MYH7

MYH7
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	3DTP, 4DB1, 4P7H, 4XA1, 4XA3, 4XA4, 4XA6, 4PA0, 5CHX, 5CJ0, 5CJ4, 5CJ1, 2FXO, 2FXM
Identifikatori
Aliasi	MYH7
Vanjski ID-jevi	OMIM: 160760 MGI: 2155600 HomoloGene: 68044 GeneCards: MYH7
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	23,435,660 bp
Lokacija gena (miš)
Hrom.	Hromosom 14 (miš)
Kraj	55,232,083 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• nucleotide binding; • calmodulin binding; • GO:0001948, GO:0016582 vezivanje za proteine; • actin binding; • cytoskeletal motor activity; • ATP binding; • ATPase activity; • microfilament motor activity; • actin filament binding; • microtubule motor activity; • microtubule binding;
Ćelijska komponenta	• citoplazma; • stress fiber; • Z discdkac; • myosin filament; • myosin complex; • muscle myosin complex; • Miofibril; • Sarkomera;
Biološki proces	• cardiac muscle contraction; • adult heart development; • transition between fast and slow fiber; • regulation of the force of heart contraction; • skeletal muscle contraction; • regulation of slow-twitch skeletal muscle fiber contraction; • regulation of heart rate; • ventricular cardiac muscle tissue morphogenesis; • ATP metabolic process; • muscle filament sliding; • striated muscle contraction; • regulation of the force of skeletal muscle contraction; • Mišićna kontrakcija; • cardiac muscle hypertrophy in response to stress; • microtubule-based movement;
	Izvori:Amigo / QuickGO
Ortolozi
	4625
	140781
	ENSG00000092054
	ENSMUSG00000053093
	P12883
	Q91Z83
	NM_000257
	NM_080728; NM_001361607
	NP_000248
	NP_542766; NP_001348536
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

MYH7 je gen koji kodira sporokolntrahirajuću izoformu miozinskog teškog lanca beta (MHC-β), eksprimiranu prvenstveno u srcu, ali i u skeletnim mišićima (vlakna tipa I).^[5] Ova izoforma razlikuje se od brze izoforme teškog lanca srčanog miozina, MYH6, koja se naziva MHC-α. MHC-β je glavni protein koji sadrži gustu nit u srčanom mišiću i ima glavnu ulogu u srčanoj kontrakciji mišića.

Struktura

MHC-β je protein od 223 kDa koji se sastoji od 1935 aminokiselina.^[6]^[7] MHC-β je heksamerni, asimetrični motorni protein koji čini glavninu debelog vlakna u srčanom mišiću. MHC-β sastavljen je od N-terminalnih loptastih glava (20 nm) koje strše bočno i alfa-heliksnih repova (130 nm) koji se dimeriziraju i multimeriziraju u motiv sa upredenom zavojnicom da formiraju lahki meromiozin (LMM), debeli šipkasti filament. Područje alfa-heliksnog vrata od 9 nm u svakoj glavi MHC-β nekovalentno veže dva lahka lanca, osnovni lahki lanac (MYL3) i regulatorni lahki lanac (MYL2).^[8] Otprilike 300 molekula miozina čine jedan debeli filament.^[9] Postoje dvije izoforme srčanog MHC, α i β, koje imaju 93% homologije. MHC-α i MHC-β pokazuju značajno različita enzimska svojstva, pri čemu α ima 150-300% kontraktilne brzine i 60-70% vremena vezivanja aktina kao i β.^[8]^[10] MHC-β je pretežno eksprimiran u ljudskim srčanim komorama, dok je MHC-α pretežno izražen u ljudskim pretkomorama.

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 1.935 aminokiselina, a molekulska težina 223 097 Da.^[11].

