MYOZ2

Last updated
MYOZ2
Identifiers
Aliases MYOZ2 , C4orf5, CMH16, CS-1, myozenin 2, FATZ-2
External IDs OMIM: 605602 MGI: 1913063 HomoloGene: 9583 GeneCards: MYOZ2
Orthologs
SpeciesHumanMouse
Entrez

51778

59006

Ensembl

ENSG00000172399

ENSMUSG00000028116

UniProt

Q9NPC6

Q9JJW5

RefSeq (mRNA)

NM_016599

NM_021503
NM_001355462

RefSeq (protein)

NP_057683

NP_067478
NP_001342391

Location (UCSC) Chr 4: 119.14 – 119.19 Mb Chr 3: 122.8 – 122.83 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Myozenin-2, also referred to as Calsarcin-1, is a protein that in humans is encoded by the MYOZ2 gene. [5] [6] [7] The Calsarcin-1 isoform is a muscle protein expressed in cardiac muscle and slow-twitch skeletal muscle, which functions to tether calcineurin to alpha-actinin at Z-discs, and inhibit the pathological cardiac hypertrophic response. This differs from the fast-skeletal muscle isoform, calsarcin-2.

Contents

Structure

Calsarcin-1 is a 29.9 kDa protein composed of 264 amino acids. [8] [9] Calsarcin-1 and calsarcin-2 are only 31% homologous (94 identical amino acids), exhibiting the highest homology at N- and C-termini. Calsarcin-1 binds to alpha-actinin, [10] gamma-filamin, [11] telethonin, [11] ZASP/Cypher [11] and calcineurin. [10] The binding region of calsarcin-1 to alpha-actinin is localized to amino acids 153-200, and that of calsarcin-1 to calcineurin is amino acids 217-240. [10]

Function

The function of calsarcin-1 in cardiac and slow-skeletal muscle has been illuminated through studies in transgenic animals. Mice lacking the MYOZ2 gene (MYOZ2-/-) are generally sensitized to calcineurin signaling in both muscle types. [11] In slow-skeletal muscle, MYOZ2-/- show increased slow-twitch muscle fibers. In cardiac, MYOZ2-/- show induction of the fetal gene program typical of pathologic hypertrophy, however there was no evidence of hypertrophied morphometry at baseline. However, upon calcineurin activation or pressure overload-induced pathologic hypertrophy, MYOZ2-/- exhibited exaggerated cardiac hypertrophy, demonstrating that calsarcin-1 negatively modulates the function of calcineurin during pathologic hypertrophic remodeling. [11] Additional studies supported these findings in demonstrating that adenoviral overexpression of calsarcin-1 attenuated Gq alpha subunit-stimuated hypertrophy and ANP induction, by Angiotensin II, phenylephrine and endothelin-1 agonists in neonatal cardiomyocytes. [12] Overexpression of calsarcin-1 in mice (CS1Tg) was protective against Angiotensin II-induced pathologic cardiac hypertrophy, evidenced by preserved fractional shortening and contractility, as well as a blunted induction of the fetal hypertrophic gene program and significantly reduced expression of calcineurin-stimulated MCIP1.4 gene expression. [12] Taken together, these studies strongly support a role for calsarcin-1 in suppressing pathologic cardiac hypertrophy.

Clinical Significance

Two missense mutations in MYOZ2, Ser48Pro and Ile246Met, have been shown to be causal for rare forms of familial hypertrophic cardiomyopathy. [13]

Related Research Articles

<span class="mw-page-title-main">MYH7</span> Protein-coding gene in the species Homo sapiens

MYH7 is a gene encoding a myosin heavy chain beta (MHC-β) isoform expressed primarily in the heart, but also in skeletal muscles. This isoform is distinct from the fast isoform of cardiac myosin heavy chain, MYH6, referred to as MHC-α. MHC-β is the major protein comprising the thick filament in cardiac muscle and plays a major role in cardiac muscle contraction.

TRPC is a family of transient receptor potential cation channels in animals.

<span class="mw-page-title-main">TNNT2</span> Protein-coding gene in the species Homo sapiens

Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.

<span class="mw-page-title-main">TPM1</span> Protein-coding gene in the species Homo sapiens

Tropomyosin alpha-1 chain is a protein that in humans is encoded by the TPM1 gene. This gene is a member of the tropomyosin (Tm) family of highly conserved, widely distributed actin-binding proteins involved in the contractile system of striated and smooth muscles and the cytoskeleton of non-muscle cells.

