ID MASP2_HUMAN Reviewed; 686 AA. AC O00187; A8K458; A8MWJ2; O75754; Q5TEQ5; Q5TER0; Q96QG4; Q9BZH0; AC Q9H498; Q9H499; Q9UBP3; Q9UC48; Q9ULC7; Q9UMV3; Q9Y270; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 11-JAN-2011, sequence version 4. DT 16-JAN-2019, entry version 202. DE RecName: Full=Mannan-binding lectin serine protease 2; DE EC=3.4.21.104; DE AltName: Full=MBL-associated serine protease 2; DE AltName: Full=Mannose-binding protein-associated serine protease 2; DE Short=MASP-2; DE Contains: DE RecName: Full=Mannan-binding lectin serine protease 2 A chain; DE Contains: DE RecName: Full=Mannan-binding lectin serine protease 2 B chain; DE Flags: Precursor; GN Name=MASP2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Liver; RX PubMed=9087411; DOI=10.1038/386506a0; RA Thiel S., Vorup-Jensen T., Stover C.M., Schwaeble W.J., Laursen S.B., RA Poulsen K., Willis A.C., Eggleton P., Hansen S., Holmskov U., RA Reid K.B.M., Jensenius J.C.; RT "A second serine protease associated with mannan-binding lectin that RT activates complement."; RL Nature 386:506-510(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2). RX PubMed=10330290; DOI=10.1093/intimm/11.5.859; RA Takahashi M., Endo Y., Fujita T., Matsushita M.; RT "A truncated form of mannose-binding lectin-associated serine protease RT (MASP)-2 expressed by alternative polyadenylation is a component of RT the lectin complement pathway."; RL Int. Immunol. 11:859-863(1999). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2), RP ACTIVATION BY PROTEOLYTIC CLEAVAGE, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Liver; RX PubMed=10092804; RA Stover C.M., Thiel S., Thelen M., Lynch N.J., Vorup-Jensen T., RA Jensenius J.C., Schwaeble W.J.; RT "Two constituents of the initiation complex of the mannan-binding RT lectin activation pathway of complement are encoded by a single RT structural gene."; RL J. Immunol. 162:3481-3490(1999). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Thiel S., Vorup-Jensen T., Stover C.M., Schwaeble W., Laursen S.B., RA Poulsen K., Willis A.C., Eggleton P., Hansen S., Holmskov U., RA Reid K.B.M., Jensenius J.C.; RT "Identification and characterization of a novel protein of the human RT complement system, mannan-binding lectin-associated serine protease-2 RT (MASP-2)."; RL Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT TYR-371. RA Takahashi M., Fujita T.; RT "Partial genomic structure of human MBL-associated serine protease RT (MASP)-2 (from exon 1 to exon 5)."; RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Park D., Kim B., Baek K., Yoon J.; RT "Structure of human MASP-2 gene."; RL Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Liver; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [9] RP PROTEIN SEQUENCE OF 30-45. RC TISSUE=Urine; RX PubMed=8618346; DOI=10.1016/S0022-5347(01)66119-6; RA Rasmussen H.H., Orntoft T.F., Wolf H., Celis J.E.; RT "Towards a comprehensive database of proteins from the urine of RT patients with bladder cancer."; RL J. Urol. 155:2113-2119(1996). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 149-284 AND 364-686, AND VARIANT RP ALA-377. RX PubMed=11426320; DOI=10.1038/sj.gene.6363745; RA Stover C., Endo Y., Takahashi M., Lynch N., Constantinescu C., RA Vorup-Jensen T., Thiel S., Friedl H., Hankeln T., Hall R., Gregory S., RA Fujita T., Schwaeble W.; RT "The human gene for mannan-binding lectin-associated serine protease-2 RT (MASP-2), the effector component of the lectin route of complement RT activation, is part of a tightly linked gene cluster on chromosome RT 1p36.2-3."; RL Genes Immun. 2:119-127(2001). RN [11] RP FUNCTION, AND INTERACTION WITH SERPING1. RX PubMed=10946292; DOI=10.4049/jimmunol.165.5.2637; RA Matsushita M., Thiel S., Jensenius J.C., Terai I., Fujita T.; RT "Proteolytic activities of two types of mannose-binding lectin- RT associated serine protease."; RL J. Immunol. 165:2637-2642(2000). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 16-181 (ISOFORM 2), RP CHARACTERIZATION OF VARIANT GLY-120, CALCIUM-BINDING SITES, RP DIMERIZATION, MUTAGENESIS OF TYR-74; TYR-121 AND GLU-124, INTERACTION RP WITH MBL2 AND FCN2, AND DISULFIDE BONDS. RX PubMed=15117939; DOI=10.1074/jbc.M402687200; RA Gregory L.A., Thielens N.M., Matsushita M., Sorensen R., Arlaud G.J., RA Fontecilla-Camps J.-C., Gaboriaud C.; RT "The X-ray structure of human mannan-binding lectin-associated protein RT 19 (MAp19) and its interaction site with mannan-binding lectin and L- RT ficolin."; RL J. Biol. Chem. 279:29391-29397(2004). RN [13] RP X-RAY CRYSTALLOGRAPHY (2.23 ANGSTROMS) OF 363-686, AND DISULFIDE RP BONDS. RX PubMed=15364579; DOI=10.1016/j.jmb.2004.07.014; RA Harmat V., Gal P., Kardos J., Szilagyi K., Ambrus G., Vegh B., RA Naray-Szabo G., Zavodszky P.; RT "The structure of MBL-associated serine protease-2 reveals that RT identical substrate specificities of C1s and MASP-2 are realized RT through different sets of enzyme-substrate interactions."; RL J. Mol. Biol. 342:1533-1546(2004). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.18 ANGSTROMS) OF 287-686, AUTOCATALYTIC RP CLEAVAGE AT ARG-444, AND MUTAGENESIS OF ARG-444. RX PubMed=16040602; DOI=10.1074/jbc.M506051200; RA Gal P., Harmat V., Kocsis A., Bian T., Barna L., Ambrus G., Vegh B., RA Balczer J., Sim R.B., Naray-Szabo G., Zavodszky P.; RT "A true autoactivating enzyme. Structural insight into mannose-binding RT lectin-associated serine protease-2 activations."; RL J. Biol. Chem. 280:33435-33444(2005). RN [15] RP VARIANT MASPD GLY-120, AND CHARACTERIZATION OF VARIANT MASPD GLY-120. RX PubMed=12904520; DOI=10.1056/NEJMoa022836; RA Stengaard-Pedersen K., Thiel S., Gadjeva M., Moller-Kristensen M., RA Sorensen R., Jensen L.T., Sjoeholm A.G., Fugger L., Jensenius J.C.; RT "Inherited deficiency of mannan-binding lectin-associated serine RT protease 2."; RL N. Engl. J. Med. 349:554-560(2003). RN [16] RP VARIANTS GLN-99; CYS-118; GLY-120 AND LEU-126. RX PubMed=16029433; DOI=10.1111/j.1399-0039.2005.00436.x; RA Lozano F., Suarez B., Munoz A., Jensenius J.C., Mensa J., Vives J., RA Horcajada J.P.; RT "Novel MASP2 variants detected among North African and Sub-Saharan RT individuals."; RL Tissue Antigens 66:131-135(2005). RN [17] RP VARIANTS MASPD GLY-120; LEU-126 AND HIS-ASN-HIS-156 INS, VARIANTS RP GLN-99; CYS-118 AND ALA-377, AND CHARACTERIZATION OF VARIANT ALA-377. RX PubMed=17252003; DOI=10.1038/sj.gene.6364373; RA Thiel S., Steffensen R., Christensen I.J., Ip W.K., Lau Y.L., RA Reason I.J., Eiberg H., Gadjeva M., Ruseva M., Jensenius J.C.; RT "Deficiency of mannan-binding lectin associated serine protease-2 due RT to missense polymorphisms."; RL Genes Immun. 8:154-163(2007). RN [18] RP VARIANTS MET-128 AND MET-405. RX PubMed=25930971; DOI=10.1111/cge.12605; RA Srour M., Hamdan F.F., Gan-Or Z., Labuda D., Nassif C., Oskoui M., RA Gana-Weisz M., Orr-Urtreger A., Rouleau G.A., Michaud J.L.; RT "A homozygous mutation in SLC1A4 in siblings with severe intellectual RT disability and microcephaly."; RL Clin. Genet. 88:E1-E4(2015). CC -!- FUNCTION: Serum protease that plays an important role in the CC activation of the complement system via mannose-binding lectin. CC After activation by auto-catalytic cleavage it cleaves C2 and C4, CC leading to their activation and to the formation of C3 convertase. CC {ECO:0000269|PubMed:10946292}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Selective cleavage after Arg-223 in complement component CC C2 (-Ser-Leu-Gly-Arg-|-Lys-Ile-Gln-Ile) and after Arg-76 in CC complement component C4 (-Gly-Leu-Gln-Arg-|-Ala-Leu-Glu-Ile).; CC EC=3.4.21.104; CC -!- SUBUNIT: Homodimer; disulfide-linked. Binds MBL2. Isoform 2 binds CC to MASP1. Binds SERPING1. Dimerization and MBL2 binding requires CC calcium ions. {ECO:0000269|PubMed:10946292, CC ECO:0000269|PubMed:15117939, ECO:0000269|PubMed:15364579}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O00187-1; Sequence=Displayed; CC Name=2; Synonyms=MAp19, Small MBL-associated protein, sMAP; CC IsoId=O00187-2; Sequence=VSP_005383, VSP_005384; CC -!- TISSUE SPECIFICITY: Plasma. CC -!- PTM: The iron and 2-oxoglutarate dependent 3-hydroxylation of CC aspartate and asparagine is (R) stereospecific within EGF domains. CC {ECO:0000250}. CC -!