Play Video
1
Anticoagulation - Protein C, Protein S & Plasmin
Anticoagulation - Protein C, Protein S & Plasmin
::2013/10/23::
Play Video
2
Easy Coagulation Cascade (2 of 2) - A little more detail...
Easy Coagulation Cascade (2 of 2) - A little more detail...
::2011/05/23::
Play Video
3
Tissue Plasminogen Activator (TPA)
Tissue Plasminogen Activator (TPA)
::2011/08/14::
Play Video
4
Coagulation Factors: Its Role in Hemostasis
Coagulation Factors: Its Role in Hemostasis
::2012/02/14::
Play Video
5
Plasmin TVC
Plasmin TVC
::2007/05/11::
Play Video
6
Bosland Plasmin Capsule
Bosland Plasmin Capsule
::2011/01/10::
Play Video
7
Plasmin Free You
Plasmin Free You
::2009/06/23::
Play Video
8
Bosland Plasmin Product Part 1
Bosland Plasmin Product Part 1
::2008/09/19::
Play Video
9
How to pronounce plasmin
How to pronounce plasmin
::2014/07/12::
Play Video
10
Suy giảm Plasmin
Suy giảm Plasmin
::2012/08/08::
Play Video
11
Anticoagulation and thrombolysis
Anticoagulation and thrombolysis
::2014/06/03::
Play Video
12
How To lower Blood Pressure Naturally With Nattokinase And Exercise
How To lower Blood Pressure Naturally With Nattokinase And Exercise
::2013/04/06::
Play Video
13
Alpha-2 Antiplasmin Market - Global Industry Analysis, Size, Share, Growth, Trends And Forecast, 201
Alpha-2 Antiplasmin Market - Global Industry Analysis, Size, Share, Growth, Trends And Forecast, 201
::2014/03/12::
Play Video
14
Alpha-2 Antiplasmin Market - Global Industry Analysis, Size, Share, Growth, Trends
Alpha-2 Antiplasmin Market - Global Industry Analysis, Size, Share, Growth, Trends
::2014/03/19::
Play Video
15
Proteomic depletion, Rate My Science
Proteomic depletion, Rate My Science
::2008/10/15::
Play Video
16
3 - Plasma Thrombin
3 - Plasma Thrombin
::2007/10/31::
Play Video
17
Neprinol AFD by Arthur Andrew Medical
Neprinol AFD by Arthur Andrew Medical
::2014/02/04::
Play Video
18
15. Kevin Ahern
15. Kevin Ahern's Biochemistry - Blood Clotting
::2013/11/04::
Play Video
19
How to Pronounce Urokinase
How to Pronounce Urokinase
::2012/12/03::
Play Video
20
#16 Biochemistry Blood Clotting/Carbohydrates I Lecture for Kevin Ahern
#16 Biochemistry Blood Clotting/Carbohydrates I Lecture for Kevin Ahern's BB 450/550
::2011/11/02::
Play Video
21
Red Blood Cell Lecture Physio Mon 10-21-13
Red Blood Cell Lecture Physio Mon 10-21-13
::2013/10/22::
Play Video
22
Allostery and Regulation II
Allostery and Regulation II
::2010/10/20::
Play Video
23
Kevin Ahern
Kevin Ahern's Bite-Sized Biochemistry #16: Carbohydrates I (Structure and Function)
::2011/06/09::
Play Video
24
Streptokinase
Streptokinase
::2014/10/15::
Play Video
25
anthony, nancy, and fredy
anthony, nancy, and fredy's Anatomy Project
::2014/05/20::
Play Video
26
Natto, the sexiest, healthiest, stickiest Japanese food
Natto, the sexiest, healthiest, stickiest Japanese food
::2014/10/07::
Play Video
27
Sex Education.  MENSTRUATION CYCLE
Sex Education. MENSTRUATION CYCLE
::2009/12/16::
Play Video
28
Thrombus/Embolus Formation Demonstration w/ Targeted Release Treatment
Thrombus/Embolus Formation Demonstration w/ Targeted Release Treatment
::2011/05/08::
Play Video
29
Sex Education:  Menstruation 101
