Trombin

Trombin
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1A2C, 1A3B, 1A3E, 1ABI, 1ABJ, 1AD8, 1AE8, 1AI8, 1AIX, 1AWF, 1AWH, 1AY6, 1B5G, 1B7X, 1BA8, 1BB0, 1BCU, 1BHX, 1BMM, 1BMN, 1BTH, 1C1U, 1C1V, 1C1W, 1C4U, 1C4V, 1C4Y, 1C5L, 1C5N, 1C5O, 1CA8, 1D3D, 1D3P, 1D3Q, 1D3T, 1D4P, 1D6W, 1D9I, 1DE7, 1DIT, 1DM4, 1DOJ, 1DWB, 1DWC, 1DWD, 1DX5, 1E0F, 1EB1, 1EOJ, 1EOL, 1FPC, 1G30, 1G32, 1G37, 1GHV, 1GHW, 1GHX, 1GHY, 1GJ4, 1GJ5, 1H8D, 1H8I, 1HAI, 1HAO, 1HAP, 1HBT, 1HLT, 1HUT, 1HXE, 1HXF, 1IHS, 1JMO, 1JOU, 1JWT, 1K21, 1K22, 1KTS, 1KTT, 1LHC, 1LHD, 1LHE, 1LHF, 1LHG, 1MH0, 1MU6, 1MU8, 1MUE, 1NM6, 1NRN, 1NRO, 1NRP, 1NRQ, 1NRR, 1NRS, 1NT1, 1NU7, 1NU9, 1NY2, 1NZQ, 1O0D, 1O2G, 1O5G, 1OOK, 1OYT, 1P8V, 1PPB, 1QBV, 1QHR, 1QJ1, 1QJ6, 1QJ7, 1QUR, 1RD3, 1RIW, 1SB1, 1SFQ, 1SG8, 1SGI, 1SHH, 1SL3, 1SR5, 1T4U, 1T4V, 1TA2, 1TA6, 1TB6, 1THP, 1THR, 1THS, 1TMB, 1TMU, 1TOM, 1TQ0, 1TQ7, 1TWX, 1UVS, 1VR1, 1VZQ, 1W7G, 1WAY, 1WBG, 1XM1, 1XMN, 1YPE, 1YPG, 1YPJ, 1YPK, 1YPL, 1YPM, 1Z71, 1Z8I, 1Z8J, 1ZGI, 1ZGV, 1ZRB, 2A0Q, 2A2X, 2A45, 2AFQ, 2ANK, 2ANM, 2B5T, 2BDY, 2BVR, 2BVS, 2BVX, 2BXT, 2BXU, 2C8Y, 2FEQ, 2FES, 2GDE, 2GP9, 2H9T, 2HGT, 2HNT, 2HPP, 2HPQ, 2HWL, 2JH0, 2JH6, 2OD3, 2PGB, 2PGQ, 2PW8, 2R2M, 2THF, 2ZFQ, 2ZFR, 2ZG0, 2ZHE, 2ZHF, 2ZHW, 2ZI2, 2ZIQ, 2ZNK, 2ZO3, 3B23, 3B9F, 3BEF, 3BEI, 3BF6, 3BIU, 3BIV, 3BV9, 3C1K, 3C27, 3D49, 3DA9, 3DD2, 3DT0, 3DUX, 3E6P, 3EE0, 3EQ0, 3F68, 3GIC, 3GIS, 3HAT, 3HKJ, 3HTC, 3JZ2, 3LDX, 3LU9, 3NXP, 3P17, 3P6Z, 3P70, 3PO1, 3QGN, 3QLP, 3QTO, 3QTV, 3QWC, 3QX5, 3R3G, 3RLW, 3RLY, 3RM0, 3RM2, 3RML, 3RMM, 3RMN, 3RMO, 3S7H, 3S7K, 3SHA, 3SHC, 3SI3, 3SI4, 3SQE, 3SQH, 3SV2, 3T5F, 3TU7, 3U69, 3U8O, 3U8R, 3U8T, 3U98, 3U9A, 3UTU, 3UWJ, 3VXE, 3VXF, 4BAH, 4BAK, 4BAM, 4BAN, 4BAO, 4BAQ, 4BOH, 4DIH, 4DII, 4DT7, 4DY7, 4E05, 4E06, 4E7R, 4H6S, 4H6T, 4HFP, 4HTC, 4THN, 5GDS, 7KME, 8KME, 1A46, 1A4W, 1A5G, 1A61, 1AFE, 1AHT, 1DWE, 1FPH, 1HAG, 1HAH, 1HDT, 1HGT, 1IHT, 1NO9, 1TBZ, 1TMT, 1UMA, 2C8W, 2C8X, 2C8Z, 2C90, 2C93, 2CF8, 2CF9, 2CN0, 2JH5, 2PKS, 2UUF, 2UUJ, 2UUK, 2V3H, 2V3O, 2ZC9, 2ZDA, 2ZDV, 2ZF0, 2ZFF, 2ZFP, 2ZGB, 2ZGX, 2ZHQ, 3DHK, 3EGK, 3JZ1, 3K65, 3PMH, 3QDZ, 4AX9, 4AYV, 4AYY, 4AZ2, 4CH2, 4CH8, 4HZH, 4I7Y, 4LOY, 4LXB, 4LZ1, 4LZ4, 4MLF, 4N3L, 4NZE, 4NZQ, 4O03, 4RKJ, 4RKO, 4RN6, 4YES, 4UD9, 4UDW, 4UE7, 4UEH, 5AF9, 5AFY, 5AFZ, 5AHG, 5CMX, 4UFD, 5EDM, 5E8E, 5EDK, 4UFE, 4UFG, 4UFF, 5A2M, 5JDU
Identifikatori
Aliasi	F2
Vanjski ID-jevi	OMIM: 176930 MGI: 88380 HomoloGene: 426 GeneCards: F2
Lokacija gena (čovjek)
Hrom.	Hromosom 11 (čovjek)
Kraj	46,739,506 bp
Lokacija gena (miš)
Hrom.	Hromosom 2 (miš)
Kraj	91,466,759 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• calcium ion binding; • signaling receptor binding; • GO:0070122 peptidase activity; • hydrolase activity; • growth factor activity; • serine-type peptidase activity; • thrombospondin receptor activity; • GO:0001948, GO:0016582 vezivanje za proteine; • serine-type endopeptidase activity; • lipopolysaccharide binding; • heparin binding; • GO:0010577 enzyme activator activity;
