1p8v - Revision history

OCA at 05:53, 17 April 2024

2024-04-17T05:53:37Z

←Older revision		Revision as of 05:53, 17 April 2024
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	<StructureSection load='1p8v' size='340' side='right'caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='1p8v' size='340' side='right'caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1p8v]] is a 3 chain structure with sequence from ~~[https://en.wikipedia.org/wiki/Human Human] and~~ [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P8V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1p8v]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P8V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>~~</td></tr>~~	+	</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution\|Resolution]] 2.6Å</td></tr>
-	~~<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat">~~<scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene~~></td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>~~	+
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>	+
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [https://pdbe.org/1p8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [https://www.ebi.ac.uk/pdbsum/1p8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p8v ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [https://pdbe.org/1p8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [https://www.ebi.ac.uk/pdbsum/1p8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p8v ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[https://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[https://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[https://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[https://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref> [[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[https://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[https://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[https://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>	+	[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[https://omim.org/entry/258660 258660]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[https://omim.org/entry/231200 231200]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[https://omim.org/entry/153670 153670]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[https://omim.org/entry/177820 177820]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium. [[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>	+	[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium.
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
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	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1p8v ConSurf].		</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1p8v ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
-	<div style="background-color:#fffaf0;">
-	== Publication Abstract from PubMed ==
-	Direct interaction between platelet receptor glycoprotein Ibalpha (GpIbalpha) and thrombin is required for platelet aggregation and activation at sites of vascular injury. Abnormal GpIbalpha-thrombin binding is associated with many pathological conditions,including occlusive arterial thrombosis and bleeding disorders. The crystal structure of the GpIbalpha-thrombin complex at 2.6 angstrom resolution reveals simultaneous interactions of GpIbalpha with exosite I of one thrombin molecule,and with exosite II of a second thrombin molecule. In the crystal lattice,the periodic arrangement of GpIbalpha-thrombin complexes mirrors a scaffold that could serve as a driving force for tight platelet adhesion. The details of these interactions reconcile GpIbalpha-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs.
-
-	Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation.,Dumas JJ, Kumar R, Seehra J, Somers WS, Mosyak L Science. 2003 Jul 11;301(5630):222-6. PMID:12855811<ref>PMID:12855811</ref>
-
-	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	</div>
-	<div class="pdbe-citations 1p8v" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
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	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Human]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	~~[[Category: Thrombin]]~~	+	[[Category: Dumas JJ]]
-	[[Category: Dumas~~, J J~~]]	+	[[Category: Kumar R]]
-	[[Category: Kumar, R]]	+	[[Category: Mosyak L]]
-	[[Category: Mosyak, L]]	+	[[Category: Seehra J]]
-	[[Category: Seehra, J]]	+	[[Category: Somers WS]]
-	[[Category: Somers~~, W S]]~~	+
-	~~[[Category: Leucine rich repeat domain]]~~	+
-	~~[[Category: Membrane protein-hydrolase complex]]~~	+
-	~~[[Category: Platelet glycoprotein receptor~~]]	+

OCA at 15:13, 27 October 2021

2021-10-27T15:13:34Z

OCA at 07:26, 9 December 2020

2020-12-09T07:26:08Z

←Older revision		Revision as of 07:26, 9 December 2020
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	==CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A==		==CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A==
-	<StructureSection load='1p8v' size='340' side='right' caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>	+	<StructureSection load='1p8v' size='340' side='right'caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1p8v]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8V OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1P8V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1p8v]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8V OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1P8V FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [http://pdbe.org/1p8v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [http://www.ebi.ac.uk/pdbsum/1p8v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p8v ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [http://pdbe.org/1p8v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [http://www.ebi.ac.uk/pdbsum/1p8v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p8v ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
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	</div>		</div>
	<div class="pdbe-citations 1p8v" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1p8v" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Platelet glycoprotein\|Platelet glycoprotein]]
		+	*[[Thrombin 3D Structures\|Thrombin 3D Structures]]
	== References ==		== References ==
	<references/>		<references/>
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	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Dumas, J J]]		[[Category: Dumas, J J]]