- PTM: Activated by cleavage after Arg-444. The uncleaved zymogen is CC inactive towards synthetic substrates, but has sufficient activity CC to effect autocatalytic cleavage. CC -!- DISEASE: MASP2 deficiency (MASPD) [MIM:613791]: A disorder that CC results in autoimmune manifestations, recurrent severe infections, CC and chronic inflammatory disease. {ECO:0000269|PubMed:12904520, CC ECO:0000269|PubMed:17252003}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the peptidase S1 family. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. CC -!- WEB RESOURCE: Name=MASP2base; Note=MASP2 mutation db; CC URL="http://structure.bmc.lu.se/idbase/MASP2base/"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; Y09926; CAA71059.1; -; mRNA. DR EMBL; AB008047; BAA78616.1; -; mRNA. DR EMBL; Y18281; CAB50728.1; -; mRNA. DR EMBL; Y18282; CAB50729.1; -; mRNA. DR EMBL; Y18283; CAB50730.1; -; mRNA. DR EMBL; Y18284; CAB50731.1; -; mRNA. DR EMBL; Y18286; CAB50732.1; -; Genomic_DNA. DR EMBL; Y18286; CAB50733.1; -; Genomic_DNA. DR EMBL; Y18287; CAB50734.1; -; Genomic_DNA. DR EMBL; Y18287; CAB50735.1; -; Genomic_DNA. DR EMBL; X98400; CAA67050.1; -; mRNA. DR EMBL; AB033742; BAA85658.1; -; Genomic_DNA. DR EMBL; AB033742; BAA85659.1; -; Genomic_DNA. DR EMBL; AF321558; AAG50275.1; -; Genomic_DNA. DR EMBL; AF321562; AAG50274.1; -; Genomic_DNA. DR EMBL; AF321558; AAG50274.1; JOINED; Genomic_DNA. DR EMBL; AF321559; AAG50274.1; JOINED; Genomic_DNA. DR EMBL; AF321560; AAG50274.1; JOINED; Genomic_DNA. DR EMBL; AF321561; AAG50274.1; JOINED; Genomic_DNA. DR EMBL; AK290823; BAF83512.1; -; mRNA. DR EMBL; AL109811; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AJ297949; CAC17138.1; -; Genomic_DNA. DR EMBL; AJ297949; CAC17139.1; -; Genomic_DNA. DR EMBL; AJ300188; CAC15568.1; -; Genomic_DNA. DR CCDS; CCDS123.1; -. [O00187-1] DR CCDS; CCDS124.1; -. [O00187-2] DR PIR; A59271; A59271. DR RefSeq; NP_006601.2; NM_006610.3. [O00187-1] DR RefSeq; NP_631947.1; NM_139208.2. [O00187-2] DR UniGene; Hs.655645; -. DR PDB; 1Q3X; X-ray; 2.23 A; A/B=363-686. DR PDB; 1SZB; X-ray; 2.50 A; A/B=16-181. DR PDB; 1ZJK; X-ray; 2.18 A; A=287-686. DR PDB; 3TVJ; X-ray; 1.28 A; A=363-444, B=445-686. DR PDB; 4FXG; X-ray; 3.75 A; G/I=291-444, H/J=445-686. DR PDB; 5JPM; X-ray; 3.75 A; G/I=291-444, H/J=445-686. DR PDBsum; 1Q3X; -. DR PDBsum; 1SZB; -. DR PDBsum; 1ZJK; -. DR PDBsum; 3TVJ; -. DR PDBsum; 4FXG; -. DR PDBsum; 5JPM; -. DR ProteinModelPortal; O00187; -. DR SMR; O00187; -. DR BioGrid; 115970; 4. DR IntAct; O00187; 1. DR MINT; O00187; -. DR STRING; 9606.ENSP00000383690; -. DR DrugBank; DB04527; Beta-Hydroxyasparagine. DR MEROPS; S01.229; -. DR iPTMnet; O00187; -. DR PhosphoSitePlus; O00187; -. DR BioMuta; MASP2; -. DR PaxDb; O00187; -. DR