Ćelijska komponenta	• Egzosom; • blood microparticle; • endoplasmic reticulum lumen; • Golgi lumen; • ćelijska membrana; • extracellular region; • Vanćelijsko; • external side of plasma membrane; • collagen-containing extracellular matrix;
Biološki proces	• blood coagulation, intrinsic pathway; • regulation of blood coagulation; • positive regulation of phosphatidylinositol 3-kinase signaling; • positive regulation of collagen biosynthetic process; • multicellular organism development; • peptidyl-glutamic acid carboxylation; • acute-phase response; • positive regulation of reactive oxygen species metabolic process; • endoplasmic reticulum to Golgi vesicle-mediated transport; • positive regulation of cell growth; • cell surface receptor signaling pathway; • Regulacija ekspresije gena; • positive regulation of release of sequestered calcium ion into cytosol; • positive regulation of cell population proliferation; • leukocyte migration; • negative regulation of fibrinolysis; • positive regulation of blood coagulation; • regulation of cytosolic calcium ion concentration; • response to wounding; • signal peptide processing; • positive regulation of phospholipase C-activating G protein-coupled receptor signaling pathway; • regulation of cell shape; • Hemostaza; • negative regulation of proteolysis; • negative regulation of platelet activation; • negative regulation of astrocyte differentiation; • positive regulation of protein phosphorylation; • Fibrinoliza; • Koagulacija (krv); • Proteoliza; • platelet activation; • positive regulation of protein localization to nucleus; • positive regulation of lipid kinase activity; • regulation of complement activation; • antimicrobial humoral immune response mediated by antimicrobial peptide; • negative regulation of cytokine production involved in inflammatory response; • regulation of signaling receptor activity; • G protein-coupled receptor signaling pathway; • positive regulation of receptor signaling pathway via JAK-STAT; • blood coagulation, fibrin clot formation;
	Izvori:Amigo / QuickGO
Ortolozi
	2147
	14061
	ENSG00000180210
	ENSMUSG00000027249
	P00734
	P19221
	NM_000506; NM_001311257
	NM_010168
	NP_000497
	NP_034298
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Trombin (EC 3.4.21.5, fibrinogenaza, trombaza, trombofort, trombin-C, tropostazin, aktivirani faktor zgrušavanja krvi II, faktor zgrušavanja krvi IIa, faktor IIa, E-trombin, beta-trombin, gama-trombin) jest serin-proteaza, enzim koji je kod ljudi kodiran genom F2 sa hromosoma 11.^[5]^[6] Protrombin (faktor zgrušavanja II) se proteolitski cijepa kako bi se formirao trombin u proces zgrušavanja. Trombin zauzvrat djeluje kao serinska proteaza koja pretvara rastvorljivi fibrinogen u netopive niti fibrina, katalizirajući i mnoge druge reakcije povezane sa koagulacijom.