OCA at 07:58, 15 February 2018

2018-02-15T07:58:52Z

←Older revision		Revision as of 07:58, 15 February 2018
Line 1:		Line 1:
		+
	==CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A==		==CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A==
	<StructureSection load='1p8v' size='340' side='right' caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='1p8v' size='340' side='right' caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>
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	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [http://pdbe.org/1p8v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [http://www.ebi.ac.uk/pdbsum/1p8v PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [http://pdbe.org/1p8v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [http://www.ebi.ac.uk/pdbsum/1p8v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1p8v ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 17:		Line 18:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p8/1p8v_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p8/1p8v_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1p8v ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 32:		Line 33:
	</div>		</div>
	<div class="pdbe-citations 1p8v" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 1p8v" style="background-color:#fffaf0;"></div>
-
-	==See Also==
-	*[[Platelet-receptor glycoprotein Ib alpha\|Platelet-receptor glycoprotein Ib alpha]]
-	*[[Thrombin\|Thrombin]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 01:54, 12 September 2015

2015-09-12T01:54:54Z

←Older revision		Revision as of 01:54, 12 September 2015
Line 2:		Line 2:
	<StructureSection load='1p8v' size='340' side='right' caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='1p8v' size='340' side='right' caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1p8v]] is a 3 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=1P8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P8V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1p8v]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P8V FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 ~~Homo sapiens~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [http://www.ebi.ac.uk/pdbsum/1p8v PDBsum]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [http://pdbe.org/1p8v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [http://www.ebi.ac.uk/pdbsum/1p8v PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 31:		Line 31:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 1p8v" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 40:		Line 41:
	</StructureSection>		</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
		+	[[Category: Human]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
	[[Category: Dumas, J J]]		[[Category: Dumas, J J]]

OCA at 07:31, 6 January 2015

2015-01-06T07:31:31Z

←Older revision		Revision as of 07:31, 6 January 2015
Line 1:		Line 1:
-	~~{{STRUCTURE_1p8v\| PDB=1p8v \| SCENE= }}~~	+	==CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A==
-	===CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A===	+	<StructureSection load='1p8v' size='340' side='right' caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>
-	~~{{ABSTRACT_PUBMED_12855811}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[1p8v]] is a 3 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=1P8V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P8V FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [http://www.ebi.ac.uk/pdbsum/1p8v PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref> [[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[http://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[http://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[http://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[http://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium. [[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/p8/1p8v_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Direct interaction between platelet receptor glycoprotein Ibalpha (GpIbalpha) and thrombin is required for platelet aggregation and activation at sites of vascular injury. Abnormal GpIbalpha-thrombin binding is associated with many pathological conditions,including occlusive arterial thrombosis and bleeding disorders. The crystal structure of the GpIbalpha-thrombin complex at 2.6 angstrom resolution reveals simultaneous interactions of GpIbalpha with exosite I of one thrombin molecule,and with exosite II of a second thrombin molecule. In the crystal lattice,the periodic arrangement of GpIbalpha-thrombin complexes mirrors a scaffold that could serve as a driving force for tight platelet adhesion. The details of these interactions reconcile GpIbalpha-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs.