Sex Education: Menstruation 101
::2009/12/16::
Play Video
30
Sex EDUCATION:  The SECRET in the drawer.  Menstruation.
Sex EDUCATION: The SECRET in the drawer. Menstruation.
::2009/12/16::
Play Video
31
Pidol Alay sa Kalusugan
Pidol Alay sa Kalusugan
::2013/11/18::
Play Video
32
Nattokinase Natto
Nattokinase Natto
::2012/01/02::
Play Video
33
Bioshock 2 Final Scene (Deutsch)
Bioshock 2 Final Scene (Deutsch)
::2010/02/12::
Play Video
34
Point-of-Care/POC Coagulation Testing Market
Point-of-Care/POC Coagulation Testing Market
::2014/06/09::
Play Video
35
You Can Beat Heart Disease
You Can Beat Heart Disease
::2012/04/29::
Play Video
36
Yüksek Tansiyona Evde Doğal Çözüm Tansiyon Nasıl Düşer Tansiyon Düşürücü Bitk
Yüksek Tansiyona Evde Doğal Çözüm Tansiyon Nasıl Düşer Tansiyon Düşürücü Bitk
::2014/01/26::
Play Video
37
What are Enzymes and Why We Need Them Part 3
What are Enzymes and Why We Need Them Part 3
::2011/06/24::
Play Video
38
Bharat Book Presents : Global Coagulation Testing Market 2013
Bharat Book Presents : Global Coagulation Testing Market 2013
::2013/08/20::
Play Video
39
Una càpsula del temps contindrà els missatges que els barcelonins vulguin adreçar al futur
Una càpsula del temps contindrà els missatges que els barcelonins vulguin adreçar al futur
::2010/03/23::
Play Video
40
Bioshock 2 Gameplay
Bioshock 2 Gameplay
::2010/02/12::
Play Video
41
Minecraft: Dungeon Runner Part 1!
Minecraft: Dungeon Runner Part 1!
::2013/03/06::
Play Video
42
Virchow
Virchow's Triad
::2014/09/28::
Play Video
43
tutorial hijab pashmina
tutorial hijab pashmina
::2012/12/19::
Play Video
44
Cara Pakai Pashmina - Colourful Collections
Cara Pakai Pashmina - Colourful Collections
::2011/05/31::
Play Video
45
La cesárea según la organización mundial de la salud
La cesárea según la organización mundial de la salud
::2013/12/21::
Play Video
46
Minister Louis Farrakhan- Beside Every Great Man Is A Woman
Minister Louis Farrakhan- Beside Every Great Man Is A Woman
::2012/10/25::
Play Video
47
Peace and Love - The Nebraska Medical Center
Peace and Love - The Nebraska Medical Center
::2013/04/22::
Play Video
48
Hemostasis
Hemostasis
::2012/12/04::
Play Video
49
The New Anticoagulants in Cardiovascular Disease: Atrial Fibrillation and Beyond
The New Anticoagulants in Cardiovascular Disease: Atrial Fibrillation and Beyond
::2013/02/08::
Play Video
50
What are B Cells?
What are B Cells?
::2014/03/07::
NEXT >>
RESULTS [51 .. 101]
From Wikipedia, the free encyclopedia
  (Redirected from Plasminogen)
Jump to: navigation, search
Plasminogen
Plasminogenpress.png
PDB rendering based on 4dur.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols PLG ; DKFZp779M0222
External IDs OMIM173350 MGI97620 HomoloGene55452 ChEMBL: 1801 GeneCards: PLG Gene
EC number 3.4.21.7
RNA expression pattern
PBB GE PLG 209978 s at tn.png
PBB GE PLG 209977 at tn.png
PBB GE PLG 205871 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5340 18815
Ensembl ENSG00000122194 ENSMUSG00000059481
UniProt P00747 P20918
RefSeq (mRNA) NM_000301 NM_008877
RefSeq (protein) NP_000292 NP_032903
Location (UCSC) Chr 6:
161.12 – 161.17 Mb
Chr 17:
12.38 – 12.42 Mb
PubMed search [1] [2]