Struktura

Sidrenje goveđeg protrombina na membranu kroz njegov Gla domen.^[7]

Molekulska težina protrombina je približno 72.000 Da. Katalitski domen se oslobađa iz protrombinskog fragmenta 1.2, kako bi se stvorio aktivni enzim trombin, koji ima molekulsku težinu od 36.000 Da. Strukturno, član je velikog PA-klana proteaza.

Protrombin se sastoji od četiri domena; N-terminal Gla domen, dva Kringelova domen]]a i C-terminalni tripsinu-sličan domen serin-proteaza. Faktor Xa sa faktorom V kao kofaktorom dovodi do cijepanja Gla i dva Kringleova domena (formirajući zajedno fragment nazvan fragment 1.2) i ostavlja trombin, koji se sastoji isključivo od domen serinske proteaze.^[8]

Kao što je slučaj sa svim serin-proteazama, protrombin se pretvara u aktivni trombin proteolizom unutrašnje peptidne veze, izlažući novi N-terminalni Ile-NH3. Historijski model aktivacije serinskih proteaza uključuje inserciju ovog novoformiranog N-kraja teškog lanca u β-barelsko podsticanje ispravne konformacije katalitskih ostataka.^[9] Za razliku od kristalnih struktura aktivnog trombina, studije masene spektrometrije razmjene vodika i deuterija pokazuju da se ovaj N-terminalni Ile-NH3 ne ubacuje u β-barel u apo obliku trombina. Međutim, čini se da vezivanje aktivnog fragmenta trombomodulina alosterno promoviše aktivnu konformaciju trombina insercijom ovog N-terminalnog regiona.^[10]

Gen

Gen za trombin (protrombin) nalazi se na hromosomu 11, regija p11-q12.^[5]

Procjenjuje se da u svijetu postoji oko 30 ljudi kojima je dijagnosticiran urođeni oblik nedostatka faktora II,^[11] koji ne treba brkati sa mutacijom protrombin G20210A, koja se također naziva mutacijom faktora II. Prothrombin G20210A je urođen.^[12]

Protrombin G20210A obično nije praćen drugim mutacijama faktora (tj. najčešći je faktora V Leiden). Gen može biti naslijeđen heterozigotno (1 par), ili mnogo rjeđe, homozigotno (2 para), i nije povezan sa spolom ili krvnom grupom. Homozigotne mutacije povećavaju rizik od tromboze više od heterozigotnih mutacija, ali relativno povećan rizik nije dobro dokumentiran. Ostali potencijalni rizici za trombozu, kao što su oralni kontraceptivi mogu biti dodatni. Prethodno prijavljeni odnos upalne bolesti crijeva (tj. Crohnova bolest ili ulcerozni kolitis) i mutacije protrombina G20210A ili faktor V Leidenove mutacije je suprotstavljen istraživanjima.^[13]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 622 aminokiseline, a molekulska težina 70.037 Da.