-	~~==Disease==~~	+	Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation.,Dumas JJ, Kumar R, Seehra J, Somers WS, Mosyak L Science. 2003 Jul 11;301(5630):222-6. PMID:12855811<ref>PMID:12855811</ref>
-	~~[[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause~~ of ~~susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to~~ the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-~~existent cups have an anatomical predisposition~~ for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet ~~disease (GPD)~~. BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref><ref>PMID:7690774</ref><ref>PMID:7819107</ref><ref>PMID:7873390</ref><ref>PMID:9639514</ref><ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, ~~normal platelet function~~, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref><ref>PMID:2052556</ref><ref>PMID:8486780</ref><ref>PMID:8384898</ref> [[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[http://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref><ref>PMID:6405779</ref><ref>PMID:3771562</ref><ref>PMID:3567158</ref><ref>PMID:3801671</ref><ref>PMID:3242619</ref><ref>PMID:2719946</ref><ref>PMID:1354985</ref><ref>PMID:1421398</ref><ref>PMID:1349838</ref><ref>PMID:7865694</ref><ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[http://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, ~~sensory and/or cognitive function. Ischemic strokes~~, ~~resulting from vascular occlusion~~, ~~is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors~~.~~<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect~~ (~~THPH1~~) ~~[MIM~~:[http://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-~~prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis~~. ~~Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM~~:[http://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:~~11506076~~</ref>	+

-	~~==Function==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[http://www.uniprot.org/uniprot~~/~~GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib~~, a ~~surface membrane protein~~ of ~~platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to~~ the ~~subendothelium~~. ~~[[http://www~~.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<~~ref~~>~~PMID:2856554~~</~~ref~~>	+	</div>
-		+
-	~~==About this Structure==~~	+
-	[[1p8v]] is a 3 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=1P8V OCA].	+

	==See Also==		==See Also==
	*[[Platelet-receptor glycoprotein Ib alpha\|Platelet-receptor glycoprotein Ib alpha]]		*[[Platelet-receptor glycoprotein Ib alpha\|Platelet-receptor glycoprotein Ib alpha]]
	*[[Thrombin\|Thrombin]]		*[[Thrombin\|Thrombin]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	~~<ref group="xtra">PMID:012855811</ref><ref group="xtra">PMID:016342940</ref><ref group="xtra">PMID:016673263</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
-	[[Category: Dumas, J J.]]	+	[[Category: Dumas, J J]]
-	[[Category: Kumar, R.]]	+	[[Category: Kumar, R]]
-	[[Category: Mosyak, L.]]	+	[[Category: Mosyak, L]]
-	[[Category: Seehra, J.]]	+	[[Category: Seehra, J]]
-	[[Category: Somers, W S.]]	+	[[Category: Somers, W S]]
	[[Category: Leucine rich repeat domain]]		[[Category: Leucine rich repeat domain]]
	[[Category: Membrane protein-hydrolase complex]]		[[Category: Membrane protein-hydrolase complex]]
	[[Category: Platelet glycoprotein receptor]]		[[Category: Platelet glycoprotein receptor]]

OCA at 06:16, 25 March 2013

2013-03-25T06:16:31Z

←Older revision		Revision as of 06:16, 25 March 2013
Line 1:		Line 1:
-	[[Image:1p8v.png\|left\|200px]]
-
	{{STRUCTURE_1p8v\| PDB=1p8v \| SCENE= }}		{{STRUCTURE_1p8v\| PDB=1p8v \| SCENE= }}
-
	===CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A===		===CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A===
		+	{{ABSTRACT_PUBMED_12855811}}

-	~~{{ABSTRACT_PUBMED_12855811}}~~	+	==Disease==
		+	[[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[http://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[http://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref><ref>PMID:7690774</ref><ref>PMID:7819107</ref><ref>PMID:7873390</ref><ref>PMID:9639514</ref><ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[http://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[http://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref><ref>PMID:2052556</ref><ref>PMID:8486780</ref><ref>PMID:8384898</ref> [[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[http://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref><ref>PMID:6405779</ref><ref>PMID:3771562</ref><ref>PMID:3567158</ref><ref>PMID:3801671</ref><ref>PMID:3242619</ref><ref>PMID:2719946</ref><ref>PMID:1354985</ref><ref>PMID:1421398</ref><ref>PMID:1349838</ref><ref>PMID:7865694</ref><ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[http://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[http://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[http://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
		+
		+	==Function==
		+	[[http://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium. [[http://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>