10	20	30	40	50
MGDSEMAVFG	AAAPYLRKSE	KERLEAQTRP	FDLKKDVFVP	DDKQEFVKAK
IVSREGGKVT	AETEYGKTVT	VKEDQVMQQN	PPKFDKIEDM	AMLTFLHEPA
VLYNLKDRYG	SWMIYTYSGL	FCVTVNPYKW	LPVYTPEVVA	AYRGKKRSEA
PPHIFSISDN	AYQYMLTDRE	NQSILITGES	GAGKTVNTKR	VIQYFAVIAA
IGDRSKKDQS	PGKGTLEDQI	IQANPALEAF	GNAKTVRNDN	SSRFGKFIRI
HFGATGKLAS	ADIETYLLEK	SRVIFQLKAE	RDYHIFYQIL	SNKKPELLDM
LLITNNPYDY	AFISQGETTV	ASIDDAEELM	ATDNAFDVLG	FTSEEKNSMY
KLTGAIMHFG	NMKFKLKQRE	EQAEPDGTEE	ADKSAYLMGL	NSADLLKGLC
HPRVKVGNEY	VTKGQNVQQV	IYATGALAKA	VYERMFNWMV	TRINATLETK
QPRQYFIGVL	DIAGFEIFDF	NSFEQLCINF	TNEKLQQFFN	HHMFVLEQEE
YKKEGIEWTF	IDFGMDLQAC	IDLIEKPMGI	MSILEEECMF	PKATDMTFKA
KLFDNHLGKS	ANFQKPRNIK	GKPEAHFSLI	HYAGIVDYNI	IGWLQKNKDP
LNETVVGLYQ	KSSLKLLSTL	FANYAGADAP	IEKGKGKAKK	GSSFQTVSAL
HRENLNKLMT	NLRSTHPHFV	RCIIPNETKS	PGVMDNPLVM	HQLRCNGVLE
GIRICRKGFP	NRILYGDFRQ	RYRILNPAAI	PEGQFIDSRK	GAEKLLSSLD
IDHNQYKFGH	TKVFFKAGLL	GLLEEMRDER	LSRIITRIQA	QSRGVLARME
YKKLLERRDS	LLVIQWNIRA	FMGVKNWPWM	KLYFKIKPLL	KSAEREKEMA
SMKEEFTRLK	EALEKSEARR	KELEEKMVSL	LQEKNDLQLQ	VQAEQDNLAD
AEERCDQLIK	NKIQLEAKVK	EMNERLEDEE	EMNAELTAKK	RKLEDECSEL
KRDIDDLELT	LAKVEKEKHA	TENKVKNLTE	EMAGLDEIIA	KLTKEKKALQ
EAHQQALDDL	QAEEDKVNTL	TKAKVKLEQQ	VDDLEGSLEQ	EKKVRMDLER
AKRKLEGDLK	LTQESIMDLE	NDKQQLDERL	KKKDFELNAL	NARIEDEQAL
GSQLQKKLKE	LQARIEELEE	ELEAERTARA	KVEKLRSDLS	RELEEISERL
EEAGGATSVQ	IEMNKKREAE	FQKMRRDLEE	ATLQHEATAA	ALRKKHADSV
AELGEQIDNL	QRVKQKLEKE	KSEFKLELDD	VTSNMEQIIK	AKANLEKMCR
TLEDQMNEHR	SKAEETQRSV	NDLTSQRAKL	QTENGELSRQ	LDEKEALISQ
LTRGKLTYTQ	QLEDLKRQLE	EEVKAKNALA	HALQSARHDC	DLLREQYEEE
TEAKAELQRV	LSKANSEVAQ	WRTKYETDAI	QRTEELEEAK	KKLAQRLQEA
EEAVEAVNAK	CSSLEKTKHR	LQNEIEDLMV	DVERSNAAAA	ALDKKQRNFD
KILAEWKQKY	EESQSELESS	QKEARSLSTE	LFKLKNAYEE	SLEHLETFKR
ENKNLQEEIS	DLTEQLGSSG	KTIHELEKVR	KQLEAEKMEL	QSALEEAEAS
LEHEEGKILR	AQLEFNQIKA	EIERKLAEKD	EEMEQAKRNH	LRVVDSLQTS
LDAETRSRNE	ALRVKKKMEG	DLNEMEIQLS	HANRMAAEAQ	KQVKSLQSLL
KDTQIQLDDA	VRANDDLKEN	IAIVERRNNL	LQAELEELRA	VVEQTERSRK
LAEQELIETS	ERVQLLHSQN	TSLINQKKKM	DADLSQLQTE	VEEAVQECRN
AEEKAKKAIT	DAAMMAEELK	KEQDTSAHLE	RMKKNMEQTI	KDLQHRLDEA
EQIALKGGKK	QLQKLEARVR	ELENELEAEQ	KRNAESVKGM	RKSERRIKEL
TYQTEEDRKN	LLRLQDLVDK	LQLKVKAYKR	QAEEAEEQAN	TNLSKFRKVQ
HELDEAEERA	DIAESQVNKL	RAKSRDIGTK	GLNEE

