Summary: Beta-2-glycoprotein-1 fifth domain
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Apolipoprotein H Edit Wikipedia article
|Apolipoprotein H (beta-2-glycoprotein I)|
Derived from PDB structure 1C1Z. Blue regions are positively charged and red regions are negatively charged.
|Symbols||; B2G1; B2GP1; BG|
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
Apolipoprotein H (Apo-H), previously known as (β2-glycoprotein I, beta-2 glycoprotein I), is a multifunctional apolipoprotein that in humans is encoded by the APOH gene. One of its functions is to bind cardiolipin. When bound the structure of cardiolipin and Apo-H both undergo large changes in structure. Within the structure of Apo-H is a stretch of positively charged amino acids, (protein sequence positions 282-287) Lys-Asn-Lys-Glu-Lys-Lys, are involved in phospholipid binding (See image on right).
Apo-H has a complex involvement in agglutination, it appears to alter ADP mediated agglutination of platelets. Normally Apo-H assumes an anti-coagulation activity in serum (by inhibiting coagulation factors), however changes in blood factors can result of a reversal of that activity.
Apo-H appears to completely inhibit serotonin release by the platelets and prevents subsequent waves of the ADP-induced aggregation. The activity of Apo-H appears to involve the binding of agglutinating, negatively charged compounds, and inhibits agglutination by the contact activation of the intrinsic blood coagulation pathway. Apo-H causes a reduction of the prothrombinase binding sites on platelets and reduces the activation caused by collagen when thrombin is present at physiological serum concentrations of Apo-H suggesting a regulatory role of Apo-H in coagulation.
In addition, Apo-H inhibits the activation of protein C blocking its activity on phosphatidylserine:phosphatidylcholine vesicles however once protein C is activated, Apo-H fails to inhibit activity. Since protein C is involved in factor Va degradation Apo-H indirectly inhibits the degradation of factor Va. This inhibitory activity was diminished by adding phospholipids suggesting the Apo-H inhibition of protein C is phospholipid competitive. This indicates that under certain conditions Apo-H takes on a procoagulation properties.
Anti-cardiolipin antibodies are found in both infectious (syphilis) and autoimmune disease (sclerosis, lupus). The activity of anti-cardiolipin antibodies in autoimmune antiphospholipid syndrome requires apolipoprotein H. The subset of antibodies that bind Apo-H and alter its activity are considered different from antibodies that bind thrombin, serum phospholipids and are called anti-apolipoprotein antibodies. In autoimmune disease, anti-apolipoprotein antibodies (Anti β2 glycoprotein I antibodies) strongly associate with thrombotic forms of lupus and sclerosis.
Sushi 2 protein domain
NMR structure of the fifth domain of human beta-2-glycoprotein I
In molecular biology, the protein domain Sushi 2 is also known as the fifth protein domain of beta-2-glycoprotein-1 (b2GP-1). This protein domain is only found in eukaryotes. The first four domains found in Apolipoprotein H resemble each other, however the fifth one appears to be different.
This protein domain is composed of four well-defined anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop. Additionally, the fifth protein domain appears to resemble the other four in Apolipoprotein with the exception of three internal disulfide bonds and an extra C-terminal loop.
Its exact function remains to be fully elucidated, however it is known to play an important role in the binding of b2GP-1 to negatively charged compounds and subsequent capture for binding of anti-b2GP-1 antibodies. Problems such as a mutation in this protein would lead to Antiphospholipid syndrome which often leads to pregnancy complications.
- Borchman D, Harris EN, Pierangeli SS, Lamba OP (1995). "Interactions and molecular structure of cardiolipin and beta 2-glycoprotein 1 (beta 2-GP1)". Clin. Exp. Immunol. 102 (2): 373–8. doi:10.1111/j.1365-2249.1995.tb03792.x. PMC 1553418. PMID 7586693.
- Sheng Y, Sali A, Herzog H, Lahnstein J, Krilis SA (1996). "Site-directed mutagenesis of recombinant human beta 2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity". J. Immunol. 157 (8): 3744–51. PMID 8871678.
- Nimpf J, Wurm H, Kostner GM (1985). "Interaction of beta 2-glycoprotein-I with human blood platelets: influence upon the ADP-induced aggregation". Thromb. Haemost. 54 (2): 397–401. PMID 4082080.
- Nimpf J, Wurm H, Kostner GM (1987). "Beta 2-glycoprotein-I (apo-H) inhibits the release reaction of human platelets during ADP-induced aggregation". Atherosclerosis 63 (2–3): 109–14. doi:10.1016/0021-9150(87)90110-9. PMID 3827975.
- Schousboe I (1985). "beta 2-Glycoprotein I: a plasma inhibitor of the contact activation of the intrinsic blood coagulation pathway". Blood 66 (5): 1086–91. PMID 4052628.
- Nimpf J, Bevers EM, Bomans PH; et al. (1986). "Prothrombinase activity of human platelets is inhibited by beta 2-glycoprotein-I". Biochim. Biophys. Acta 884 (1): 142–9. doi:10.1016/0304-4165(86)90237-0. PMID 3768409.
