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

80-786 (Myosin head, motor domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q5SX40

Entry ID Method Resolution Chain Position Source
AF-Q5SX40-F1 Predicted AlphaFoldDB

81 variants for Q5SX40

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3389162521 44 K>E No EVA
rs3389165392 49 K>* No EVA
rs3389141910 64 T>I No EVA
rs3389163780 78 Y>* No EVA
rs3389166851 94 M>T No EVA
rs3402451641 133 P>T No EVA
rs3402344809 136 N>T No EVA
rs3413126634 148 R>H No EVA
rs3389179689 170 R>G No EVA
rs265789682 211 T>P No EVA
rs3401752751 252 R>G No EVA
rs3389104969 279 Q>R No EVA
rs3389166433 292 I>N No EVA
rs3389130193 302 E>G No EVA
rs3389166872 305 L>Q No EVA
rs3389166832 375 Q>L No EVA
rs3389141936 393 L>R No EVA
rs232837029 404 Y>* No EVA
rs3389141966 408 K>N No EVA
rs3389162494 415 T>I No EVA
rs3389141962 419 T>I No EVA
rs3389179673 514 I>V No EVA
rs3389162483 605 N>D No EVA
rs3389154765 608 V>M No EVA
rs3402244176 661 N>S No EVA
rs3389131217 680 I>L No EVA
rs3389162446 741 Q>* No EVA
rs3389163706 777 L>P No EVA
rs3389166831 827 A>D No EVA
rs3389131229 837 M>K No EVA
rs3389141949 868 E>* No EVA
rs3389176236 978 T>A No EVA
rs3389179686 1001 K>M No EVA
rs3389176281 1014 L>M No EVA
rs3389174912 1040 D>N No EVA
rs3389169668 1040 D>V No EVA
rs26892416 1076 V>I No EVA
rs3389131242 1214 I>F No EVA
rs3389143142 1244 V>L No EVA
rs3389143109 1257 R>H No EVA
rs3402350785 1274 Q>P No EVA
rs3401988038 1275 R>L No EVA
rs3402327443 1277 I>F No EVA
rs3389179702 1286 R>G No EVA
rs3389131286 1321 E>V No EVA
rs3389166848 1362 A>G No EVA
rs3389166805 1417 K>E No EVA
rs3389169589 1426 Q>H No EVA
rs217154446 1444 A>S No EVA
rs3389139069 1451 K>R No EVA
rs3389178040 1461 A>E No EVA
rs3389139090 1463 W>R No EVA
rs3389169671 1507 R>S No EVA
rs3389143095 1510 K>N No EVA
rs3412089151 1528 K>T No EVA
rs3389179721 1556 A>T No EVA
rs3389174861 1565 I>F No EVA
rs3389131290 1578 E>D No EVA
rs3389169614 1580 D>E No EVA
rs3389174881 1615 R>K No EVA
rs3389178054 1666 D>V No EVA
rs3389166858 1672 E>K No EVA
rs3389154774 1686 N>D No EVA
rs3389162448 1693 E>D No EVA
rs3389139022 1698 T>I No EVA
rs3389162508 1703 E>G No EVA
rs3389163738 1706 R>M No EVA
rs3389162460 1767 T>N No EVA
rs3402352502 1774 E>V No EVA
rs3401752783 1775 E>V No EVA
rs3389179719 1782 T>I No EVA
rs3389154779 1784 A>V No EVA
rs3389178013 1787 E>Q No EVA
rs3548746620 1793 L>M No EVA
rs3389162451 1794 E>* No EVA
rs3389139016 1797 V>A No EVA
rs3389131213 1803 R>S No EVA
rs3389139100 1837 Q>* No EVA
rs3389170146 1895 Q>H No EVA
rs3389154731 1905 K>R No EVA
rs3389165686 1940 S>C No EVA

1 associated diseases with Q5SX40

[MIM: 620430]: Autoimmune disease, multisystem, infantile-onset, 3 (ADMIO3)

An autosomal recessive disorder characterized by autoimmune manifestations apparent in the first months or years of life. Clinical features may include hypothyroidism, type 1 diabetes mellitus, systemic inflammatory manifestations such as fever and hepatomegaly, and autoimmune cytopenias. . Note=The disease is caused by variants affecting the gene represented in this entry.

