Plasma serine protease inhibitor (SERPINA5)
The protein contains 406 amino acids for an estimated molecular weight of 45675 Da.
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. I (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Blood coagulation
Fusion of sperm to egg plasma membrane involved in single fertilization
Lipid transport
Negative regulation of endopeptidase activity
Negative regulation of hydrolase activity
Seminal vesicle development
Spermatogenesis
Cellular Component
Acrosomal membrane
External side of plasma membrane
Extracellular exosome
Extracellular region
Extracellular space
Membrane
Platelet alpha granule
Platelet dense tubular network
Protein C inhibitor-coagulation factor V complex
Protein C inhibitor-coagulation factor Xa complex
Protein C inhibitor-coagulation factor XI complex
Protein C inhibitor-KLK3 complex
Protein C inhibitor-plasma kallikrein complex
Protein C inhibitor-PLAT complex
Protein C inhibitor-PLAU complex
Protein C inhibitor-thrombin complex
Protein C inhibitor-TMPRSS11E complex
Protein C inhibitor-TMPRSS7 complex
Protein-containing complex
The reference OMIM entry for this protein is 601841
Serpin peptidase inhibitor, clade a, member 5; serpina5
Protein c inhibitor; pci
CLONING
Marlar and Griffin (1980) identified in normal plasma a protein inhibitor of activated protein C (612283). Protein C is a vitamin K-dependent serine protease zymogen present in human plasma. Activated protein C is a potent anticoagulant. Suzuki et al. (1987) determined the sequence of cDNA for human protein C inhibitor (PCI). A high degree of homology of the deduced amino acid sequence to that of other known inhibitors clearly demonstrated that protein C inhibitor is a member of the superfamily of serine protease inhibitors including alpha-1-antichymotrypsin (AACT; 107280), alpha-1-antitrypsin (AAT; PI; 107400), antithrombin III (AT3; 107300), and angiotensinogen (AGT; 106150). Protein C inhibitor is sometimes referred to as plasminogen activator inhibitor-3 (PAI3) because it also inhibits plasminogen activators (Meijers and Chung, 1991). Plasminogen activator inhibitor-1 (PAI1; 173360) has structural similarities to PCI.GENE STRUCTURE
Meijers and Chung (1991) determined that the SERPINA5 gene contains 5 exons spanning 11.5 kb.MAPPING
By PCR analysis of human-hamster hybrid cell lines, Meijers and Chung (1991) assigned the PROCI gene to chromosome 14. Using pulsed-field gel electrophoresis, Billingsley et al. (1993) showed that the PCI gene is located in a cluster in 14q32.1 with other members of the serine protease inhibitor (serpin) superfamily: AACT, which is very close to PCI; PI, which is approximately 220 kb from PCI; and corticosteroid binding globulin (CBG; 122500). The PI-like gene (PIL; 107410), which is not expressed, lies between PI and CBG.EVOLUTION
Meijers and Chung (1991) noted that the organization of the PCI gene is similar to that of PI and AACT, both of which map to chromosome 14, suggesting a recent evolution of these genes from a common ancestor.MOLECULAR GENETICS
Yasuda et al. (1992) studied an electrophoretic polymorphism of human plasma PCI. The combined techniques of polyacrylamide gel isoelectric focusing and immunoblotting with 3 different antibodies resolved the plasma PCI into several isoprotein bands. Two common phenotypes were recognized and family studies showed that they represented homozygosity or heterozygosity for 2 autosomal codominant alleles, PCI*1 and PCI*2. A population study of plasma samples collected from 977 Japanese persons indicated that the frequencies of these alleles were 0.988 and 0.012, respectively. Ashbourne et al. (1993) demonstrated a 2-allele RFLP of the PCI gene.HISTORY
Deficiency of protein C inhibitor was thought at one time to be the basic cause of combined deficiency of coagulation factors V and VIII (227300). This was disproved in part by the demonstration that the PCI gene maps to chromosome 14 (Billingsley et al., 1993) and the clinical phenotype of the combined coagulation factor deficiency maps to chromosome 18 (Nichols et al., 1997). Sadler (1997) pointed out that before the study by Nichols et al. (1997), deficiency of PCI as the basic defect had been excluded on several grounds. ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 601841 was added.
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).