Plasminogen activator inhibitor-2

Serpin peptidase inhibitor, clade B (ovalbumin), member 2

PDB rendering based on 1by7.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1BY7, 1JRR, 2ARQ, 2ARR

Identifiers

Symbols

SERPINB2 ; HsT1201; PAI; PAI-2; PAI2; PLANH2

External IDs

OMIM: 173390 MGI: 97609 HomoloGene: 20571 GeneCards: SERPINB2 Gene

Gene ontology
Molecular function	• serine-type endopeptidase inhibitor activity
Cellular component	• extracellular region • extracellular space • cytoplasm • plasma membrane
Biological process	• blood coagulation • negative regulation of endopeptidase activity • regulation of proteolysis • fibrinolysis • negative regulation of apoptotic process
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 18:
61.54 – 61.57 Mb

Chr 1:
107.51 – 107.54 Mb

PubMed search

Plasminogen activator inhibitor-2 (placental PAI) is a coagulation factor that inactivates tPA and urokinase. It is present in most cells, especially monocytes/macrophages. PAI-2 exists in two forms, a 60-kDa extracellular glycosylated form and a 43-kDa intracellular form.

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

It is present only at detectable quantities in blood during pregnancy, as it is produced by the placenta, and may explain partially the increased rate of thrombosis during pregnancy. The majority of expressed PAI-2 remains unsecreted due to the presence of an inefficient internal signal peptide.

Interactions

Plasminogen activator inhibitor-2 (SerpinB2) has been reported to bind a series of intracellular and extracellular proteins. Whether SerpinB2's physiological function is inhibition of the extracellular protease urokinase and/or whether SerpinB2 has intracellular activities remains controversial. At least one of SerpinB2's physiological functions may involve regulation of adaptive immunity.^[1]

Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J (1992). "Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes". Electrophoresis 13 (12): 960–9. doi:10.1002/elps.11501301199. PMID 1286667.
Ellis V, Wun TC, Behrendt N, Rønne E, Danø K (1990). "Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors". J. Biol. Chem. 265 (17): 9904–8. PMID 2161846.
Estreicher A, Mühlhauser J, Carpentier JL, Orci L, Vassalli JD (1990). "The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes". J. Cell Biol. 111 (2): 783–92. doi:10.1083/jcb.111.2.783. PMC 2116194. PMID 2166055.
Samia JA, Alexander SJ, Horton KW, Auron PE, Byers MG, Shows TB et al. (1990). "Chromosomal organization and localization of the human urokinase inhibitor gene: perfect structural conservation with ovalbumin". Genomics 6 (1): 159–67. doi:10.1016/0888-7543(90)90461-3. PMID 2303256.
Schwartz BS, Monroe MC, Bradshaw JD (1989). "Endotoxin-induced production of plasminogen activator inhibitor by human monocytes is autonomous and can be inhibited by lipid X". Blood 73 (8): 2188–95. PMID 2471561.
Ye RD, Ahern SM, Le Beau MM, Lebo RV, Sadler JE (1989). "Structure of the gene for human plasminogen activator inhibitor-2. The nearest mammalian homologue of chicken ovalbumin". J. Biol. Chem. 264 (10): 5495–502. PMID 2494165.
Laug WE, Aebersold R, Jong A, Rideout W, Bergman BL, Baker J (1989). "Isolation of multiple types of plasminogen activator inhibitors from vascular smooth muscle cells". Thromb. Haemost. 61 (3): 517–21. PMID 2799763.
Kruithof EK, Cousin E (1988). "Plasminogen activator inhibitor 2. Isolation and characterization of the promoter region of the gene". Biochem. Biophys. Res. Commun. 156 (1): 383–8. doi:10.1016/S0006-291X(88)80852-0. PMID 2845977.
Ye RD, Wun TC, Sadler JE (1987). "cDNA cloning and expression in Escherichia coli of a plasminogen activator inhibitor from human placenta". J. Biol. Chem. 262 (8): 3718–25. PMID 3029122.
Antalis TM, Clark MA, Barnes T, Lehrbach PR, Devine PL, Schevzov G et al. (1988). "Cloning and expression of a cDNA coding for a human monocyte-derived plasminogen activator inhibitor". Proc. Natl. Acad. Sci. U.S.A. 85 (4): 985–9. doi:10.1073/pnas.85.4.985. PMC 279685. PMID 3257578.
Schleuning WD, Medcalf RL, Hession C, Rothenbühler R, Shaw A, Kruithof EK (1987). "Plasminogen activator inhibitor 2: regulation of gene transcription during phorbol ester-mediated differentiation of U-937 human histiocytic lymphoma cells". Mol. Cell. Biol. 7 (12): 4564–7. PMC 368144. PMID 3325828.
Webb AC, Collins KL, Snyder SE, Alexander SJ, Rosenwasser LJ, Eddy RL et al. (1987). "Human monocyte Arg-Serpin cDNA. Sequence, chromosomal assignment, and homology to plasminogen activator-inhibitor". J. Exp. Med. 166 (1): 77–94. doi:10.1084/jem.166.1.77. PMC 2188630. PMID 3496414.
Dickinson JL, Bates EJ, Ferrante A, Antalis TM (1995). "Plasminogen activator inhibitor type 2 inhibits tumor necrosis factor alpha-induced apoptosis. Evidence for an alternate biological function". J. Biol. Chem. 270 (46): 27894–904. doi:10.1074/jbc.270.46.27894. PMID 7499264.
Mikus P, Urano T, Liljeström P, Ny T (1993). "Plasminogen-activator inhibitor type 2 (PAI-2) is a spontaneously polymerising SERPIN. Biochemical characterisation of the recombinant intracellular and extracellular forms". Eur. J. Biochem. 218 (3): 1071–82. doi:10.1111/j.1432-1033.1993.tb18467.x. PMID 7506655.
Jensen PJ, Wu Q, Janowitz P, Ando Y, Schechter NM (1995). "Plasminogen activator inhibitor type 2: an intracellular keratinocyte differentiation product that is incorporated into the cornified envelope". Exp. Cell Res. 217 (1): 65–71. doi:10.1006/excr.1995.1064. PMID 7867722.
Akiyama H, Ikeda K, Kondo H, Kato M, McGeer PL (1993). "Microglia express the type 2 plasminogen activator inhibitor in the brain of control subjects and patients with Alzheimer's disease". Neurosci. Lett. 164 (1-2): 233–5. doi:10.1016/0304-3940(93)90899-V. PMID 8152607.
Ragno P, Montuori N, Vassalli JD, Rossi G (1993). "Processing of complex between urokinase and its type-2 inhibitor on the cell surface. A possible regulatory mechanism of urokinase activity". FEBS Lett. 323 (3): 279–84. doi:10.1016/0014-5793(93)81357-6. PMID 8388810.
Bartuski AJ, Kamachi Y, Schick C, Overhauser J, Silverman GA (1997). "Cytoplasmic antiproteinase 2 (PI8) and bomapin (PI10) map to the serpin cluster at 18q21.3". Genomics 43 (3): 321–8. doi:10.1006/geno.1997.4827. PMID 9268635.
Mahony D, Stringer BW, Dickinson JL, Antalis TM (1998). "DNase I hypersensitive sites in the 5' flanking region of the human plasminogen activator inhibitor type 2 (PAI-2) gene are associated with basal and tumor necrosis factor-alpha-induced transcription in monocytes". Eur. J. Biochem. 256 (3): 550–9. doi:10.1046/j.1432-1327.1998.2560550.x. PMID 9780231.
Nishida Y, Hayashi Y, Imai Y, Itoh H (1998). "Expression and localization of the urokinase-type plasminogen activator receptor (uPAR) in the human placenta". Kobe J Med Sci 44 (1): 31–43. PMID 9846056.