PeptideAtlas; O00187; -. DR PRIDE; O00187; -. DR ProteomicsDB; 47767; -. DR ProteomicsDB; 47768; -. [O00187-2] DR Ensembl; ENST00000400897; ENSP00000383690; ENSG00000009724. [O00187-1] DR Ensembl; ENST00000400898; ENSP00000383691; ENSG00000009724. [O00187-2] DR GeneID; 10747; -. DR KEGG; hsa:10747; -. DR UCSC; uc001aru.4; human. [O00187-1] DR CTD; 10747; -. DR DisGeNET; 10747; -. DR EuPathDB; HostDB:ENSG00000009724.16; -. DR GeneCards; MASP2; -. DR HGNC; HGNC:6902; MASP2. DR HPA; HPA029313; -. DR HPA; HPA029314; -. DR MalaCards; MASP2; -. DR MIM; 605102; gene. DR MIM; 613791; phenotype. DR neXtProt; NX_O00187; -. DR OpenTargets; ENSG00000009724; -. DR Orphanet; 331187; Immunodeficiency due to MASP-2 deficiency. DR PharmGKB; PA30645; -. DR eggNOG; KOG3627; Eukaryota. DR eggNOG; COG5640; LUCA. DR GeneTree; ENSGT00940000153970; -. DR HOVERGEN; HBG000559; -. DR InParanoid; O00187; -. DR KO; K03993; -. DR OMA; MFVDIPI; -. DR OrthoDB; 156878at2759; -. DR PhylomeDB; O00187; -. DR TreeFam; TF330373; -. DR BRENDA; 3.4.21.104; 2681. DR Reactome; R-HSA-166662; Lectin pathway of complement activation. DR Reactome; R-HSA-166663; Initial triggering of complement. DR Reactome; R-HSA-2855086; Ficolins bind to repetitive carbohydrate structures on the target cell surface. DR SABIO-RK; O00187; -. DR EvolutionaryTrace; O00187; -. DR GenomeRNAi; 10747; -. DR PRO; PR:O00187; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; ENSG00000009724; Expressed in 101 organ(s), highest expression level in right lobe of liver. DR Genevisible; O00187; HS. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0048306; F:calcium-dependent protein binding; IPI:UniProtKB. DR GO; GO:0001855; F:complement component C4b binding; IDA:BHF-UCL. DR GO; GO:0008233; F:peptidase activity; IDA:UniProtKB. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0006956; P:complement activation; TAS:Reactome. DR GO; GO:0006958; P:complement activation, classical pathway; IEA:UniProtKB-KW. DR GO; GO:0001867; P:complement activation, lectin pathway; IDA:UniProtKB. DR CDD; cd00033; CCP; 2. DR CDD; cd00041; CUB; 2. DR CDD; cd00190; Tryp_SPc; 1. DR Gene3D; 2.60.120.290; -; 2. DR InterPro; IPR000859; CUB_dom. DR InterPro; IPR001881; EGF-like_Ca-bd_dom. DR InterPro; IPR013032; EGF-like_CS. DR InterPro; IPR000742; EGF-like_dom. DR InterPro; IPR000152; EGF-type_Asp/Asn_hydroxyl_site. DR InterPro; IPR018097; EGF_Ca-bd_CS. DR InterPro; IPR037571; MASP2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR035914; Sperma_CUB_dom_sf. DR InterPro; IPR035976; Sushi/SCR/CCP_sf. DR InterPro; IPR000436; Sushi_SCR_CCP_dom. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24255:SF10; PTHR24255:SF10; 1. DR Pfam; PF00431; CUB; 2. DR Pfam; PF07645; EGF_CA; 1. DR Pfam; PF00084; Sushi; 2. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00032; CCP; 2. DR SMART; SM00042; CUB; 2. DR SMART; SM00181; EGF; 1. DR SMART; SM00179; EGF_CA; 1. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF49854; SSF49854; 2. DR SUPFAM; SSF50494; SSF50494; 1. DR SUPFAM; SSF57535; SSF57535; 2. DR PROSITE; PS00010; ASX_HYDROXYL; 1. DR PROSITE; PS01180; CUB; 2. DR PROSITE; PS01186; EGF_2; 1. DR PROSITE; PS01187; EGF_CA; 1. DR PROSITE; PS50923; SUSHI; 2. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autocatalytic cleavage; Calcium; KW Complement pathway; Complete proteome; Direct protein sequencing; KW Disease mutation; Disulfide bond; EGF-like domain; Hydrolase; KW Hydroxylation; Immunity; Innate immunity; Metal-binding; Polymorphism; KW Protease; Reference proteome; Repeat; Secreted; Serine protease; KW Signal; Sushi. FT SIGNAL 1 15 {ECO:0000255}. FT CHAIN 16 686 Mannan-binding lectin serine protease 2. FT /FTId=PRO_0000027598. FT CHAIN 16 444 Mannan-binding lectin serine protease 2 A FT chain. FT /FTId=PRO_0000027599. FT CHAIN 445 686 Mannan-binding lectin serine protease 2 B FT chain. FT /FTId=PRO_0000027600. FT DOMAIN 16 137 CUB 1. {ECO:0000255|PROSITE- FT ProRule:PRU00059}. FT DOMAIN 138 181 EGF-like; calcium-binding. FT DOMAIN 184 296 CUB 2. {ECO:0000255|PROSITE- FT ProRule:PRU00059}. FT DOMAIN 298 363 Sushi 1. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 364 432 Sushi 2. {ECO:0000255|PROSITE- FT ProRule:PRU00302}. FT DOMAIN 445 684 Peptidase S1. {ECO:0000255|PROSITE- FT ProRule:PRU00274}. FT ACT_SITE 483 483 Charge relay system. FT ACT_SITE 532 532 Charge relay system. FT ACT_SITE 633 633 Charge relay system. FT METAL 67 67 Calcium 1. FT METAL 75 75 Calcium 1. FT METAL 120 120 Calcium 1. FT METAL 122 122 Calcium 1; via carbonyl oxygen. FT METAL 123 123 Calcium 1. FT METAL 138 138 Calcium 2. FT METAL 139 139 Calcium 2; via carbonyl oxygen. FT METAL 141 141 Calcium 2. FT METAL 158 158 Calcium 2. FT METAL 159 159 Calcium 2; via carbonyl oxygen. FT METAL 162 162 Calcium 2; via carbonyl oxygen. FT SITE 444 445 Cleavage; by autolysis. FT {ECO:0000269|PubMed:16040602}. FT MOD_RES 158 158 (3R)-3-hydroxyasparagine. {ECO:0000255}. FT DISULFID 72 90 FT DISULFID 142 156 FT DISULFID 152 165 FT DISULFID 167 180 FT DISULFID 184 211 {ECO:0000250}. FT DISULFID 241 259 {ECO:0000250}. FT DISULFID 300 348 {ECO:0000250}. FT DISULFID 328 361 {ECO:0000250}. FT DISULFID 366 412 FT DISULFID 396 430 FT DISULFID 434 552 Interchain (between A and B chains). FT DISULFID 598 618 FT DISULFID 629 660 FT VAR_SEQ 182 185 ALCS -> EQSL (in isoform 2). FT {ECO:0000303|PubMed:10092804, FT ECO:0000303|PubMed:10330290}. FT /FTId=VSP_005383. FT VAR_SEQ 186 686 Missing (in isoform 2). FT {ECO:0000303|PubMed:10092804, FT