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MAHVRGLQLP	GCLALAALCS	LVHSQHVFLA	PQQARSLLQR	VRRANTFLEE
VRKGNLEREC	VEETCSYEEA	FEALESSTAT	DVFWAKYTAC	ETARTPRDKL
AACLEGNCAE	GLGTNYRGHV	NITRSGIECQ	LWRSRYPHKP	EINSTTHPGA
DLQENFCRNP	DSSTTGPWCY	TTDPTVRRQE	CSIPVCGQDQ	VTVAMTPRSE
GSSVNLSPPL	EQCVPDRGQQ	YQGRLAVTTH	GLPCLAWASA	QAKALSKHQD
FNSAVQLVEN	FCRNPDGDEE	GVWCYVAGKP	GDFGYCDLNY	CEEAVEEETG
DGLDEDSDRA	IEGRTATSEY	QTFFNPRTFG	SGEADCGLRP	LFEKKSLEDK
TERELLESYI	DGRIVEGSDA	EIGMSPWQVM	LFRKSPQELL	CGASLISDRW
VLTAAHCLLY	PPWDKNFTEN	DLLVRIGKHS	RTRYERNIEK	ISMLEKIYIH
PRYNWRENLD	RDIALMKLKK	PVAFSDYIHP	VCLPDRETAA	SLLQAGYKGR
VTGWGNLKET	WTANVGKGQP	SVLQVVNLPI	VERPVCKDST	RIRITDNMFC
AGYKPDEGKR	GDACEGDSGG	PFVMKSPFNN	RWYQMGIVSW	GEGCDRDGKY
GFYTHVFRLK	KWIQKVIDQF	GE

Sinteza

Trombin se proizvodi enzimskim cijepanjem dva mjesta na protrombinu aktiviranim faktorom X (Xa). Aktivnost faktora Xa je znatno poboljšana vezivanjem za aktivirani faktor V (Va), nazvan protrobinazni kompleks. Protrombin se proizvodi u jetri i kotranslacijski modificira u reakciji ovisnoj o vitaminu K koja pretvara 10-12 glutaminskih kiselina na N-kraju molekule u gama-karboksiglutaminsku kiselinu (Gla).^[14] U prisustvu kalcija, Gla ostaci pospešuju vezivanje protrombina za fosfolipidne dvoslojeve. Nedostatak vitamina K ili primjena antikoagulansa varfarina inhibira proizvodnju ostataka gama-karboksiglutaminske kiseline, usporavajući aktivaciju koagulacijske kaskade.

Kod odraslih ljudi, normalan nivo aktivnosti antitrombina u krvi je izmjeren na oko 1,1 jedinica/mL. Nivo trombina u novorođenčadi se stalno povećava nakon rođenja, kako bi dostigao normalne nivoe kod odraslih, od nivoa od oko 0,5 jedinica/ml 1 dan nakon rođenja, do nivoa od oko 0,9 jedinica/ml nakon 6 mjeseci života.^[15]

Klinički značaj

Aktivacija protrombina je ključna u fiziološkoj i patološkoj koagulaciji. Opisane su različite rijetke bolesti koje uključuju protrombin (npr. hipoprotrombinemija). Antiprotrombinska antitela u autoimunskoj bolesti može biti faktor u formiranju lupus-antikoagulansa (također poznatog kao antifosfolipidni sindrom). Hiperprotrombinemija može biti uzrokovana mutacijom G20210A.

Trombin, snažan vazokonstriktor i mitogen, uključeni su kao glavni faktori u vazospazamu nakon subarahnoidalnog krvarenja. Krv iz rupture moždane aneurizme zgrušava se oko cerebralnih arterija, oslobađajući trombin. Ovo može izazvati akutno i produženo sužavanje krvnog suda, što može dovesti do cerebralne ishemije i infarkta (moždani udar).

Osim ključne uloge u dinamičkom procesu stvaranja tromba, trombin ima izražen proupalni karakter, koji može uticati na nastanak i napredovanje ateroskleroze. Djelujući preko svojih specifičnih receptora na ćelijskoj membrani (receptora aktiviranih proteazom: PAR-1, PAR-3 i PAR-4), koji su obilno eksprimirani u svim sastojcima zidova arterijskih sudova , trombin ima potencijal da ispoljava proaterogeno djelovanje kao što su upala, regrutacija leukocita u aterosklerotski plak, pojačani oksidativni stres, migracija i proliferacija vaskularnih glatkih mišićnih ćelija, apoptoza i angiogeneza.^[16]^[17]^[18]

Trombin je uključen u fiziologiju krvnih ugruška. Njegovo prisustvo ukazuje na postojanje ugruška. U 2013. godini razvijen je sistem za detekciju prisustva trombina kod miševa. Kombinira peptidom obložen gvožđe-oksid povezan sa "reporterskim hemikalijama". Kada se peptid veže za molekulu trombina, oslobađa se reporter i pojavljuje u urinu, gdje se može otkriti. Testiranje na ljudima nije sprovedeno.^[19]