References

↑ Schroder WA, Major L, Suhrbier A (2011). "The role of SerpinB2 in immunity". Crit. Rev. Immunol. 31 (1): 15–30. doi:10.1615/critrevimmunol.v31.i1.20. PMID 21395508.

External links

The MEROPS online database for peptidases and their inhibitors: I04.007
Plasminogen Activator Inhibitor 2 at the US National Library of Medicine Medical Subject Headings (MeSH)

PDB gallery

1by7: HUMAN PLASMINOGEN ACTIVATOR INHIBITOR-2. LOOP (66-98) DELETION MUTANT

1jrr: HUMAN PLASMINOGEN ACTIVATOR INHIBITOR-2.[LOOP (66-98) DELETIONMUTANT] COMPLEXED WITH PEPTIDE MIMIckING THE REACTIVE CENTER LOOP

2arq: Human plasminogen activator inhibitor-2.[loop (66-98) deletion mutant] complexed with peptide n-acetyl-teaaagdggvmtgr-oh

2arr: Human plasminogen activator inhibitor-2.[loop (66-98) deletion mutant] complexed with peptide n-acetyl-teaaagmggvmtgr-oh

Proteins: coagulation

Coagulation factors

Primary hemostasis	vWF platelet membrane glycoproteins: Ib (A B IX) IIb/IIIa (IIb IIIa) VI

Intrinsic pathway	HMWK/Bradykinin Prekallikrein/Kallikrein XII "Hageman" XI IX VIII

Extrinsic pathway	III "Tissue factor" VII

Common pathway	X V II "(Pro)thrombin" I "Fibrin" Fibrinogen (FGA, FGG) XIII

Coagulation inhibitors

Thrombolysis/fibrinolysis

Index of cells from bone marrow

Description	Immune system Cells Physiology coagulation proteins granule contents colony-stimulating heme and porphyrin metabolism intermediates

Disease	Red blood cell Monocyte and granulocyte Neoplasms and cancer Histiocytosis Symptoms and signs eponymous Blood tests findings

Treatment	Transfusion Drugs thrombosis bleeding other

Serpins

inhibitory	Alpha 1-antichymotrypsin Alpha 1-antitrypsin Alpha 2-antiplasmin Antithrombin C1-inhibitor Heparin cofactor II Protein C inhibitor Plasminogen activator inhibitor-1 Plasminogen activator inhibitor-2 Protein Z-related protease inhibitor SERPINA1 SERPINA2 SERPINA3 SERPINA4 SERPINA5 SERPINA6 SERPINA7 SERPINA8 SERPINA9 SERPINA14 SERPINB1 SERPINB2 SERPINB3 SERPINB4 SERPINB5 SERPINB6 SERPINB7 SERPINB8 SERPINB9 SERPINB13 SERPINC1 SERPIND1 SERPINE1 SERPINE2 SERPINE2 SERPINF1 SERPING1 SERPINH1 SERPINI1 SERPINI2

Cross class inhibitory	MENT SCCA-1 crmA

noninhibitory	Heat shock protein 47 Maspin Ovalbumin SERPINF1 Thyroxine-binding globulin Transcortin SERPINF1

see also disorders of globin and globulin proteins

Plasminogen activator inhibitor-2

Interactions

See also

Further reading

References

External links