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

Funkcija

Enzimska aktivnost ATPaza u glavi miozina je ta koja ciklično hidrolizira ATP, podstičući miozinski udar. Ovaj postupak pretvara hemijsku u mehaničku energiju i pokreće skraćivanje sarkomera, kako bi se stvorio unutarkomorski pritisak i snaga. Prihvaćeni mehanizam ovog procesa je da se miozin vezan za ADP veže za aktin, dok se tropomiozin uvlači unutra,^[12] kada se miozinska poluga S1-S2 okreće za oko 70° oko domena pretvarača i pokreće aktinske filamente prema M-liniji.^[13]

Klinički značaj

Nekoliko mutacija MYH7 povezano je sa nasljednim kardiomiopatijama. Lowrance etal. su prvi identificirali uzročnu mutaciju Arg 403 Gln za hipetrofijsku kardiomiopatiju (HCM) u genu MYH7.^[14] Od tada su studije identificirale još nekoliko mutacija MYH7, za koje se procjenjuje da su uzročne u približno 40% HCM. Ovo stanje je autosomno-dominantna bolest, u kojem jedna kopija varijantnog gena uzrokuje povećanje lijeve srčane komore. Pojava bolesti obično se javlja kasnije u životu, možda podstaknuta promjenama u funkciji hormona štitnjače i/ili fizičkim stresom.

Sljedeće stanje povezano s mutacijama ovog gena je parakičmenompždinska i proksimalna mišićna atrofija.^[15]

Svinjska miopatija izazvana mutacijom caused by a gena MYH7

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000092054 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000053093 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Quiat D, Voelker KA, Pei J, Grishin NV, Grange RW, Bassel-Duby R, Olson EN (Jun 2011). "Concerted regulation of myofiber-specific gene expression and muscle performance by the transcriptional repressor Sox6". Proceedings of the National Academy of Sciences of the United States of America. 108 (25): 10196–201. doi:10.1073/pnas.1107413108. PMC 3121857. PMID 21633012.
^ "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)". heartproteome.org. Arhivirano s originala, 4. 3. 2016. Pristupljeno 14. 10. 2015.
^ Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (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.
^ ^a ^b Palmer BM (Sep 2005). "Thick filament proteins and performance in human heart failure". Heart Failure Reviews. 10 (3): 187–97. doi:10.1007/s10741-005-5249-1. PMID 16416042.
^ Harris SP, Lyons RG, Bezold KL (Mar 2011). "In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament". Circulation Research. 108 (6): 751–764. doi:10.1161/CIRCRESAHA.110.231670. PMC 3076008. PMID 21415409.
^ Alpert NR, Brosseau C, Federico A, Krenz M, Robbins J, Warshaw DM (Oct 2002). "Molecular mechanics of mouse cardiac myosin isoforms". American Journal of Physiology. Heart and Circulatory Physiology. 283 (4): H1446-54. doi:10.1152/ajpheart.00274.2002. PMID 12234796.
^ "UniProt, P12883". Pristupljeno 27. 7. 2021.
^ McKillop DF, Geeves MA (Aug 1993). "Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament". Biophysical Journal. 65 (2): 693–701. doi:10.1016/S0006-3495(93)81110-X. PMC 1225772. PMID 8218897.
^ Tyska MJ, Warshaw DM (Jan 2002). "The myosin power stroke". Cell Motility and the Cytoskeleton. 51 (1): 1–15. doi:10.1002/cm.10014. PMID 11810692.
^ Geisterfer-Lowrance, A. A.; Kass, S; Tanigawa, G; Vosberg, H. P.; McKenna, W; Seidman, C. E.; Seidman, J. G. (1990). "A molecular basis for familial hypertrophic cardiomyopathy: A beta cardiac myosin heavy chain gene missense mutation". Cell. 62 (5): 999–1006. doi:10.1016/0092-8674(90)90274-i. PMID 1975517.
^ Park JM, Kim YJ, Yoo JH, Hong YB, Park JH, Koo H, Chung KW, Choi BO (Jul 2013). "A novel MYH7 mutation with prominent paraspinal and proximal muscle involvement". Neuromuscular Disorders. 23 (7): 580–6. doi:10.1016/j.nmd.2013.04.003. PMID 23707328.