Without disease ID
  • An autosomal recessive disorder characterized by autoimmune manifestations apparent in the first months or years of life. Clinical features may include hypothyroidism, type 1 diabetes mellitus, systemic inflammatory manifestations such as fever and hepatomegaly, and autoimmune cytopenias. . Note=The disease is caused by variants affecting the gene represented in this entry.

4 regional properties for Q5SX40

Type Name Position InterPro Accession
domain Protein kinase domain 16 - 269 IPR000719
active_site Serine/threonine-protein kinase, active site 135 - 147 IPR008271
domain Ubiquitin-associated domain 291 - 334 IPR015940
binding_site Protein kinase, ATP binding site 22 - 45 IPR017441

Functions

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

7 GO annotations of cellular component

Name Definition
A band The dark-staining region of a sarcomere, in which myosin thick filaments are present; the center is traversed by the paler H zone, which in turn contains the M line.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytoplasmic ribonucleoprotein granule A ribonucleoprotein granule located in the cytoplasm.
intercalated disc A complex cell-cell junction at which myofibrils terminate in cardiomyocytes; mediates mechanical and electrochemical integration between individual cardiomyocytes. The intercalated disc contains regions of tight mechanical attachment (fasciae adherentes and desmosomes) and electrical coupling (gap junctions) between adjacent cells.
muscle myosin complex A filament of myosin found in a muscle cell of any type.
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.

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.

1 GO annotations of biological process

Name Definition
muscle contraction A process in which force is generated within 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.

