MASP1 (protein)

MASP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3DEM, 3GOV, 4AQB, 4DJZ, 4IGD, 4IW4, 4KKD
Identifiers
Aliases	MASP1, 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 IDs	OMIM: 600521; MGI: 88492; HomoloGene: 89143; GeneCards: MASP1; OMA:MASP1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q27.3 Start 187,217,282 bp[1] End 187,291,980 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 B1 Start 23,268,167 bp[2] End 23,339,565 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in canal of the cervix right lobe of liver apex of heart body of uterus ectocervix stromal cell of endometrium left ventricle ventricular zone muscle layer of sigmoid colon urethra Top expressed in decidua left lobe of liver ventricular zone saccule cumulus cell gastrula genital tubercle stroma of bone marrow lumbar subsegment of spinal cord right ventricle More reference expression data BioGPS n/a
Gene ontology Molecular function calcium ion binding peptidase activity serine-type peptidase activity protein binding hydrolase activity protein homodimerization activity calcium-dependent protein binding metal ion binding serine-type endopeptidase activity Cellular component extracellular region extracellular space nucleoplasm cytosol Biological process complement activation, lectin pathway receptor-mediated endocytosis proteolysis negative regulation of complement activation immune system process innate immune response complement activation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5648 17174 Ensembl ENSG00000127241 ENSMUSG00000022887 UniProt P48740 P98064 RefSeq (mRNA) NM_001031849 NM_001879 NM_139125 NM_008555 NM_001359083 RefSeq (protein) NP_001027019 NP_001870 NP_624302 NP_032581 NP_001346012 Location (UCSC) Chr 3: 187.22 – 187.29 Mb Chr 16: 23.27 – 23.34 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.[5][6][7]

MASP-1 is involved in the lectin pathway of the complement system and is responsible for activating MASP-2 and MASP-3.[8] It is also involved in the process of cleaving complement proteins, C4 and C2, into fragments to form a C3-convertase.[9]

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.[10] 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.[11] 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.[12][11] A spliced variant of this gene, which lacks the serine protease domain, functions as an inhibitor of the complement pathway.[7]

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).[13] 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.[14]

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.[15] Furthermore, single-nucleotide polymorphisms (SNPs) in MASP1 genes can lead to impaired blood clotting and complement activation.[16] 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.[16]

See also

• Complement system
• Mannan-binding lectin
• MASP2 (protein)

References

1. GRCh38: Ensembl release 89: ENSG00000127241 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022887 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: mannan-binding lectin serine peptidase 1 (C4/C2 activating component of Ra-reactive factor)".
8. 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.
9. 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.
10. Atik T, Koparir A, Bademci G, Foster J, Altunoglu U, Mutlu GY, et al. (September 2015). "Serine Proteases in the Lectin Pathway of the Complement System". Proteases in Physiology and Pathology. Vol. 10. pp. 397–420. doi:10.1007/978-981-10-2513-6_18. ISBN 978-981-10-2512-9. PMC 7120406. PMID 26419238. {{cite book}}: |journal= ignored (help)
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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