Također pogledajte

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000180210 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000027249 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b Royle NJ, Irwin DM, Koschinsky ML, MacGillivray RT, Hamerton JL (maj 1987). "Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively". Somatic Cell and Molecular Genetics. 13 (3): 285–92. doi:10.1007/BF01535211. PMID 3474786. S2CID 45686258.
^ Degen SJ, Davie EW (septembar 1987). "Nucleotide sequence of the gene for human prothrombin". Biochemistry. 26 (19): 6165–77. doi:10.1021/bi00393a033. PMID 2825773.
^ PDB 1nl2; Huang M, Rigby AC, Morelli X, Grant MA, Huang G, Furie B, Seaton B, Furie BC (septembar 2003). "Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins". Nature Structural Biology. 10 (9): 751–6. doi:10.1038/nsb971. PMID 12923575. S2CID 7751100.
^ Davie EW, Kulman JD (april 2006). "An overview of the structure and function of thrombin". Seminars in Thrombosis and Hemostasis. 32 Suppl 1: 3–15. doi:10.1055/s-2006-939550. PMID 16673262.
^ Huber R, Bode W (1. 3. 1978). "Structural basis of the activation and action of trypsin". Accounts of Chemical Research. 11 (3): 114–122. doi:10.1021/ar50123a006. ISSN 0001-4842.
^ Handley LD, Treuheit NA, Venkatesh VJ, Komives EA (novembar 2015). "Thrombomodulin Binding Selects the Catalytically Active Form of Thrombin". Biochemistry. 54 (43): 6650–8. doi:10.1021/acs.biochem.5b00825. PMC 4697735. PMID 26468766.
^ Degen SJ, McDowell SA, Sparks LM, Scharrer I (februar 1995). "Prothrombin Frankfurt: a dysfunctional prothrombin characterized by substitution of Glu-466 by Ala". Thrombosis and Haemostasis. 73 (2): 203–9. doi:10.1055/s-0038-1653751. PMID 7792730.
^ Varga EA, Moll S (juli 2004). "Cardiology patient pages. Prothrombin 20210 mutation (factor II mutation)". Circulation. 110 (3): e15–8. doi:10.1161/01.CIR.0000135582.53444.87. PMID 15262854.
^ Bernstein CN, Sargent M, Vos HL, Rosendaal FR (februar 2007). "Mutations in clotting factors and inflammatory bowel disease". The American Journal of Gastroenterology. 102 (2): 338–43. doi:10.1111/j.1572-0241.2006.00974.x. PMID 17156138. S2CID 19895315.
^ Knorre DG, Kudryashova NV, Godovikova TS (oktobar 2009). "Chemical and functional aspects of posttranslational modification of proteins". Acta Naturae. 1 (3): 29–51. doi:10.32607/20758251-2009-1-3-29-51. PMC 3347534. PMID 22649613.
^ Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, Powers P (juli 1987). "Development of the human coagulation system in the full-term infant". Blood. 70 (1): 165–72. doi:10.1182/blood.V70.1.165.165. PMID 3593964.
^ Borissoff JI, Spronk HM, Heeneman S, ten Cate H (juni 2009). "Is thrombin a key player in the 'coagulation-atherogenesis' maze?". Cardiovascular Research. 82 (3): 392–403. doi:10.1093/cvr/cvp066. PMID 19228706.
^ Borissoff JI, Heeneman S, Kilinç E, Kassák P, Van Oerle R, Winckers K, Govers-Riemslag JW, Hamulyák K, Hackeng TM, Daemen MJ, ten Cate H, Spronk HM (august 2010). "Early atherosclerosis exhibits an enhanced procoagulant state". Circulation. 122 (8): 821–30. doi:10.1161/CIRCULATIONAHA.109.907121. PMID 20697022.
^ Borissoff JI, Spronk HM, ten Cate H (maj 2011). "The hemostatic system as a modulator of atherosclerosis". The New England Journal of Medicine. 364 (18): 1746–60. doi:10.1056/NEJMra1011670. PMID 21542745.
^ Economist (5. 11. 2013). "Nanomedicine: Particle physiology". The Economist. Pristupljeno 15. 12. 2013.

