Biology:MASP1 (protein)

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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

  1. ↑ "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. 
  2. ↑ "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. ↑ 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. 
  4. ↑ "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. 
  5. ↑ "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. 
  6. ↑ "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. ↑ 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. 
  8. ↑ "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. 
  9. ↑ "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. 
  10. ↑ "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. 
  11. ↑ "Components of the Lectin Pathway of Complement in Haematologic Malignancies". Cancers 12 (7): 1792. July 2020. doi:10.3390/cancers12071792. PMID 32635486. 
  12. ↑ 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

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.




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