MYH10: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{WikiDoc Cardiology Network Infobox}} +, -<references /> +{{reflist|2}}, -{{reflist}} +{{reflist|2}}))
 
m (Bot: HTTP→HTTPS (v470))
 
Line 1: Line 1:
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Myosin-10''' also known as '''myosin heavy chain 10''' or '''non-muscle myosin IIB (NM-IIB)''' is a [[protein]] that in humans is encoded by the ''MYH10'' [[gene]].<ref name="pmid1860190">{{cite journal | vauthors = Simons M, Wang M, McBride OW, Kawamoto S, Yamakawa K, Gdula D, Adelstein RS, Weir L | title = Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes | journal = Circulation Research | volume = 69 | issue = 2 | pages = 530–9 | date = Aug 1991 | pmid = 1860190 | pmc = | doi = 10.1161/01.res.69.2.530 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MYH10 myosin, heavy chain 10, non-muscle| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4628| accessdate = }}</ref> Non-muscle myosins are expressed in a wide variety of tissues, but NM-IIB is the only non-muscle myosin II [[isoform]] expressed in [[cardiac muscle]], where it localizes to [[adherens junction]]s within [[intercalated disc]]s. NM-IIB is essential for normal development of [[cardiac muscle]] and for integrity of [[intercalated disc]]s. Mutations in MYH10 have been identified in patients with [[left atrial enlargement]].
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Structure ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =  
| Name = Myosin, heavy chain 10, non-muscle
| HGNCid = 7568
| Symbol = MYH10
| AltSymbols =; MGC134913; MGC134914; NMMHCB
| OMIM = 160776
| ECnumber = 
| Homologene = 55941
| MGIid = 1930780
| GeneAtlas_image1 = PBB_GE_MYH10_212372_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0003774 |text = motor activity}} {{GNF_GO|id=GO:0003779 |text = actin binding}} {{GNF_GO|id=GO:0005516 |text = calmodulin binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}}
| Component = {{GNF_GO|id=GO:0001725 |text = stress fiber}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0005938 |text = cell cortex}} {{GNF_GO|id=GO:0016459 |text = myosin complex}} {{GNF_GO|id=GO:0030496 |text = midbody}} {{GNF_GO|id=GO:0032154 |text = cleavage furrow}}
| Process = {{GNF_GO|id=GO:0001764 |text = neuron migration}} {{GNF_GO|id=GO:0001778 |text = plasma membrane repair}} {{GNF_GO|id=GO:0006887 |text = exocytosis}} {{GNF_GO|id=GO:0006930 |text = substrate-bound cell migration, cell extension}} {{GNF_GO|id=GO:0007512 |text = adult heart development}} {{GNF_GO|id=GO:0008150 |text = biological_process}} {{GNF_GO|id=GO:0008360 |text = regulation of cell shape}} {{GNF_GO|id=GO:0021670 |text = lateral ventricle development}} {{GNF_GO|id=GO:0030239 |text = myofibril assembly}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 4628
    | Hs_Ensembl = ENSG00000133026
    | Hs_RefseqProtein = NP_005955
    | Hs_RefseqmRNA = NM_005964
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 8318248
    | Hs_GenLoc_end = 8474804
    | Hs_Uniprot = P35580
    | Mm_EntrezGene = 77579
    | Mm_Ensembl = ENSMUSG00000020900
    | Mm_RefseqmRNA = NM_175260
    | Mm_RefseqProtein = NP_780469
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 68508129
    | Mm_GenLoc_end = 68632825
    | Mm_Uniprot = Q4KMN4
  }}
}}
'''Myosin, heavy chain 10, non-muscle''', also known as '''MYH10''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: MYH10 myosin, heavy chain 10, non-muscle| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4628| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
NM-IIB is 228.9 kDa [[protein]] composed of 1976 [[amino acid]]s.<ref>{{cite web|title=Protein sequence of human MYH10 (Uniprot ID: P35580)|url=http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=P35580|website=Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)|accessdate=17 July 2015}}</ref> NM-IIB has an [[N-terminus|N-terminal]] globular head that harbors the catalytically active, magnesium(Mg)-ATPase. The [[C-terminus|C-terminal]] rod domain is an [[alpha helix|alpha helical]] [[coiled-coil]] that can multimerize with other myosin molecules to form a filament. Bound to the neck region of NM-IIB are two light chains; first, [[MYL6|MLC17]] stabilizes the molecule, while the second light chain, [[MYL9|MLC20]], modulates contraction.<ref name = "Conti_2008">{{cite journal | vauthors = Conti MA, Adelstein RS | title = Nonmuscle myosin II moves in new directions | journal = Journal of Cell Science | volume = 121 | issue = Pt 1 | pages = 11–8 | date = Jan 2008 | pmid = 18096687 | doi = 10.1242/jcs.007112 }}</ref> The exception to this rule is the [[alternative splicing|alternatively spliced]] NM-IIB2 [[isoform]], which has a 21 [[amino acid]] inserted into loop 2, near the actin-binding domain; actomyosin MgATPase activity of this [[isoform]] is not enhanced by [[phosphorylation]] of the regulatory light chain [[MYL9|MLC20]].<ref>{{cite journal | vauthors = Kim KY, Kawamoto S, Bao J, Sellers JR, Adelstein RS | title = The B2 alternatively spliced isoform of nonmuscle myosin II-B lacks actin-activated MgATPase activity and in vitro motility | journal = Biochemical and Biophysical Research Communications | volume = 369 | issue = 1 | pages = 124–34 | date = Apr 2008 | pmid = 18060863 | doi = 10.1016/j.bbrc.2007.11.108 | pmc=2366080}}</ref>
{{PBB_Summary
| section_title =  
| summary_text =  
}}