ECO:0000303|PubMed:10330290}. FT /FTId=VSP_005384. FT VARIANT 99 99 R -> Q (in dbSNP:rs61735600). FT {ECO:0000269|PubMed:16029433, FT ECO:0000269|PubMed:17252003}. FT /FTId=VAR_025344. FT VARIANT 118 118 R -> C (in dbSNP:rs147270785). FT {ECO:0000269|PubMed:16029433, FT ECO:0000269|PubMed:17252003}. FT /FTId=VAR_025345. FT VARIANT 120 120 D -> G (in MASPD; found in a patient FT suffering from frequent infections and FT chronic inflammatory disease; strongly FT decreases affinity for MBL2 and FCN2; FT dbSNP:rs72550870). FT {ECO:0000269|PubMed:12904520, FT ECO:0000269|PubMed:15117939, FT ECO:0000269|PubMed:16029433, FT ECO:0000269|PubMed:17252003}. FT /FTId=VAR_025346. FT VARIANT 126 126 P -> L (in MASPD; dbSNP:rs56392418). FT {ECO:0000269|PubMed:16029433, FT ECO:0000269|PubMed:17252003}. FT /FTId=VAR_025347. FT VARIANT 128 128 T -> M (in dbSNP:rs141145402). FT {ECO:0000269|PubMed:25930971}. FT /FTId=VAR_075087. FT VARIANT 155 155 H -> R (in dbSNP:rs2273343). FT /FTId=VAR_028784. FT VARIANT 156 156 C -> CHNH (in MASPD). FT /FTId=VAR_065814. FT VARIANT 371 371 D -> Y (in dbSNP:rs12711521). FT {ECO:0000269|Ref.5}. FT /FTId=VAR_028785. FT VARIANT 377 377 V -> A (associated with reduced MASP2 FT levels in plasma; no effect on catalytic FT activity; dbSNP:rs2273346). FT {ECO:0000269|PubMed:11426320, FT ECO:0000269|PubMed:17252003}. FT /FTId=VAR_028786. FT VARIANT 405 405 V -> M (in dbSNP:rs61735594). FT {ECO:0000269|PubMed:25930971}. FT /FTId=VAR_075088. FT VARIANT 439 439 R -> H (in dbSNP:rs12085877). FT /FTId=VAR_028787. FT MUTAGEN 74 74 Y->A: Strongly decreases affinity for FT MBL2. Decreases affinity for FCN2. FT {ECO:0000269|PubMed:15117939}. FT MUTAGEN 121 121 Y->A: Strongly decreases affinity for FT MBL2, but not for FCN2. FT {ECO:0000269|PubMed:15117939}. FT MUTAGEN 124 124 E->A: Decreases affinity for MBL2. Slight FT decrease in affinity for FCN2. FT {ECO:0000269|PubMed:15117939}. FT MUTAGEN 444 444 R->Q: Abolishes autocatalytic cleavage. FT {ECO:0000269|PubMed:16040602}. FT CONFLICT 41 41 N -> S (in Ref. 7; BAF83512). FT {ECO:0000305}. FT CONFLICT 225 225 L -> P (in Ref. 7; BAF83512). FT {ECO:0000305}. FT CONFLICT 298 299 QP -> HA (in Ref. 1; CAA71059, 3; FT CAB50733/CAB50735, 4; CAA67050 and 6; FT AAG50274). {ECO:0000305}. FT CONFLICT 361 362 Missing (in Ref. 3; CAB50733/CAB50735). FT {ECO:0000305}. FT CONFLICT 372 372 L -> LCS (in Ref. 3; CAB50733/CAB50735). FT {ECO:0000305}. FT CONFLICT 399 399 T -> A (in Ref. 7; BAF83512). FT {ECO:0000305}. FT CONFLICT 442 442 G -> E (in Ref. 6; AAG50274). FT {ECO:0000305}. FT CONFLICT 447 447 G -> E (in Ref. 6; AAG50274). FT {ECO:0000305}. FT CONFLICT 461 462 Missing (in Ref. 3; CAB50733/CAB50735). FT {ECO:0000305}. FT CONFLICT 473 473 L -> LIL (in Ref. 