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

79-784 (Myosin head, motor domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for O08638

Entry ID Method Resolution Chain Position Source
AF-O08638-F1 Predicted AlphaFoldDB

No variants for O08638

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for O08638

No associated diseases with O08638

9 regional properties for O08638

Type Name Position InterPro Accession
domain Protein kinase domain 62 - 321 IPR000719-1
domain Protein kinase domain 418 - 675 IPR000719-2
domain AGC-kinase, C-terminal 322 - 391 IPR000961
active_site Serine/threonine-protein kinase, active site 183 - 195 IPR008271-1
active_site Serine/threonine-protein kinase, active site 531 - 543 IPR008271-2
binding_site Protein kinase, ATP binding site 68 - 94 IPR017441-1
binding_site Protein kinase, ATP binding site 424 - 447 IPR017441-2
domain Protein kinase, C-terminal 344 - 381 IPR017892
domain Ribosomal S6 kinase, N-terminal catalytic domain 66 - 382 IPR041906

Functions

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

10 GO annotations of cellular component

Name Definition
brush border The dense covering of microvilli on the apical surface of an epithelial cell in tissues such as the intestine, kidney, and choroid plexus; the microvilli aid absorption by increasing the surface area of the cell.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
melanosome A tissue-specific, membrane-bounded cytoplasmic organelle within which melanin pigments are synthesized and stored. Melanosomes are synthesized in melanocyte cells.
muscle myosin complex A filament of myosin found in a muscle cell of any type.
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 complex A protein complex, formed of one or more myosin heavy chains plus associated light chains and other proteins, that functions as a molecular motor; uses the energy of ATP hydrolysis to move actin filaments or to move vesicles or other cargo on fixed actin filaments; has magnesium-ATPase activity and binds actin. Myosin classes are distinguished based on sequence features of the motor, or head, domain, but also have distinct tail regions that are believed to bind specific cargoes.
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.
smooth muscle contractile fiber The contractile fiber of smooth muscle cells.
stress fiber A contractile actin filament bundle that consists of short actin filaments with alternating polarity, cross-linked by alpha-actinin and possibly other actin bundling proteins, and with myosin present in a periodic distribution along the fiber.

6 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.
cytoskeletal motor activity Generation of force resulting in movement, for example along a microfilament or microtubule, or in torque resulting in membrane scission or rotation of a flagellum. The energy required is obtained either from the hydrolysis of a nucleoside triphosphate or by an electrochemical proton gradient (proton-motive force).
microfilament motor activity A motor activity that generates movement along a microfilament, driven by ATP hydrolysis.
structural constituent of muscle The action of a molecule that contributes to the structural integrity of a muscle fiber.

5 GO annotations of biological process

Name Definition
actomyosin structure organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures containing both actin and myosin or paramyosin. The myosin may be organized into filaments.
cardiac muscle cell development The process whose specific outcome is the progression of a cardiac muscle cell over time, from its formation to the mature state.
elastic fiber assembly Assembly of the extracellular matrix fibers that enables the matrix to recoil after transient stretching.
skeletal muscle myosin thick filament assembly The aggregation, arrangement and bonding together of proteins to form the myosin-based thick filaments of myofibrils in skeletal muscle.
smooth muscle contraction A process in which force is generated within smooth muscle tissue, resulting in a change in muscle geometry. Force generation involves a chemo-mechanical energy conversion step that is carried out by the actin/myosin complex activity, which generates force through ATP hydrolysis. Smooth muscle differs from striated muscle in the much higher actin/myosin ratio, the absence of conspicuous sarcomeres and the ability to contract to a much smaller fraction of its resting length.