==References==
NM-IIB is part of the larger myosin II subfamily of [[protein]]s, which also includes [[skeletal muscle]], [[cardiac muscle]] and [[smooth muscle]] [[myosin]]s. NM-IIB, and non-muscle myosins in general, are widely expressed in every tissue in humans.
{{reflist|2}}
 
==Further reading==
== Function ==
{{refbegin | 2}}
 
{{PBB_Further_reading
NM-IIB has many properties that are similar to those of [[smooth muscle]] [[myosin]]s, such as the permissive nature of [[phosphorylation]] of the 20 kDa regulatory light chain for [[Muscle contraction|contraction]]. In [[skeletal muscle]] and [[MYH7|cardiac muscle]] myosins, contraction is activated through [[thin filament]] proteins [[troponin]] and [[tropomyosin]], whereas in NM-IIB and [[smooth muscle]] [[myosin]], contraction initiates via regulatory light chain ([[MYL9|MLC20]]) [[phosphorylation]].<ref>{{cite journal | vauthors = Adelstein RS, Conti MA | title = Phosphorylation of platelet myosin increases actin-activated myosin ATPase activity | journal = Nature | volume = 256 | issue = 5518 | pages = 597–8 | date = Aug 1975 | pmid = 170529 | doi=10.1038/256597a0}}</ref>
| citations =
 
*{{cite journal  | author=Simons M, Wang M, McBride OW, ''et al.'' |title=Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes. |journal=Circ. Res. |volume=69 |issue= 2 |pages= 530-9 |year= 1991 |pmid= 1860190 |doi= }}
Various functions of NM-IIB require the phosphorylation of the regulatory light chain [[MYL9|MLC20]], including cell migration and cell adhesion. The two primary kinases catalyzing this reaction are the [[calcium]]-[[calmodulin]]-dependent, [[MYLK|myosin light chain kinase]] and the Rho-GTP dependent, [[Rho-associated protein kinase|Rho kinase (ROCK)]]. NM-IIB is [[Dephosphorylation|dephosphorylated]] by a myosin phosphatase.<ref>{{cite journal | vauthors = Ito M, Nakano T, Erdodi F, Hartshorne DJ | title = Myosin phosphatase: structure, regulation and function | journal = Molecular and Cellular Biochemistry | volume = 259 | issue = 1–2 | pages = 197–209 | date = Apr 2004 | pmid = 15124925 | doi=10.1023/b:mcbi.0000021373.14288.00}}</ref>
*{{cite journal  | author=Phillips CL, Yamakawa K, Adelstein RS |title=Cloning of the cDNA encoding human nonmuscle myosin heavy chain-B and analysis of human tissues with isoform-specific antibodies. |journal=J. Muscle Res. Cell. Motil. |volume=16 |issue= 4 |pages= 379-89 |year= 1996 |pmid= 7499478 |doi= }}
 
*{{cite journal  | author=Strand D, Unger S, Corvi R, ''et al.'' |title=A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain. |journal=Oncogene |volume=11 |issue= 2 |pages= 291-301 |year= 1995 |pmid= 7542763 |doi= }}
Detailed kinetic studies on NM-IIB show that this [[isoform]] of non-muscle myosin II has a slower actomyosin ATPase cycle relative to other myosin II isoforms, and that the markedly high affinity of NM-IIB head for ADP as well as the slow rate of ADP release can mechanistically explain affinity this finding. These data indicate that NM-IIB spends a large amount of its kinetic cycle in a configuration where it is strongly attached to [[actin]].<ref>{{cite journal | vauthors = Wang F, Kovacs M, Hu A, Limouze J, Harvey EV, Sellers JR | title = Kinetic mechanism of non-muscle myosin IIB: functional adaptations for tension generation and maintenance | journal = The Journal of Biological Chemistry | volume = 278 | issue = 30 | pages = 27439–48 | date = Jul 2003 | pmid = 12704189 | doi = 10.1074/jbc.M302510200 }}</ref>
*{{cite journal  | author=Maupin P, Phillips CL, Adelstein RS, Pollard TD |title=Differential localization of myosin-II isozymes in human cultured cells and blood cells. |journal=J. Cell. Sci. |volume=107 ( Pt 11) |issue= |pages= 3077-90 |year= 1995 |pmid= 7699007 |doi= }}
 
