MYH6

Protein identityUniProt · HPA

UniProt accession

P13533

Gene

MYH6

Ensembl

ENSG00000197616

Chromosome

14

Canonical length

1939 aa

Protein class

Candidate cardiovascular disease genes, Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins

Subcellular location

Focal adhesion sites

OverviewNCBI Gene

Cardiac muscle myosin is a hexamer consisting of two heavy chain subunits, two light chain subunits, and two regulatory subunits. This gene encodes the alpha heavy chain subunit of cardiac myosin. The gene is located approximately 4kb downstream of the gene encoding the beta heavy chain subunit of cardiac myosin. Mutations in this gene cause familial hypertrophic cardiomyopathy and atrial septal defect 3. [provided by RefSeq, Feb 2017]

Canonical amino-acid sequenceUniProt

1939 residues, UniProt reviewed canonical sequence.

>P13533|MYH6
     1  MTDAQMADFG AAAQYLRKSE KERLEAQTRP FDIRTECFVP DDKEEFVKAK ILSREGGKVI
    61  AETENGKTVT VKEDQVLQQN PPKFDKIEDM AMLTFLHEPA VLFNLKERYA AWMIYTYSGL
   121  FCVTVNPYKW LPVYNAEVVA AYRGKKRSEA PPHIFSISDN AYQYMLTDRE NQSILITGES
   181  GAGKTVNTKR VIQYFASIAA IGDRGKKDNA NANKGTLEDQ IIQANPALEA FGNAKTVRND
   241  NSSRFGKFIR IHFGATGKLA SADIETYLLE KSRVIFQLKA ERNYHIFYQI LSNKKPELLD
   301  MLLVTNNPYD YAFVSQGEVS VASIDDSEEL MATDSAFDVL GFTSEEKAGV YKLTGAIMHY
   361  GNMKFKQKQR EEQAEPDGTE DADKSAYLMG LNSADLLKGL CHPRVKVGNE YVTKGQSVQQ
   421  VYYSIGALAK AVYEKMFNWM VTRINATLET KQPRQYFIGV LDIAGFEIFD FNSFEQLCIN
   481  FTNEKLQQFF NHHMFVLEQE EYKKEGIEWT FIDFGMDLQA CIDLIEKPMG IMSILEEECM
   541  FPKATDMTFK AKLYDNHLGK SNNFQKPRNI KGKQEAHFSL IHYAGTVDYN ILGWLEKNKD
   601  PLNETVVALY QKSSLKLMAT LFSSYATADT GDSGKSKGGK KKGSSFQTVS ALHRENLNKL
   661  MTNLRTTHPH FVRCIIPNER KAPGVMDNPL VMHQLRCNGV LEGIRICRKG FPNRILYGDF
   721  RQRYRILNPV AIPEGQFIDS RKGTEKLLSS LDIDHNQYKF GHTKVFFKAG LLGLLEEMRD
   781  ERLSRIITRM QAQARGQLMR IEFKKIVERR DALLVIQWNI RAFMGVKNWP WMKLYFKIKP
   841  LLKSAETEKE MATMKEEFGR IKETLEKSEA RRKELEEKMV SLLQEKNDLQ LQVQAEQDNL
   901  NDAEERCDQL IKNKIQLEAK VKEMNERLED EEEMNAELTA KKRKLEDECS ELKKDIDDLE
   961  LTLAKVEKEK HATENKVKNL TEEMAGLDEI IAKLTKEKKA LQEAHQQALD DLQVEEDKVN
  1021  SLSKSKVKLE QQVDDLEGSL EQEKKVRMDL ERAKRKLEGD LKLTQESIMD LENDKLQLEE
  1081  KLKKKEFDIN QQNSKIEDEQ VLALQLQKKL KENQARIEEL EEELEAERTA RAKVEKLRSD
  1141  LSRELEEISE RLEEAGGATS VQIEMNKKRE AEFQKMRRDL EEATLQHEAT AAALRKKHAD
  1201  SVAELGEQID NLQRVKQKLE KEKSEFKLEL DDVTSNMEQI IKAKANLEKV SRTLEDQANE
  1261  YRVKLEEAQR SLNDFTTQRA KLQTENGELA RQLEEKEALI SQLTRGKLSY TQQMEDLKRQ
  1321  LEEEGKAKNA LAHALQSARH DCDLLREQYE EETEAKAELQ RVLSKANSEV AQWRTKYETD
  1381  AIQRTEELEE AKKKLAQRLQ DAEEAVEAVN AKCSSLEKTK HRLQNEIEDL MVDVERSNAA
  1441  AAALDKKQRN FDKILAEWKQ KYEESQSELE SSQKEARSLS TELFKLKNAY EESLEHLETF
  1501  KRENKNLQEE ISDLTEQLGE GGKNVHELEK VRKQLEVEKL ELQSALEEAE ASLEHEEGKI
  1561  LRAQLEFNQI KAEIERKLAE KDEEMEQAKR NHQRVVDSLQ TSLDAETRSR NEVLRVKKKM
  1621  EGDLNEMEIQ LSHANRMAAE AQKQVKSLQS LLKDTQIQLD DAVRANDDLK ENIAIVERRN
  1681  NLLQAELEEL RAVVEQTERS RKLAEQELIE TSERVQLLHS QNTSLINQKK KMESDLTQLQ
  1741  SEVEEAVQEC RNAEEKAKKA ITDAAMMAEE LKKEQDTSAH LERMKKNMEQ TIKDLQHRLD
  1801  EAEQIALKGG KKQLQKLEAR VRELEGELEA EQKRNAESVK GMRKSERRIK ELTYQTEEDK
  1861  KNLLRLQDLV DKLQLKVKAY KRQAEEAEEQ ANTNLSKFRK VQHELDEAEE RADIAESQVN
  1921  KLRAKSRDIG AKQKMHDEE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MYH6 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.38

