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MAS1

Family: Class A Orphans

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Gene Expression and Pathophysiology
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 325 6q24-q27 MAS1 MAS1 oncogene 26
Mouse 7 324 17 A1 Mas1 MAS1 oncogene
Rat 7 324 1q11-q12 Mas1 MAS1 oncogene
Previous and Unofficial Names
Names References
MGC119966
MAS
angiotensin 1-7 receptor 13
c-mas
MAS proto-oncogene
MAS1 oncogene
angiotensin-(1-7) receptor
proto-oncogene Mas
Mas-1
Database Links
Ensembl ENSG00000130368 (Hs), ENSMUSG00000068037 (Mm), ENSRNOG00000014971 (Rn)
Entrez Gene 4142 (Hs), 17171 (Mm), 25153 (Rn)
GeneCards MAS1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Mas1 (Mm)
HomoloGene 1782 (Hs)
Human Protein Reference Database 01306 (Hs)
InterPro P04201 (Hs), P30554 (Mm), P12526 (Rn)
KEGG Gene hsa:4142 (Hs), mmu:17171 (Mm), rno:25153 (Rn)
OMIM 165180 (Hs)
PharmGKB Gene PA30643 (Hs)
PhosphoSitePlus P04201 (Hs), P30554 (Mm), P12526 (Rn)
Protein Ontology (PRO) PRO:000001563 (Hs)
RefSeq Nucleotide NM_002377 (Hs), NM_008552 (Mm), NM_012757 (Rn)
RefSeq Protein NP_002377 (Hs), NP_032578 (Mm), NP_036889 (Rn)
TreeFam ENSG00000130368 (Hs), ENSMUSG00000068037 (Mm), ENSRNOG00000014971 (Rn)
UniGene Hs. 99900 (Hs)
UniProt P04201 (Hs), P30554 (Mm), P12526 (Rn)
Wikipedia MAS1
Orphan and other 7TM receptors
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]angiotensin-(1-7) Mm Full agonist 9.08 pKd 14
AVE 0991 Mm Full agonist 7.32 pIC50 12
Agonist Comments
Jackson et al. reported that angiotensins I and II activated the MAS1 receptor [10]. However, Dong et al. did not detect responses in MAS1-expressing cells exposed to angiotensins I and II [7]. It was then reported that angiotensin-(1-7) binds to Mas-transfected cells and elicits arachidonic acid release [14]. Angiotensin III and IV can also induce a significant but less pronounced arachidonic acid release [9].
Antagonist Comments
A-779 has been reported to be a MAS1 antagonist [14].
Primary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Phospholipase C stimulation
References: 
Tissue Distribution
Hippocampus and cerebral cortex
Species:  Human
Technique:  Northern blot
References:  10
Forebrain, areas of the hippocampus and cerebral cortex (dentate gyrus, the CA3, CA2, and CAI area of the gyrus hippocampi, olfactory tubercle, piriform cortex, and olfactory bulb), cortical areas. Not detectable in medulla oblongata.
Species:  Mouse
Technique:  in situ hybridisation
References:  11
Testis, kidney, heart and brain (especially in forebrain and low amounts of MAS1 mRNA in medulla oblongata).
Species:  Mouse
Technique:  RNase protection assay
References:  11
Leydig cells, Sertoli cells, primary spermatocytes
Species:  Mouse
Technique:  in situ hybridisation
References:  1
Knee joint
Species:  Mouse
Technique:  Western blot
References:  15
Heart and cardiomyocytes
Species:  Rat
Technique:  RT-PCR and Western blot
References:  16
Smooth muscle bundles and in arteriolar endothelial and smooth muscle cells of the rat corpus cavernosum
Species:  Rat
Technique:  Immunofluorescence
References:  5
Strong labelling in the dentate gyrus, the CA3 and CA4 areas of the hippocampus, the olfactory tubercle (medial part), the piriform cortex and the olfactory bulb. Weak to moderate labelling in the neocortex and frontal lobe.
Species:  Rat
Technique:  in situ hybridisation
References:  3
Hippocampus and cerebral cortex
Species:  Rat
Technique:  Northern blot
References:  25
Myocardium
Species:  Rat
Technique:  Western blot
References:  2
Tissue Distribution Comments
The expression of MAS1 was higher in decidual explants from women carrying a female fetus than from women carrying a male fetus [21]. MAS1 mRNAs were not detected in human placenta when examined by quantitative real-time PCR [13].
Expression Datasets