*{{cite journal | author=Itoh K, Adelstein RS |title=Neuronal cell expression of inserted isoforms of vertebrate nonmuscle myosin heavy chain II-B. |journal=J. Biol. Chem. |volume=270 |issue= 24 |pages= 14533-40 |year= 1995 |pmid= 7782316 |doi= }}
NM-IIB, along with the other non-muscle myosin isoforms IIA and IIC, play a role in cell-cell and cell-matrix adhesion, cell migration, cell polarity, and embryonic stem cell apoptosis.<ref>{{cite journal | vauthors = Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR | title = Non-muscle myosin II takes centre stage in cell adhesion and migration | journal = Nature Reviews Molecular Cell Biology | volume = 10 | issue = 11 | pages = 778–90 | date = Nov 2009 | pmid = 19851336 | doi = 10.1038/nrm2786 | pmc=2834236}}</ref><ref>{{cite journal | vauthors = Walker A, Su H, Conti MA, Harb N, Adelstein RS, Sato N | title = Non-muscle myosin II regulates survival threshold of pluripotent stem cells | journal = Nature Communications | volume = 1 | pages = 71 | date = 7 September 2010 | pmid = 20842192 | doi = 10.1038/ncomms1074 | pmc=3430968}}</ref> Insights into the function of NM-IIB specifically have come from studies employing transgenic animals. NM-IIB is clearly required for normal development of [[cardiac muscle]]. Targeted gene disruption of NM-IIB resulted in approximately 65% embryonic lethality, and those that survived suffered from [[congestive heart failure]] and died day 1 following birth. Feature observed in NM-IIB knockouts was an increase in the transverse diameters of [[cardiomyocyte]]s, [[Interventricular septum|ventricular septal defects]], as well as other muscular abnormalities.<ref>{{cite journal | vauthors = Tullio AN, Accili D, Ferrans VJ, Yu ZX, Takeda K, Grinberg A, Westphal H, Preston YA, Adelstein RS | title = Nonmuscle myosin II-B is required for normal development of the mouse heart | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 94 | issue = 23 | pages = 12407–12 | date = Nov 1997 | pmid = 9356462 | doi=10.1073/pnas.94.23.12407 | pmc=24969}}</ref> NM-IIB is expressed early during embryonic development in cardiomyocytes,<ref>{{cite journal | vauthors = Wang A, Ma X, Conti MA, Liu C, Kawamoto S, Adelstein RS | title = Nonmuscle myosin II isoform and domain specificity during early mouse development | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 33 | pages = 14645–50 | date = Aug 2010 | pmid = 20679233 | doi = 10.1073/pnas.1004023107 | pmc=2930417}}</ref> and appears to play a role in karyokinesis; ablation of NM-IIB caused defects in chromatid segregation and mitotic spindle formation, as well as abnormal structure of centrosomes.<ref>{{cite journal | vauthors = Takeda K, Kishi H, Ma X, Yu ZX, Adelstein RS | title = Ablation and mutation of nonmuscle myosin heavy chain II-B results in a defect in cardiac myocyte cytokinesis | journal = Circulation Research | volume = 93 | issue = 4 | pages = 330–7 | date = Aug 2003 | pmid = 12893741 | doi = 10.1161/01.RES.0000089256.00309.CB }}</ref><ref>{{cite journal | vauthors = Ma X, Jana SS, Conti MA, Kawamoto S, Claycomb WC, Adelstein RS | title = Ablation of nonmuscle myosin II-B and II-C reveals a role for nonmuscle myosin II in cardiac myocyte karyokinesis | journal = Molecular Biology of the Cell | volume = 21 | issue = 22 | pages = 3952–62 | date = Nov 2010 | pmid = 20861308 | doi = 10.1091/mbc.E10-04-0293 | pmc=2982113}}</ref>
*{{cite journal  | author=Aikawa M, Sivam PN, Kuro-o M, ''et al.'' |title=Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis. |journal=Circ. Res. |volume=73 |issue= 6 |pages= 1000-12 |year= 1993 |pmid= 7916668 |doi= }}
 