- Shi W, Chong BH, Hogg PJ, Chesterman CN (1993). "Anticardiolipin antibodies block the inhibition by beta 2-glycoprotein I of the factor Xa generating activity of platelets". Thromb. Haemost. 70 (2): 342–5. PMID 8236146.
- Schousboe I, Rasmussen MS (1995). "Synchronized inhibition of the phospholipid mediated autoactivation of factor XII in plasma by beta 2-glycoprotein I and anti-beta 2-glycoprotein I". Thromb. Haemost. 73 (5): 798–804. PMID 7482406.
- Keeling DM, Wilson AJ, Mackie IJ, Isenberg DA, Machin SJ (1993). "Role of beta 2-glycoprotein I and anti-phospholipid antibodies in activation of protein C in vitro". J. Clin. Pathol. 46 (10): 908–11. doi:10.1136/jcp.46.10.908. PMC 501616. PMID 8227406.
- Matsuda J, Gohchi K, Kawasugi K, Gotoh M, Saitoh N, Tsukamoto M (1995). "Inhibitory activity of anti-beta 2-glycoprotein I antibody on factor Va degradation by activated-protein C and its cofactor protein S". Am. J. Hematol. 49 (1): 89–91. doi:10.1002/ajh.2830490116. PMID 7741146.
- Mori T, Takeya H, Nishioka J, Gabazza EC, Suzuki K (1996). "beta 2-Glycoprotein I modulates the anticoagulant activity of activated protein C on the phospholipid surface". Thromb. Haemost. 75 (1): 49–55. PMID 8713779.
- Kumar KS, Jyothy A, Prakash MS, Rani HS, Reddy PP (2002). "Beta2-glycoprotein I dependent anticardiolipin antibodies and lupus anticoagulant in patients with recurrent pregnancy loss". Journal of postgraduate medicine 48 (1): 5–10. PMID 12082318.
- McNeil HP, Simpson RJ, Chesterman CN, Krilis SA (1990). "Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H)". Proc. Natl. Acad. Sci. U.S.A. 87 (11): 4120–4. doi:10.1073/pnas.87.11.4120. PMC 54059. PMID 2349221.
- Hunt JE, McNeil HP, Morgan GJ, Crameri RM, Krilis SA (1992). "A phospholipid-beta 2-glycoprotein I complex is an antigen for anticardiolipin antibodies occurring in autoimmune disease but not with infection". Lupus 1 (2): 75–81. doi:10.1177/096120339200100204. PMID 1301967.
- Shi T, Giannakopoulos B, Iverson GM, Cockerill KA, Linnik MD, Krilis SA (2005). "Domain V of beta2-glycoprotein I binds factor XI/XIa and is cleaved at Lys317-Thr318.". J Biol Chem 280 (2): 907–12. doi:10.1074/jbc.M410291200. PMID 15522884.
- Hoshino M, Hagihara Y, Nishii I, Yamazaki T, Kato H, Goto Y (December 2000). "Identification of the phospholipid-binding site of human beta(2)-glycoprotein I domain V by heteronuclear magnetic resonance". J. Mol. Biol. 304 (5): 927–39. doi:10.1006/jmbi.2000.4243. PMID 11124037.
- Apolipoprotein H at the US National Library of Medicine Medical Subject Headings (MeSH)
- Apolipoprotein H and Applied Research
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Beta-2-glycoprotein-1 fifth domain Provide feedback
The fifth domain of beta-2-glycoprotein-1 (b2GP-1) is composed of four well-defined anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop. It plays an important role in the binding of b2GP-1 to negatively charged compounds and subsequent capture for binding of anti-b2GP-1 antibodies .
Hoshino M, Hagihara Y, Nishii I, Yamazaki T, Kato H, Goto Y; , J Mol Biol. 2000;304:927-939.: Identification of the phospholipid-binding site of human beta(2)-glycoprotein I domain V by heteronuclear magnetic resonance. PUBMED:11124037 EPMC:11124037
This tab holds annotation information from the InterPro database.
InterPro entry IPR015104
The fifth domain of beta-2-glycoprotein-1 (b2GP-1) is composed of four well-defined anti-parallel beta-strands and two short alpha-helices, as well as a long highly flexible loop. It plays an important role in the binding of b2GP-1 to negatively charged compounds and subsequent capture for binding of anti-b2GP-1 antibodies [PUBMED:11124037].
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|Author:||Mistry J, Sammut SJ|
|Number in seed:||25|
|Number in full:||85|
|Average length of the domain:||84.90 aa|
|Average identity of full alignment:||48 %|
|Average coverage of the sequence by the domain:||24.29 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||7|
|Download:||download the raw HMM for this family|
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There are 3 interactions for this family. More...
We determine these interactions using iPfam, which considers the interactions between residues in three-dimensional protein structures and maps those interactions back to Pfam families. You can find more information about the iPfam algorithm in the journal article that accompanies the website.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Sushi_2 domain has been found. There are 8 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
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