Gene Symbol: Serpine2
Description: serine (or cysteine) peptidase inhibitor, clade E, member 2
Alias: B230326M24Rik, PAI-1, PI-7, PI7, PN-1, Spi4, glia-derived nexin, GDN, peptidase inhibitor 7, protease nexin 1, protease nexin I, serine (or cysteine) proteinase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2, serine (or cysteine) proteinase inhibitor, clade E, member 2, serine protease-inhibitor 4, serpin E2
Species: mouse
Products:     Serpine2

Top Publications

  1. Odet F, Guyot R, Leduque P, le Magueresse Battistoni B. Evidence for similar expression of protein C inhibitor and the urokinase-type plasminogen activator system during mouse testis development. Endocrinology. 2004;145:1481-9 pubmed
    ..It will be important to determine how this role is linked to the phenotype of sterility reported elsewhere in male mice with pci deleted. ..
  2. Lu C, Lee R, Hwu Y, Chu S, Chen Y, Chang W, et al. SERPINE2, a serine protease inhibitor extensively expressed in adult male mouse reproductive tissues, may serve as a murine sperm decapacitation factor. Biol Reprod. 2011;84:514-25 pubmed publisher
    b>SERPINE2, one of the potent serine protease inhibitors that modulates the activity of plasminogen activator and thrombin, is implicated in many biological processes...
  3. Chern S, Li S, Lu C, Chen E. Spatiotemporal expression of the serine protease inhibitor, SERPINE2, in the mouse placenta and uterus during the estrous cycle, pregnancy, and lactation. Reprod Biol Endocrinol. 2010;8:127 pubmed publisher
    b>SERPINE2, also known as glia-derived nexin or protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily...
  4. Mansuy I, van Der Putten H, Schmid P, Meins M, Botteri F, Monard D. Variable and multiple expression of Protease Nexin-1 during mouse organogenesis and nervous system development. Development. 1993;119:1119-34 pubmed
    Protease Nexin-1 (PN-1) also known as Glia-Derived Nexin (GDN) inhibits the activity of several serine proteases including thrombin, tissue (tPA)- and urokinase (uPA)-type plasminogen activators...
  5. Vassalli J, Huarte J, Bosco D, Sappino A, Sappino N, Velardi A, et al. Protease-nexin I as an androgen-dependent secretory product of the murine seminal vesicle. EMBO J. 1993;12:1871-8 pubmed
    ..PN-I levels are much lower in immature animals, and strongly decreased upon castration. Testosterone treatment of castrated males rapidly restores PN-I mRNA levels, indicating that PN-I gene expression is under androgen control. ..
  6. Murer V, Spetz J, Hengst U, Altrogge L, De Agostini A, Monard D. Male fertility defects in mice lacking the serine protease inhibitor protease nexin-1. Proc Natl Acad Sci U S A. 2001;98:3029-33 pubmed
    ..The data demonstrate that the level of extracellular proteolytic activity is a critical element in controlling male fertility. ..
  7. Minami Y, Horikawa K, Akiyama M, Shibata S. Restricted feeding induces daily expression of clock genes and Pai-1 mRNA in the heart of Clock mutant mice. FEBS Lett. 2002;526:115-8 pubmed
    ..The present results demonstrate that daily Pai-1 gene expression depends on clock gene expression in the heart and that a functional Clock gene is not required for restricted feeding-induced resetting of the peripheral clock. ..
  8. Fayard B, Bianchi F, Dey J, Moreno E, Djaffer S, Hynes N, et al. The serine protease inhibitor protease nexin-1 controls mammary cancer metastasis through LRP-1-mediated MMP-9 expression. Cancer Res. 2009;69:5690-8 pubmed publisher
    ..These results suggest that PN-1 might become a prognostic marker in breast cancer. ..
  9. Kim T, Loh Y. Protease nexin-1 promotes secretory granule biogenesis by preventing granule protein degradation. Mol Biol Cell. 2006;17:789-98 pubmed
    ..We conclude that CgA increases DCG biogenesis in endocrine cells by up-regulating PN-1 expression to stabilize granule proteins against degradation. ..