46 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9BE40 MYH1 Myosin-1 Bos taurus (Bovine) SS
Q9BE41 MYH2 Myosin-2 Bos taurus (Bovine) SS
Q27991 MYH10 Myosin-10 Bos taurus (Bovine) SS
Q9BE39 MYH7 Myosin-7 Bos taurus (Bovine) SS
P14105 MYH9 Myosin-9 Gallus gallus (Chicken) SS
P02565 MYH1B Myosin-1B Gallus gallus (Chicken) SS
P13538 Myosin heavy chain, skeletal muscle, adult Gallus gallus (Chicken) SS
P10587 MYH11 Myosin-11 Gallus gallus (Chicken) SS
P05661 Mhc Myosin heavy chain, muscle Drosophila melanogaster (Fruit fly) SS
Q99323 zip Myosin heavy chain, non-muscle Drosophila melanogaster (Fruit fly) SS
P35579 MYH9 Myosin-9 Homo sapiens (Human) SS
P12882 MYH1 Myosin-1 Homo sapiens (Human) SS
Q9UKX2 MYH2 Myosin-2 Homo sapiens (Human) SS
Q9Y623 MYH4 Myosin-4 Homo sapiens (Human) SS
A7E2Y1 MYH7B Myosin-7B Homo sapiens (Human) SS
Q9Y2K3 MYH15 Myosin-15 Homo sapiens (Human) SS
P12883 MYH7 Myosin-7 Homo sapiens (Human) EV
P35580 MYH10 Myosin-10 Homo sapiens (Human) SS
P13535 MYH8 Myosin-8 Homo sapiens (Human) SS
P13533 MYH6 Myosin-6 Homo sapiens (Human) SS
Q9UKX3 MYH13 Myosin-13 Homo sapiens (Human) SS
P11055 MYH3 Myosin-3 Homo sapiens (Human) SS
Q7Z406 MYH14 Myosin-14 Homo sapiens (Human) SS
P35749 MYH11 Myosin-11 Homo sapiens (Human) SS
A2AQP0 Myh7b Myosin-7B Mus musculus (Mouse) SS
P13541 Myh3 Myosin-3 Mus musculus (Mouse) SS
P13542 Myh8 Myosin-8 Mus musculus (Mouse) SS
Q02566 Myh6 Myosin-6 Mus musculus (Mouse) SS
Q5SX39 Myh4 Myosin-4 Mus musculus (Mouse) SS
Q5SX40 Myh1 Myosin-1 Mus musculus (Mouse) SS
Q61879 Myh10 Myosin-10 Mus musculus (Mouse) SS
Q6URW6 Myh14 Myosin-14 Mus musculus (Mouse) SS
Q8VDD5 Myh9 Myosin-9 Mus musculus (Mouse) SS
Q91Z83 Myh7 Myosin-7 Mus musculus (Mouse) SS
P79293 MYH7 Myosin-7 Sus scrofa (Pig) SS
Q9TV63 MYH2 Myosin-2 Sus scrofa (Pig) SS
P12847 Myh3 Myosin-3 Rattus norvegicus (Rat) SS
P02563 Myh6 Myosin-6 Rattus norvegicus (Rat) SS
P02564 Myh7 Myosin-7 Rattus norvegicus (Rat) SS
Q62812 Myh9 Myosin-9 Rattus norvegicus (Rat) SS
Q29RW1 Myh4 Myosin-4 Rattus norvegicus (Rat) SS
Q9JLT0 Myh10 Myosin-10 Rattus norvegicus (Rat) SS
P02566 unc-54 Myosin-4 Caenorhabditis elegans SS
P12844 myo-3 Myosin-3 Caenorhabditis elegans SS
P02567 myo-1 Myosin-1 Caenorhabditis elegans SS
P12845 myo-2 Myosin-2 Caenorhabditis elegans SS
10 20 30 40 50 60
MAQKGQLSDD EKFLFVDKNF MNSPMAQADW VAKKLVWVPS EKQGFEAASI KEEKGDEVVV
70 80 90 100 110 120
ELVENGKKVT VGKDDIQKMN PPKFSKVEDM AELTCLNEAS VLHNLRERYF SGLIYTYSGL
130 140 150 160 170 180
FCVVVNPYKY LPIYSEKIVD MYKGKKRHEM PPHIYAIADT AYRSMLQDRE DQSILCTGES
190 200 210 220 230 240
GAGKTENTQK VIQYLAVVAS SHKGKKDSSI TGELEKQLLQ ANPILEAFGN AKTVKNDNSS
250 260 270 280 290 300