46 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q9BE41 MYH2 Myosin-2 Bos taurus (Bovine) SS
Q27991 MYH10 Myosin-10 Bos taurus (Bovine) SS
Q9BE39 MYH7 Myosin-7 Bos taurus (Bovine) SS
Q9BE40 MYH1 Myosin-1 Bos taurus (Bovine) SS
P10587 MYH11 Myosin-11 Gallus gallus (Chicken) SS
P14105 MYH9 Myosin-9 Gallus gallus (Chicken) SS
P13538 Myosin heavy chain, skeletal muscle, adult Gallus gallus (Chicken) SS
P02565 MYH1B Myosin-1B Gallus gallus (Chicken) SS
Q99323 zip Myosin heavy chain, non-muscle Drosophila melanogaster (Fruit fly) SS
P05661 Mhc Myosin heavy chain, muscle Drosophila melanogaster (Fruit fly) SS
P35579 MYH9 Myosin-9 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
P35749 MYH11 Myosin-11 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
P12882 MYH1 Myosin-1 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
Q61879 Myh10 Myosin-10 Mus musculus (Mouse) SS
Q8VDD5 Myh9 Myosin-9 Mus musculus (Mouse) SS
Q91Z83 Myh7 Myosin-7 Mus musculus (Mouse) SS
Q6URW6 Myh14 Myosin-14 Mus musculus (Mouse) SS
O08638 Myh11 Myosin-11 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
P02567 myo-1 Myosin-1 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
MSSDAEMAVF GEAAPYLRKS EKERIEAQNK PFDAKSSVFV VDAKESFVKA TVQSREGGKV
70 80 90 100 110 120
TAKTEGGTTV TVKDDQVYPM NPPKYDKIED MAMMTHLHEP AVLYNLKERY AAWMIYTYSG
130 140 150 160 170 180
LFCVTVNPYK WLPVYNAEVV AAYRGKKRQE APPHIFSISD NAYQFMLTDR ENQSILITGE
190 200 210 220 230 240
SGAGKTVNTK RVIQYFATIA VTGEKKKEEA TSGKMQGTLE DQIISANPLL EAFGNAKTVR
250 260 270 280 290 300
NDNSSRFGKF IRIHFGTTGK LASADIETYL LEKSRVTFQL KAERSYHIFY QIMSNKKPDL
310 320 330 340 350 360
IEMLLITTNP YDYAFVSQGE ITVPSIDDQE ELMATDSAID ILGFTSDERV SIYKLTGAVM
370 380 390 400 410 420
HYGNMKFKQK QREEQAEPDG TEVADKAAYL QNLNSADLLK ALCYPRVKVG NEYVTKGQTV
430 440 450 460 470 480
QQVYNSVGAL AKAVYEKMFL WMVTRINQQL DTKQPRQYFI GVLDIAGFEI FDFNSLEQLC
490 500 510 520 530 540
INFTNEKLQQ FFNHHMFVLE QEEYKKEGIE WEFIDFGMDL AACIELIEKP MGIFSILEEE
550 560 570 580 590 600
CMFPKATDTS FKNKLYEQHL GKSNNFQKPK PAKGKVEAHF SLVHYAGTVD YNIAGWLDKN
610 620 630 640 650 660
KDPLNETVVG LYQKSSMKTL AYLFSGAAAA AEAESGGGGG KKGAKKKGSS FQTVSALFRE
670 680 690 700 710 720
NLNKLMTNLR STHPHFVRCI IPNETKTPGA MEHELVLHQL RCNGVLEGIR ICRKGFPSRI
730 740 750 760 770 780
LYADFKQRYK VLNASAIPEG QFIDSKKASE KLLGSIDIDH TQYKFGHTKV FFKAGLLGLL
790 800 810 820 830 840
EEMRDDKLAQ LITRTQAMCR GYLARVEYQK MVERRESIFC IQYNVRAFMN VKHWPWMKLY
850 860 870 880 890 900
FKIKPLLKSA ETEKEMANMK EEFEKAKENL AKAEAKRKEL EEKMVALMQE KNDLQLQVQS
910 920 930 940 950 960
EADSLADAEE RCDQLIKTKI QLEAKIKEVT ERAEDEEEIN AELTAKKRKL EDECSELKKD
970 980 990 1000 1010 1020
IDDLELTLAK VEKEKHATEN KVKNLTEEMA GLDETIAKLT KEKKALQEAH QQTLDDLQAE
1030 1040 1050 1060 1070 1080
EDKVNTLTKA KIKLEQQVDD LEGSLEQEKK IRMDLERAKR KLEGDLKLAQ ESTMDVENDK
1090 1100 1110 1120 1130 1140
QQLDEKLKKK EFEMSNLQSK IEDEQALGMQ LQKKIKELQA RIEELEEEIE AERASRAKAE
1150 1160 1170 1180 1190 1200
KQRSDLSREL EEISERLEEA GGATSAQIEM NKKREAEFQK MRRDLEEATL QHEATAATLR
1210 1220 1230 1240 1250 1260
KKHADSVAEL GEQIDNLQRV KQKLEKEKSE MKMEIDDLAS NMEVISKSKG NLEKMCRTLE
1270 1280 1290 1300 1310 1320
DQVSELKTKE EEQQRLINEL TAQRGRLQTE SGEYSRQLDE KDSLVSQLSR GKQAFTQQIE
1330 1340 1350 1360 1370 1380
ELKRQLEEEI KAKSALAHAL QSSRHDCDLL REQYEEEQEA KAELQRAMSK ANSEVAQWRT
1390 1400 1410 1420 1430 1440
KYETDAIQRT EELEEAKKKL AQRLQDAEEH VEAVNAKCAS LEKTKQRLQN EVEDLMIDVE
1450 1460 1470 1480 1490 1500
RTNAACAALD KKQRNFDKIL AEWKQKYEET HAELEASQKE SRSLSTELFK IKNAYEESLD
1510 1520 1530 1540 1550 1560
HLETLKRENK NLQQEISDLT EQIAEGGKRI HELEKIKKQI EQEKSELQAA LEEAEASLEH
1570 1580 1590 1600 1610 1620
EEGKILRIQL ELNQVKSEID RKIAEKDEEI DQLKRNHIRV VESMQSTLDA EIRSRNDAIR
1630 1640 1650 1660 1670 1680
LKKKMEGDLN EMEIQLNHSN RMAAEALRNY RNTQGILKDT QLHLDDALRG QEDLKEQLAM
1690 1700 1710 1720 1730 1740
VERRANLLQA EIEELRATLE QTERSRKIAE QELLDASERV QLLHTQNTSL INTKKKLETD
1750 1760 1770 1780 1790 1800
ISQIQGEMED IVQEARNAEE KAKKAITDAA MMAEELKKEQ DTSAHLERMK KNLEQTVKDL
1810 1820 1830 1840 1850 1860
QHRLDEAEQL ALKGGKKQIQ KLEARVRELE GEVENEQKRN VEAIKGLRKH ERRVKELTYQ
1870 1880 1890 1900 1910 1920
TEEDRKNVLR LQDLVDKLQS KVKAYKRQAE EAEEQSNVNL AKFRKIQHEL EEAEERADIA
1930 1940
ESQVNKLRVK SREVHTKIIS EE