Highest tissue expression

4,840 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MYH6.

Disease | AllUniProt

Conditions MYH6 is implicated in, by any mechanism.

• Atrial septal defect 3 (ASD3) MIM:614089
• Cardiomyopathy, familial hypertrophic, 14 (CMH14) MIM:613251
• Cardiomyopathy, dilated, 1EE (CMD1EE) MIM:613252
• Sick sinus syndrome 3 (SSS3) MIM:614090

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 2,959 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Hypertrophic cardiomyopathy 14
• MYH6-related disorder
• Dilated cardiomyopathy 1EE
• Inborn genetic diseases
• Atrial septal defect 3

Disease | ImmuneIEDB

Conditions an epitope on MYH6 was assayed in.

• myocarditis T cell

ReferencesPubMed · IEDB

Publications for MYH6 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.86

gnomAD pLI

0

gnomAD missense Z

0.86

DepMap mean gene effect

-0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult heart development
• ATP metabolic process
• atrial cardiac muscle tissue morphogenesis
• cardiac muscle cell development
• cardiac muscle contraction
• cardiac muscle hypertrophy in response to stress
• in utero embryonic development
• muscle contraction
• muscle filament sliding
• myofibril assembly
• regulation of blood pressure
• regulation of heart contraction
• regulation of heart growth
• regulation of heart rate
• regulation of the force of heart contraction
• sarcomere organization
• striated muscle contraction
• ventricular cardiac muscle tissue morphogenesis
• visceral muscle development

Molecular functions

• actin filament binding
• ATP binding
• calmodulin binding
• microfilament motor activity
• myosin phosphatase activity
• protein kinase binding

Cellular components

• cytoplasm
• cytosol
• muscle myosin complex
• myofibril
• myosin complex
• myosin filament
• myosin II complex
• sarcomere
• stress fiber
• Z disc

Protein domainsUniProt · Pfam · InterPro

• Myosin head, motor domain-like
• Myosin tail
• Myosin, SH3 domain
• Myosin S1 fragment, N-terminal
• DNA repair protein XRCC4-like, C-terminal
• P-loop containing nucleoside triphosphate hydrolase
• Kinesin motor domain superfamily
• Myosin head (motor domain)
• Myosin tail
• Myosin N-terminal SH3-like domain

KeywordsUniProt

• Actin-binding
• ATP-binding
• Atrial septal defect
• Calmodulin-binding
• Cardiomyopathy
• Coiled coil
• Cytoplasm
• Methylation
• Motor protein
• Muscle protein
• Myosin
• Nucleotide-binding
• Phosphoprotein
• Thick filament