RFGKFIRINF DVTGYIVGAN IETYLLEKSR AIRQARDERT FHIFYYLLAG AKEKMKSDLL
310 320 330 340 350 360
LESFNSYTFL SNGFVPIPAA QDDEMFQETL EAMSIMGFNE EEQLAILKVV SSVLQLGNIV
370 380 390 400 410 420
FKKERNTDQA SMPDNTAAQK VCHLVGINVT DFTRAILTPR IKVGRDVVQK AQTKEQADFA
430 440 450 460 470 480
IEALAKATYE RLFRWILSRV NKALDKTHRQ GASFLGILDI AGFEIFEVNS FEQLCINYTN
490 500 510 520 530 540
EKLQQLFNHT MFILEQEEYQ REGIEWNFID FGLDLQPSIE LIERPNNPPG VLALLDEECW
550 560 570 580 590 600
FPKATDKSFV EKLCSEQGNH PKFQKPKQLK DKTEFSIIHY AGKVDYNASA WLTKNMDPLN
610 620 630 640 650 660
DNVTSLLNAS SDKFVADLWK DVDRIVGLDQ MAKMTESSLP SASKTKKGMF RTVGQLYKEQ
670 680 690 700 710 720
LGKLMATLRN TTANFVRCII PNHEKRSGKL DAFLVLEQLR CNGVLEGIRI CRQGFPNRIV
730 740 750 760 770 780
FQEFRQRYEI LAANAIPKGF MDGKQACILM IKALELDPNL YRIGQSKIFF RTGVLAHLEE
790 800 810 820 830 840
ERDLKITDVI MAFQAMCRGY LARKAFTKRQ QQLTAMKVIQ RNCAAYLKLR NWQWWRLFTK
850 860 870 880 890 900
VKPLLQVTRQ EEEMQAKEEE MQKITERQQK AETELKELEQ KHTQLAEEKT LLQEQLQAET
910 920 930 940 950 960
ELYAESEEMR VRLAAKKQEL EEILHEMEAR LEEEEDRRQQ LQAERKKMAQ QMLDLEEQLE
970 980 990 1000 1010 1020
EEEAARQKLQ LEKVTAEAKI KKLEDDILVM DDQNSKLSKE RKLLEERVSD LTTNLAEEEE
1030 1040 1050 1060 1070 1080
KAKNLTKLKS KHESMISELE VRLKKEEKSR QELEKLKRKL EGDASDFHEQ IADLQAQIAE
1090 1100 1110 1120 1130 1140
LKMQLAKKEE ELQAALARLD EEIAQKNNAL KKIRELEGHI SDLQEDLDSE RAARNKAEKQ
1150 1160 1170 1180 1190 1200
KRDLGEELEA LKTELEDTLD STATQQELRA KREQEVTVLK KALDEETRSH EAQVQEMRQK
1210 1220 1230 1240 1250 1260
HTQAVEELTE QLEQFKRAKA NLDKSKQTLE KENADLAGEL RVLGQAKQEV EHKKKKLEVQ
1270 1280 1290 1300 1310 1320
LQDLQSKCSD GERARAELSD KVHKLQNEVE SVTGMLNEAE GKAIKLAKDV ASLGSQLQDT
1330 1340 1350 1360 1370 1380
QELLQEETRQ KLNVSTKLRQ LEDERNSLQD QLDEEMEAKQ NLERHVSTLN IQLSDSKKKL
1390 1400 1410 1420 1430 1440
QDFASTIEVM EEGKKRLQKE MEGLSQQYEE KAAAYDKLEK TKNRLQQELD DLVVDLDNQR
1450 1460 1470 1480 1490 1500
QLVSNLEKKQ KKFDQLLAEE KNISSKYADE RDRAEAEARE KETKALSLAR ALEEALEAKE
1510 1520 1530 1540 1550 1560
ELERTNKMLK AEMEDLVSSK DDVGKNVHEL EKSKRALETQ MEEMKTQLEE SEDDVQATED
1570 1580 1590 1600 1610 1620
AKLRLEVNMQ ALKGQFERDL QARDEQNEEK RRQLQRQLHE YETELEDERK QRALAAAAKK
1630 1640 1650 1660 1670 1680
KLEGDLKDLE LQADSAIKGR EEAIKQLRKL QAQMKDFQRE LDDARASRDE IFATSKENEK
1690 1700 1710 1720 1730 1740
KAKSLEADLM QLQEDLAAAE RARKQADLEK EELAEELASS LSGRNTLQDE KRRLEARIAQ
1750 1760 1770 1780 1790 1800
LEEELEEEQG NMEAMSDRVR KATLQAEQLS NELATERSTA QKNESARQQL ERQNKELRSK
1810 1820 1830 1840 1850 1860
LQEVEGAVKA KLKSTVAALE AKIAQLEEQV EQEAREKQAA TKSLKQKDKK LKEVLLQVED
1870 1880 1890 1900 1910 1920
ERKMAEQYKE QAEKGNTKVK QLKRQLEEAE EESQCINANR RKLQRELDEA TESNEAMGRE
1930 1940 1950 1960 1970
VNALKSKLRR GNEASFVPSR RAGGRRVIEN TDGSEEEMDA RDSDFNGTKA SE