3; CAB50733/CAB50735). FT {ECO:0000305}. FT STRAND 27 31 {ECO:0000244|PDB:1SZB}. FT TURN 33 36 {ECO:0000244|PDB:1SZB}. FT STRAND 44 50 {ECO:0000244|PDB:1SZB}. FT STRAND 55 65 {ECO:0000244|PDB:1SZB}. FT STRAND 74 89 {ECO:0000244|PDB:1SZB}. FT TURN 93 96 {ECO:0000244|PDB:1SZB}. FT STRAND 98 100 {ECO:0000244|PDB:1SZB}. FT STRAND 109 118 {ECO:0000244|PDB:1SZB}. FT STRAND 129 138 {ECO:0000244|PDB:1SZB}. FT STRAND 151 159 {ECO:0000244|PDB:1SZB}. FT STRAND 162 166 {ECO:0000244|PDB:1SZB}. FT STRAND 171 173 {ECO:0000244|PDB:1SZB}. FT STRAND 309 313 {ECO:0000244|PDB:1ZJK}. FT STRAND 323 328 {ECO:0000244|PDB:1ZJK}. FT STRAND 332 336 {ECO:0000244|PDB:1ZJK}. FT STRAND 345 348 {ECO:0000244|PDB:1ZJK}. FT STRAND 350 356 {ECO:0000244|PDB:1ZJK}. FT STRAND 360 363 {ECO:0000244|PDB:1ZJK}. FT STRAND 375 382 {ECO:0000244|PDB:3TVJ}. FT STRAND 391 396 {ECO:0000244|PDB:3TVJ}. FT TURN 398 400 {ECO:0000244|PDB:3TVJ}. FT STRAND 401 403 {ECO:0000244|PDB:3TVJ}. FT STRAND 409 412 {ECO:0000244|PDB:3TVJ}. FT STRAND 416 420 {ECO:0000244|PDB:3TVJ}. FT STRAND 430 432 {ECO:0000244|PDB:3TVJ}. FT STRAND 459 473 {ECO:0000244|PDB:3TVJ}. FT TURN 474 476 {ECO:0000244|PDB:3TVJ}. FT STRAND 477 480 {ECO:0000244|PDB:3TVJ}. FT HELIX 482 485 {ECO:0000244|PDB:3TVJ}. FT TURN 487 490 {ECO:0000244|PDB:3TVJ}. FT STRAND 496 500 {ECO:0000244|PDB:3TVJ}. FT STRAND 510 519 {ECO:0000244|PDB:3TVJ}. FT STRAND 534 540 {ECO:0000244|PDB:3TVJ}. FT HELIX 558 561 {ECO:0000244|PDB:3TVJ}. FT STRAND 567 573 {ECO:0000244|PDB:3TVJ}. FT STRAND 577 579 {ECO:0000244|PDB:1ZJK}. FT STRAND 586 592 {ECO:0000244|PDB:3TVJ}. FT HELIX 595 603 {ECO:0000244|PDB:3TVJ}. FT STRAND 604 606 {ECO:0000244|PDB:1ZJK}. FT STRAND 616 620 {ECO:0000244|PDB:3TVJ}. FT STRAND 636 641 {ECO:0000244|PDB:3TVJ}. FT TURN 642 645 {ECO:0000244|PDB:3TVJ}. FT STRAND 646 659 {ECO:0000244|PDB:3TVJ}. FT STRAND 667 671 {ECO:0000244|PDB:3TVJ}. FT HELIX 672 675 {ECO:0000244|PDB:3TVJ}. FT HELIX 676 685 {ECO:0000244|PDB:3TVJ}. SQ SEQUENCE 686 AA; 75702 MW; ED952085FA115E21 CRC64; MRLLTLLGLL CGSVATPLGP KWPEPVFGRL ASPGFPGEYA NDQERRWTLT APPGYRLRLY FTHFDLELSH LCEYDFVKLS SGAKVLATLC GQESTDTERA PGKDTFYSLG SSLDITFRSD YSNEKPFTGF EAFYAAEDID ECQVAPGEAP TCDHHCHNHL GGFYCSCRAG YVLHRNKRTC SALCSGQVFT QRSGELSSPE YPRPYPKLSS CTYSISLEEG FSVILDFVES FDVETHPETL CPYDFLKIQT DREEHGPFCG KTLPHRIETK SNTVTITFVT DESGDHTGWK IHYTSTAQPC PYPMAPPNGH VSPVQAKYIL KDSFSIFCET GYELLQGHLP LKSFTAVCQK DGSWDRPMPA CSIVDCGPPD DLPSGRVEYI TGPGVTTYKA VIQYSCEETF YTMKVNDGKY VCEADGFWTS SKGEKSLPVC EPVCGLSART TGGRIYGGQK AKPGDFPWQV LILGGTTAAG ALLYDNWVLT AAHAVYEQKH DASALDIRMG TLKRLSPHYT QAWSEAVFIH EGYTHDAGFD NDIALIKLNN KVVINSNITP ICLPRKEAES FMRTDDIGTA SGWGLTQRGF LARNLMYVDI PIVDHQKCTA AYEKPPYPRG SVTANMLCAG LESGGKDSCR GDSGGALVFL DSETERWFVG GIVSWGSMNC GEAGQYGVYT KVINYIPWIE NIISDF //