MASP1 (protein)

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.[3][4][5]

MASP1
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesMASP1, 3MC1, CRARF, CRARF1, MAP1, MASP, MASP3, MAp44, PRSS5, RaRF, mannan binding lectin serine peptidase 1, Mannan-binding lectin serine protease 1, MBL associated serine protease 1, MASP-3, MAP-1
External IDsOMIM: 600521 HomoloGene: 89143 GeneCards: MASP1
Orthologs
SpeciesHumanMouse
Entrez

5648

n/a

Ensembl

ENSG00000127241

n/a

UniProt

P48740

n/a

RefSeq (mRNA)

NM_001031849
NM_001879
NM_139125

n/a

RefSeq (protein)

NP_001027019
NP_001870
NP_624302

n/a

Location (UCSC)Chr 3: 187.22 – 187.29 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

MASP-1 is involved in the lectin pathway of the complement system and is responsible for activating MASP-2 and MASP-3.[6] It is also involved in the process of cleaving complement proteins, C4 and C2, into fragments to form a C3-convertase.[7]

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.[8] 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.[9] 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.[10][9] A spliced variant of this gene, which lacks the serine protease domain, functions as an inhibitor of the complement pathway.[5]

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).[11] 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.[12]

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.[13] Furthermore, single-nucleotide polymorphisms (SNPs) in MASP1 genes can lead to impaired blood clotting and complement activation.[14] 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.[14]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000127241 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Takada F, Takayama Y, Hatsuse H, Kawakami M (October 1993). "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. doi:10.1006/bbrc.1993.2349. PMID 8240317.
  4. Sato T, Endo Y, Matsushita M, Fujita T (April 1994). "Molecular characterization of a novel serine protease involved in activation of the complement system by mannose-binding protein". International Immunology. 6 (4): 665–669. doi:10.1093/intimm/6.4.665. PMID 8018603.
  5. "Entrez Gene: mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive factor)".
  6. Sekine H, Takahashi M, Iwaki D, Fujita T (2013). "The role of MASP-1/3 in complement activation". In Lambris JD, Holers VM, Ricklin D (eds.). Complement Therapeutics. Advances in Experimental Medicine and Biology. Vol. 735. New York, NY: Springer US. pp. 41–53. doi:10.1007/978-1-4614-4118-2_3. ISBN 978-1-4614-4118-2. PMID 23402018.
  7. Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T (September 2000). "Proteolytic activities of two types of mannose-binding lectin-associated serine protease". Journal of Immunology. 165 (5): 2637–2642. doi:10.4049/jimmunol.165.5.2637. PMID 10946292.
  8. Atik T, Koparir A, Bademci G, Foster J, Altunoglu U, Mutlu GY, et al. (September 2015). "Novel MASP1 mutations are associated with an expanded phenotype in 3MC1 syndrome". Orphanet Journal of Rare Diseases. 10: 397–420. doi:10.1007/978-981-10-2513-6_18. ISBN 978-981-10-2512-9. PMC 7120406. PMID 26419238.
  9. Dobó J, Schroeder V, Jenny L, Cervenak L, Závodszky P, Gál P (October 2014). "Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation" (PDF). Molecular Immunology. XXV International Complement Workshop September 14-18, 2014 - Rio de Janeiro, Brazil. 61 (2): 69–78. doi:10.1016/j.molimm.2014.05.013. PMID 24935208.
  10. Kjaer TR, Thiel S, Andersen GR (December 2013). "Toward a structure-based comprehension of the lectin pathway of complement" (PDF). Molecular Immunology. 56 (4): 413–422. doi:10.1016/j.molimm.2013.05.007. PMID 23911397.
  11. Takahashi M, Mori S, Shigeta S, Fujita T (2007). "Role of MBL-associated serine protease (MASP) on activation of the lectin complement pathway". In Lambris JD (ed.). Current Topics in Innate Immunity. Advances in Experimental Medicine and Biology. Vol. 598. Springer. pp. 93–104. doi:10.1007/978-0-387-71767-8_8. ISBN 978-0-387-71767-8. PMID 17892207.
  12. Garred P, Genster N, Pilely K, Bayarri-Olmos R, Rosbjerg A, Ma YJ, Skjoedt MO (November 2016). "A journey through the lectin pathway of complement-MBL and beyond". Immunological Reviews. 274 (1): 74–97. doi:10.1111/imr.12468. PMID 27782323. S2CID 37084404.
  13. Cedzyński M, Świerzko AS (July 2020). "Components of the Lectin Pathway of Complement in Haematologic Malignancies". Cancers. 12 (7): 1792. doi:10.3390/cancers12071792. PMC 7408476. PMID 32635486.
  14. Beltrame MH, Boldt AB, Catarino SJ, Mendes HC, Boschmann SE, Goeldner I, Messias-Reason I (September 2015). "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. doi:10.1016/j.molimm.2015.03.245. PMC 7112674. PMID 25862418.

Further reading

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