P70458 · IPSP_MOUSE
- ProteinPlasma serine protease inhibitor
- GeneSerpina5
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids405 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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 pro-inflammatory 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).
Activity regulation
Its inhibitory activity is greatly enhanced in the presence of glycosaminoglycans, heparin, thrombomodulin and phospholipids vesicles.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 372-373 | Reactive bond | ||||
Sequence: SA |
GO annotations
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended namePlasma serine protease inhibitor
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP70458
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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 spermatozoa. 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).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
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.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 59 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for signal, propeptide, chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-19 | |||||
Sequence: MRFFPILCLVLFISHGVAS | ||||||
Propeptide | PRO_0000414092 | 20-24 | Removed in mature form | |||
Sequence: RRHSH | ||||||
Chain | PRO_0000032428 | 25-405 | Plasma serine protease inhibitor | |||
Sequence: SKKKKAKESSVGAVGPPSSKDFAFRLYRALVSESPGQNVFFSPLSVSMSLGMLSLGAGLKTKTQILDGLGLSLQQGQEDKLHKGFQQLLQRFRQPSDGLQLSLGSALFKDPAVHIRDDFLSAMKTLYMSDTFSTNFGNPEIAKKQINNYVAKQTKGKIVDFIKDLDSTHVMIVVNYIFFKAKWQTAFSETNTHKMDFHVTPKRTTQVPMMNREDGYSYYLDQNISCTVVGIPYQGNAIALFILPSEGKMKQVEDGLDERTLRNWLKMFTKRRLDLYLPKFSIEATYKLENVLPKLGIQDVFTTHADLSGITDHTNIKLSEMVHKSMMEVEESGTTAAAITGAIFTFRSARPSSLKIEFTRPFLLTLMEDSHILFVGKVTRP | ||||||
Glycosylation | 247 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Post-translational modification
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Not detected in blood plasma (at protein level). Expressed in testis, epididymis, seminal vesicles, prostate and ovaries.
Gene expression databases
Interaction
Subunit
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P70458 | Tmprss11e Q5S248 | 2 | EBI-490966, EBI-490889 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Domain
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).
Sequence similarities
Belongs to the serpin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length405
- Mass (Da)45,600
- Last updated2011-07-27 v2
- Checksum0E7377A3F8C1A464
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 55 | in Ref. 1; AAC53063 and 4; AAH90981 | ||||
Sequence: V → A | ||||||
Sequence conflict | 185 | in Ref. 1; AAC53063 and 4; AAH90981 | ||||
Sequence: F → L | ||||||
Sequence conflict | 227-230 | in Ref. 1; AAC53063 and 4; AAH90981 | ||||
Sequence: RTTQ → KTIR | ||||||
Sequence conflict | 239 | in Ref. 1; AAC53063 and 4; AAH90981 | ||||
Sequence: G → E |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U67878 EMBL· GenBank· DDBJ | AAC53063.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK087714 EMBL· GenBank· DDBJ | BAC39979.1 EMBL· GenBank· DDBJ | mRNA | ||
CH466549 EMBL· GenBank· DDBJ | EDL18804.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC090981 EMBL· GenBank· DDBJ | AAH90981.1 EMBL· GenBank· DDBJ | mRNA |