<span class="mw-page-title-main">ACTC1</span> Protein-coding gene in the species Homo sapiens

ACTC1 encodes cardiac muscle alpha actin. This isoform differs from the alpha actin that is expressed in skeletal muscle, ACTA1. Alpha cardiac actin is the major protein of the thin filament in cardiac sarcomeres, which are responsible for muscle contraction and generation of force to support the pump function of the heart.

<span class="mw-page-title-main">Alpha-actinin-2</span> Protein-coding gene in the species Homo sapiens

Alpha-actinin-2 is a protein which in humans is encoded by the ACTN2 gene. This gene encodes an alpha-actinin isoform that is expressed in both skeletal and cardiac muscles and functions to anchor myofibrillar actin thin filaments and titin to Z-discs.

<span class="mw-page-title-main">FLNC (gene)</span> Protein-coding gene in the species Homo sapiens

Filamin-C (FLN-C) also known as actin-binding-like protein (ABPL) or filamin-2 (FLN2) is a protein that in humans is encoded by the FLNC gene. Filamin-C is mainly expressed in cardiac and skeletal muscles, and functions at Z-discs and in subsarcolemmal regions.

<span class="mw-page-title-main">Telethonin</span>

Telethonin, also known as Tcap, is a protein that in humans is encoded by the TCAP gene. Telethonin is expressed in cardiac and skeletal muscle at Z-discs and functions to regulate sarcomere assembly, T-tubule function and apoptosis. Telethonin has been implicated in several diseases, including limb-girdle muscular dystrophy, hypertrophic cardiomyopathy, dilated cardiomyopathy and idiopathic cardiomyopathy.

<span class="mw-page-title-main">MYL2</span> Protein-coding gene in the species Homo sapiens

Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC-2) also known as the regulatory light chain of myosin (RLC) is a protein that in humans is encoded by the MYL2 gene. This cardiac ventricular RLC isoform is distinct from that expressed in skeletal muscle (MYLPF), smooth muscle (MYL12B) and cardiac atrial muscle (MYL7).

<span class="mw-page-title-main">MYH6</span> Protein-coding gene in the species Homo sapiens

Myosin heavy chain, α isoform (MHC-α) is a protein that in humans is encoded by the MYH6 gene. This isoform is distinct from the ventricular/slow myosin heavy chain isoform, MYH7, referred to as MHC-β. MHC-α isoform is expressed predominantly in human cardiac atria, exhibiting only minor expression in human cardiac ventricles. It is the major protein comprising the cardiac muscle thick filament, and functions in cardiac muscle contraction. Mutations in MYH6 have been associated with late-onset hypertrophic cardiomyopathy, atrial septal defects and sick sinus syndrome.

<span class="mw-page-title-main">MYL3</span> Protein-coding gene in the species Homo sapiens

Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the MYL3 gene. This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (MYL1) and cardiac atrial muscle (MYL4). Ventricular ELC is part of the myosin molecule and is important in modulating cardiac muscle contraction.

<span class="mw-page-title-main">MYL4</span> Protein-coding gene in the species Homo sapiens

Atrial Light Chain-1 (ALC-1), also known as Essential Light Chain, Atrial is a protein that in humans is encoded by the MYL4 gene. ALC-1 is expressed in fetal cardiac ventricular and fetal skeletal muscle, as well as fetal and adult cardiac atrial tissue. ALC-1 expression is reactivated in human ventricular myocardium in various cardiac muscle diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and congenital heart diseases.

<span class="mw-page-title-main">ANKRD1</span> Protein-coding gene in the species Homo sapiens

Ankyrin repeat domain-containing protein 1, or Cardiac ankyrin repeat protein is a protein that in humans is encoded by the ANKRD1 gene also known as CARP. CARP is highly expressed in cardiac and skeletal muscle, and is a transcription factor involved in development and under conditions of stress. CARP has been implicated in several diseases, including dilated cardiomyopathy, hypertrophic cardiomyopathy, and several skeletal muscle myopathies.

<span class="mw-page-title-main">CSRP3</span> Protein-coding gene in the species Homo sapiens

Cysteine and glycine-rich protein 3 also known as cardiac LIM protein (CLP) or muscle LIM protein (MLP) is a protein that in humans is encoded by the CSRP3 gene.

<span class="mw-page-title-main">LDB3</span> Protein-coding gene in the species Homo sapiens

LIM domain binding 3 (LDB3), also known as Z-band alternatively spliced PDZ-motif (ZASP), is a protein which in humans is encoded by the LDB3 gene. ZASP belongs to the Enigma subfamily of proteins and stabilizes the sarcomere during contraction, through interactions with actin in cardiac and skeletal muscles. Mutations in the ZASP gene has been associated with several muscular diseases.

