Target Information
| Target General Information | Top | |||||
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| Target ID |
T53350
(Former ID: TTDR01035)
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| Target Name |
Bone morphogenetic protein 1 (BMP1)
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| Synonyms |
Procollagen C-proteinase; PCP protein; PCOLC; Mammalian tolloid protein; MTld; BMP-1
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| Gene Name |
BMP1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Induces cartilage and bone formation. May participate in dorsoventral patterning during early development by cleaving chordin (CHRD). Responsible for the proteolytic activation of lysyl oxidase LOX. Cleaves the C-terminal propeptides of procollagen I, II and III.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.24.19
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| Sequence |
MPGVARLPLLLGLLLLPRPGRPLDLADYTYDLAEEDDSEPLNYKDPCKAAAFLGDIALDE
EDLRAFQVQQAVDLRRHTARKSSIKAAVPGNTSTPSCQSTNGQPQRGACGRWRGRSRSRR AATSRPERVWPDGVIPFVIGGNFTGSQRAVFRQAMRHWEKHTCVTFLERTDEDSYIVFTY RPCGCCSYVGRRGGGPQAISIGKNCDKFGIVVHELGHVVGFWHEHTRPDRDRHVSIVREN IQPGQEYNFLKMEPQEVESLGETYDFDSIMHYARNTFSRGIFLDTIVPKYEVNGVKPPIG QRTRLSKGDIAQARKLYKCPACGETLQDSTGNFSSPEYPNGYSAHMHCVWRISVTPGEKI ILNFTSLDLYRSRLCWYDYVEVRDGFWRKAPLRGRFCGSKLPEPIVSTDSRLWVEFRSSS NWVGKGFFAVYEAICGGDVKKDYGHIQSPNYPDDYRPSKVCIWRIQVSEGFHVGLTFQSF EIERHDSCAYDYLEVRDGHSESSTLIGRYCGYEKPDDIKSTSSRLWLKFVSDGSINKAGF AVNFFKEVDECSRPNRGGCEQRCLNTLGSYKCSCDPGYELAPDKRRCEAACGGFLTKLNG SITSPGWPKEYPPNKNCIWQLVAPTQYRISLQFDFFETEGNDVCKYDFVEVRSGLTADSK LHGKFCGSEKPEVITSQYNNMRVEFKSDNTVSKKGFKAHFFSDKDECSKDNGGCQQDCVN TFGSYECQCRSGFVLHDNKHDCKEAGCDHKVTSTSGTITSPNWPDKYPSKKECTWAISST PGHRVKLTFMEMDIESQPECAYDHLEVFDGRDAKAPVLGRFCGSKKPEPVLATGSRMFLR FYSDNSVQRKGFQASHATECGGQVRADVKTKDLYSHAQFGDNNYPGGVDCEWVIVAEEGY GVELVFQTFEVEEETDCGYDYMELFDGYDSTAPRLGRYCGSGPPEEVYSAGDSVLVKFHS DDTITKKGFHLRYTSTKFQDTLHSRK Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| 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: PMID11934595C2 | Ligand Info | |||||
| Structure Description | BMP1 complexed with a hydroxamate - compound 2 | PDB:6BTQ | ||||
| Method | X-ray diffraction | Resolution | 1.75 Å | Mutation | Yes | [3] |
| PDB Sequence |
AATSRPERVW
10 PDGVIPFVIG20 GNFTGSQRAV30 FRQAMRHWEK40 HTCVTFLERT50 DEDSYIVFTY 60 RPCGCCSYVG70 RRGGGPQAIS80 IGKNCDKFGI90 VVHELGHVVG100 FWHEHTRPDR 110 DRHVSIVREN120 IQPGQEYNFL130 KMEPQEVESL140 GETYDFDSIM150 HYARNTFSRG 160 IFLDTIVPKY170 EVNGVKPPIG180 QRTRLSKGDI190 AQARKLYKCP200 A |
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CYS63
3.713
GLY64
3.142
CYS65
3.361
CYS66
4.387
SER67
4.793
ASN84
3.886
CYS85
3.829
ILE90
3.917
HIS93
3.102
GLU94
3.080
HIS97
2.855
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| Ligand Name: (2S)-2-[[2-ethoxy-4-[5-[[[(2R)-2-[(1R)-1-[formyl(hydroxy)amino]propyl]heptanoyl]amino]methylcarbamoyl]furan-2-yl]benzoyl]amino]butanedioic acid | Ligand Info | |||||
| Structure Description | BMP1 complexed with a reverse hydroxymate - compound 22 | PDB:6BSL | ||||
| Method | X-ray diffraction | Resolution | 1.45 Å | Mutation | Yes | [3] |
| PDB Sequence |
AATSRPERVW
10 PDGVIPFVIG20 GNFTGSQRAV30 FRQAMRHWEK40 HTCVTFLERT50 DEDSYIVFTY 60 RPCGCCSYVG70 RRGGGPQAIS80 IGKNCDKFGI90 VVHELGHVVG100 FWHEHTRPDR 110 DRHVSIVREN120 IQPGQEYNFL130 KMEPQEVESL140 GETYDFDSIM150 HYARNTFSRG 160 IFLDTIVPKY170 EVNGVKPPIG180 QRTRLSKGDI190 AQARKLYKCP200 A |
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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).
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
Biological Network Descriptors
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| Protein Name | Pfam ID | Percentage of Identity (%) | E value |
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| Transmembrane protease serine 6 (TMPRSS6) | 23.718 (37/156) | 4.02E-05 |
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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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| Degree | 14 | Degree centrality | 1.50E-03 | Betweenness centrality | 2.62E-04 |
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| Closeness centrality | 1.87E-01 | Radiality | 1.31E+01 | Clustering coefficient | 8.79E-02 |
| Neighborhood connectivity | 8.36E+00 | Topological coefficient | 1.29E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | TGF-beta signaling pathway | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Degradation of the extracellular matrix | |||||
| 2 | Collagen biosynthesis and modifying enzymes | |||||
| 3 | Anchoring fibril formation | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Cardiac Progenitor Differentiation | |||||
| 2 | Adipogenesis | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Amino acid derived sulfonamide hydroxamates as inhibitors of procollagen C-proteinase. Part 2: Solid-phase optimization of side chains. Bioorg Med Chem Lett. 2002 Apr 22;12(8):1233-5. | |||||
| REF 2 | Succinyl hydroxamates as potent and selective non-peptidic inhibitors of procollagen C-proteinase: design, synthesis, and evaluation as topically a... Bioorg Med Chem Lett. 2008 Dec 15;18(24):6562-7. | |||||
| REF 3 | Reverse Hydroxamate Inhibitors of Bone Morphogenetic Protein 1. ACS Med Chem Lett. 2018 Jul 2;9(7):736-740. | |||||
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