*{{cite journal  | author=Shoeman RL, Sachse C, Höner B, ''et al.'' |title=Cleavage of human and mouse cytoskeletal and sarcomeric proteins by human immunodeficiency virus type 1 protease. Actin, desmin, myosin, and tropomyosin. |journal=Am. J. Pathol. |volume=142 |issue= 1 |pages= 221-30 |year= 1993 |pmid= 8424456 |doi=  }}
In adult cardiomyocytes, NM-IIB redistributes from a diffuse [[cytoplasm]]ic pattern in development to a localized [[sarcomere|Z-disc]] and [[intercalated disc]] distribution, where it colocalizes with [[actinin, alpha 2|alpha-actinin]]. NM-IIB is the only non-muscle myosin II isoform expressed in adult cardiac muscle (both IIa and IIB are expressed in [[skeletal muscle]] [[sarcomere|Z-discs]], suggesting a specific function of NM-IIB in this cell type.<ref>{{cite journal | vauthors = Takeda K, Yu ZX, Qian S, Chin TK, Adelstein RS, Ferrans VJ | title = Nonmuscle myosin II localizes to the Z-lines and intercalated discs of cardiac muscle and to the Z-lines of skeletal muscle | journal = Cell Motility and the Cytoskeleton | volume = 46 | issue = 1 | pages = 59–68 | date = May 2000 | pmid = 10842333 | doi = 10.1002/(SICI)1097-0169(200005)46:1<59::AID-CM6>3.0.CO;2-Q }}</ref> NM-IIB may play a role in formation of mature [[sarcomere]]s in [[myofibril]]s.<ref>{{cite journal | vauthors = Sanger JW, Kang S, Siebrands CC, Freeman N, Du A, Wang J, Stout AL, Sanger JM | title = How to build a myofibril | journal = Journal of Muscle Research and Cell Motility | volume = 26 | issue = 6–8 | pages = 343–54 | date = 2005 | pmid = 16465476 | doi = 10.1007/s10974-005-9016-7 }}</ref> It appears that NM-IIB plays an essential role in maintaining normal [[adherens junction]] integrity and structure. A cardiac muscle-specific knockout of NM-IIB using the [[MYH6|alpha-myosin heavy chain]] promoter-driven cre-recombinase develop enlarged cardiomyocytes, consistent with the defects previously observed with [[cytokinesis]]; widened [[adherens junction]]s; and progressive [[hypertrophic cardiomyopathy]] at 6 months.<ref>{{cite journal | vauthors = Ma X, Takeda K, Singh A, Yu ZX, Zerfas P, Blount A, Liu C, Towbin JA, Schneider MD, Adelstein RS, Wei Q | title = Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice | journal = Circulation Research | volume = 105 | issue = 11 | pages = 1102–9 | date = Nov 2009 | pmid = 19815823 | doi = 10.1161/CIRCRESAHA.109.200303 | pmc=2792753}}</ref> These data indicate that NM-IIB functions in ensuring the proper maintenance of [[intercalated disc]] structures.<ref>{{cite journal | vauthors = Ma X, Adelstein RS | title = In vivo studies on nonmuscle myosin II expression and function in heart development | journal = Frontiers in Bioscience | volume = 17 | pages = 545–55 | date = 1 January 2012 | pmid = 22201759 | doi=10.2741/3942 | pmc=3476727}}</ref>
*{{cite journal  | author=Kawamoto S |title=Neuron-specific alternative splicing of nonmuscle myosin II heavy chain-B pre-mRNA requires a cis-acting intron sequence. |journal=J. Biol. Chem. |volume=271 |issue= 30 |pages= 17613-6 |year= 1996 |pmid= 8663598 |doi= }}
 
*{{cite journal | author=Weir L, Chen D |title=Characterization of the nonmuscle myosin heavy chain IIB promoter: regulation by E2F. |journal=Gene Expr. |volume=6 |issue= 1 |pages= 45-57 |year= 1997 |pmid= 8931991 |doi= }}
== Clinical Significance ==
*{{cite journal | author=Ford HL, Silver DL, Kachar B, ''et al.'' |title=Effect of Mts1 on the structure and activity of nonmuscle myosin II. |journal=Biochemistry |volume=36 |issue= 51 |pages= 16321-7 |year= 1998 |pmid= 9405067 |doi= 10.1021/bi971182l }}
[[Single nucleotide polymorphism]]s in ''MYH10'' were detected in patients with [[left atrial enlargement]]. ''MYH10'' was identified to be a susceptibility gene using non-biased [[genome]]-wide linkage and peak-wide association analysis.<ref>{{cite journal | vauthors = Wang L, Di Tullio MR, Beecham A, Slifer S, Rundek T, Homma S, Blanton SH, Sacco RL | title = A comprehensive genetic study on left atrium size in Caribbean Hispanics identifies potential candidate genes in 17p10 | journal = Circulation: Cardiovascular Genetics | volume = 3 | issue = 4 | pages = 386–92 | date = Aug 2010 | pmid = 20562446 | doi = 10.1161/CIRCGENETICS.110.938381 | pmc=2923674}}</ref>
*{{cite journal  | author=Lin VK, Wang D, Lee IL, ''et al.'' |title=Myosin heavy chain gene expression in normal and hyperplastic human prostate tissue. |journal=Prostate |volume=44 |issue= 3 |pages= 193-203 |year= 2000 |pmid= 10906735 |doi= }}
 
*{{cite journal  | author=Nguyen M, Breckenridge DG, Ducret A, Shore GC |title=Caspase-resistant BAP31 inhibits fas-mediated apoptotic membrane fragmentation and release of cytochrome c from mitochondria. |journal=Mol. Cell. Biol. |volume=20 |issue= 18 |pages= 6731-40 |year= 2000 |pmid= 10958671 |doi=  }}
== Interactions ==
*{{cite journal | author=Wei Q, Adelstein RS |title=Conditional expression of a truncated fragment of nonmuscle myosin II-A alters cell shape but not cytokinesis in HeLa cells. |journal=Mol. Biol. Cell |volume=11 |issue= 10 |pages= 3617-27 |year= 2000 |pmid= 11029059 |doi= }}
 
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
MYH10 has been shown to [[protein-protein interaction|interact]] with:
*{{cite journal | author=Wang F, Kovacs M, Hu A, ''et al.'' |title=Kinetic mechanism of non-muscle myosin IIB: functional adaptations for tension generation and maintenance. |journal=J. Biol. Chem. |volume=278 |issue= 30 |pages= 27439-48 |year= 2003 |pmid= 12704189 |doi= 10.1074/jbc.M302510200 }}
 
