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4fxg

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[[Image:4fxg.png|left|200px]]
 
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{{STRUCTURE_4fxg| PDB=4fxg | SCENE= }}
{{STRUCTURE_4fxg| PDB=4fxg | SCENE= }}
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===Complement C4 in complex with MASP-2===
===Complement C4 in complex with MASP-2===
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{{ABSTRACT_PUBMED_22949645}}
{{ABSTRACT_PUBMED_22949645}}
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==Disease==
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[[http://www.uniprot.org/uniprot/MASP2_HUMAN MASP2_HUMAN]] Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:[http://omim.org/entry/613791 613791]]. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.<ref>PMID:12904520</ref><ref>PMID:17252003</ref> [[http://www.uniprot.org/uniprot/CO4A_HUMAN CO4A_HUMAN]] Defects in C4A are the cause of complement component 4A deficiency (C4AD) [MIM:[http://omim.org/entry/614380 614380]]. A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis.<ref>PMID:8473511</ref> Defects in C4A are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:[http://omim.org/entry/152700 152700]]. A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Note=Interindividual copy-number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE.<ref>PMID:17503323</ref>
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==Function==
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[[http://www.uniprot.org/uniprot/MASP2_HUMAN MASP2_HUMAN]] Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.<ref>PMID:10946292</ref> [[http://www.uniprot.org/uniprot/CO4A_HUMAN CO4A_HUMAN]] C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.
==About this Structure==
==About this Structure==
[[4fxg]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FXG OCA].
[[4fxg]] is a 10 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FXG OCA].
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==Reference==
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<references group="xtra"/><references/>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Mannan-binding lectin-associated serine protease-2]]
[[Category: Mannan-binding lectin-associated serine protease-2]]

Revision as of 12:09, 24 March 2013

Template:STRUCTURE 4fxg

Contents

Complement C4 in complex with MASP-2

Template:ABSTRACT PUBMED 22949645

Disease

[MASP2_HUMAN] Defects in MASP2 are the cause of MASP2 deficiency (MASPD) [MIM:613791]. MASPD is a disorder that results in autoimmune manifestations, recurrent severe infections, and chronic inflammatory disease.[1][2] [CO4A_HUMAN] Defects in C4A are the cause of complement component 4A deficiency (C4AD) [MIM:614380]. A rare defect of the complement classical pathway associated with the development of autoimmune disorders, mainly systemic lupus with or without associated glomerulonephritis.[3] Defects in C4A are a cause of susceptibility to systemic lupus erythematosus (SLE) [MIM:152700]. A chronic, inflammatory and often febrile multisystemic disorder of connective tissue. It affects principally the skin, joints, kidneys and serosal membranes. It is thought to represent a failure of the regulatory mechanisms of the autoimmune system. Note=Interindividual copy-number variation (CNV) of complement component C4 and associated polymorphisms result in different susceptibilities to SLE. The risk of SLE susceptibility has been shown to be significantly increased among subjects with only two copies of total C4. A high copy number is a protective factor against SLE.[4]

Function

[MASP2_HUMAN] Serum protease that plays an important role in the activation of the complement system via mannose-binding lectin. After activation by auto-catalytic cleavage it cleaves C2 and C4, leading to their activation and to the formation of C3 convertase.[5] [CO4A_HUMAN] C4 plays a central role in the activation of the classical pathway of the complement system. It is processed by activated C1 which removes from the alpha chain the C4a anaphylatoxin. The remaining alpha chain fragment C4b is the major activation product and is an essential subunit of the C3 convertase (C4b2a) and the C5 convertase (C3bC4b2a) enzymes of the classical complement pathway. Derived from proteolytic degradation of complement C4, C4a anaphylatoxin is a mediator of local inflammatory process. It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.

About this Structure

4fxg is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

  1. ↑ Stengaard-Pedersen K, Thiel S, Gadjeva M, Moller-Kristensen M, Sorensen R, Jensen LT, Sjoholm AG, Fugger L, Jensenius JC. Inherited deficiency of mannan-binding lectin-associated serine protease 2. N Engl J Med. 2003 Aug 7;349(6):554-60. PMID:12904520 doi:http://dx.doi.org/10.1056/NEJMoa022836
  2. ↑ Thiel S, Steffensen R, Christensen IJ, Ip WK, Lau YL, Reason IJ, Eiberg H, Gadjeva M, Ruseva M, Jensenius JC. Deficiency of mannan-binding lectin associated serine protease-2 due to missense polymorphisms. Genes Immun. 2007 Mar;8(2):154-63. Epub 2007 Jan 25. PMID:17252003 doi:10.1038/sj.gene.6364373
  3. ↑ Barba G, Rittner C, Schneider PM. Genetic basis of human complement C4A deficiency. Detection of a point mutation leading to nonexpression. J Clin Invest. 1993 Apr;91(4):1681-6. PMID:8473511 doi:http://dx.doi.org/10.1172/JCI116377
  4. ↑ Yang Y, Chung EK, Wu YL, Savelli SL, Nagaraja HN, Zhou B, Hebert M, Jones KN, Shu Y, Kitzmiller K, Blanchong CA, McBride KL, Higgins GC, Rennebohm RM, Rice RR, Hackshaw KV, Roubey RA, Grossman JM, Tsao BP, Birmingham DJ, Rovin BH, Hebert LA, Yu CY. Gene copy-number variation and associated polymorphisms of complement component C4 in human systemic lupus erythematosus (SLE): low copy number is a risk factor for and high copy number is a protective factor against SLE susceptibility in European Americans. Am J Hum Genet. 2007 Jun;80(6):1037-54. Epub 2007 Apr 26. PMID:17503323 doi:10.1086/518257
  5. ↑ Matsushita M, Thiel S, Jensenius JC, Terai I, Fujita T. Proteolytic activities of two types of mannose-binding lectin-associated serine protease. J Immunol. 2000 Sep 1;165(5):2637-42. PMID:10946292

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