Target Information
| Target General Information | Top | |||||
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| Target ID |
T07507
(Former ID: TTDI02131)
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| Target Name |
Myosin-7 (MYH7)
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| Synonyms |
Myosin heavy chain, cardiac muscle beta isoform; Myosin heavy chain slow isoform; Myosin heavy chain 7; MyHCslow; MyHCbeta; MYH7
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| Gene Name |
MYH7
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Deafness [ICD-11: AB52] | |||||
| 2 | Inherited retinal dystrophy [ICD-11: 9B70] | |||||
| Function |
Muscle contraction.
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| BioChemical Class |
TRAFAC class myosin-kinesin ATPase
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| UniProt ID | ||||||
| Sequence |
MGDSEMAVFGAAAPYLRKSEKERLEAQTRPFDLKKDVFVPDDKQEFVKAKIVSREGGKVT
AETEYGKTVTVKEDQVMQQNPPKFDKIEDMAMLTFLHEPAVLYNLKDRYGSWMIYTYSGL FCVTVNPYKWLPVYTPEVVAAYRGKKRSEAPPHIFSISDNAYQYMLTDRENQSILITGES GAGKTVNTKRVIQYFAVIAAIGDRSKKDQSPGKGTLEDQIIQANPALEAFGNAKTVRNDN SSRFGKFIRIHFGATGKLASADIETYLLEKSRVIFQLKAERDYHIFYQILSNKKPELLDM LLITNNPYDYAFISQGETTVASIDDAEELMATDNAFDVLGFTSEEKNSMYKLTGAIMHFG NMKFKLKQREEQAEPDGTEEADKSAYLMGLNSADLLKGLCHPRVKVGNEYVTKGQNVQQV IYATGALAKAVYERMFNWMVTRINATLETKQPRQYFIGVLDIAGFEIFDFNSFEQLCINF TNEKLQQFFNHHMFVLEQEEYKKEGIEWTFIDFGMDLQACIDLIEKPMGIMSILEEECMF PKATDMTFKAKLFDNHLGKSANFQKPRNIKGKPEAHFSLIHYAGIVDYNIIGWLQKNKDP LNETVVGLYQKSSLKLLSTLFANYAGADAPIEKGKGKAKKGSSFQTVSALHRENLNKLMT NLRSTHPHFVRCIIPNETKSPGVMDNPLVMHQLRCNGVLEGIRICRKGFPNRILYGDFRQ RYRILNPAAIPEGQFIDSRKGAEKLLSSLDIDHNQYKFGHTKVFFKAGLLGLLEEMRDER LSRIITRIQAQSRGVLARMEYKKLLERRDSLLVIQWNIRAFMGVKNWPWMKLYFKIKPLL KSAEREKEMASMKEEFTRLKEALEKSEARRKELEEKMVSLLQEKNDLQLQVQAEQDNLAD AEERCDQLIKNKIQLEAKVKEMNERLEDEEEMNAELTAKKRKLEDECSELKRDIDDLELT LAKVEKEKHATENKVKNLTEEMAGLDEIIAKLTKEKKALQEAHQQALDDLQAEEDKVNTL TKAKVKLEQQVDDLEGSLEQEKKVRMDLERAKRKLEGDLKLTQESIMDLENDKQQLDERL KKKDFELNALNARIEDEQALGSQLQKKLKELQARIEELEEELEAERTARAKVEKLRSDLS RELEEISERLEEAGGATSVQIEMNKKREAEFQKMRRDLEEATLQHEATAAALRKKHADSV AELGEQIDNLQRVKQKLEKEKSEFKLELDDVTSNMEQIIKAKANLEKMCRTLEDQMNEHR SKAEETQRSVNDLTSQRAKLQTENGELSRQLDEKEALISQLTRGKLTYTQQLEDLKRQLE EEVKAKNALAHALQSARHDCDLLREQYEEETEAKAELQRVLSKANSEVAQWRTKYETDAI QRTEELEEAKKKLAQRLQEAEEAVEAVNAKCSSLEKTKHRLQNEIEDLMVDVERSNAAAA ALDKKQRNFDKILAEWKQKYEESQSELESSQKEARSLSTELFKLKNAYEESLEHLETFKR ENKNLQEEISDLTEQLGSSGKTIHELEKVRKQLEAEKMELQSALEEAEASLEHEEGKILR AQLEFNQIKAEIERKLAEKDEEMEQAKRNHLRVVDSLQTSLDAETRSRNEALRVKKKMEG DLNEMEIQLSHANRMAAEAQKQVKSLQSLLKDTQIQLDDAVRANDDLKENIAIVERRNNL LQAELEELRAVVEQTERSRKLAEQELIETSERVQLLHSQNTSLINQKKKMDADLSQLQTE VEEAVQECRNAEEKAKKAITDAAMMAEELKKEQDTSAHLERMKKNMEQTIKDLQHRLDEA EQIALKGGKKQLQKLEARVRELENELEAEQKRNAESVKGMRKSERRIKELTYQTEEDRKN LLRLQDLVDKLQLKVKAYKRQAEEAEEQANTNLSKFRKVQHELDEAEERADIAESQVNKL RAKSRDIGTKGLNEE Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T78QVQ | |||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | UshStat | Drug Info | Phase 1/2 | Deafness | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | UshStat | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: AMP-PNP | Ligand Info | |||||
| Structure Description | Cardiac human myosin S1dC, beta isoform complexed with Mn-AMPPNP | PDB:4DB1 | ||||
| Method | X-ray diffraction | Resolution | 2.60 Å | Mutation | No | [3] |
| PDB Sequence |
GGDSEMAVFG