*{{cite journal  | author=Huang H, Paliouras M, Rambaldi I, ''et al.'' |title=Nonmuscle myosin promotes cytoplasmic localization of PBX. |journal=Mol. Cell. Biol. |volume=23 |issue= 10 |pages= 3636-45 |year= 2003 |pmid= 12724421 |doi= }}
* [[MYL6]]<ref name = "Conti_2008"/> and
*{{cite journal  | author=Trinczek B, Brajenovic M, Ebneth A, Drewes G |title=MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating kinase that binds to the cellular microtubule network and to centrosomes. |journal=J. Biol. Chem. |volume=279 |issue= 7 |pages= 5915-23 |year= 2004 |pmid= 14594945 |doi= 10.1074/jbc.M304528200 }}
* [[MYL9]].<ref name = "Conti_2008"/>
*{{cite journal  | author=Straight AF, Field CM, Mitchison TJ |title=Anillin binds nonmuscle myosin II and regulates the contractile ring. |journal=Mol. Biol. Cell |volume=16 |issue= 1 |pages= 193-201 |year= 2005 |pmid= 15496454 |doi= 10.1091/mbc.E04-08-0758 }}
 
*{{cite journal | author=Bastian P, Lang K, Niggemann B, ''et al.'' |title=Myosin regulation in the migration of tumor cells and leukocytes within a three-dimensional collagen matrix. |journal=Cell. Mol. Life Sci. |volume=62 |issue= 1 |pages= 65-76 |year= 2005 |pmid= 15619008 |doi= 10.1007/s00018-004-4391-6 }}
== References ==
*{{cite journal  | author=Nakasawa T, Takahashi M, Matsuzawa F, ''et al.'' |title=Critical regions for assembly of vertebrate nonmuscle myosin II. |journal=Biochemistry |volume=44 |issue= 1 |pages= 174-83 |year= 2005 |pmid= 15628858 |doi= 10.1021/bi048807h }}
{{reflist|33em}}
}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Phillips CL, Yamakawa K, Adelstein RS | title = Cloning of the cDNA encoding human nonmuscle myosin heavy chain-B and analysis of human tissues with isoform-specific antibodies | journal = Journal of Muscle Research and Cell Motility | volume = 16 | issue = 4 | pages = 379–89 | date = Aug 1995 | pmid = 7499478 | doi = 10.1007/BF00114503 }}
* {{cite journal | vauthors = Strand D, Unger S, Corvi R, Hartenstein K, Schenkel H, Kalmes A, Merdes G, Neumann B, Krieg-Schneider F, Coy JF | title = A human homologue of the Drosophila tumour suppressor gene l(2)gl maps to 17p11.2-12 and codes for a cytoskeletal protein that associates with nonmuscle myosin II heavy chain | journal = Oncogene | volume = 11 | issue = 2 | pages = 291–301 | date = Jul 1995 | pmid = 7542763 | doi = }}
* {{cite journal | vauthors = Maupin P, Phillips CL, Adelstein RS, Pollard TD | title = Differential localization of myosin-II isozymes in human cultured cells and blood cells | journal = Journal of Cell Science | volume = 107 | issue = 11 | pages = 3077–90 | date = Nov 1994 | pmid = 7699007 | doi =  }}
* {{cite journal | vauthors = Itoh K, Adelstein RS | title = Neuronal cell expression of inserted isoforms of vertebrate nonmuscle myosin heavy chain II-B | journal = The Journal of Biological Chemistry | volume = 270 | issue = 24 | pages = 14533–40 | date = Jun 1995 | pmid = 7782316 | doi = 10.1074/jbc.270.24.14533 }}
* {{cite journal | vauthors = Aikawa M, Sivam PN, Kuro-o M, Kimura K, Nakahara K, Takewaki S, Ueda M, Yamaguchi H, Yazaki Y, Periasamy M | title = Human smooth muscle myosin heavy chain isoforms as molecular markers for vascular development and atherosclerosis | journal = Circulation Research | volume = 73 | issue = 6 | pages = 1000–12 | date = Dec 1993 | pmid = 7916668 | doi = 10.1161/01.res.73.6.1000 }}
* {{cite journal | vauthors = Shoeman RL, Sachse C, Höner B, Mothes E, Kaufmann M, Traub P | title = Cleavage of human and mouse cytoskeletal and sarcomeric proteins by human immunodeficiency virus type 1 protease. Actin, desmin, myosin, and tropomyosin | journal = The American Journal of Pathology | volume = 142 | issue = 1 | pages = 221–30 | date = Jan 1993 | pmid = 8424456 | pmc = 1886840 | doi =  }}
* {{cite journal | vauthors = Kawamoto S | title = Neuron-specific alternative splicing of nonmuscle myosin II heavy chain-B pre-mRNA requires a cis-acting intron sequence | journal = The Journal of Biological Chemistry | volume = 271 | issue = 30 | pages = 17613–6 | date = Jul 1996 | pmid = 8663598 | doi = 10.1074/jbc.271.30.17613 }}
