Descriptions

Myosin-7 (MYH7, also named Myosin heavy chain, cardiac muscle β isoform) is an actin-based motor molecule with ATPase activity essential for muscle contraction. Several mutations in MYH7 are frequent causes of hypertrophic cardiomyopathy (HCM), a disease characterized by hypercontractility and eventual hypertrophy of the left ventricle. Many HCM-causing mutations appear to reduce myosin's ability to form an autoinhibited state. In an autoinhibited state, the myosin heads fold back onto their own subfragment 2 (S2) tail in a conformation known as the interacting heads motif (IHM). One of the two heads in the dimer has its actin-binding interface buried in the folded structure; this head is referred to as the blocked head, while the other is called the free head, since its actin-binding interface is not hidden structurally. Many myosin types have the folded back IHM structure. The IHM structure correlates to an ultra-low basal ATPase rate in the absence of an action called the 'super relaxed state'. Heads lacking the S2 tail mostly have a faster basal ATPase rate referred to as the 'disordered relaxed state'. Especially, mutations in the myosin lever arm or the pliant region of the lever arm can affect myosin function either by altering its intrinsic motor activity, and/or reducing its ability to form the autoinhibited state.

Autoinhibitory domains (AIDs)

Target domain

79-779 (Myosin head, motor domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for P49824

Entry ID Method Resolution Chain Position Source
AF-P49824-F1 Predicted AlphaFoldDB

12 variants for P49824

Variant ID(s) Position Change Description Diseaes Association Provenance
rs850880343 728 A>T No EVA
rs3332234469 747 S>G No EVA
rs3332654724 869 R>H No EVA
rs3332723493 975 V>A No EVA
rs851869078 1197 A>P No EVA
rs3332234525 1666 D>N No EVA
rs3332519130 1674 V>M No EVA
rs3332723651 1691 V>M No EVA
rs3332475787 1702 A>V No EVA
rs24543377 1731 D>E No EVA
rs3332519105 1789 T>A No EVA
rs3332723552 1803 I>M No EVA

No associated diseases with P49824

3 regional properties for P49824

Type Name Position InterPro Accession
domain Myosin head, motor domain 79 - 779 IPR001609
domain Myosin tail 846 - 1923 IPR002928
domain Myosin, N-terminal, SH3-like 32 - 81 IPR004009

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm, myofibril
  • Cytoplasm, myofibril, sarcomere
  • Thick filaments of the myofibrils
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

5 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
myofibril The contractile element of skeletal and cardiac muscle; a long, highly organized bundle of actin, myosin, and other proteins that contracts by a sliding filament mechanism.
myosin filament A supramolecular fiber containing myosin heavy chains, plus associated light chains and other proteins, in which the myosin heavy chains are arranged into a filament.
myosin II complex A myosin complex containing two class II myosin heavy chains, two myosin essential light chains and two myosin regulatory light chains. Also known as classical myosin or conventional myosin, the myosin II class includes the major muscle myosin of vertebrate and invertebrate muscle, and is characterized by alpha-helical coiled coil tails that self assemble to form a variety of filament structures.
sarcomere The repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs.

4 GO annotations of molecular function

Name Definition
actin filament binding Binding to an actin filament, also known as F-actin, a helical filamentous polymer of globular G-actin subunits.
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
calmodulin binding Binding to calmodulin, a calcium-binding protein with many roles, both in the calcium-bound and calcium-free states.
microfilament motor activity A motor activity that generates movement along a microfilament, driven by ATP hydrolysis.

4 GO annotations of biological process

Name Definition
adult heart development The process whose specific outcome is the progression of the adult heart over time, from its formation to the mature structure.
cardiac muscle contraction Muscle contraction of cardiac muscle tissue.
muscle filament sliding The sliding of actin thin filaments and myosin thick filaments past each other in muscle contraction. This involves a process of interaction of myosin located on a thick filament with actin located on a thin filament. During this process ATP is split and forces are generated.
sarcomere organization The myofibril assembly process that results in the organization of muscle actomyosin into sarcomeres. The sarcomere is the repeating unit of a myofibril in a muscle cell, composed of an array of overlapping thick and thin filaments between two adjacent Z discs.