Dopunska literatura

Jaaskelainen P, Miettinen R, Karkkainen P, Toivonen L, Laakso M, Kuusisto J (2004). "Genetics of hypertrophic cardiomyopathy in eastern Finland: few founder mutations with benign or intermediary phenotypes". Annals of Medicine. 36 (1): 23–32. doi:10.1080/07853890310017161. PMID 15000344.
Kamisago M, Schmitt JP, McNamara D, Seidman C, Seidman JG (2007). "Sarcomere protein gene mutations and inherited heart disease: a beta-cardiac myosin heavy chain mutation causing endocardial fibroelastosis and heart failure". Novartis Foundation Symposium. 274: 176–89, discussion 189–95, 272–6. doi:10.1002/0470029331.ch11. PMID 17019812.

Vanjski linkovi

Mass spectrometry characterization of MYH7 at COPaKB Arhivirano 4. 3. 2016. na Wayback Machine ^[1]
GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview
GeneReviews/NCBI/NIH/UW entry on Laing Distal Myopathy
MYH7 protein, human na US National Library of Medicine Medical Subject Headings (MeSH)

^ Greška kod citiranja: Nevaljana oznaka <ref>; nije naveden tekst za reference s imenom ReferenceA

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000092054 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000053093 - Ensembl, maj 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] Quiat D, Voelker KA, Pei J, Grishin NV, Grange RW, Bassel-Duby R, Olson EN (Jun 2011). "Concerted regulation of myofiber-specific gene expression and muscle performance by the transcriptional repressor Sox6". Proceedings of the National Academy of Sciences of the United States of America. 108 (25): 10196–201. doi:10.1073/pnas.1107413108. PMC 3121857. PMID 21633012.

[6] "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB)". heartproteome.org. Arhivirano s originala, 4. 3. 2016. Pristupljeno 14. 10. 2015.

[ReferenceA-7] Zong, N. C.; Li, H; Li, H; Lam, M. P.; Jimenez, R. C.; Kim, C. S.; Deng, N; Kim, A. K.; Choi, J. H.; Zelaya, I; Liem, D; Meyer, D; Odeberg, J; Fang, C; Lu, H. J.; Xu, T; Weiss, J; Duan, H; Uhlen, M; Yates Jr, 3rd; Apweiler, R; Ge, J; Hermjakob, H; Ping, P (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.

[Thick_filament_proteins_and_perform-8] Palmer BM (Sep 2005). "Thick filament proteins and performance in human heart failure". Heart Failure Reviews. 10 (3): 187–97. doi:10.1007/s10741-005-5249-1. PMID 16416042.

[9] Harris SP, Lyons RG, Bezold KL (Mar 2011). "In the thick of it: HCM-causing mutations in myosin binding proteins of the thick filament". Circulation Research. 108 (6): 751–764. doi:10.1161/CIRCRESAHA.110.231670. PMC 3076008. PMID 21415409.

[10] Alpert NR, Brosseau C, Federico A, Krenz M, Robbins J, Warshaw DM (Oct 2002). "Molecular mechanics of mouse cardiac myosin isoforms". American Journal of Physiology. Heart and Circulatory Physiology. 283 (4): H1446-54. doi:10.1152/ajpheart.00274.2002. PMID 12234796.

[UniProt-11] "UniProt, P12883". Pristupljeno 27. 7. 2021.

[12] McKillop DF, Geeves MA (Aug 1993). "Regulation of the interaction between actin and myosin subfragment 1: evidence for three states of the thin filament". Biophysical Journal. 65 (2): 693–701. doi:10.1016/S0006-3495(93)81110-X. PMC 1225772. PMID 8218897.

[13] Tyska MJ, Warshaw DM (Jan 2002). "The myosin power stroke". Cell Motility and the Cytoskeleton. 51 (1): 1–15. doi:10.1002/cm.10014. PMID 11810692.

[14] Geisterfer-Lowrance, A. A.; Kass, S; Tanigawa, G; Vosberg, H. P.; McKenna, W; Seidman, C. E.; Seidman, J. G. (1990). "A molecular basis for familial hypertrophic cardiomyopathy: A beta cardiac myosin heavy chain gene missense mutation". Cell. 62 (5): 999–1006. doi:10.1016/0092-8674(90)90274-i. PMID 1975517.

[15] Park JM, Kim YJ, Yoo JH, Hong YB, Park JH, Koo H, Chung KW, Choi BO (Jul 2013). "A novel MYH7 mutation with prominent paraspinal and proximal muscle involvement". Neuromuscular Disorders. 23 (7): 580–6. doi:10.1016/j.nmd.2013.04.003. PMID 23707328.

[ReferenceA-16] Greška kod citiranja: Nevaljana oznaka <ref>; nije naveden tekst za reference s imenom ReferenceA

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