MYH2 (human, Q9UKX2) curation notes

Gene identity

MYH2 encodes myosin-2, the fast type IIa skeletal muscle myosin heavy chain (MyHC-IIa,
MyHC-2a), a 1941-residue class II sarcomeric myosin in the chromosome 17p13 skeletal MyHC
cluster. UniProt layout: N-terminal SH3-like domain (33-82), motor domain (86-784) with the
ATP-binding P-loop (179-186) and actin-binding regions (661-683, 763-777), an IQ motif/lever
arm (787-816), and a coiled-coil rod (845-1941). It is a skeletal isoform, not cardiac.

• Expression: major MyHC of fast, oxidative type 2A fibres PMID:22918376; PMID:11114175.
• Complex: hexamer of 2 heavy chains, 2 essential and 2 regulatory light chains
  [file:human/MYH2/MYH2-uniprot.txt "Muscle myosin is a hexameric protein that consists of 2
  heavy chain subunits (MHC), 2 alkali light chain subunits (MLC) and 2 regulatory light chain
  subunits (MLC-2)"].
• Full-length human coding sequence first reported with the rest of the sarcomeric family
  PMID:10388558.

Molecular function: actin-activated ATPase motor

• Recombinant human skeletal isoforms, including IIa, expressed in muscle cells and assayed
  PMID:20080549;
  IIa is the slowest adult-fast isoform PMID:20080549.
• Transient kinetics: ADP affinity of actomyosin distinguishes the fast isoforms
  PMID:23908353
  (IId, IIa, IIb respectively).
• E706K (SH1 helix) severely impairs motor function in patient fibres PMID:17005402.
• Single human fibres typed by MHC isoform, including pure IIA fibres, used to relate Vmax to
  isoform PMID:8145163.

Thick filament (rod) and super-relaxed state

• MyHC forms the thick filament backbone PMID:22918376.
• MYH2 LMM forms filaments; L1870P gives shorter, narrower filaments PMID:37788100.
• LMM variants reduce the super-relaxed state in patient type IIA fibres PMID:37788100, with
  contractility unaffected.
• Truncating MYH2 variants: altered relaxed-state ATP demand, faster kinetics, lower force
  PMID:36745529.

Disease (context only, not converted to GO terms)

• Dominant E706K myopathy with contractures, ophthalmoplegia, rimmed vacuoles PMID:11114175; mutant expression increases with age PMID:11889243.
• S2 rod variants V970I, L1061V PMID:15741996.
• Recessive truncating variants abolish IIa protein and type 2A fibres PMID:20418530; recessive missense variants too PMID:24193343; PMID:23388406.
• C. elegans unc-54 E710K model: paralysis but thick filaments still form, i.e. functional not
  structural defect PMID:16130113.
• 20418530 says the isoform is "necessary for normal muscle development and function"; this is
  necessity evidence and was not converted into a developmental process term (consistent with
  MYH7, where cardiomyopathy phenotypes were not turned into heart development terms).

Annotation review decisions (27 GOA rows + 1 NEW)

• Tally: ACCEPT 8, MODIFY 14, REMOVE 4, TOO_GENERAL 1 (27 GOA rows), plus 1 NEW.
• ACCEPT (8): microfilament motor activity (IBA, TAS), ATP binding (IEA), muscle myosin complex
  (NAS, TAS), muscle filament sliding (NAS), actin filament binding (IBA, IEA).
• MODIFY (14): general location terms (cytoplasm IBA, myofibril IDA/IEA, sarcomere NAS, myosin
  filament IBA, contractile muscle fiber IEA) -> GO:0005863 striated muscle myosin thick
  filament, as for MYH7; myosin complex / myosin II complex -> GO:0005859 muscle myosin complex;
  cytoskeletal motor activity -> GO:0000146; muscle contraction (IBA, IDA, TAS) and system
  process -> GO:0031443 fast-twitch skeletal muscle fiber contraction (counterpart of MYH7's
  slow-twitch choice).
• TOO_GENERAL: protein-containing complex (GO_REF:0000054), entailed by muscle myosin complex.
• REMOVE:
• cell-cell junction (IMP, PMID:25753039): full text is endothelial HDMEC "myosin IIA", i.e.
  non-muscle myosin IIA (MYH9). Name collision with MyHC-IIa; the reference is on the MYH2
  GOA file but not on MYH9's. PMID:25753039; PMID:22918376.
• cytosol (TAS, two Reactome phagocytosis events): non-muscle myosin II reactions with every
  class II heavy chain bundled in [Reactome:R-HSA-2029476 "Nonmuscle myosin II, is a motor
  protein known to generate intracellular contractile forces and tension by associating with
  F-actin."].
• protein binding (IPI, HGAL/GCSAM): uninformative; lymphocyte myosin II is presumably
  non-muscle.
• NEW: GO:0008307 structural constituent of muscle (PMID:37788100). Comparator check via QuickGO
  (2026-10-16): MYH8 (NAS, PMID:2715179) and MYH11 (IMP, PMID:16444274) carry GO:0008307; MYH7
  review proposes it as NEW.

Deep research

• Provider: openscientist (falcon not used: Edison auth failing on 2026-10-16). The run
  completed (~23 min) and wrote MYH2-deep-research-openscientist.md plus artifacts.
• The report agrees with the review: motor head = actin-activated ATPase, rod = thick-filament
  self-assembly domain, location = A-band thick filament of type 2A fibres
  [file:human/MYH2/MYH2-deep-research-openscientist.md "Its long C-terminal coiled-coil tail is a
  structural element that dimerizes and self-assembles into the thick-filament backbone."].
• Leads from the report not used as evidence (not fetched/verified here): F516V relay-loop
  variant and Q1111* tail truncation with filamentous tangles (PMID:33926564); dominant splice
  variant deleting residues 1860-1891 in the assembly region (PMID:36380287). Its claim that
  ophthalmoplegia shows extraocular muscle is especially MYH2-dependent is an inference, kept
  as a suggested question rather than a statement.