* {{cite journal | vauthors = Weir L, Chen D | title = Characterization of the nonmuscle myosin heavy chain IIB promoter: regulation by E2F | journal = Gene Expression | volume = 6 | issue = 1 | pages = 45–57 | year = 1997 | pmid = 8931991 | doi =  }}
* {{cite journal | vauthors = Ford HL, Silver DL, Kachar B, Sellers JR, Zain SB | title = Effect of Mts1 on the structure and activity of nonmuscle myosin II | journal = Biochemistry | volume = 36 | issue = 51 | pages = 16321–7 | date = Dec 1997 | pmid = 9405067 | doi = 10.1021/bi971182l }}
* {{cite journal | vauthors = Lin VK, Wang D, Lee IL, Vasquez D, Fagelson JE, McConnell JD | title = Myosin heavy chain gene expression in normal and hyperplastic human prostate tissue | journal = The Prostate | volume = 44 | issue = 3 | pages = 193–203 | date = Aug 2000 | pmid = 10906735 | doi = 10.1002/1097-0045(20000801)44:3<193::AID-PROS3>3.0.CO;2-A }}
* {{cite journal | vauthors = Nguyen M, Breckenridge DG, Ducret A, Shore GC | title = Caspase-resistant BAP31 inhibits fas-mediated apoptotic membrane fragmentation and release of cytochrome c from mitochondria | journal = Molecular and Cellular Biology | volume = 20 | issue = 18 | pages = 6731–40 | date = Sep 2000 | pmid = 10958671 | pmc = 86192 | doi = 10.1128/MCB.20.18.6731-6740.2000 }}
* {{cite journal | vauthors = Wei Q, Adelstein RS | title = Conditional expression of a truncated fragment of nonmuscle myosin II-A alters cell shape but not cytokinesis in HeLa cells | journal = Molecular Biology of the Cell | volume = 11 | issue = 10 | pages = 3617–27 | date = Oct 2000 | pmid = 11029059 | pmc = 15019 | doi = 10.1091/mbc.11.10.3617 }}
* {{cite journal | vauthors = Huang H, Paliouras M, Rambaldi I, Lasko P, Featherstone M | title = Nonmuscle myosin promotes cytoplasmic localization of PBX | journal = Molecular and Cellular Biology | volume = 23 | issue = 10 | pages = 3636–45 | date = May 2003 | pmid = 12724421 | pmc = 164772 | doi = 10.1128/MCB.23.10.3636-3645.2003 }}
* {{cite journal | vauthors = Trinczek B, Brajenovic M, Ebneth A, Drewes G | title = MARK4 is a novel microtubule-associated proteins/microtubule affinity-regulating kinase that binds to the cellular microtubule network and to centrosomes | journal = The Journal of Biological Chemistry | volume = 279 | issue = 7 | pages = 5915–23 | date = Feb 2004 | pmid = 14594945 | doi = 10.1074/jbc.M304528200 }}
* {{cite journal | vauthors = Straight AF, Field CM, Mitchison TJ | title = Anillin binds nonmuscle myosin II and regulates the contractile ring | journal = Molecular Biology of the Cell | volume = 16 | issue = 1 | pages = 193–201 | date = Jan 2005 | pmid = 15496454 | pmc = 539163 | doi = 10.1091/mbc.E04-08-0758 }}
* {{cite journal | vauthors = Bastian P, Lang K, Niggemann B, Zaenker KS, Entschladen F | title = Myosin regulation in the migration of tumor cells and leukocytes within a three-dimensional collagen matrix | journal = Cellular and Molecular Life Sciences | volume = 62 | issue = 1 | pages = 65–76 | date = Jan 2005 | pmid = 15619008 | doi = 10.1007/s00018-004-4391-6 }}
* {{cite journal | vauthors = Nakasawa T, Takahashi M, Matsuzawa F, Aikawa S, Togashi Y, Saitoh T, Yamagishi A, Yazawa M | title = Critical regions for assembly of vertebrate nonmuscle myosin II | journal = Biochemistry | volume = 44 | issue = 1 | pages = 174–83 | date = Jan 2005 | pmid = 15628858 | doi = 10.1021/bi048807h }}
{{refend}}
{{refend}}


{{protein-stub}}
{{Cytoskeletal Proteins}}
{{WikiDoc Sources}}

Latest revision as of 01:55, 27 October 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Myosin-10 also known as myosin heavy chain 10 or non-muscle myosin IIB (NM-IIB) is a protein that in humans is encoded by the MYH10 gene.[1][2] Non-muscle myosins are expressed in a wide variety of tissues, but NM-IIB is the only non-muscle myosin II isoform expressed in cardiac muscle, where it localizes to adherens junctions within intercalated discs. NM-IIB is essential for normal development of cardiac muscle and for integrity of intercalated discs. Mutations in MYH10 have been identified in patients with left atrial enlargement.

