Biology:MASP1 (protein)
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Mannan-binding lectin serine protease 1 also known as mannose-associated serine protease 1 (MASP-1) is an enzyme that in humans is encoded by the MASP1 gene.[1][2][3]
MASP-1 is involved in the lectin pathway of the complement system and is responsible for activating MASP-2 and MASP-3.[4] It is also involved in the process of cleaving complement proteins, C4 and C2, into fragments to form a C3-convertase.[5]
Function
MASP-1 is a serine protease that functions as a component of the lectin pathway of complement activation. The complement pathway plays an essential role in the innate and adaptive immune response as it allows the body to clear foreign material.[6] MASP-1 is synthesized as a zymogen and is activated when it creates a complex of proteins with the pathogen recognition molecules oft the lectin pathway: the mannose-binding lectin and the ficolins. This protein is directly involved in complement activation because MASP-1 activates MASP-2 by cleaving (cutting off a piece) a MASP-2 zymogen.[7] MASP-2 is then able to cleave C4 into proteins C4a and C4b. MASP-1 is also responsible for creating C3 convertase by cleaving C2 into C2b and C2a. C2a and C4b are used to create C3 convertase, a complex that will then be able to cleave C3 into C3a and C3b. However, MASP-1 is useful for biological pathways other than the complement pathway, such as blood clots. MASP-1 can cleave coagulation pathway proteins such as PAR-4, fibrinogen, and factor XIII which leads to high clot and fibrin generation.[8][7] A spliced variant of this gene, which lacks the serine protease domain, functions as an inhibitor of the complement pathway.[3]
Structure
MASP-1’s structure is similar to other MASP proteins. The MASP1 gene encodes MASP-1 as well as MASP-3 (via alternative splicing).[9] Despite being made from different genes and spliced genes, all MASP proteins have the same structure of a heavy/alpha chain, a light/beta chain, and an interconnecting cysteine disulfide bond. The heavy chain is made up of two CUB domains and two complement control protein (CCP) domains that are connected by an epidermal growth factor segment (EGF). However, the full crystal structure of MASP proteins has not yet been formulated.[10]
Clinical significance
MASP1 gene changes can lead to several diseases in patients due to subsequent MASP-1 protein changes. MASP1 gene changes (polymorphisms) can lead to systemic inflammatory response syndrome (SIRS)/sepsis, malpuech facial clefting (3MC) syndrome, and bacterial colonization in those with cystic fibrosis. Also, MASP-1 is essential for stem cell transplantation as it is involved in the transportation of bone marrow stem cells to the blood.[11] Furthermore, single-nucleotide polymorphisms (SNPs) in MASP1 genes can lead to impaired blood clotting and complement activation.[12] Overproduction of MASP-1 proteins can also be related to some diseases. For example, cardiovascular diseases increase MASP-1 levels, especially in cases such as subacute myocardial infarction. MASP-1 is also upregulated in patients with uterine leiomyosarcoma, and it can potentially activate the alternative pathway of complement in inflammatory arthritis patients. Hepatitis C (HCV), a liver disease, is associated with MASP-1 due to the localization of high concentrations of MASP-1 in infected livers. Higher levels of MASP-1 correlated with severe HCV-related liver fibrosis.[12]
See also
References
- ↑ "A new member of the C1s family of complement proteins found in a bactericidal factor, Ra-reactive factor, in human serum". Biochemical and Biophysical Research Communications 196 (2): 1003–1009. October 1993. doi:10.1006/bbrc.1993.2349. PMID 8240317.
- ↑ "Molecular characterization of a novel serine protease involved in activation of the complement system by mannose-binding protein". International Immunology 6 (4): 665–669. April 1994. doi:10.1093/intimm/6.4.665. PMID 8018603.
- ↑ 3.0 3.1 "Entrez Gene: mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive factor)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5648.
- ↑ "The Role of MASP-1/3 in Complement Activation". Complement Therapeutics. Advances in Experimental Medicine and Biology. 735. New York, NY: Springer US. 2013. pp. 41–53. doi:10.1007/978-1-4614-4118-2_3. ISBN 978-1-4614-4118-2.
- ↑ "Proteolytic activities of two types of mannose-binding lectin-associated serine protease". Journal of Immunology 165 (5): 2637–2642. September 2000. doi:10.4049/jimmunol.165.5.2637. PMID 10946292.
- ↑ "Serine Proteases in the Lectin Pathway of the Complement System". Proteases in Physiology and Pathology. 10. September 2015. 397–420. doi:10.1007/978-981-10-2513-6_18. ISBN 978-981-10-2512-9.
- ↑ 7.0 7.1 "Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation". Molecular Immunology. XXV International Complement Workshop September 14-18, 2014 - Rio de Janeiro, Brazil 61 (2): 69–78. October 2014. doi:10.1016/j.molimm.2014.05.013. PMID 24935208. http://real.mtak.hu/18794/1/MASP_review_szerzoi_u_165917.185483.pdf.
- ↑ "Toward a structure-based comprehension of the lectin pathway of complement". Molecular Immunology 56 (4): 413–422. December 2013. doi:10.1016/j.molimm.2013.05.007. PMID 23911397. https://pure.au.dk/ws/files/81380790/LP_review_published.pdf.
- ↑ "Role of MBL-associated Serine Protease (MASP) on Activation of the Lectin Complement Pathway". Current Topics in Innate Immunity. Advances in Experimental Medicine and Biology. 598. Springer. 2007. pp. 93–104. doi:10.1007/978-0-387-71767-8_8. ISBN 978-0-387-71767-8.