Click here to show/hide data

Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Physiological Functions
Activation of the MAS1 receptor, by AVE 0991 or angiotensin-(1-7), reduced the neutrophil accumulation, hypernociception and production of TNF-α, IL-1β, CXCL1 and histopathological changes evoked in antigen-induced arthritis.
Species:  Mouse
Tissue:  Knee joint
References:  6
MAS1 has been proposed to be involved in angiotensin-(1-7)-mediated anti-inflammatory pathway in allergic asthma
Species:  Mouse
Tissue:  Lung
References:  8
Angiotensin-(1-7)-MAS1 axis has been proposed to play a role in normal erectile function
Species:  Rat
Tissue:  Penile structures
References:  5
Activation of MAS1 receptor by angiotensin-(1-7) inhibited protein synthesis in cardiac myocytes.
Species:  Rat
Tissue:  Cardiac myocytes
References:  16
Physiological Consequences of Altering Gene Expression
Mice with deletion or blockade of MAS1 receptor show a substantial increase in the coronary perfusion pressure in the baseline and reperfusion periods
Species:  Mouse
Tissue:  Heart
Technique:  Gene knockouts and perfusion with MAS1 antagonist A-779
References:  4
MAS1-deficient mice subjected to antigen-induced arthritis showed greater neutrophil accumulation and cytokine release
Species:  Mouse
Tissue:  Knee joint
Technique:  Gene knockouts
References:  6
MAS1-deficient mice showed elevated blood pressure, impaired endothelial function and an imbalance between NO and reactive oxygen species
Species:  Mouse
Tissue:  Not specified
Technique:  Gene knockouts
References:  22
Angiotensin-(1-7)-induced relaxation response of the aorta was abolished in MAS1-deficient mice
Species:  Mouse
Tissue:  Aorta
Technique:  Gene knockouts
References:  14
The binding of angiotensin-(1-7) to mouse kidney was abolished in MAS1-deficient mice
Species:  Mouse
Tissue:  Kidney
Technique:  Gene knockouts
References:  14
Transfection of neonatal rat myocytes with an antisense oligonucleotide to the MAS1 receptor blocked angiotensin-(1-7)-mediated inhibition of serum-stimulated MAP kinase activation
Species:  Rat
Tissue:  Myocytes
Technique:  Transfection with antisense oligonucleotides
References:  16
Mice with MAS1 receptor knockout showed increased duration of long term potentiation in the dentate gyrus, increased anxiety and alterations in the onset of depotentiation
Species:  Mouse
Tissue:  Dendrate gyrus
Technique:  Gene knockouts
References:  19
Mice with MAS1 receptor knockout showed erectile dysfunction and a marked increase in fibrous tissue in the penile corpus cavernosum
Species:  Mouse
Tissue:  Penile corpus cavernosum
Technique:  Gene knockouts
References:  5
Overexpression of MAS1 in cones of retina induced cell death without the formation of tumours
Species:  Mouse
Tissue:  Retina
Technique:  Gene overexpression
References:  24
The antidiuretic action of angiotensin-(1-7) after an acute water load was absent in MAS1 deficient mice
Species:  Mouse
Tissue:  Not specified
Technique:  Gene knockouts
References:  14
MAS1-deficient female mice showed a marked reduction of heart rate variability, whereas MAS1-deficient male mice showed a significant increase in blood pressure variability. MAS1-deficient mice of both genders displayed increased sympathetic tone
Species:  Mouse
Tissue:  Not specified
Technique:  Gene knockouts
References:  20
Depletion of MAS1 affects the expression of proteins involved in mitochondrial function and steroidogenesis in the testis
Species:  Mouse
Tissue:  Testis
Technique:  Gene knockouts
References:  23
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Mas1tm1Bdr Mas1tm1Bdr/Mas1tm1Bdr
involves: 129P2/OlaHsd		 MGI:96918  MP:0003008 enhanced long term potentiation PMID: 9565612 
Mas1tm1Bdr Mas1tm1Bdr/Mas1tm1Bdr
involves: 129P2/OlaHsd		 MGI:96918  MP:0001363 increased anxiety-related response PMID: 9565612 
Gene Expression and Pathophysiology Comments
A recurring translocation site in chromosome 6q that contains MAS1 has been found to be associated with human malignant melanoma [17].
General Comments
MAS1 is a human cellular oncogene [26]. MAS1 is maternally imprinted in fetal mice [18], but not in adult mice and humans [19].