More Information


  1. Everett C, Auchincloss C, Kaufman M, Abbott C, West J. Genetic influences on ovulation of primary oocytes in LT/Sv strain mice. Reproduction. 2004;128:565-71 pubmed
    ..Identification of these two chromosomal regions should facilitate the identification of genes involved in mammalian oocyte maturation and the control of meiosis. ..
  2. Scott K, Norris R, Potter S, Norrington D, Baybo M, Hicklin D, et al. GeneChip microarrays facilitate identification of Protease Nexin-1 as a target gene of the Prx2 (S8) homeoprotein. DNA Cell Biol. 2003;22:95-105 pubmed
    ..The GeneChip analysis generated a prioritized list of other potential targets. The utility and limitations of cell culture models combined with microarray analysis for elucidating complex regulatory cascades are discussed. ..
  3. Chang W, Chang N, Lin S, Wu C, Wu F. Tissue-specific cancer-related serpin gene cluster at human chromosome band 3q26. Genes Chromosomes Cancer. 2000;29:240-55 pubmed
    ..appears identical in the genomic structures of human plasminogen activator inhibitor-1 (PAI1) at 7q21 and protease nexin 1 (PI7) at 2q33-35, confirming that these four genes in three different chromosomes form a discrete subset ..
  4. Ibrahim A, Yahata T, Onizuka M, Dan T, van Ypersele de Strihou C, Miyata T, et al. Inhibition of plasminogen activator inhibitor type-1 activity enhances rapid and sustainable hematopoietic regeneration. Stem Cells. 2014;32:946-58 pubmed publisher
    ..Our results indicate that the inhibition of PAI-1 activity could be a therapeutic approach to facilitate the rapid recovery and sustained hematopoiesis after HSCT. ..
  5. Solleti S, Srisuma S, Bhattacharya S, Rangel Moreno J, Bijli K, Randall T, et al. Serpine2 deficiency results in lung lymphocyte accumulation and bronchus-associated lymphoid tissue formation. FASEB J. 2016;30:2615-26 pubmed publisher
    Serine proteinase inhibitor, clade E, member 2 (SERPINE2), is a cell- and extracellular matrix-associated inhibitor of thrombin...
  6. Carter R, Cerosaletti K, Burkin D, Fournier R, Jones C, Greenberg B, et al. The gene for the serpin thrombin inhibitor (PI7), protease nexin I, is located on human chromosome 2q33-q35 and on syntenic regions in the mouse and sheep genomes. Genomics. 1995;27:196-9 pubmed
    b>Protease nexin I (PNI) is the most important physiologic regulator of alpha-thrombin in tissues...
  7. Wakida N, Kitamura K, Tuyen D, Maekawa A, Miyoshi T, Adachi M, et al. Inhibition of prostasin-induced ENaC activities by PN-1 and regulation of PN-1 expression by TGF-beta1 and aldosterone. Kidney Int. 2006;70:1432-8 pubmed
    ..PN-1 could represent a new factor that contributes to regulation of ENaC activity in the kidney. ..
  8. Wells J, Strickland S. Aprotinin, a Kunitz-type protease inhibitor, stimulates skeletal muscle differentiation. Development. 1994;120:3639-47 pubmed
    ..These data indicate that Kunitz-domain containing protease inhibitors may help orchestrate the onset of myogenesis, possibly by regulating the activity of TGF beta-like molecules. ..
  9. Vaillant C, Valdivieso P, Nuciforo S, Kool M, Schwarzentruber Schauerte A, Méreau H, et al. Serpine2/PN-1 Is Required for Proliferative Expansion of Pre-Neoplastic Lesions and Malignant Progression to Medulloblastoma. PLoS ONE. 2015;10:e0124870 pubmed publisher
    ..Transcriptome analysis of human medulloblastomas shows that SERPINE2, also called Protease Nexin-1 (PN-1) is overexpressed in most medulloblastomas, in particular in the SHH and WNT ..
  10. Stettler H, Beuret N, Prescianotto Baschong C, Fayard B, Taupenot L, Spiess M. Determinants for chromogranin A sorting into the regulated secretory pathway are also sufficient to generate granule-like structures in non-endocrine cells. Biochem J. 2009;418:81-91 pubmed publisher
    ..The results support the notion that self-aggregation is at the core of granule formation and sorting into the regulated pathway. ..
