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Prothrombin structure
P00734
THRB_HUMAN
F2

Prothrombin

Homo sapiensTaxon: 9606

3D-structureAcute phaseBlood coagulationCalciumCleavage on pair of basic residuesDirect protein sequencingDisease variantDisulfide bondGamma-carboxyglutamic acidGlycoproteinHemostasisHydrolase+11
配列長

622

アミノ酸

分子量

70.0 kDa

理論値

実験構造

50

PDB エントリー

関連疾患

4

記録済み

機能記述

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. Activates coagulation factor XI (F11); activation is promoted by the contact with negatively charged surfaces (PubMed:2019570, PubMed:21976677). Triggers the production of pro-inflammatory cytokines, such as MCP-1/CCL2 and IL8/CXCL8, in endothelial cells (PubMed:30568593, PubMed:9780208)
凝血酶在精氨酸和赖氨酸后裂解键，将纤维蛋白原转化为纤维蛋白，并激活因子 V、VII、VIII、XIII，并与血栓调节蛋白复合，激活蛋白 C。在血液稳态、炎症和伤口愈合中发挥作用。 激活凝血因子 XI (F11)； 与带负电的表面接触会促进激活（PubMed：2019570，PubMed：21976677）。 触发内皮细胞中促炎细胞因子的产生，例如 MCP-1/CCL2 和 IL8/CXCL8 (PubMed:30568593、PubMed:9780208)
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局在と分布

組織特異性

Expressed by the liver and secreted in plasma

関連疾患

Factor II deficiency

A very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.

Ischemic stroke

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.

Thrombophilia due to thrombin defect

A multifactorial disorder of hemostasis characterized by abnormal platelet aggregation in response to various agents and recurrent thrombi formation.

Pregnancy loss, recurrent, 2

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.

アミノ酸配列

MAHVRGLQLPGCLALAALCSLVHSQHVFLAPQQARSLLQRVRRANTFLEEVRKGNLEREC
VEETCSYEEAFEALESSTATDVFWAKYTACETARTPRDKLAACLEGNCAEGLGTNYRGHV
NITRSGIECQLWRSRYPHKPEINSTTHPGADLQENFCRNPDSSTTGPWCYTTDPTVRRQE
CSIPVCGQDQVTVAMTPRSEGSSVNLSPPLEQCVPDRGQQYQGRLAVTTHGLPCLAWASA

FASTA 形式 · 622 アミノ酸 · 分子量 70.0 kDa

実験構造

50 PDB エントリー
1A2C1A3B1A3E1A461A4W1A5G1A611ABI1ABJ1AD81AE81AFE1AHT1AI81AIX1AWF1AWH1AY61B5G1B7X1BA81BB01BCU1BHX1BMM1BMN1BTH1C1U1C1V1C1W1C4U1C4V1C4Y1C5L1C5N1C5O1CA81D3D1D3P1D3Q1D3T1D4P1D6W1D9I1DE71DIT1DM41DOJ1DWB1DWC

翻訳後修飾

  • •The gamma-carboxyglutamyl residues, which bind calcium ions, result from the carboxylation of glutamyl residues by a microsomal enzyme, the vitamin K-dependent carboxylase. The modified residues are necessary for the calcium-dependent interaction with a negatively charged phospholipid surface, which is essential for the conversion of prothrombin to thrombin
  • •N-glycosylated. N-glycan heterogeneity at Asn-121: Hex3HexNAc3 (minor), Hex4HexNAc3 (minor) and Hex5HexNAc4 (major). At Asn-143: Hex4HexNAc3 (minor) and Hex5HexNAc4 (major)
  • •In the penultimate step of the coagulation cascade, prothrombin is converted to thrombin by the prothrombinase complex composed of factor Xa (F10), cofactor Va (F5), and phospholipids. This activation requires factor Xa-catalyzed sequential cleavage at 2 sites, Arg-314 and Arg-363, along 2 possible pathways. In the first pathway, the first cleavage occurs at Arg-314, leading to the formation of the inactive intermediate prethrombin-2. This pathway preferentially occurs on platelets and in the absence of cofactor Va. In the second pathway, the first cleavage occurs at Arg-363, which separates protease domain into 2 chains that remain connected through a disulfide bond and generates the active intermediate meizothrombin. The presence of cofactor Va directs activation along the meizothrombin pathway and greatly accelerates the rate of cleavage at Arg-363, but has a smaller effect on the cleavage of meizothrombin at Arg-314. Meizothrombin accumulates as an intermediate when prothrombinase is assembled on the membrane of red blood cells