Dopunska literatura

Esmon CT (juli 1995). "Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface". FASEB Journal. 9 (10): 946–55. doi:10.1096/fasebj.9.10.7615164. PMID 7615164. S2CID 19565674.
Wu H, Zhang Z, Li Y, Zhao R, Li H, Song Y, Qi J, Wang J (oktobar 2010). "Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats: correlation with brain edema". Neurochemistry International. 57 (3): 248–53. doi:10.1016/j.neuint.2010.06.002. PMC 2910823. PMID 20541575.
Lenting PJ, van Mourik JA, Mertens K (decembar 1998). "The life cycle of coagulation factor VIII in view of its structure and function". Blood. 92 (11): 3983–96. doi:10.1182/blood.V92.11.3983. PMID 9834200.
Plow EF, Cierniewski CS, Xiao Z, Haas TA, Byzova TV (juli 2001). "AlphaIIbbeta3 and its antagonism at the new millennium". Thrombosis and Haemostasis. 86 (1): 34–40. doi:10.1055/s-0037-1616198. PMID 11487023.
Maragoudakis ME, Tsopanoglou NE, Andriopoulou P (april 2002). "Mechanism of thrombin-induced angiogenesis". Biochemical Society Transactions. 30 (2): 173–7. doi:10.1042/BST0300173. PMID 12023846.
Howell DC, Laurent GJ, Chambers RC (april 2002). "Role of thrombin and its major cellular receptor, protease-activated receptor-1, in pulmonary fibrosis". Biochemical Society Transactions. 30 (2): 211–6. doi:10.1042/BST0300211. PMID 12023853. S2CID 32822567.
Firth SM, Baxter RC (decembar 2002). "Cellular actions of the insulin-like growth factor binding proteins". Endocrine Reviews. 23 (6): 824–54. doi:10.1210/er.2001-0033. PMID 12466191.
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De Cristofaro R, De Candia E (juni 2003). "Thrombin domains: structure, function and interaction with platelet receptors". Journal of Thrombosis and Thrombolysis. 15 (3): 151–63. doi:10.1023/B:THRO.0000011370.80989.7b. PMID 14739624.
Tsopanoglou NE, Maragoudakis ME (februar 2004). "Role of thrombin in angiogenesis and tumor progression". Seminars in Thrombosis and Hemostasis. 30 (1): 63–9. doi:10.1055/s-2004-822971. PMID 15034798.
Bode W (2007). "Structure and interaction modes of thrombin". Blood Cells, Molecules & Diseases. 36 (2): 122–30. doi:10.1016/j.bcmd.2005.12.027. PMID 16480903.
Wolberg AS (maj 2007). "Thrombin generation and fibrin clot structure". Blood Reviews. 21 (3): 131–42. doi:10.1016/j.blre.2006.11.001. PMID 17208341.
Degen S (1995). "Prothrombin". u High K, Roberts H (ured.). Molecular Basis of Thrombosis and Hemostasis. Marcel Dekker. str. 75. ISBN 9780824795016.

Vanjski linkovi

The MEROPS online database for peptidases and their inhibitors: S01.217 Arhivirano 19. 9. 2019. na Wayback Machine
Kujovich JL (februar 2021). Adam MP, Ardinger HH, Pagon RA, et al. (ured.). "Prothrombin Thrombophilia". GeneReviews. Seattle WA: University of Washington, Seattle. PMID 20301327. NBK1148.
Anti-coagulation & proteases na YouTubeu by The Proteolysis Map-animation
[1] PMAP: The Proteolysis Map/Thrombin
Thrombin: RCSB PDB Molecule of the Month Arhivirano 5. 10. 2013. na Wayback Machine
Prothrombin Structure
PDBe-KB provides an overview of all the structure information available in the PDB for Human Thrombin.
PDBe-KB provides an overview of all the structure information available in the PDB for Mouse Thrombin.

Portal Biologija

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000180210 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000027249 - Ensembl, maj 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid3474786-5] Royle NJ, Irwin DM, Koschinsky ML, MacGillivray RT, Hamerton JL (maj 1987). "Human genes encoding prothrombin and ceruloplasmin map to 11p11-q12 and 3q21-24, respectively". Somatic Cell and Molecular Genetics. 13 (3): 285–92. doi:10.1007/BF01535211. PMID 3474786. S2CID 45686258.

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