  11. Smirnova T, Bonapace L, MacDonald G, Kondo S, Wyckoff J, Ebersbach H, et al. Serpin E2 promotes breast cancer metastasis by remodeling the tumor matrix and polarizing tumor associated macrophages. Oncotarget. 2016;7:82289-82304 pubmed publisher
    The extracellular serine protease inhibitor serpinE2 is overexpressed in breast cancer and has been shown to foster metastatic spread...
  12. Suzuki S, Singhirunnusorn P, Nakano H, Doi T, Saiki I, Sakurai H. Identification of TNF-alpha-responsive NF-kappaB p65-binding element in the distal promoter of the mouse serine protease inhibitor SerpinE2. FEBS Lett. 2006;580:3257-62 pubmed
    Serine protease inhibitor SerpinE2 is known as a cytokine-inducible gene...
  13. Winokur P, Subramanian P, Bullock J, Arocas V, Becerra S. Comparison of two neurotrophic serpins reveals a small fragment with cell survival activity. Mol Vis. 2017;23:372-384 pubmed
    Protease nexin-1 (PN-1), a serpin encoded by the SERPINE2 gene, has serine protease inhibitory activity and neurotrophic properties in the brain...
  14. Moll S, Schaeren Wiemers N, Wohlwend A, Pastore Y, Fulpius T, Monard D, et al. Protease nexin 1 in the murine kidney: glomerular localization and up-regulation in glomerulopathies. Kidney Int. 1996;50:1936-45 pubmed
    b>Protease nexin 1 (PN-1), a potent serpin-class antiprotease, is thought to be synthesized in the murine kidney. However, neither the cellular localization of PN-1 synthesis nor its role has yet been defined...
  15. Kury P, Schaeren Wiemers N, Monard D. Protease nexin-1 is expressed at the mouse met-/mesencephalic junction and FGF signaling regulates its promoter activity in primary met-/mesencephalic cells. Development. 1997;124:1251-62 pubmed
  16. Kvajo M, Albrecht H, Meins M, Hengst U, Troncoso E, Lefort S, et al. Regulation of brain proteolytic activity is necessary for the in vivo function of NMDA receptors. J Neurosci. 2004;24:9734-43 pubmed
    ..Thus, a tight control of serine protease activity is critical for the in vivo function of the NMDA receptors and the proper function of sensory pathways. ..
  17. Selbonne S, François D, Raoul W, Boulaftali Y, Sennlaub F, Jandrot Perrus M, et al. Protease nexin-1 regulates retinal vascular development. Cell Mol Life Sci. 2015;72:3999-4011 pubmed publisher
    We recently identified protease nexin-1 (PN-1) or serpinE2, as a possibly underestimated player in maintaining angiogenic balance...
  18. Selbonne S, Azibani F, Iatmanen S, Boulaftali Y, Richard B, Jandrot Perrus M, et al. In vitro and in vivo antiangiogenic properties of the serpin protease nexin-1. Mol Cell Biol. 2012;32:1496-505 pubmed publisher
    ..Taken together, our results demonstrate that PN-1 has direct antiangiogenic properties and is a yet-unrecognized player in the angiogenic balance. ..
  19. Taneda S, Hudkins K, Mühlfeld A, Kowalewska J, Pippin J, Shankland S, et al. Protease nexin-1, tPA, and PAI-1 are upregulated in cryoglobulinemic membranoproliferative glomerulonephritis. J Am Soc Nephrol. 2008;19:243-51 pubmed publisher
  20. Bouton M, Boulaftali Y, Richard B, Arocas V, Michel J, Jandrot Perrus M. Emerging role of serpinE2/protease nexin-1 in hemostasis and vascular biology. Blood. 2012;119:2452-7 pubmed publisher
    ..The roles of PN-1 in the areas of hemostasis and thrombosis summarized here provide insights that may allow the development of drugs and treatment strategies to prevent or limit thrombotic disorders. ..
  21. Meins M, Herry C, Muller C, Ciocchi S, Moreno E, Lüthi A, et al. Impaired fear extinction in mice lacking protease nexin-1. Eur J Neurosci. 2010;31:2033-42 pubmed publisher
    ..They also suggest a new role for serine protease inhibitors such as PN-1 in modulating fear conditioning and extinction. ..