REFERENCES

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1. Alenina, N; Baranova, T; Smirnow, E; Bader, M; Lippoldt, A; Patkin, E; Walther, T. (2002) Cell type-specific expression of the Mas proto-oncogene in testis. J. Histochem. Cytochem., 50 (5): 691-6. [PMID:11967280]

2. Arumugam, S; Thandavarayan, RA; Palaniyandi, SS; Giridharan, VV; Arozal, W; Sari, FR; Soetikno, V; Harima, M; Suzuki, K; Kodama, M; et al.. (2012) Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: involvement of ACE2-Ang (1-7)-mas axis. Toxicology, 291 (1-3): 139-45. [PMID:22120037]

3. Bunnemann, B; Fuxe, K; Metzger, R; Mullins, J; Jackson, TR; Hanley, MR; Ganten, D. (1990) Autoradiographic localization of mas proto-oncogene mRNA in adult rat brain using in situ hybridization. Neurosci. Lett., 114 (2): 147-53. [PMID:2203997]

4. Castro, CH; Santos, RA; Ferreira, AJ; Bader, M; Alenina, N; Almeida, AP. (2006) Effects of genetic deletion of angiotensin-(1-7) receptor Mas on cardiac function during ischemia/reperfusion in the isolated perfused mouse heart. Life Sci., 80 (3): 264-8. [PMID:17055538]

5. da Costa Gonçalves, AC; Leite, R; Fraga-Silva, RA; Pinheiro, SV; Reis, AB; Reis, FM; Touyz, RM; Webb, RC; Alenina, N; Bader, M; et al.. (2007) Evidence that the vasodilator angiotensin-(1-7)-Mas axis plays an important role in erectile function. Am. J. Physiol. Heart Circ. Physiol., 293 (4): H2588-96. [PMID:17616753]

6. da Silveira, KD; Coelho, FM; Vieira, AT; Sachs, D; Barroso, LC; Costa, VV; Bretas, TL; Bader, M; de Sousa, LP; da Silva, TA; et al.. (2010) Anti-inflammatory effects of the activation of the angiotensin-(1-7) receptor, MAS, in experimental models of arthritis. J. Immunol., 185 (9): 5569-76. [PMID:20935211]

7. Dong, X; Han, S; Zylka, MJ; Simon, MI; Anderson, DJ. (2001) A diverse family of GPCRs expressed in specific subsets of nociceptive sensory neurons. Cell, 106 (5): 619-32. [PMID:11551509]

8. El-Hashim, AZ; Renno, WM; Raghupathy, R; Abduo, HT; Akhtar, S; Benter, IF. (2012) Angiotensin-(1-7) inhibits allergic inflammation, via the MAS1 receptor, through suppression of ERK1/2- and NF-κB-dependent pathways. Br. J. Pharmacol., 166 (6): 1964-76. [PMID:22339213]

9. Gembardt, F; Grajewski, S; Vahl, M; Schultheiss, HP; Walther, T. (2008) Angiotensin metabolites can stimulate receptors of the Mas-related genes family. Mol. Cell. Biochem., 319 (1-2): 115-23. [PMID:18636314]

10. Jackson, TR; Blair, LA; Marshall, J; Goedert, M; Hanley, MR. (1988) The mas oncogene encodes an angiotensin receptor. Nature, 335 (6189): 437-40. [PMID:3419518]

11. Metzger, R; Bader, M; Ludwig, T; Berberich, C; Bunnemann, B; Ganten, D. (1995) Expression of the mouse and rat mas proto-oncogene in the brain and peripheral tissues. FEBS Lett., 357 (1): 27-32. [PMID:8001672]

12. Pinheiro, SV; Simões e Silva, AC; Sampaio, WO; de Paula, RD; Mendes, EP; Bontempo, ED; Pesquero, JB; Walther, T; Alenina, N; Bader, M; et al.. (2004) Nonpeptide AVE 0991 is an angiotensin-(1-7) receptor Mas agonist in the mouse kidney. Hypertension, 44 (4): 490-6. [PMID:15326087]