<span class="mw-page-title-main">Myopalladin</span> Protein-coding gene in the species Homo sapiens

Myopalladin is a protein that in humans is encoded by the MYPN gene. Myopalladin is a muscle protein responsible for tethering proteins at the Z-disc and for communicating between the sarcomere and the nucleus in cardiac and skeletal muscle

<span class="mw-page-title-main">MYOZ1</span> Protein-coding gene in the species Homo sapiens

Myozenin-1 is a protein that in humans is encoded by the MYOZ1 gene.

<span class="mw-page-title-main">PDLIM3</span> Protein-coding gene in the species Homo sapiens

Actin-associated LIM protein (ALP), also known as PDZ and LIM domain protein 3 is a protein that in humans is encoded by the PDLIM3 gene. ALP is highly expressed in cardiac and skeletal muscle, where it localizes to Z-discs and intercalated discs. ALP functions to enhance the crosslinking of actin by alpha-actinin-2 and also appears to be essential for right ventricular chamber formation and contractile function.

<span class="mw-page-title-main">PPP3CA</span> Protein-coding gene in the species Homo sapiens

Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform (PP2BA) is a protein that in humans is encoded by the PPP3CA gene.

<span class="mw-page-title-main">MYL7</span> Protein-coding gene in the species Homo sapiens

Atrial Light Chain-2 (ALC-2) also known as Myosin regulatory light chain 2, atrial isoform (MLC2a) is a protein that in humans is encoded by the MYL7 gene. ALC-2 expression is restricted to cardiac muscle atria in healthy individuals, where it functions to modulate cardiac development and contractility. In human diseases, including hypertrophic cardiomyopathy, dilated cardiomyopathy, ischemic cardiomyopathy and others, ALC-2 expression is altered.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000172399 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028116 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Andersson B, Wentland MA, Ricafrente JY, Liu W, Gibbs RA (April 1996). "A "double adaptor" method for improved shotgun library construction". Analytical Biochemistry. 236 (1): 107–13. doi:10.1006/abio.1996.0138. PMID   8619474.
  6. ↑ Yu W, Andersson B, Worley KC, Muzny DM, Ding Y, Liu W, Ricafrente JY, Wentland MA, Lennon G, Gibbs RA (April 1997). "Large-scale concatenation cDNA sequencing". Genome Research. 7 (4): 353–8. doi:10.1101/gr.7.4.353. PMC   139146 . PMID   9110174.
  7. ↑ "Entrez Gene: MYOZ2 myozenin 2".
  8. ↑ http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q9NPC6
  9. ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC   4076475 . PMID   23965338.
  10. 1 2 3 Frey N, Richardson JA, Olson EN (December 2000). "Calsarcins, a novel family of sarcomeric calcineurin-binding proteins". Proceedings of the National Academy of Sciences of the United States of America. 97 (26): 14632–7. Bibcode:2000PNAS...9714632F. doi: 10.1073/pnas.260501097 . PMC   18970 . PMID   11114196.
  11. 1 2 3 4 5 Frey N, Barrientos T, Shelton JM, Frank D, Rütten H, Gehring D, Kuhn C, Lutz M, Rothermel B, Bassel-Duby R, Richardson JA, Katus HA, Hill JA, Olson EN (December 2004). "Mice lacking calsarcin-1 are sensitized to calcineurin signaling and show accelerated cardiomyopathy in response to pathological biomechanical stress". Nature Medicine. 10 (12): 1336–43. doi:10.1038/nm1132. PMID   15543153. S2CID   33712044.
  12. 1 2 Frank D, Kuhn C, van Eickels M, Gehring D, Hanselmann C, Lippl S, Will R, Katus HA, Frey N (November 2007). "Calsarcin-1 protects against angiotensin-II induced cardiac hypertrophy". Circulation. 116 (22): 2587–96. doi: 10.1161/CIRCULATIONAHA.107.711317 . PMID   18025526.
  13. ↑ Osio A, Tan L, Chen SN, Lombardi R, Nagueh SF, Shete S, Roberts R, Willerson JT, Marian AJ (March 2007). "Myozenin 2 is a novel gene for human hypertrophic cardiomyopathy". Circulation Research. 100 (6): 766–8. doi:10.1161/01.RES.0000263008.66799.aa. PMC   2775141 . PMID   17347475.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.