P70458 (IPSP_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 93. History...
Names and origin
|Protein names||Recommended name:|
Plasma serine protease inhibitor
Plasminogen activator inhibitor 3
Protein C inhibitor
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||405 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and proinflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue-and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid By similarity.
Its inhibitory activity is greatly enhanced in the presence of glycosaminoglycans, heparin, thrombomodulin and phospholipids vesicles.
Forms protease inhibiting heterodimers in extracellular body fluids with serine proteases such as activated protein C/coagulation factor V/F5, acrosin/ACR, chymotrypsinogen B/CTRB1, prothrombin/F2, factor Xa/F10, factor XI/F11, kallikrein/KLKB1, tissue kallikrein, trypsin/PRSS1, prostate specific antigen/KLK3, tissue plasminogen activator/PLAT and urinary plasminogen activator/PLAU. Forms membrane-anchored serine proteases inhibiting heterodimers with TMPRSS7 and TMPRSS11E. Interacts with SEMG2 By similarity.
Secreted › extracellular space By similarity. Note: Localized on the plasma membrane overlying the acrosomal head of spermatozoa of ependymal spermatozoa and ejaculated sperm. Localized at the equatorial segment of acrosome-reacted spematozoa. Localized in alpha granules in resting platelets and on the external plasma membrane and within the surface-connected cannalicular system in activated platelets By similarity.
Not detected in blood plasma (at protein level). Expressed in testis, epididymis, seminal vesicles, prostate and ovaries. Ref.6
The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable By similarity.
N-glycosylated; glycans consist of a mixture of sialylated bi- (including sialyl-Lewis X epitopes), tri- and tetra-antennary complex-type chains; affects the maximal heparin- and thrombomodulin-enhanced rates of thrombin inhibition. O-glycosylated; further modified with 2 sialic acid residues. Proteolytically cleaved at the N-terminus; inhibits slightly the heparin- and thrombomodulin-enhanced rates of thrombin inhibition By similarity.
Proteolytically cleaved. Inhibition of proteases is accompanied by formation of a stable enzyme-inhibitor complex and by degradation of the serpin to lower molecular weight derivatives By similarity.
Mice are healthy but males are infertile; spermatozoa are morphologically abnormal, most lacked tails and malformed heads. The lumina of the seminiferous tubules are filled with cells in different stages of spermatogenesis and are sometimes necrotic. The cytoplasm of Sertoli cells contained vacuoles and appeared necrotic. The Sertoli cell barrier appeared disrupted. Ref.5
Belongs to the serpin family.
According to Ref.5 it is not detectable in blood plasma.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Signal peptide||1 – 19||19||Potential|
|Propeptide||20 – 24||5||Removed in mature form By similarity||PRO_0000414092|
|Chain||25 – 405||381||Plasma serine protease inhibitor||PRO_0000032428|
|Site||372 – 373||2||Reactive bond|
Amino acid modifications
|Glycosylation||247||1||N-linked (GlcNAc...) Potential|
|Sequence conflict||55||1||V → A in AAC53063. Ref.1|
|Sequence conflict||55||1||V → A in AAH90981. Ref.4|
|Sequence conflict||185||1||F → L in AAC53063. Ref.1|
|Sequence conflict||185||1||F → L in AAH90981. Ref.4|
|Sequence conflict||227 – 230||4||RTTQ → KTIR in AAC53063. Ref.1|
|Sequence conflict||227 – 230||4||RTTQ → KTIR in AAH90981. Ref.4|
|Sequence conflict||239||1||G → E in AAC53063. Ref.1|
|Sequence conflict||239||1||G → E in AAH90981. Ref.4|
|||"Molecular cloning and sequence analysis of the mouse protein C inhibitor gene."|
Zechmeister-Machhart M., Hufnagl P., Uhrin P., Korschineck I., Binder B.R., Geiger M.
Gene 186:61-66(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Liver and Testis.
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.|
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
|||"Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility."|
Uhrin P., Dewerchin M., Hilpert M., Chrenek P., Schofer C., Zechmeister-Machhart M., Kronke G., Vales A., Carmeliet P., Binder B.R., Geiger M.
J. Clin. Invest. 106:1531-1539(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
|||"Characterization of a novel human protein C inhibitor (PCI) gene transgenic mouse useful for studying the role of PCI in physiological and pathological conditions."|
Hayashi T., Nishioka J., Kamada H., Asanuma K., Kondo H., Gabazza E.C., Ido M., Suzuki K.
J. Thromb. Haemost. 2:949-961(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
|+||Additional computationally mapped references.|
|U67878 Genomic DNA. Translation: AAC53063.1.|
AK087714 mRNA. Translation: BAC39979.1.
CH466549 Genomic DNA. Translation: EDL18804.1.
BC090981 mRNA. Translation: AAH90981.1.
|RefSeq||NP_766541.2. NM_172953.3. |
3D structure databases
|HSSP||HSSP built from PDB template 1LQ8 based on UniProtKB P05154. |
|SMR||P70458. Positions 44-405. |
Protein-protein interaction databases
|IntAct||P70458. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000021495; ENSMUSP00000021495; ENSMUSG00000041550. |
|MGI||MGI:107817. Serpina5. |
Gene expression databases
|GermOnline||ENSMUSG00000041550. Mus musculus. |
Family and domain databases
|InterPro||IPR023796. Serpin_dom. |
|PANTHER||PTHR11461. PTHR11461. 1 hit. |
|Pfam||PF00079. Serpin. 1 hit. |
|SMART||SM00093. SERPIN. 1 hit. |
|SUPFAM||SSF56574. Prot_inh_serpin. 1 hit. |
|PROSITE||PS00284. SERPIN. False negative. |
|Accession||Primary (citable) accession number: P70458|
Secondary accession number(s): Q5BKQ8, Q8BU50
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|