Plasmin is an important enzyme (EC 3.4.21.7) present in blood that degrades many blood plasma proteins, including fibrin clots. The degradation of fibrin is termed fibrinolysis. In humans, the plasmin protein is encoded by the PLG gene.[1]

Function[edit]

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

Plasmin is a serine protease that acts to dissolve fibrin blood clots. Apart from fibrinolysis, plasmin proteolyses proteins in various other systems: It activates collagenases, some mediators of the complement system and weakens the wall of the Graafian follicle (leading to ovulation). It cleaves fibrin, fibronectin, thrombospondin, laminin, and von Willebrand factor. Plasmin, like trypsin, belongs to the family of serine proteases.

Plasmin is released as a zymogen called plasminogen (PLG) from the liver into the systemic circulation. Two major glycoforms of plasminogen are present in humans - type I plasminogen contains two glycosylation moieties (N-linked to N289 and O-linked to T346), whereas type II plasminogen contains only a single O-linked sugar (O-linked to T346). Type II plasminogen is preferentially recruited to the cell surface over the type I glycoform. Conversely, type I plasminogen appears more readily recruited to blood clots.

In circulation, plasminogen adopts a closed, activation resistant conformation. Upon binding to clots, or to the cell surface, plasminogen adopts an open form that can be converted into active plasmin by a variety of enzymes, including tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), kallikrein, and factor XII (Hageman factor). Fibrin is a cofactor for plasminogen activation by tissue plasminogen activator. Urokinase plasminogen activator receptor (uPAR) is a cofactor for plasminogen activation by urokinase plasminogen activator. The conversion of plasminogen to plasmin involves the cleavage of the peptide bond between Arg-561 and Val-562.[1][2][3][4]

Plasmin cleavage produces angiostatin.

Structure and mechanism of plasminogen activation to plasmin[edit]

Full length plasminogen comprises seven domains. In addition to a C-terminal chymotrypsin-like serine protease domain, plasminogen contains an N-terminal Pan Apple domain (PAp) together with five Kringle domains (KR1-5). The Pan-Apple domain contains important determinants for maintaining plasminogen in the closed form, and the kringle domains are responsible for binding to lysine residues present in receptors and substrates.

The X-ray crystal structure of closed plasminogen reveals that the PAp and SP domains maintain the closed conformation through interactions made throughout the kringle array .[4] Chloride ions further bridge the PAp / KR4 and SP / KR2 interfaces, explaining the physiological role of serum chloride in stabilizing the closed conformer. The structural studies also reveal that differences in glycosylation alter the position of KR3. These data help explain the functional differences between the type I and type II plasminogen glycoforms.

In closed plasminogen, access to the activation bond (R561/V562) targeted for cleavage by tPA and uPA is blocked through the position of the KR3/KR4 linker sequence and the O-linked sugar on T346. The position of KR3 may also hinder access to the activation loop. The Inter-domain interactions also block all kringle ligand-binding sites apart from that of KR-1, suggesting that the latter domain governs pro-enzyme recruitment to targets. Analysis of an intermediate plasminogen structure suggests that plasminogen conformational change to the open form is initiated through KR-5 transiently peeling away from the PAp domain. These movements expose the KR5 lysine-binding site to potential binding partners, and suggest a requirement for spatially distinct lysine residues in eliciting plasminogen recruitment and conformational change respectively.[4]

Pathology[edit]

Deficiency in plasmin may lead to thrombosis, as clots are not degraded adequately. Plasminogen deficiency in mice leads to defective liver repair,[5] defective wound healing, reproductive abnormalities.[citation needed]

In humans, a rare disorder called plasminogen deficiency type I (Online 'Mendelian Inheritance in Man' (OMIM) 217090) is caused by mutations of the PLG gene and is often manifested by ligneous conjunctivitis.