11 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9BE39 MYH7 Myosin-7 Bos taurus (Bovine) SS
P05661 Mhc Myosin heavy chain, muscle Drosophila melanogaster (Fruit fly) SS
Q8MJU9 MYH7 Myosin-7 Equus caballus (Horse) SS
P12883 MYH7 Myosin-7 Homo sapiens (Human) EV
Q91Z83 Myh7 Myosin-7 Mus musculus (Mouse) SS
P79293 MYH7 Myosin-7 Sus scrofa (Pig) SS
P02564 Myh7 Myosin-7 Rattus norvegicus (Rat) SS
P02567 myo-1 Myosin-1 Caenorhabditis elegans SS
P02566 unc-54 Myosin-4 Caenorhabditis elegans SS
P12844 myo-3 Myosin-3 Caenorhabditis elegans SS
P12845 myo-2 Myosin-2 Caenorhabditis elegans SS
10 20 30 40 50 60
MVDAEMAAFG AAAPFLRKSE KERLEAQTRP FDLKKDVFVP DDKEEFVKAK IVSREGGKVT
70 80 90 100 110 120
AETENGKTVT VKEDQVMQQN PPKFDKIEDM AMLTFLHEPA VLYNLKERYA SWMIYTYSGL
130 140 150 160 170 180
FCVTVNPYKW LPVYNAEVVA AYRGKKRSEA PPHIFSISDN AYQYMLTDRE NQSILITGES
190 200 210 220 230 240
GAGKTVNTKR VIQYFAVIAA IGDRSKKDQT PGKGTLEDQI IQANPALEAF GNAKTVRNDN
250 260 270 280 290 300
SSRFGKFIRI HFGATGKLAS ADIETYLLEK SRVIFQLKAE RDYHIFYQIL SNKKPELLDM
310 320 330 340 350 360
LLITNNPYDY AFISQGETTV ASIDDSEELM ATDNAFDVLG FTSEEKNSMY KLTGAIMHFG
370 380 390 400 410 420
NMKFKQKQRE EQAEPDGTEE ADKSAYLMGL NSADLLKGLC HPRVKVGNEY VTKGQNVQQV
430 440 450 460 470 480
AYATGALAKA VYEKMFNWMV TRINATLETK QPRQYFIGVL DIAGFEIFDF NSFEQLCINF
490 500 510 520 530 540
TNEKLQQFFN HHMFVLEQEE YKKEGIEWEF IDFGMDLQAC IDLIEKPMGI MSILEEECMF
550 560 570 580 590 600
PKATDMTFKA KLYDNHLGKS NNFQKPRNIK GKQEAHFSLI HYAGTVDYNI LGWLQKNKDP
610 620 630 640 650 660
LNETVVALYQ KSSLKLLSNL FANYAGADAP VEKGKGKAKK GSSFQTVSAL HRENLNKLMT
670 680 690 700 710 720
NLRSTHPHFV RCIIPNETKS PGVIDNPLVM HQLRCNGVLE GIRICRKGFP NRILYGDFRQ
730 740 750 760 770 780
RYRILNPAAI PEGQFIDSRK GAEKLLSSLD IDHNQYKFGH TKVFFKAGLL GLLEEMRDER
790 800 810 820 830 840
LSRIITRIQA QSRGVLSRME YKKLLERRDS LLIIQWNIRA FMGVKNWPWM KLYFKIKPLL
850 860 870 880 890 900
KSAETEKEMA TMKEEFARIK EALEKSEARR KELEEKMVSL LQEKNDLQLQ VQAEQDNLAD
910 920 930 940 950 960
AEERCDQLIK NKIQLEAKVK EMTERLEDEE EMNAELTAKK RKLEDECSEL KRDIDDLELT
970 980 990 1000 1010 1020
LAKVEKEKHA TENKVKNLTE EMAGLDEIIA KLTKEKKALQ EAHQQALDDL QAEEDKVNTL
1030 1040 1050 1060 1070 1080
TKAKVKLEQQ VDDLEGSLEQ EKKVRMDLER AKRKLEGDLK LTQESIMDLE NDKQQLDERL
1090 1100 1110 1120 1130 1140
KKKDFELNAL NARIEDEQAL GSQLQKKLKE LQARIEELEE ELEAERTARA KVEKLRSDLS
1150 1160 1170 1180 1190 1200
RELEEISERL EEAGGATSVQ IEMNKKREAE FQKMRRDLEE ATLQHEATAA ALRKKHADSV
1210 1220 1230 1240 1250 1260
AELGEQIDNL QRVKQKLEKE KSEFKLELDD VTSNMEQIIK AKANLEKMCR TLEDQMNEHR
1270 1280 1290 1300 1310 1320
SKAEETQRSV NDLTSQRAKL QTENGELSRQ LDEKEALISQ LTRGKLTYTQ QLEDLKRQLE
1330 1340 1350 1360 1370 1380
EEVKAKNALA HALQSARHDC DLLREQYEEE TEAKAELQRV LSKANSEVAQ WRTKYETDAI
1390 1400 1410 1420 1430 1440
QRTEELEEAK KKLAQRLQDA EEAVEAVNAK CSSLEKTKHR LQNEIEDLMV DVERSNAAAA
1450 1460 1470 1480 1490 1500
ALDKKQRNFD KILAEWKQKY EESQSELESS QKEARSLSTE LFKLKNAYEE SLEHLETFKR
1510 1520 1530 1540 1550 1560
ENKNLQEEIS DLTEQLGSSG KTIHELEKVR KQLEAEKLEL QSALEEAEAS LEHEEGKILR
1570 1580 1590 1600 1610 1620
AQLEFNQIKA EIERKLAEKD EEMEQAKRNH LRVVDSLQTS LDAETRSRNE ALRVKKKMEG
1630 1640 1650 1660 1670 1680
DLNEMEIQLS HANRMAAEAQ KQVKGLQSLL KDTQIQLDDA VRANDDLKEN IAIVERRNNL
1690 1700 1710 1720 1730 1740
LQAELEELRA VVEQTERSRK LAEQELIETS ERVQLLHSQN TSLINQKKKM DADLSQLQTE
1750 1760 1770 1780 1790 1800
VEEAVQECRN AEEKAKKAIT DAAMMAEELK KEQDTSAHLE RMKKNMEQTI KDLQHRLDEA
1810 1820 1830 1840 1850 1860
EQIALKGGKK QLQKLEARVR ELENELEAEQ KRNAESVKGM RKSERRIKEL TYQTEEDRKN
1870 1880 1890 1900 1910 1920
LLRLQDLVDK LQLKVKAYKR QAEEAEEQAN TNLSKFRKVQ HELDEAEERA DIAESQVNKL
1930
RAKSRDIGAK GLNEE