- ↑ "A journey through the lectin pathway of complement-MBL and beyond". Immunological Reviews 274 (1): 74–97. November 2016. doi:10.1111/imr.12468. PMID 27782323.
- ↑ "Components of the Lectin Pathway of Complement in Haematologic Malignancies". Cancers 12 (7): 1792. July 2020. doi:10.3390/cancers12071792. PMID 32635486.
- ↑ 12.0 12.1 "MBL-associated serine proteases (MASPs) and infectious diseases". Molecular Immunology. 15th European Meeting on Complement in Human Disease 2015, Uppsala, Sweden 67 (1): 85–100. September 2015. doi:10.1016/j.molimm.2015.03.245. PMID 25862418.
Further reading
- "Genetic susceptibility to distinct bladder cancer subphenotypes". European Urology 57 (2): 283–292. February 2010. doi:10.1016/j.eururo.2009.08.001. PMID 19692168.
- "The mannan-binding lectin pathway of complement activation: biology and disease association". Molecular Immunology 38 (2–3): 133–149. August 2001. doi:10.1016/S0161-5890(01)00038-4. PMID 11532276.
- "Common variation in genes related to innate immunity and risk of adult glioma". Cancer Epidemiology, Biomarkers & Prevention 18 (5): 1651–1658. May 2009. doi:10.1158/1055-9965.EPI-08-1041. PMID 19423540.
- "MASP-1, a promiscuous complement protease: structure of its catalytic region reveals the basis of its broad specificity". Journal of Immunology 183 (2): 1207–1214. July 2009. doi:10.4049/jimmunol.0901141. PMID 19564340.
- "A novel mannose-binding lectin/ficolin-associated protein is highly expressed in heart and skeletal muscle tissues and inhibits complement activation". The Journal of Biological Chemistry 285 (11): 8234–8243. March 2010. doi:10.1074/jbc.M109.065805. PMID 20053996.
- "Polymorphisms in innate immunity genes and risk of childhood leukemia". Human Immunology 71 (7): 727–730. July 2010. doi:10.1016/j.humimm.2010.04.004. PMID 20438785.
- "Selective inhibition of the lectin pathway of complement with phage display selected peptides against mannose-binding lectin-associated serine protease (MASP)-1 and -2: significant contribution of MASP-1 to lectin pathway activation". Journal of Immunology 185 (7): 4169–4178. October 2010. doi:10.4049/jimmunol.1001819. PMID 20817870.
- "Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome". Nature Genetics 43 (3): 197–203. March 2011. doi:10.1038/ng.757. PMID 21258343.
- "Complement protease MASP-1 activates human endothelial cells: PAR4 activation is a link between complement and endothelial function". Journal of Immunology 183 (5): 3409–3416. September 2009. doi:10.4049/jimmunol.0900879. PMID 19667088.
- "MASP1 mutations in patients with facial, umbilical, coccygeal, and auditory findings of Carnevale, Malpuech, OSA, and Michels syndromes". American Journal of Human Genetics 87 (5): 679–686. November 2010. doi:10.1016/j.ajhg.2010.09.018. PMID 21035106.
- "PTEN identified as important risk factor of chronic obstructive pulmonary disease". Respiratory Medicine 103 (12): 1866–1870. December 2009. doi:10.1016/j.rmed.2009.06.016. PMID 19625176.
- "Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway". Carcinogenesis 29 (10): 1938–1943. October 2008. doi:10.1093/carcin/bgn178. PMID 18676680.
- "Identification of novel candidate target genes, including EPHB3, MASP1 and SST at 3q26.2-q29 in squamous cell carcinoma of the lung". BMC Cancer 9: 237. July 2009. doi:10.1186/1471-2407-9-237. PMID 19607727.
- "MBL-associated serine protease-3 circulates in high serum concentrations predominantly in complex with Ficolin-3 and regulates Ficolin-3 mediated complement activation". Immunobiology 215 (11): 921–931. November 2010. doi:10.1016/j.imbio.2009.10.006. PMID 19939495.
- "MAp44, a human protein associated with pattern recognition molecules of the complement system and regulating the lectin pathway of complement activation". Journal of Immunology 183 (11): 7371–7378. December 2009. doi:10.4049/jimmunol.0902388. PMID 19917686.
- "Risk of meningioma and common variation in genes related to innate immunity". Cancer Epidemiology, Biomarkers & Prevention 19 (5): 1356–1361. May 2010. doi:10.1158/1055-9965.EPI-09-1151. PMID 20406964.
- "Association between the SERPING1 gene and age-related macular degeneration: a two-stage case-control study". Lancet 372 (9652): 1828–1834. November 2008. doi:10.1016/S0140-6736(08)61348-3. PMID 18842294.
- "Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China". Environmental and Molecular Mutagenesis 50 (4): 285–290. May 2009. doi:10.1002/em.20452. PMID 19170196.
- "CD91 interacts with mannan-binding lectin (MBL) through the MBL-associated serine protease-binding site". The FEBS Journal 277 (23): 4956–4964. December 2010. doi:10.1111/j.1742-4658.2010.07901.x. PMID 21054788.
- "Biological variations of MASP-3 and MAp44, two splice products of the MASP1 gene involved in regulation of the complement system". Journal of Immunological Methods 361 (1–2): 37–50. September 2010. doi:10.1016/j.jim.2010.07.006. PMID 20673767.
External links
- MASP+Proteases at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
![]() | Original source: https://en.wikipedia.org/wiki/MASP1 (protein).
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