	==About this Structure==		==About this Structure==
Line 15:		Line 17:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:012855811</ref><ref group="xtra">PMID:016342940</ref><ref group="xtra">PMID:016673263</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012855811</ref><ref group="xtra">PMID:016342940</ref><ref group="xtra">PMID:016673263</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thrombin]]		[[Category: Thrombin]]

OCA at 22:19, 20 October 2012

2012-10-20T22:19:04Z

←Older revision		Revision as of 22:19, 20 October 2012
Line 8:		Line 8:

	==About this Structure==		==About this Structure==
-	[[1p8v]] is a 3 chain structure ~~of [[Platelet-receptor glycoprotein Ib alpha]] and [[Thrombin]]~~ 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=1P8V OCA].	+	[[1p8v]] is a 3 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=1P8V OCA].

	==See Also==		==See Also==

OCA: Protected "1p8v" [edit=sysop:move=sysop]

2012-07-27T15:55:12Z

Protected "1p8v" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:55, 27 July 2012

OCA at 15:55, 27 July 2012

2012-07-27T15:55:10Z

←Older revision		Revision as of 15:55, 27 July 2012
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-	{{Seed}}
	[[Image:1p8v.png\|left\|200px]]		[[Image:1p8v.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_1p8v\| PDB=1p8v \| SCENE= }}		{{STRUCTURE_1p8v\| PDB=1p8v \| SCENE= }}

	===CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A===		===CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_12855811}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 12855811 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_12855811}}		{{ABSTRACT_PUBMED_12855811}}
-
-	==Disease==
-	Known disease associated with this structure: Bernard-Soulier syndrome, benign autosomal dominant OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]], Bernard-Soulier syndrome, type A OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]], von Willebrand disease, platelet-type OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]], Nonarteritic anterior ischemic optic neuropathy, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=606672 606672]]

	==About this Structure==		==About this Structure==
-	~~1P8V~~ is a 3 ~~chains~~ structure of ~~sequences~~ 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=1P8V OCA].	+	[[1p8v]] is a 3 chain structure of [[Platelet-receptor glycoprotein Ib alpha]] and [[Thrombin]] 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=1P8V OCA].
		+
		+	==See Also==
		+	*[[Platelet-receptor glycoprotein Ib alpha\|Platelet-receptor glycoprotein Ib alpha]]
		+	*[[Thrombin\|Thrombin]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~12855811~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:012855811</ref><ref group="xtra">PMID:016342940</ref><ref group="xtra">PMID:016673263</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Thrombin]]		[[Category: Thrombin]]
Line 35:		Line 24:
	[[Category: Somers, W S.]]		[[Category: Somers, W S.]]
	[[Category: Leucine rich repeat domain]]		[[Category: Leucine rich repeat domain]]
		+	[[Category: Membrane protein-hydrolase complex]]
	[[Category: Platelet glycoprotein receptor]]		[[Category: Platelet glycoprotein receptor]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Feb 18 09:34:34 2009''

