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plasminogen; contains: plasmin heavy chain A; activation peptide; angiostatin; plasmin light chain B (PLG)

Function: - plasminogen contains, in addition to binding site(s) for fibrin, site(s) for binding to the surface of platelets - plasmin formed of the surface of platelets has the ability to degrade glycoprotein Ib & glycoprotein IIb/IIIa & the vWF/VIII complex disrupting adhesion & aggregation of platelets - plasminogen also binds to the surface of endothelial cells - release of tissue plasminogen activator by endothelial cells, results in generation of plasmin at the surface of intact endothelium, limiting fibrin formation to the site of vascular injury - converted into plasmin by plasminogen activators, both plasminogen & its activator being bound to fibrin - activated with catalytic amounts of streptokinase - in the presence of plaminogen activator inhibitor, activation involves only cleavage after Arg-580, yielding two chains held together by two disulfide bonds. - in the absence of plaminogen activator inhibitor, activation involves additionally the removal of the activation peptide - interacts with CSPG4 & AMOT - interacts (via the Kringle domains) with HRG - interaction tethers PLG to the cell surface & enhances its activation (putative) Structure: - N-linked glycan contains N-acetyllactosamine & sialic acid - O-linked glycans consist of gal-galNAc disaccharide modified with up to 2 sialic acid residues (microheterogeneity) - Kringle domains mediate interaction with CSPG4 - belongs to the peptidase S1 family, plasminogen subfamily - contains 5 kringle domains - contains 1 PAN domain - contains 1 peptidase S1 domain Compartment: - secreted. - locates to the cell surface where it is proteolytically cleaved to produce the active plasmin - interaction with HRG tethers it to the cell surface Expression: - present in plasma & many other extracellular fluids. - synthesized in the liver Pathology: - defects in plasminogen are a cause of hypercoagulability - defects in plasminogen are the cause of plasminogen deficiency

Interactions

molecular events

Related

plasmin; fibrinolysin

Specific

Plasminogen Parenteral

General

coagulation factor fibrinolytic agent (thrombolytic agent) glycoprotein phosphoprotein protein precursor