  22. Grimmond S, Van Hateren N, Siggers P, Arkell R, Larder R, Soares M, et al. Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development. Hum Mol Genet. 2000;9:1553-60 pubmed
  23. Boulaftali Y, Adam F, Venisse L, Ollivier V, Richard B, Taieb S, et al. Anticoagulant and antithrombotic properties of platelet protease nexin-1. Blood. 2010;115:97-106 pubmed publisher
    ..Platelet PN-1 is thus a key player in the thrombotic process, whose negative regulatory role has been, up to now, markedly underestimated. ..
  24. McKee C, Xu D, Cao Y, Kabraji S, Allen D, Kersemans V, et al. Protease nexin 1 inhibits hedgehog signaling in prostate adenocarcinoma. J Clin Invest. 2012;122:4025-36 pubmed publisher
    ..Here, we identify the serine protease inhibitor protease nexin 1 (PN1) as a negative regulator of Hh signaling in prostate...
  25. Meins M, Piosik P, Schaeren Wiemers N, Franzoni S, Troncoso E, Kiss J, et al. Progressive neuronal and motor dysfunction in mice overexpressing the serine protease inhibitor protease nexin-1 in postmitotic neurons. J Neurosci. 2001;21:8830-41 pubmed
    ..These mice can serve to study early stages of in vivo neuronal dysfunction not yet associated with cell loss. ..
  26. Voss G, Botteri F, Monard D, Jockusch H. Localization of protease nexin-1 gene Spi4 between villin and acetylcholine receptor gamma genes on mouse Chromosome 1. Mamm Genome. 1996;7:167-8 pubmed
  27. Arndt P, Young S, Poch K, Nick J, Falk S, Schrier R, et al. Systemic inhibition of the angiotensin-converting enzyme limits lipopolysaccharide-induced lung neutrophil recruitment through both bradykinin and angiotensin II-regulated pathways. J Immunol. 2006;177:7233-41 pubmed
  28. Boettger Tong H, Rohozinski J, Agoulnik A, Dohmae K, Nishimune Y, Levy N, et al. Identification and sequencing the juvenile spermatogonial depletion critical interval on mouse chromosome 1 reveals the presence of eight candidate genes. Biochem Biophys Res Commun. 2001;288:1129-35 pubmed
    ..The critical 0.4 cM jsd interval corresponds to a physical distance of approximately 1.5 Mb. Eight genes have been identified in this interval, two of which appear to be possible candidates for the jsd mutation. ..
  29. Feutz A, Barrandon Y, Monard D. Control of thrombin signaling through PI3K is a mechanism underlying plasticity between hair follicle dermal sheath and papilla cells. J Cell Sci. 2008;121:1435-43 pubmed publisher
    ..The thrombin inhibitor protease nexin 1 [PN-1, also known as SERPINE2) regulates all those effects in vitro...
  30. Nieuwenhuis E, Barnfield P, Makino S, Hui C. Epidermal hyperplasia and expansion of the interfollicular stem cell compartment in mutant mice with a C-terminal truncation of Patched1. Dev Biol. 2007;308:547-60 pubmed
    ..Increased expression of regulators of epidermal homeostasis, c-Myc and p63, was also observed in Ptc1(mes/mes) adult skin. These results suggest that the CTD of Ptc1 is involved in regulating epidermal homeostasis in mature skin. ..
  31. Kaneko M, Minematsu T, Yoshida M, Nishijima Y, Noguchi H, Ohta Y, et al. Compression-induced HIF-1 enhances thrombosis and PAI-1 expression in mouse skin. Wound Repair Regen. 2015;23:657-63 pubmed publisher
    ..These findings may suggest new strategies in pressure ulcer management. ..
  32. Luthi A, van Der Putten H, Botteri F, Mansuy I, Meins M, Frey U, et al. Endogenous serine protease inhibitor modulates epileptic activity and hippocampal long-term potentiation. J Neurosci. 1997;17:4688-99 pubmed
    ..Compensatory changes in GABA-mediated inhibition in Thy 1/PN-1 mice suggest that altered brain PN-1 levels lead to an imbalance between excitatory and inhibitory synaptic transmission. ..
