Target Information
| Target General Information | Top | |||||
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| Target ID |
T91894
(Former ID: TTDI02313)
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| Target Name |
Proto-oncogene Mas (MAS)
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| Synonyms |
MGRA; MAS1 proto-oncogene, G protein-coupled receptor
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| Gene Name |
MAS1
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 2 Target-related Diseases | + | ||||
| 1 | Diabetic foot ulcer [ICD-11: BD54] | |||||
| 2 | Sarcoma [ICD-11: 2A60-2C35] | |||||
| Function |
Acts specifically as a functional antagonist of AGTR1 (angiotensin-2 type 1 receptor), although it up-regulates AGTR1 receptor levels. Positive regulation of AGTR1 levels occurs through activation of the G-proteins GNA11 and GNAQ, and stimulation of the protein kinase C signaling cascade. The antagonist effect on AGTR1 function is probably due to AGTR1 being physically altered by MAS1. Receptor for angiotensin 1-7.
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| BioChemical Class |
GPCR rhodopsin
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| UniProt ID | ||||||
| Sequence |
MDGSNVTSFVVEEPTNISTGRNASVGNAHRQIPIVHWVIMSISPVGFVENGILLWFLCFR
MRRNPFTVYITHLSIADISLLFCIFILSIDYALDYELSSGHYYTIVTLSVTFLFGYNTGL YLLTAISVERCLSVLYPIWYRCHRPKYQSALVCALLWALSCLVTTMEYVMCIDREEESHS RNDCRAVIIFIAILSFLVFTPLMLVSSTILVVKIRKNTWASHSSKLYIVIMVTIIIFLIF AMPMRLLYLLYYEYWSTFGNLHHISLLFSTINSSANPFIYFFVGSSKKKRFKESLKVVLT RAFKDEMQPRRQKDNCNTVTVETVV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
| 1 | Angiotensin-(1-7) | Drug Info | Phase 3 | Sarcoma | [1], [2] | |
| 2 | DSC-127 | Drug Info | Phase 3 | Diabetic foot ulcer | [1], [3] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Agonist | [+] 4 Agonist drugs | + | ||||
| 1 | Angiotensin-(1-7) | Drug Info | [1] | |||
| 2 | DSC-127 | Drug Info | [1] | |||
| 3 | AR234960 | Drug Info | [4] | |||
| 4 | AVE 0991 | Drug Info | [5] | |||
| Antagonist | [+] 1 Antagonist drugs | + | ||||
| 1 | AR244555 | Drug Info | [4] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| 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 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).
Human Similarity Proteins
Human Pathway Affiliation
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Neuroactive ligand-receptor interaction | hsa04080 | Affiliated Target |
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| Class: Environmental Information Processing => Signaling molecules and interaction | Pathway Hierarchy | ||
| Renin-angiotensin system | hsa04614 | Affiliated Target |
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| Class: Organismal Systems => Endocrine system | Pathway Hierarchy | ||
| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Neuroactive ligand-receptor interaction | |||||
| 2 | Renin-angiotensin system | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | ACE Inhibitor Pathway | |||||
| 2 | GPCRs, Class A Rhodopsin-like | |||||
| References | Top | |||||
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| REF 1 | New therapeutic pathways in the RAS. J Renin Angiotensin Aldosterone Syst. 2012 Dec;13(4):505-8. | |||||
| REF 2 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 582). | |||||
| REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8300). | |||||
| REF 4 | Inhibition of Mas G-protein signaling improves coronary blood flow, reduces myocardial infarct size, and provides long-term cardioprotection. Am J Physiol Heart Circ Physiol. 2012 Jan 1;302(1):H299-311. | |||||
| REF 5 | Nonpeptide AVE 0991 is an angiotensin-(1-7) receptor Mas agonist in the mouse kidney. Hypertension. 2004 Oct;44(4):490-6. | |||||
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