• Guey LT, García-Closas M, Murta-Nascimento C, Lloreta J, Palencia L, Kogevinas M, et al. (February 2010). "Genetic susceptibility to distinct bladder cancer subphenotypes". European Urology. 57 (2): 283–292. doi:10.1016/j.eururo.2009.08.001. PMC 3220186. PMID 19692168.
• Petersen SV, Thiel S, Jensenius JC (August 2001). "The mannan-binding lectin pathway of complement activation: biology and disease association". Molecular Immunology. 38 (2–3): 133–149. doi:10.1016/S0161-5890(01)00038-4. PMID 11532276.
• Rajaraman P, Brenner AV, Butler MA, Wang SS, Pfeiffer RM, Ruder AM, et al. (May 2009). "Common variation in genes related to innate immunity and risk of adult glioma". Cancer Epidemiology, Biomarkers & Prevention. 18 (5): 1651–1658. doi:10.1158/1055-9965.EPI-08-1041. PMC 2771723. PMID 19423540.
• Dobó J, Harmat V, Beinrohr L, Sebestyén E, Závodszky P, Gál P (July 2009). "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. doi:10.4049/jimmunol.0901141. PMID 19564340.
• Skjoedt MO, Hummelshoj T, Palarasah Y, Honore C, Koch C, Skjodt K, Garred P (March 2010). "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. doi:10.1074/jbc.M109.065805. PMC 2832975. PMID 20053996.
• Han S, Lan Q, Park AK, Lee KM, Park SK, Ahn HS, et al. (July 2010). "Polymorphisms in innate immunity genes and risk of childhood leukemia". Human Immunology. 71 (7): 727–730. doi:10.1016/j.humimm.2010.04.004. PMC 2967770. PMID 20438785.
• Kocsis A, Kékesi KA, Szász R, Végh BM, Balczer J, Dobó J, et al. (October 2010). "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. doi:10.4049/jimmunol.1001819. hdl:10831/91219. PMID 20817870.
• Rooryck C, Diaz-Font A, Osborn DP, Chabchoub E, Hernandez-Hernandez V, Shamseldin H, et al. (March 2011). "Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome". Nature Genetics. 43 (3): 197–203. doi:10.1038/ng.757. PMC 3045628. PMID 21258343.
• Megyeri M, Makó V, Beinrohr L, Doleschall Z, Prohászka Z, Cervenak L, et al. (September 2009). "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. doi:10.4049/jimmunol.0900879. PMID 19667088.
• Sirmaci A, Walsh T, Akay H, Spiliopoulos M, Sakalar YB, Hasanefendioğlu-Bayrak A, et al. (November 2010). "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. doi:10.1016/j.ajhg.2010.09.018. PMC 2978960. PMID 21035106.
• Hosgood HD, Menashe I, He X, Chanock S, Lan Q (December 2009). "PTEN identified as important risk factor of chronic obstructive pulmonary disease". Respiratory Medicine. 103 (12): 1866–1870. doi:10.1016/j.rmed.2009.06.016. PMC 2783799. PMID 19625176.
• Hosgood HD, Menashe I, Shen M, Yeager M, Yuenger J, Rajaraman P, et al. (October 2008). "Pathway-based evaluation of 380 candidate genes and lung cancer susceptibility suggests the importance of the cell cycle pathway". Carcinogenesis. 29 (10): 1938–1943. doi:10.1093/carcin/bgn178. PMC 2722857. PMID 18676680.
• Kang JU, Koo SH, Kwon KC, Park JW, Kim JM (July 2009). "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. doi:10.1186/1471-2407-9-237. PMC 2716371. PMID 19607727.
• Skjoedt MO, Palarasah Y, Munthe-Fog L, Jie Ma Y, Weiss G, Skjodt K, et al. (November 2010). "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. doi:10.1016/j.imbio.2009.10.006. PMID 19939495.
• Degn SE, Hansen AG, Steffensen R, Jacobsen C, Jensenius JC, Thiel S (December 2009). "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. doi:10.4049/jimmunol.0902388. PMID 19917686.
• Rajaraman P, Brenner AV, Neta G, Pfeiffer R, Wang SS, Yeager M, et al. (May 2010). "Risk of meningioma and common variation in genes related to innate immunity". Cancer Epidemiology, Biomarkers & Prevention. 19 (5): 1356–1361. doi:10.1158/1055-9965.EPI-09-1151. PMC 3169167. PMID 20406964.
• Ennis S, Jomary C, Mullins R, Cree A, Chen X, Macleod A, et al. (November 2008). "Association between the SERPING1 gene and age-related macular degeneration: a two-stage case-control study". Lancet. 372 (9652): 1828–1834. doi:10.1016/S0140-6736(08)61348-3. PMC 5983350. PMID 18842294.
• Shen M, Vermeulen R, Rajaraman P, Menashe I, He X, Chapman RS, et al. (May 2009). "Polymorphisms in innate immunity genes and lung cancer risk in Xuanwei, China". Environmental and Molecular Mutagenesis. 50 (4): 285–290. Bibcode:2009EnvMM..50..285S. doi:10.1002/em.20452. PMC 2666781. PMID 19170196.
• Duus K, Thielens NM, Lacroix M, Tacnet P, Frachet P, Holmskov U, Houen G (December 2010). "CD91 interacts with mannan-binding lectin (MBL) through the MBL-associated serine protease-binding site". The FEBS Journal. 277 (23): 4956–4964. doi:10.1111/j.1742-4658.2010.07901.x. PMID 21054788. S2CID 31526986.
• Degn SE, Jensen L, Gál P, Dobó J, Holmvad SH, Jensenius JC, Thiel S (September 2010). "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. doi:10.1016/j.jim.2010.07.006. PMID 20673767.

External links

• MASP+Proteases at the U.S. 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.