13. Pringle, KG; Tadros, MA; Callister, RJ; Lumbers, ER. (2011) The expression and localization of the human placental prorenin/renin-angiotensin system throughout pregnancy: roles in trophoblast invasion and angiogenesis?. Placenta, 32 (12): 956-62. [PMID:22018415]

14. Santos, RA; Simoes e Silva, AC; Maric, C; Silva, DM; Machado, RP; de Buhr, I; Heringer-Walther, S; Pinheiro, SV; Lopes, MT; Bader, M; et al.. (2003) Angiotensin-(1-7) is an endogenous ligand for the G protein-coupled receptor Mas. Proc. Natl. Acad. Sci. U.S.A., 100 (14): 8258-63. [PMID:12829792]

15. Sugino, N; Sanaka, T; Mineshima, M. (1990) New trends of dialysis therapy from the 1990s to the 21st century. Contrib Nephrol, 82: 107-11. [PMID:2093521]

16. Tallant, EA; Ferrario, CM; Gallagher, PE. (2005) Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am. J. Physiol. Heart Circ. Physiol., 289 (4): H1560-6. [PMID:15951342]

17. Trent, JM; Thompson, FH; Meyskens, FL. (1989) Identification of a recurring translocation site involving chromosome 6 in human malignant melanoma. Cancer Res., 49 (2): 420-3. [PMID:2642739]

18. Villar, AJ; Pedersen, RA. (1994) Parental imprinting of the Mas protooncogene in mouse. Nat. Genet., 8 (4): 373-9. [PMID:7894489]

19. Walther, T; Balschun, D; Voigt, JP; Fink, H; Zuschratter, W; Birchmeier, C; Ganten, D; Bader, M. (1998) Sustained long term potentiation and anxiety in mice lacking the Mas protooncogene. J. Biol. Chem., 273 (19): 11867-73. [PMID:9565612]

20. Walther, T; Wessel, N; Kang, N; Sander, A; Tschöpe, C; Malberg, H; Bader, M; Voss, A. (2000) Altered heart rate and blood pressure variability in mice lacking the Mas protooncogene. Braz. J. Med. Biol. Res., 33 (1): 1-9. [PMID:10625868]

21. Wang, Y; Pringle, KG; Sykes, SD; Marques, FZ; Morris, BJ; Zakar, T; Lumbers, ER. (2012) Fetal sex affects expression of renin-angiotensin system components in term human decidua. Endocrinology, 153 (1): 462-8. [PMID:22045662]

22. Xu, P; Costa-Goncalves, AC; Todiras, M; Rabelo, LA; Sampaio, WO; Moura, MM; Santos, SS; Luft, FC; Bader, M; Gross, V; et al.. (2008) Endothelial dysfunction and elevated blood pressure in MAS gene-deleted mice. Hypertension, 51 (2): 574-80. [PMID:18180400]

23. Xu, P; Santos, RA; Bader, M; Alenina, N. (2007) Alterations in gene expression in the testis of angiotensin-(1-7)-receptor Mas-deficient mice. Regul. Pept., 138 (2-3): 51-5. [PMID:17196677]

24. Xu, X; Quiambao, AB; Roveri, L; Pardue, MT; Marx, JL; Röhlich, P; Peachey, NS; Al-Ubaidi, MR. (2000) Degeneration of cone photoreceptors induced by expression of the Mas1 protooncogene. Exp. Neurol., 163 (1): 207-19. [PMID:10785460]

25. Young, D; O'Neill, K; Jessell, T; Wigler, M. (1988) Characterization of the rat mas oncogene and its high-level expression in the hippocampus and cerebral cortex of rat brain. Proc. Natl. Acad. Sci. U.S.A., 85 (14): 5339-42. [PMID:2455902]

26. Young, D; Waitches, G; Birchmeier, C; Fasano, O; Wigler, M. (1986) Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains. Cell, 45 (5): 711-9. [PMID:3708691]

To cite this database page, please use the following:

Wen Chiy Liew.
Class A Orphans: MAS1. Last modified on 07/01/2013. Accessed on 25/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=150.


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