←Older revision		Revision as of 15:13, 27 October 2021
Line 3:		Line 3:
	<StructureSection load='1p8v' size='340' side='right'caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>		<StructureSection load='1p8v' size='340' side='right'caption='[[1p8v]], [[Resolution\|resolution]] 2.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[1p8v]] is a 3 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human] and [~~http~~://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8V OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=1P8V FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[1p8v]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1P8V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P8V FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DFP:DIISOPROPYL+PHOSPHONATE'>DFP</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>		<tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue\|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TYS:O-SULFO-L-TYROSINE'>TYS</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GP1BA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
-	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [~~http~~://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>	+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [~~http~~://pdbe.org/1p8v PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/1p8v PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=1p8v ProSAT]</span></td></tr>	+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1p8v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p8v OCA], [https://pdbe.org/1p8v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p8v RCSB], [https://www.ebi.ac.uk/pdbsum/1p8v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p8v ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[[~~http~~://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[~~http~~://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[~~http~~://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[~~http~~://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[~~http~~://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref> [[~~http~~://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[~~http~~://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[~~http~~://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[~~http~~://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[~~http~~://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>	+	[[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] Genetic variations in GP1BA may be a cause of susceptibility to non-arteritic anterior ischemic optic neuropathy (NAION) [MIM:[https://omim.org/entry/258660 258660]]. NAION is an ocular disease due to ischemic injury to the optic nerve. It usually affects the optic disk and leads to visual loss and optic disk swelling of a pallid nature. Visual loss is usually sudden, or over a few days at most and is usually permanent, with some recovery possibly occurring within the first weeks or months. Patients with small disks having smaller or non-existent cups have an anatomical predisposition for non-arteritic anterior ischemic optic neuropathy. As an ischemic episode evolves, the swelling compromises circulation, with a spiral of ischemia resulting in further neuronal damage.<ref>PMID:14711733</ref> Defects in GP1BA are a cause of Bernard-Soulier syndrome (BSS) [MIM:[https://omim.org/entry/231200 231200]]; also known as giant platelet disease (GPD). BSS patients have unusually large platelets and have a clinical bleeding tendency.<ref>PMID:1730088</ref> <ref>PMID:7690774</ref> <ref>PMID:7819107</ref> <ref>PMID:7873390</ref> <ref>PMID:9639514</ref> <ref>PMID:10089893</ref> Defects in GP1BA are the cause of benign mediterranean macrothrombocytopenia (BMM) [MIM:[https://omim.org/entry/153670 153670]]; also known as autosomal dominant benign Bernard-Soulier syndrome. BMM is characterized by mild or no clinical symptoms, normal platelet function, and normal megakaryocyte count.<ref>PMID:11222377</ref> Defects in GP1BA are the cause of pseudo-von Willebrand disease (VWDP) [MIM:[https://omim.org/entry/177820 177820]]. A bleeding disorder is caused by an increased affinity of GP-Ib for soluble vWF resulting in impaired hemostatic function due to the removal of vWF from the circulation.<ref>PMID:14521605</ref> <ref>PMID:2052556</ref> <ref>PMID:8486780</ref> <ref>PMID:8384898</ref> [[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Defects in F2 are the cause of factor II deficiency (FA2D) [MIM:[https://omim.org/entry/613679 613679]]. It is a very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.<ref>PMID:14962227</ref> <ref>PMID:6405779</ref> <ref>PMID:3771562</ref> <ref>PMID:3567158</ref> <ref>PMID:3801671</ref> <ref>PMID:3242619</ref> <ref>PMID:2719946</ref> <ref>PMID:1354985</ref> <ref>PMID:1421398</ref> <ref>PMID:1349838</ref> <ref>PMID:7865694</ref> <ref>PMID:7792730</ref> Genetic variations in F2 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:15534175</ref> Defects in F2 are the cause of thrombophilia due to thrombin defect (THPH1) [MIM:[https://omim.org/entry/188050 188050]]. It is a multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation. Note=A common genetic variation in the 3-prime untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increased risk of venous thrombosis. Defects in F2 are associated with susceptibility to pregnancy loss, recurrent, type 2 (RPRGL2) [MIM:[https://omim.org/entry/614390 614390]]. A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions.<ref>PMID:11506076</ref>
	== Function ==		== Function ==
-	[[~~http~~://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium. [[~~http~~://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>	+	[[https://www.uniprot.org/uniprot/GP1BA_HUMAN GP1BA_HUMAN]] GP-Ib, a surface membrane protein of platelets, participates in the formation of platelet plugs by binding to the A1 domain of vWF, which is already bound to the subendothelium. [[https://www.uniprot.org/uniprot/THRB_HUMAN THRB_HUMAN]] Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.<ref>PMID:2856554</ref>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]