Properties

SIZE: entity length = 810 aa MW = 91 kD COMPARTMENT: plasma MOTIF: signal sequence {1-19} PAN {20-98} MOTIF: cysteine residue {C49} MODIFICATION: cysteine residue {C73} cysteine residue {C53} MODIFICATION: cysteine residue {C61} cysteine residue {C61} MODIFICATION: cysteine residue {C53} cysteine residue {C73} MODIFICATION: cysteine residue {C49} proteolytic site {78-79} Kringle 1 {103-181} MOTIF: cysteine residue {C103} MODIFICATION: cysteine residue {C181} cysteine residue {C124} MODIFICATION: cysteine residue {C164} binding site SITE: 134-134 FOR-BINDING-OF: Fibrin binding site SITE: 136-136 FOR-BINDING-OF: Fibrin binding site SITE: 136-136 FOR-BINDING-OF: Omega-aminocarboxylic acids cysteine residue {C152} MODIFICATION: cysteine residue {C176} binding site SITE: 158-158 FOR-BINDING-OF: Omega-aminocarboxylic acids cysteine residue {C164} MODIFICATION: cysteine residue {C124} binding site SITE: 172-172 FOR-BINDING-OF: Omega-aminocarboxylic acids cysteine residue {C176} MODIFICATION: cysteine residue {C152} cysteine residue {C181} MODIFICATION: cysteine residue {C103} Kringle 2 {184-262} MOTIF: cysteine residue {C185} MODIFICATION: cysteine residue {C262} cysteine residue {C188} MODIFICATION: cysteine residue {C316} cysteine residue {C206} MODIFICATION: cysteine residue {C245} cysteine residue {C234} MODIFICATION: cysteine residue {C257} cysteine residue {C245} MODIFICATION: cysteine residue {C206} cysteine residue {C257} MODIFICATION: cysteine residue {C234} cysteine residue {C262} MODIFICATION: cysteine residue {C185} Ser glycosylation site {S268} Kringle 3 {275-352} MOTIF: cysteine residue {C275} MODIFICATION: cysteine residue {C352} cysteine residue {C296} MODIFICATION: cysteine residue {C335} N-glycosylation site {N308} cysteine residue {C316} MODIFICATION: cysteine residue {C188} cysteine residue {C324} MODIFICATION: cysteine residue {C347} cysteine residue {C335} MODIFICATION: cysteine residue {C296} cysteine residue {C347} MODIFICATION: cysteine residue {C324} cysteine residue {C352} MODIFICATION: cysteine residue {C275} Thr glycosylation site {T365} Kringle 4 {377-454} MOTIF: cysteine residue {C377} MODIFICATION: cysteine residue {C454} cysteine residue {C398} MODIFICATION: cysteine residue {C437} cysteine residue {C426} MODIFICATION: cysteine residue {C449} binding site SITE: 432-432 FOR-BINDING-OF: Omega-aminocarboxylic acids cysteine residue {C437} MODIFICATION: cysteine residue {C398} binding site SITE: 445-445 FOR-BINDING-OF: Omega-aminocarboxylic acids cysteine residue {C449} MODIFICATION: cysteine residue {C426} cysteine residue {C454} MODIFICATION: cysteine residue {C377} proteolytic site {466-467} Kringle 5 {481-560} MOTIF: cysteine residue {C481} MODIFICATION: cysteine residue {C560} cysteine residue {C502} MODIFICATION: cysteine residue {C543} cysteine residue {C531} MODIFICATION: cysteine residue {C555} cysteine residue {C543} MODIFICATION: cysteine residue {C502} cysteine residue {C555} MODIFICATION: cysteine residue {C531} cysteine residue {C560} MODIFICATION: cysteine residue {C481} cysteine residue {C567} MODIFICATION: cysteine residue {C-INTERCHAIN } cysteine residue {C577} MODIFICATION: cysteine residue {C-INTERCHAIN } proteolytic site {580-581} S1 domain {581-808} MOTIF: Ser phosphorylation site {S597} cysteine residue {C607} MODIFICATION: cysteine residue {C623} histidine residue {H622} cysteine residue {C623} MODIFICATION: cysteine residue {C607} aspartate residue {D665} cysteine residue {C699} MODIFICATION: cysteine residue {C766} cysteine residue {C729} MODIFICATION: cysteine residue {C745} cysteine residue {C745} MODIFICATION: cysteine residue {C729} cysteine residue {C756} MODIFICATION: cysteine residue {C784} serine residue {S760} cysteine residue {C766} MODIFICATION: cysteine residue {C699} cysteine residue {C784} MODIFICATION: cysteine residue {C756} PRECURSOR-FOR: plasmin COMPARTMENT: plasma MOTIF: charge relay system MOTIF: aspartate residue histidine residue serine residue kringle domain allosteric site FOR-BINDING-OF: complement C1 inhibitor STATE: active state angiostatin COMPARTMENT: extracellular compartment MISC-INFO: CONCENTRATION 2.4 UM

Database Correlations

OMIM correlations MORBIDMAP 173350 UniProt P00747 PFAM correlations Entrez Gene 5340 Kegg hsa:5340 ENZYME 3.4.21.7

References

  1. UniProt :accession P00747
  2. Wikipedia; Note: plasmin entry http://en.wikipedia.org/wiki/plasmin
  3. SeattleSNPs http://pga.gs.washington.edu/data/plg/
  4. Clinical Diagnosis and Management by Laboratory Methods, 18th ed, J.B. Henry (ed), W.B. Saunders, Philadelphia, PA, 1991 pg 739
  5. Fibrinolysis, Thrombosis, & Hemostasis: Concepts, Perspectives, and Clinical Applications. S Sherry, Lea & Febiger, Philadelphia, 1992, pg 15