  33. Boulaftali Y, François D, Venisse L, Jandrot Perrus M, Arocas V, Bouton M. Endothelial protease nexin-1 is a novel regulator of A disintegrin and metalloproteinase 17 maturation and endothelial protein C receptor shedding via furin inhibition. Arterioscler Thromb Vasc Biol. 2013;33:1647-54 pubmed publisher
    ..We aimed to determine whether a serine protease inhibitor called protease nexin-1 (PN-1) or serpinE2, expressed by vascular cells, can modulate the effect of aPC on endothelial cells...
  34. DeMeo D, Mariani T, Lange C, Lake S, Litonjua A, CELEDON J, et al. The SERPINE2 gene is associated with chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2006;3:502 pubmed
  35. Crisante G, Battista L, Iwaszkiewicz J, Nesca V, Mérillat A, Sergi C, et al. The CAP1/Prss8 catalytic triad is not involved in PAR2 activation and protease nexin-1 (PN-1) inhibition. FASEB J. 2014;28:4792-805 pubmed publisher
    ..Our results demonstrate a novel inhibitory interaction between CAP1/Prss8 and nexin-1, opening the search for specific CAP1/Prss8 antagonists that are independent of its catalytic activity. ..
  36. Lino M, Atanasoski S, Kvajo M, Fayard B, Moreno E, Brenner H, et al. Mice lacking protease nexin-1 show delayed structural and functional recovery after sciatic nerve crush. J Neurosci. 2007;27:3677-85 pubmed
    ..Thus, the precise balance between distinct proteases and serpins such as PN-1 can modulate the overall impact on the kinetics of recovery. ..
  37. Lu C, Lee R, Hwu Y, Lin M, Yeh L, Chen Y, et al. Involvement of the serine protease inhibitor, SERPINE2, and the urokinase plasminogen activator in cumulus expansion and oocyte maturation. PLoS ONE. 2013;8:e74602 pubmed publisher
    The serpin peptidase inhibitor, clade E, member 2 (SERPINE2) inhibits urokinase-type plasminogen activator (PLAU) and tissue-type plasminogen activator...
  38. Boulaftali Y, Ho Tin Noe B, Pena A, Loyau S, Venisse L, François D, et al. Platelet protease nexin-1, a serpin that strongly influences fibrinolysis and thrombolysis. Circulation. 2011;123:1326-34 pubmed publisher
    ..Inhibition of PN-1 is thus predicted to promote endogenous and exogenous tissue plasminogen activator-mediated fibrinolysis and may enhance the therapeutic efficacy of thrombolytic agents. ..
  39. Citron B, Ratzlaff K, Smirnova I, Festoff B. Protease nexin I (PNI) in mouse brain is expressed from the same gene as in seminal vesicle. J Mol Neurosci. 1996;7:183-91 pubmed
    b>Protease nexin I (PNI), a serine protease inhibitor (serpin), is the most potent tissue inhibitor of thrombin. In the nervous system, PNI has been shown to participate in processes related to synaptic plasticity and neuronal survival...
  40. Sawada H, Kikukawa Y, Ban S, Kakudo T, Yokosawa H. Expression of trypsin-like proteases and protease nexin-1 in mdx mouse muscles. Biochem Biophys Res Commun. 2004;314:654-8 pubmed
  41. Vaillant C, Michos O, Orolicki S, Brellier F, Taieb S, Moreno E, et al. Protease nexin 1 and its receptor LRP modulate SHH signalling during cerebellar development. Development. 2007;134:1745-54 pubmed
    ..Here, we analyze the role of the serine-protease inhibitor protease nexin 1 (PN-1; SERPINE2) in the proliferation and differentiation of cerebellar granular neuron precursors (CGNPs) ..
  42. Festoff B, Rao J, Hantai D. Plasminogen activators and inhibitors in the neuromuscular system: III. The serpin protease nexin I is synthesized by muscle and localized at neuromuscular synapses. J Cell Physiol. 1991;147:76-86 pubmed
    ..and cross-reactivity with authenic antisera is similar to the human serine proteinase inhibitor, protease nexin I. Protease nexin I is a 43-50 kDa glycoprotein of the serpin superfamily (arg-serpin class)...