Interactions[edit]

Plasmin has been shown to interact with Thrombospondin 1,[6][7] Alpha 2-antiplasmin[8][9] and IGFBP3.[10]

References[edit]

  1. ^ a b "Entrez Gene: plasminogen". 
  2. ^ Miyata T, Iwanaga S, Sakata Y, Aoki N (October 1982). "Plasminogen Tochigi: inactive plasmin resulting from replacement of alanine-600 by threonine in the active site". Proc. Natl. Acad. Sci. U.S.A. 79 (20): 6132–6. Bibcode:1982PNAS...79.6132M. doi:10.1073/pnas.79.20.6132. PMC 347073. PMID 6216475. 
  3. ^ Forsgren M, Råden B, Israelsson M, Larsson K, Hedén LO (March 1987). "Molecular cloning and characterization of a full-length cDNA clone for human plasminogen". FEBS Lett. 213 (2): 254–60. doi:10.1016/0014-5793(87)81501-6. PMID 3030813. 
  4. ^ a b c Law RHP, Caradoc-Davies T, Cowieson N, Horvath AJ, Quek AJ, Encarnacao JA, Steer D, Cowan A, Zhang Q, Lu BGC, Pike RN, Smith AI, Coughlin PB, Whisstock JC (2012). "The X-ray Crystal Structure of Full-Length Human Plasminogen". Cell Reports 1 (3): 185. doi:10.1016/j.celrep.2012.02.012. 
  5. ^ Jorge A. Bezerra, Thomas H. Bugge, Hector Melin-Aldana, Gregg Sabla, Keith W. Kombrinck, David P. Witte, and Jay L. Degen; Bugge; Melin-Aldana; Sabla; Kombrinck; Witte; Degen (December 21, 1999). "Plasminogen deficiency leads to impaired remodeling after a toxic injury to the liver". Proceedings of the National Academy of Sciences of the United States of America (Proceedings of the National Academy of Sciences of the United States of America) 96 (26): 15143–8. Bibcode:1999PNAS...9615143B. doi:10.1073/pnas.96.26.15143. PMC 24787. PMID 10611352. Retrieved June 3, 2011. 
  6. ^ Silverstein, R L; Leung L L; Harpel P C; Nachman R L (November 1984). "Complex formation of platelet thrombospondin with plasminogen. Modulation of activation by tissue activator". J. Clin. Invest. (UNITED STATES) 74 (5): 1625–33. doi:10.1172/JCI111578. ISSN 0021-9738. PMC 425339. PMID 6438154. 
  7. ^ DePoli, P; Bacon-Baguley T; Kendra-Franczak S; Cederholm M T; Walz D A (March 1989). "Thrombospondin interaction with plasminogen. Evidence for binding to a specific region of the kringle structure of plasminogen". Blood (UNITED STATES) 73 (4): 976–82. ISSN 0006-4971. PMID 2522013. 
  8. ^ Wiman, B; Collen D (September 1979). "On the mechanism of the reaction between human alpha 2-antiplasmin and plasmin". J. Biol. Chem. (UNITED STATES) 254 (18): 9291–7. ISSN 0021-9258. PMID 158022. 
  9. ^ Shieh, B H; Travis J (May 1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. (UNITED STATES) 262 (13): 6055–9. ISSN 0021-9258. PMID 2437112. 
  10. ^ Campbell, P G; Durham S K; Suwanichkul A; Hayes J D; Powell D R (August 1998). "Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3". Am. J. Physiol. (UNITED STATES) 275 (2 Pt 1): E321–31. ISSN 0002-9513. PMID 9688635. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


Wikipedia content is licensed under the GFDL License
Powered by YouTube
LEGAL
  • Mashpedia © 2014