Target Information
| Target General Information | Top | |||||
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| Target ID |
T90987
(Former ID: TTDI03017)
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| Target Name |
ADAM metallopeptidase with thrombospondin 1 (ADAMTS1)
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| Synonyms |
METH1; METH-1; KIAA1346; ADAMTS-1; ADAM-TS1; ADAM-TS 1
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| Gene Name |
ADAMTS1
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
Has angiogenic inhibitor activity. Active metalloprotease, which may be associated with various inflammatory processes as well as development of cancer cachexia. May play a critical role in follicular rupture. Cleaves aggrecan, a cartilage proteoglycan, at the '1938-Glu-|-Leu-1939' site (within the chondroitin sulfate attachment domain), and may be involved in its turnover.
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.24.-
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| Sequence |
MQRAVPEGFGRRKLGSDMGNAERAPGSRSFGPVPTLLLLAAALLAVSDALGRPSEEDEEL
VVPELERAPGHGTTRLRLHAFDQQLDLELRPDSSFLAPGFTLQNVGRKSGSETPLPETDL AHCFYSGTVNGDPSSAAALSLCEGVRGAFYLLGEAYFIQPLPAASERLATAAPGEKPPAP LQFHLLRRNRQGDVGGTCGVVDDEPRPTGKAETEDEDEGTEGEDEGAQWSPQDPALQGVG QPTGTGSIRKKRFVSSHRYVETMLVADQSMAEFHGSGLKHYLLTLFSVAARLYKHPSIRN SVSLVVVKILVIHDEQKGPEVTSNAALTLRNFCNWQKQHNPPSDRDAEHYDTAILFTRQD LCGSQTCDTLGMADVGTVCDPSRSCSVIEDDGLQAAFTTAHELGHVFNMPHDDAKQCASL NGVNQDSHMMASMLSNLDHSQPWSPCSAYMITSFLDNGHGECLMDKPQNPIQLPGDLPGT SYDANRQCQFTFGEDSKHCPDAASTCSTLWCTGTSGGVLVCQTKHFPWADGTSCGEGKWC INGKCVNKTDRKHFDTPFHGSWGMWGPWGDCSRTCGGGVQYTMRECDNPVPKNGGKYCEG KRVRYRSCNLEDCPDNNGKTFREEQCEAHNEFSKASFGSGPAVEWIPKYAGVSPKDRCKL ICQAKGIGYFFVLQPKVVDGTPCSPDSTSVCVQGQCVKAGCDRIIDSKKKFDKCGVCGGN GSTCKKISGSVTSAKPGYHDIITIPTGATNIEVKQRNQRGSRNNGSFLAIKAADGTYILN GDYTLSTLEQDIMYKGVVLRYSGSSAALERIRSFSPLKEPLTIQVLTVGNALRPKIKYTY FVKKKKESFNAIPTFSAWVIEEWGECSKSCELGWQRRLVECRDINGQPASECAKEVKPAS TRPCADHPCPQWQLGEWSSCSKTCGKGYKKRSLKCLSHDGGVLSHESCDPLKKPKHFIDF CTMAECS 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: Marimastat | Ligand Info | |||||
| Structure Description | Crystal Structure of Human ADAMTS-1 catalytic Domain and Cysteine- Rich Domain (complex-form) | PDB:2JIH | ||||
| Method | X-ray diffraction | Resolution | 2.10 Å | Mutation | No | [2] |
| PDB Sequence |
SHRYVETMLV
265 ADQSMAEFHG275 SGLKHYLLTL285 FSVAARLYKH295 PSIRNSVSLV305 VVKILVIHDE 315 QKGPEVTSNA325 ALTLRNFCNW335 QKQHNPPSDR345 DAEHYDTAIL355 FTRQDLCGSQ 365 TCDTLGMADV375 GTVCDPSRSC385 SVIEDDGLQA395 AFTTAHELGH405 VFNMPHDDAK 415 QCASLNDSHM429 MASMLSNLDH439 SQPWSPCSAY449 MITSFLDNGH459 GECLMDKPQN 469 PIQLPGDLPG479 TSYDANRQCQ489 FTFGEDSKHC499 PTCSTLWCTG513 VLVCQTKHFP 527 WADGTSCGEG537 KWCINGKCVN547 KLVP
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| Ligand Name: N-[(2s,4s)-1-({4-[(2,4-Dichlorobenzyl)oxy]piperidin-1-Yl}sulfonyl)-4-(5-Fluoropyrimidin-2-Yl)-2-Methylpentan-2-Yl]-N-Hydroxyformamide | Ligand Info | |||||
| Structure Description | Adamts1 in complex with a novel N-hydroxyformamide inhibitors | PDB:3Q2G | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [3] |
| PDB Sequence |
SHRYVETMLV
13 ADQSMAEFHG23 SGLKHYLLTL33 FSVAARLYKH43 PSIRNSVSLV53 VVKILVIHDE 63 QKGPEVTSNA73 ALTLRNFCNW83 QKQHNPPSDR93 DAEHYDTAIL103 FTRQDLCGSQ 113 TCDTLGMADV123 GTVCDPSRSC133 SVIEDDGLQA143 AFTTAHELGH153 VFNMPHDDAK 163 QCASLNSHMM178 ASMLSNLDHS188 QPWSPCSAYM198 ITSFLDNGHG208 ECLMDKPQNP 218 IQLPGDLPGT228 SYDANRQCQF238 TFGEDSKHCP248 TCSTLWCTGL267 VCQTKHFPWA 277 DGTSCGEGKW287 CINGKCVNKL297 VP
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ASP116
4.234
THR117
3.650
LEU118
3.090
GLY119
3.272
MET120
3.881
ALA121
3.678
VAL123
3.271
GLN142
4.020
PHE145
3.460
THR146
3.245
HIS149
3.490
GLU150
2.914
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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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| Netrin receptor UNC5A (UNC5A) | 37.037 (20/54) | 2.30E-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 | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.70E-01 | Radiality | 1.27E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 1.80E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 14 |
| 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 | ||||||
| References | Top | |||||
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| REF 1 | Synthesis and structure-activity relationship of a novel, achiral series of TNF-alpha converting enzyme inhibitors. Bioorg Med Chem Lett. 2006 May 15;16(10):2699-704. | |||||
| REF 2 | Crystal structures of human ADAMTS-1 reveal a conserved catalytic domain and a disintegrin-like domain with a fold homologous to cysteine-rich domains. J Mol Biol. 2007 Nov 2;373(4):891-902. | |||||
| REF 3 | The design and synthesis of novel N-hydroxyformamide inhibitors of ADAM-TS4 for the treatment of osteoarthritis. Bioorg Med Chem Lett. 2011 Mar 1;21(5):1376-81. | |||||
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