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Protein

Plasma serine protease inhibitor

Gene

Serpina5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity

Caution

According to PubMed:11120760 it is not detectable in blood plasma.Curated

Enzyme regulationi

Its inhibitory activity is greatly enhanced in the presence of glycosaminoglycans, heparin, thrombomodulin and phospholipids vesicles.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei372 – 373Reactive bond2

GO - Molecular functioni

GO - Biological processi

  • negative regulation of hydrolase activity Source: MGI
  • spermatogenesis Source: UniProtKB

Keywordsi

Molecular functionProtease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

ReactomeiR-MMU-140837 Intrinsic Pathway of Fibrin Clot Formation
R-MMU-140875 Common Pathway of Fibrin Clot Formation

Protein family/group databases

MEROPSiI04.004

Names & Taxonomyi

Protein namesi
Recommended name:
Plasma serine protease inhibitor
Alternative name(s):
Plasminogen activator inhibitor 3
Short name:
PAI-3
Short name:
PAI3
Protein C inhibitor
Short name:
PCI
Serpin A5
Gene namesi
Name:Serpina5
Synonyms:Pci
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:107817 Serpina5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
PropeptideiPRO_000041409220 – 24Removed in mature formBy similarity5
ChainiPRO_000003242825 – 405Plasma serine protease inhibitorAdd BLAST381

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi247N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

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).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).By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP70458
PRIDEiP70458

PTM databases

iPTMnetiP70458
PhosphoSitePlusiP70458

Expressioni

Tissue specificityi

Not detected in blood plasma (at protein level). Expressed in testis, epididymis, seminal vesicles, prostate and ovaries.1 Publication

Gene expression databases

BgeeiENSMUSG00000041550
GenevisibleiP70458 MM

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Tmprss11eQ5S2482EBI-490966,EBI-490889

GO - Molecular functioni

Protein-protein interaction databases

BioGridi234523, 1 interactor
IntActiP70458, 1 interactor
STRINGi10090.ENSMUSP00000021495

Structurei

3D structure databases

ProteinModelPortaliP70458
SMRiP70458
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the serpin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2392 Eukaryota
COG4826 LUCA
GeneTreeiENSGT00760000118839
HOGENOMiHOG000238521
HOVERGENiHBG005957
InParanoidiP70458
KOiK03913
OMAiVMVNYIF
OrthoDBiEOG091G0ION
TreeFamiTF343201

Family and domain databases

InterProiView protein in InterPro
IPR023796 Serpin_dom
IPR000215 Serpin_fam
IPR036186 Serpin_sf
PANTHERiPTHR11461 PTHR11461, 1 hit
PfamiView protein in Pfam
PF00079 Serpin, 1 hit
SMARTiView protein in SMART
SM00093 SERPIN, 1 hit
SUPFAMiSSF56574 SSF56574, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P70458-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRFFPILCLV LFISHGVASR RHSHSKKKKA KESSVGAVGP PSSKDFAFRL
60 70 80 90 100
YRALVSESPG QNVFFSPLSV SMSLGMLSLG AGLKTKTQIL DGLGLSLQQG
110 120 130 140 150
QEDKLHKGFQ QLLQRFRQPS DGLQLSLGSA LFKDPAVHIR DDFLSAMKTL
160 170 180 190 200
YMSDTFSTNF GNPEIAKKQI NNYVAKQTKG KIVDFIKDLD STHVMIVVNY
210 220 230 240 250
IFFKAKWQTA FSETNTHKMD FHVTPKRTTQ VPMMNREDGY SYYLDQNISC
260 270 280 290 300
TVVGIPYQGN AIALFILPSE GKMKQVEDGL DERTLRNWLK MFTKRRLDLY
310 320 330 340 350
LPKFSIEATY KLENVLPKLG IQDVFTTHAD LSGITDHTNI KLSEMVHKSM
360 370 380 390 400
MEVEESGTTA AAITGAIFTF RSARPSSLKI EFTRPFLLTL MEDSHILFVG

KVTRP
Length:405
Mass (Da):45,600
Last modified:July 27, 2011 - v2
Checksum:i0E7377A3F8C1A464
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti55V → A in AAC53063 (PubMed:9047345).Curated1
Sequence conflicti55V → A in AAH90981 (PubMed:15489334).Curated1
Sequence conflicti185F → L in AAC53063 (PubMed:9047345).Curated1
Sequence conflicti185F → L in AAH90981 (PubMed:15489334).Curated1
Sequence conflicti227 – 230RTTQ → KTIR in AAC53063 (PubMed:9047345).Curated4
Sequence conflicti227 – 230RTTQ → KTIR in AAH90981 (PubMed:15489334).Curated4
Sequence conflicti239G → E in AAC53063 (PubMed:9047345).Curated1
Sequence conflicti239G → E in AAH90981 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U67878 Genomic DNA Translation: AAC53063.1
AK087714 mRNA Translation: BAC39979.1
CH466549 Genomic DNA Translation: EDL18804.1
BC090981 mRNA Translation: AAH90981.1
CCDSiCCDS26146.1
RefSeqiNP_766541.2, NM_172953.3
XP_006515979.1, XM_006515916.2
UniGeneiMm.73172

Genome annotation databases

EnsembliENSMUST00000021495; ENSMUSP00000021495; ENSMUSG00000041550
GeneIDi268591
KEGGimmu:268591
UCSCiuc007ows.1 mouse

Similar proteinsi

Entry informationi

Entry nameiIPSP_MOUSE
AccessioniPrimary (citable) accession number: P70458
Secondary accession number(s): Q5BKQ8, Q8BU50
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 133 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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