10 AAAPYLRKSE20 KERLEAQTRP30 FDLKKDVFVP40 DDKQEFVKAK50 IVSREGGKVT 60 AETEYGKTVT70 VKEDQVMQQN80 PPKFDKIEDM90 AMLTFLHEPA100 VLYNLKDRYG 110 SWMIYTYSGL120 FCVTVNPYKW130 LPVYTPEVVA140 AYRGKKRSEA150 PPHIFSISDN 160 AYQYMLTDRE170 NQSILITGES180 GAGKTVNTKR190 VIQYFAVIAA200 IGDRGKGTLE 217 DQIIQANPAL227 EAFGNAKTVR237 NDNSSRFGKF247 IRIHFGATGK257 LASADIETYL 267 LEKSRVIFQL277 KAERDYHIFY287 QILSNKKPEL297 LDMLLITNNP307 YDYAFISQGE 317 TTVASIDDAE327 ELMATDNAFD337 VLGFTSEEKN347 SMYKLTGAIM357 HFGNMKFKLK 367 QREEQAEPDG377 TEEADKSAYL387 MGLNSADLLK397 GLCHPRYVTK413 GQNVQQVIYA 423 TGALAKAVYE433 RMFNWMVTRI443 NATLETKQPR453 QYFIGVLDIA463 GFEIFDFNSF 473 EQLCINFTNE483 KLQQFFNHHM493 FVLEQEEYKK503 EGIEWTFIDF513 GMDLQACIDL 523 IEKPMGIMSI533 LEEECMFPKA543 TDMTFKAKLF553 DNHLGKSANF563 QKPRNPEAHF 577 SLIHYAGIVD587 YNIIGWLQKN597 KDPLNETVVG607 LYQKSSLKLL617 STLFANYAFQ 645 TVSALHRENL655 NKLMTNLRST665 HPHFVRCIIP675 NETKSPGVMD685 NPLVMHQLRC 695 NGVLEGIRIC705 RKGFPNRILY715 AEKLLSSLDI751 DHNQYKFGHT761 KVFFKAGLLG 771 LLEEMR
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TYR115
4.782
ASN126
2.923
PRO127
3.357
TYR128
3.798
LYS129
3.358
TRP130
4.117
TYR134
3.405
GLU179
3.762
SER180
2.913
GLY181
2.795
ALA182
3.404
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| cGMP-PKG signaling pathway | hsa04022 | Affiliated Target |
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| Class: Environmental Information Processing => Signal transduction | Pathway Hierarchy | ||
| Cardiac muscle contraction | hsa04260 | Affiliated Target |
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| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Adrenergic signaling in cardiomyocytes | hsa04261 | Affiliated Target |
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| Class: Organismal Systems => Circulatory system | Pathway Hierarchy | ||
| Thyroid hormone signaling pathway | hsa04919 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Degree | 8 | Degree centrality | 8.59E-04 | Betweenness centrality | 1.20E-04 |
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| Closeness centrality | 1.75E-01 | Radiality | 1.28E+01 | Clustering coefficient | 1.43E-01 |
| Neighborhood connectivity | 1.00E+01 | Topological coefficient | 2.26E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 7 KEGG Pathways | + | ||||
| 1 | cGMP-PKG signaling pathway | |||||
| 2 | Cardiac muscle contraction | |||||
| 3 | Adrenergic signaling in cardiomyocytes | |||||
| 4 | Tight junction | |||||
| 5 | Hypertrophic cardiomyopathy (HCM) | |||||
| 6 | Dilated cardiomyopathy | |||||
| 7 | Viral myocarditis | |||||
| Panther Pathway | [+] 4 Panther Pathways | + | ||||
| 1 | Cytoskeletal regulation by Rho GTPase | |||||
| 2 | Inflammation mediated by chemokine and cytokine signaling pathway | |||||
| 3 | Nicotinic acetylcholine receptor signaling pathway | |||||
| 4 | Wnt signaling pathway | |||||
| Reactome | [+] 1 Reactome Pathways | + | ||||
| 1 | Translocation of GLUT4 to the plasma membrane | |||||
| References | Top | |||||
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| REF 1 | EIAV-based retinal gene therapy in the shaker1 mouse model for usher syndrome type 1B: development of UshStat. PLoS One. 2014 Apr 4;9(4):e94272. | |||||
| REF 2 | ClinicalTrials.gov (NCT02065011) A Study to Determine the Long-Term Safety, Tolerability and Biological Activity of UshStat in Patients With Usher Syndrome Type 1B. U.S. National Institutes of Health. | |||||
| REF 3 | Cardiac human myosin S1dC, beta isoform complexed with Mn-AMPPNP | |||||
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