Structure

NM-IIB is 228.9 kDa protein composed of 1976 amino acids.[3] NM-IIB has an N-terminal globular head that harbors the catalytically active, magnesium(Mg)-ATPase. The C-terminal rod domain is an alpha helical coiled-coil that can multimerize with other myosin molecules to form a filament. Bound to the neck region of NM-IIB are two light chains; first, MLC17 stabilizes the molecule, while the second light chain, MLC20, modulates contraction.[4] The exception to this rule is the alternatively spliced NM-IIB2 isoform, which has a 21 amino acid inserted into loop 2, near the actin-binding domain; actomyosin MgATPase activity of this isoform is not enhanced by phosphorylation of the regulatory light chain MLC20.[5]

NM-IIB is part of the larger myosin II subfamily of proteins, which also includes skeletal muscle, cardiac muscle and smooth muscle myosins. NM-IIB, and non-muscle myosins in general, are widely expressed in every tissue in humans.

Function

NM-IIB has many properties that are similar to those of smooth muscle myosins, such as the permissive nature of phosphorylation of the 20 kDa regulatory light chain for contraction. In skeletal muscle and cardiac muscle myosins, contraction is activated through thin filament proteins troponin and tropomyosin, whereas in NM-IIB and smooth muscle myosin, contraction initiates via regulatory light chain (MLC20) phosphorylation.[6]

Various functions of NM-IIB require the phosphorylation of the regulatory light chain MLC20, including cell migration and cell adhesion. The two primary kinases catalyzing this reaction are the calcium-calmodulin-dependent, myosin light chain kinase and the Rho-GTP dependent, Rho kinase (ROCK). NM-IIB is dephosphorylated by a myosin phosphatase.[7]

Detailed kinetic studies on NM-IIB show that this isoform of non-muscle myosin II has a slower actomyosin ATPase cycle relative to other myosin II isoforms, and that the markedly high affinity of NM-IIB head for ADP as well as the slow rate of ADP release can mechanistically explain affinity this finding. These data indicate that NM-IIB spends a large amount of its kinetic cycle in a configuration where it is strongly attached to actin.[8]

NM-IIB, along with the other non-muscle myosin isoforms IIA and IIC, play a role in cell-cell and cell-matrix adhesion, cell migration, cell polarity, and embryonic stem cell apoptosis.[9][10] Insights into the function of NM-IIB specifically have come from studies employing transgenic animals. NM-IIB is clearly required for normal development of cardiac muscle. Targeted gene disruption of NM-IIB resulted in approximately 65% embryonic lethality, and those that survived suffered from congestive heart failure and died day 1 following birth. Feature observed in NM-IIB knockouts was an increase in the transverse diameters of cardiomyocytes, ventricular septal defects, as well as other muscular abnormalities.[11] NM-IIB is expressed early during embryonic development in cardiomyocytes,[12] and appears to play a role in karyokinesis; ablation of NM-IIB caused defects in chromatid segregation and mitotic spindle formation, as well as abnormal structure of centrosomes.[13][14]

In adult cardiomyocytes, NM-IIB redistributes from a diffuse cytoplasmic pattern in development to a localized Z-disc and intercalated disc distribution, where it colocalizes with alpha-actinin. NM-IIB is the only non-muscle myosin II isoform expressed in adult cardiac muscle (both IIa and IIB are expressed in skeletal muscle Z-discs, suggesting a specific function of NM-IIB in this cell type.[15] NM-IIB may play a role in formation of mature sarcomeres in myofibrils.[16] It appears that NM-IIB plays an essential role in maintaining normal adherens junction integrity and structure. A cardiac muscle-specific knockout of NM-IIB using the alpha-myosin heavy chain promoter-driven cre-recombinase develop enlarged cardiomyocytes, consistent with the defects previously observed with cytokinesis; widened adherens junctions; and progressive hypertrophic cardiomyopathy at 6 months.[17] These data indicate that NM-IIB functions in ensuring the proper maintenance of intercalated disc structures.[18]

Clinical Significance

Single nucleotide polymorphisms in MYH10 were detected in patients with left atrial enlargement. MYH10 was identified to be a susceptibility gene using non-biased genome-wide linkage and peak-wide association analysis.[19]

Interactions

MYH10 has been shown to interact with:

References

  1. ↑ Simons M, Wang M, McBride OW, Kawamoto S, Yamakawa K, Gdula D, Adelstein RS, Weir L (Aug 1991). "Human nonmuscle myosin heavy chains are encoded by two genes located on different chromosomes". Circulation Research. 69 (2): 530–9. doi:10.1161/01.res.69.2.530. PMID 1860190.
  2. ↑ "Entrez Gene: MYH10 myosin, heavy chain 10, non-muscle".
  3. ↑ "Protein sequence of human MYH10 (Uniprot ID: P35580)". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). Retrieved 17 July 2015.
  4. ↑ 4.0 4.1 4.2 Conti MA, Adelstein RS (Jan 2008). "Nonmuscle myosin II moves in new directions". Journal of Cell Science. 121 (Pt 1): 11–8. doi:10.1242/jcs.007112. PMID 18096687.
  5. ↑ Kim KY, Kawamoto S, Bao J, Sellers JR, Adelstein RS (Apr 2008). "The B2 alternatively spliced isoform of nonmuscle myosin II-B lacks actin-activated MgATPase activity and in vitro motility". Biochemical and Biophysical Research Communications. 369 (1): 124–34. doi:10.1016/j.bbrc.2007.11.108. PMC 2366080. PMID 18060863.
  6. ↑ Adelstein RS, Conti MA (Aug 1975). "Phosphorylation of platelet myosin increases actin-activated myosin ATPase activity". Nature. 256 (5518): 597–8. doi:10.1038/256597a0. PMID 170529.
  7. ↑ Ito M, Nakano T, Erdodi F, Hartshorne DJ (Apr 2004). "Myosin phosphatase: structure, regulation and function". Molecular and Cellular Biochemistry. 259 (1–2): 197–209. doi:10.1023/b:mcbi.0000021373.14288.00. PMID 15124925.
  8. ↑ Wang F, Kovacs M, Hu A, Limouze J, Harvey EV, Sellers JR (Jul 2003). "Kinetic mechanism of non-muscle myosin IIB: functional adaptations for tension generation and maintenance". The Journal of Biological Chemistry. 278 (30): 27439–48. doi:10.1074/jbc.M302510200. PMID 12704189.
  9. ↑ Vicente-Manzanares M, Ma X, Adelstein RS, Horwitz AR (Nov 2009). "Non-muscle myosin II takes centre stage in cell adhesion and migration". Nature Reviews Molecular Cell Biology. 10 (11): 778–90. doi:10.1038/nrm2786. PMC 2834236. PMID 19851336.
  10. ↑ Walker A, Su H, Conti MA, Harb N, Adelstein RS, Sato N (7 September 2010). "Non-muscle myosin II regulates survival threshold of pluripotent stem cells". Nature Communications. 1: 71. doi:10.1038/ncomms1074. PMC 3430968. PMID 20842192.
  11. ↑ Tullio AN, Accili D, Ferrans VJ, Yu ZX, Takeda K, Grinberg A, Westphal H, Preston YA, Adelstein RS (Nov 1997). "Nonmuscle myosin II-B is required for normal development of the mouse heart". Proceedings of the National Academy of Sciences of the United States of America. 94 (23): 12407–12. doi:10.1073/pnas.94.23.12407. PMC 24969. PMID 9356462.
  12. ↑ Wang A, Ma X, Conti MA, Liu C, Kawamoto S, Adelstein RS (Aug 2010). "Nonmuscle myosin II isoform and domain specificity during early mouse development". Proceedings of the National Academy of Sciences of the United States of America. 107 (33): 14645–50. doi:10.1073/pnas.1004023107. PMC 2930417. PMID 20679233.
  13. ↑ Takeda K, Kishi H, Ma X, Yu ZX, Adelstein RS (Aug 2003). "Ablation and mutation of nonmuscle myosin heavy chain II-B results in a defect in cardiac myocyte cytokinesis". Circulation Research. 93 (4): 330–7. doi:10.1161/01.RES.0000089256.00309.CB. PMID 12893741.
  14. ↑ Ma X, Jana SS, Conti MA, Kawamoto S, Claycomb WC, Adelstein RS (Nov 2010). "Ablation of nonmuscle myosin II-B and II-C reveals a role for nonmuscle myosin II in cardiac myocyte karyokinesis". Molecular Biology of the Cell. 21 (22): 3952–62. doi:10.1091/mbc.E10-04-0293. PMC 2982113. PMID 20861308.
  15. ↑ Takeda K, Yu ZX, Qian S, Chin TK, Adelstein RS, Ferrans VJ (May 2000). "Nonmuscle myosin II localizes to the Z-lines and intercalated discs of cardiac muscle and to the Z-lines of skeletal muscle". Cell Motility and the Cytoskeleton. 46 (1): 59–68. doi:10.1002/(SICI)1097-0169(200005)46:1<59::AID-CM6>3.0.CO;2-Q. PMID 10842333.
  16. ↑ Sanger JW, Kang S, Siebrands CC, Freeman N, Du A, Wang J, Stout AL, Sanger JM (2005). "How to build a myofibril". Journal of Muscle Research and Cell Motility. 26 (6–8): 343–54. doi:10.1007/s10974-005-9016-7. PMID 16465476.
  17. ↑ Ma X, Takeda K, Singh A, Yu ZX, Zerfas P, Blount A, Liu C, Towbin JA, Schneider MD, Adelstein RS, Wei Q (Nov 2009). "Conditional ablation of nonmuscle myosin II-B delineates heart defects in adult mice". Circulation Research. 105 (11): 1102–9. doi:10.1161/CIRCRESAHA.109.200303. PMC 2792753. PMID 19815823.
  18. ↑ Ma X, Adelstein RS (1 January 2012). "In vivo studies on nonmuscle myosin II expression and function in heart development". Frontiers in Bioscience. 17: 545–55. doi:10.2741/3942. PMC 3476727. PMID 22201759.
  19. ↑ Wang L, Di Tullio MR, Beecham A, Slifer S, Rundek T, Homma S, Blanton SH, Sacco RL (Aug 2010). "A comprehensive genetic study on left atrium size in Caribbean Hispanics identifies potential candidate genes in 17p10". Circulation: Cardiovascular Genetics. 3 (4): 386–92. doi:10.1161/CIRCGENETICS.110.938381. PMC 2923674. PMID 20562446.

Further reading

Retrieved from "https://www.wikidoc.org/index.php?title=MYH10&oldid=1417819"