated for the RLC family generically and do not show that MYL10 itself acts in smooth muscle (its closest relatives are sarcomeric RLCs, and the mouse gene is expressed in precursor lymphocytes), but the location claim stands on its own. The ARBA row is a machine-learned prediction that agrees with this, not independent evidence. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt Myosin is a hexamer of 2 heavy chains and 4 light chains. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445700 | ACCEPT | Summary: Cytosol is a correct location for a soluble myosin regulatory light chain. Reason: MYL10 is a soluble RLC-family protein, and the IBA to cytoplasm (above) establishes the compartment; cytosol is the specific soluble compartment where non-filament-bound light chains and cytoplasmic myosin II reside. The Reactome rows place MYL10 among the light chains in smooth-muscle contraction reactions; those reactions are curated for the RLC family generically and do not show that MYL10 itself acts in smooth muscle (its closest relatives are sarcomeric RLCs, and the mouse gene is expressed in precursor lymphocytes), but the location claim stands on its own. The ARBA row is a machine-learned prediction that agrees with this, not independent evidence. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt Myosin is a hexamer of 2 heavy chains and 4 light chains. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445704 | ACCEPT | Summary: Cytosol is a correct location for a soluble myosin regulatory light chain. Reason: MYL10 is a soluble RLC-family protein, and the IBA to cytoplasm (above) establishes the compartment; cytosol is the specific soluble compartment where non-filament-bound light chains and cytoplasmic myosin II reside. The Reactome rows place MYL10 among the light chains in smooth-muscle contraction reactions; those reactions are curated for the RLC family generically and do not show that MYL10 itself acts in smooth muscle (its closest relatives are sarcomeric RLCs, and the mouse gene is expressed in precursor lymphocytes), but the location claim stands on its own. The ARBA row is a machine-learned prediction that agrees with this, not independent evidence. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt Myosin is a hexamer of 2 heavy chains and 4 light chains. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445705 | ACCEPT | Summary: Cytosol is a correct location for a soluble myosin regulatory light chain. Reason: MYL10 is a soluble RLC-family protein, and the IBA to cytoplasm (above) establishes the compartment; cytosol is the specific soluble compartment where non-filament-bound light chains and cytoplasmic myosin II reside. The Reactome rows place MYL10 among the light chains in smooth-muscle contraction reactions; those reactions are curated for the RLC family generically and do not show that MYL10 itself acts in smooth muscle (its closest relatives are sarcomeric RLCs, and the mouse gene is expressed in precursor lymphocytes), but the location claim stands on its own. The ARBA row is a machine-learned prediction that agrees with this, not independent evidence. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt Myosin is a hexamer of 2 heavy chains and 4 light chains. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-445813 | ACCEPT | Summary: Cytosol is a correct location for a soluble myosin regulatory light chain. Reason: MYL10 is a soluble RLC-family protein, and the IBA to cytoplasm (above) establishes the compartment; cytosol is the specific soluble compartment where non-filament-bound light chains and cytoplasmic myosin II reside. The Reactome rows place MYL10 among the light chains in smooth-muscle contraction reactions; those reactions are curated for the RLC family generically and do not show that MYL10 itself acts in smooth muscle (its closest relatives are sarcomeric RLCs, and the mouse gene is expressed in precursor lymphocytes), but the location claim stands on its own. The ARBA row is a machine-learned prediction that agrees with this, not independent evidence. Supporting Evidence: file:human/MYL10/MYL10-uniprot.txt Myosin is a hexamer of 2 heavy chains and 4 light chains. |
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Download this section (compressed HTML)Q: PAINT propagated myosin heavy chain binding and myosin II complex only at the nonmuscle RLC node (MYL9/MYL12A/B), not to the sarcomeric-type node that includes MYL2 and MYL10. Should the sarcomeric clade, including MYL10, carry a myosin-complex or heavy-chain-binding term, given that RLC binding to the heavy-chain neck is ancestral to the whole family?
Q: Which myosin heavy chain does MYL10 load onto in precursor lymphocytes and in skeletal muscle, where its transcript is enriched?
Q: Human MYL10 retains the RLC N-terminal phosphorylation motif (RKRAEGTASSNVFSMF, compare MYL2 KKRAGGANSNVFSMF with Ser15 phosphorylated). Is the MYL10 serine aligned with MYL2 Ser15 phosphorylated in vivo, and by which kinase?
Experiment: Co-immunoprecipitation/proteomics of endogenous or tagged MYL10 from lymphoid and muscle cells to identify its myosin heavy-chain partner(s).
Experiment: Isothermal titration or fluorescence measurement of Ca2+ and Mg2+ binding by recombinant MYL10, with a D97A/E108A first-EF-hand mutant as control.
Experiment: Fractionation and imaging of endogenous MYL10 to test the mitochondrial pool, and deletion of the N-terminal extension to test whether it directs that localization.
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