MYH7 (human, P12883) curation notes

Gene identity

MYH7 encodes myosin-7, the slow/beta-cardiac myosin heavy chain (beta-MHC, MyHC-slow), a
1935-residue class II sarcomeric myosin. Domain layout from UniProt: N-terminal SH3-like
domain (32-81), motor domain (85-778) with the ATP-binding P-loop (178-185) and actin-binding
regions (655-677, 757-771), an IQ motif/lever arm (781-810) that binds the essential and
regulatory light chains, and a coiled-coil rod (839-1935) with four skip residues.

• Expression: main MyHC of ventricles and of slow type 1 skeletal fibres
  [PMID:14520662 "MYH7 encodes the slow/beta-cardiac myosin heavy chain (MyHC), which is the
  main MyHC isoform in slow, oxidative, type 1 muscle fibers of skeletal muscle"; "It is also the
  major MyHC isoform of cardiac ventricles"]; expressed in heart and skeletal muscle
  PMID:3021460. Ventricles are almost exclusively beta-MHC; atria mix alpha and beta
  PMID:15621050.
• Complex: hexamer of 2 heavy chains, 2 essential and 2 regulatory light chains (UniProt SUBUNIT).

Molecular function: actin-activated ATPase motor

• Recombinant human beta-cardiac S1 has ATPase activity, velocity and intrinsic force
  PMID:23798412.
• Patient beta-myosin moves actin in motility assays PMID:8514894.
• Head = ATPase + actin binding; rod = filament incorporation PMID:19336582.
• Beta-MHC is the slow, economical isoform; ATP use and force kinetics track beta/alpha ratio
  PMID:15621050.
• Motor domain structure with omecamtiv mecarbil PMID:26246073.

Thick filament assembly (rod)

• Skip residues guide thick filament assembly PMID:26150528.
• LMM paracrystals reproduce native thick filament spacing PMID:19336582.

Regulation: interacting-heads motif / super-relaxed state

• Purified human beta-cardiac myosin partly occupies an SRX PMID:30104387;
  HCM mutations destabilize, mavacamten promotes it PMID:30104387.
• S2- and MyBP-C-dependent sequestration PMID:28481356.
• HCM mutations at IHM interfaces free heads PMID:31213605.
• Cryo-EM IHM structure PMID:37258552.
• No GO term exists for this regulated state; raised as a suggested question rather than forced
  onto an ill-fitting term.

Disease (context only, not GO annotations)

• HCM: ~30% of genotyped cases PMID:15856146; head mutations.
• DCM PMID:11106718.
• LVNC PMID:18506004.
• Laing distal myopathy, distal rod PMID:15322983.
• Myosin storage myopathy, LMM [PMID:14520662; PMID:16684601; PMID:17336526; recessive form
  PMID:25666907; PMID:19336582].

GOA review decisions (48 rows)

Totals: ACCEPT 14, MODIFY 22, REMOVE 7, MARK_AS_OVER_ANNOTATED 5.

• ACCEPT (14): microfilament motor activity x4, ATP binding, actin filament binding x2, muscle
  myosin complex x2, muscle filament sliding x3, cardiac muscle contraction x2.
• MODIFY (22): general CC terms (cytoplasm, myofibril, sarcomere, supramolecular fiber, myosin filament)
  -> GO:0005863 striated muscle myosin thick filament; myosin complex / myosin II complex ->
  GO:0005859 muscle myosin complex; cytoskeletal motor activity -> microfilament motor activity;
  muscle/striated muscle contraction -> cardiac muscle contraction (and slow-twitch skeletal muscle
  fiber contraction where generic); skeletal muscle contraction and the two "regulation of ... force/
  slow-twitch contraction" rows -> GO:0031444 slow-twitch skeletal muscle fiber contraction (the
  motor executes, it does not regulate, contraction); regulation of the force of heart contraction
  -> cardiac muscle contraction.
• REMOVE: stress fiber (IEA; non-muscle structure), Z disc (IEA; thick filaments are not at the Z
  disc), regulation of heart rate (IDA from PMID:15621050 - the paper measured rate of force
  redevelopment in skinned cells, a cross-bridge rate, not heart rate), and four generic protein
  binding IPI rows (MYBPC3, LRRC39, KXD1, CLVS2).
• MARK_AS_OVER_ANNOTATED: adult heart development (IBA, IMP), ventricular cardiac muscle tissue
  morphogenesis (IMP x2) - disease phenotypes (hypertrophy, non-compaction) turned into process
  terms; necessity, not participation. ATP metabolic process (IDA) - ATP consumption is the motor
  activity itself.
• NEW (1): GO:0008307 structural constituent of muscle (rod builds the thick-filament backbone).
  Comparator check via QuickGO: MYH8, MYH11, Drosophila Mhc, C. elegans unc-54 and myo-1 already
  carry the term, as do MYBPC3 and the myomesins. Considered and rejected: NEW striated muscle
  myosin thick filament assembly (GO:0071688), because QuickGO shows it is annotated to assembly
  factors (unc-45, unc-89, fln) and not to myosin heavy chains; raised as a suggested question.
• PMID:12933792 (TAS for myosin complex) is about alpha-MHC (MYH6) regulation by PUR proteins; noted
  as MISCITED in reference_review, term modified rather than removed since the claim is true.

Deep research

• Falcon (just deep-research human MYH7 --provider falcon) failed: Edison client
  "Exception: Failed to authenticate".
• OpenScientist fallback succeeded (MYH7-deep-research-openscientist.md, 28 citations, ~13 min).
  Its picture matches this review: actin-activated ATPase motor plus thick-filament building block,
  ventricular and type 1 slow fibre expression, IHM/SRX regulation, HCM mutations shifting heads ON.
  Additional leads it reports, not independently verified here and not used as annotation evidence:
  DCM variant E525K stabilizing the IHM/SRX (PMID:42395535); alpha:beta MHC ~1:9 in human ventricle
  with beta-S1 slower hydrolysis and ADP release than alpha-S1 (PMID:22349210); miR-208b hosted in a
  MYH7 intron (PMID:19726871). Its caveat that SRX and IHM may not be strictly identical
  (PMID:40118457) is why core_functions describe them as 'corresponding' rather than identical.