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P70458 (IPSP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 102. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Serpina5
Synonyms:Pci
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length405 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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.

Enzyme regulation

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

Subunit structure

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.

Subcellular location

Secretedextracellular 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.

Tissue specificity

Not detected in blood plasma (at protein level). Expressed in testis, epididymis, seminal vesicles, prostate and ovaries. Ref.6

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.

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.

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. Ref.5

Sequence similarities

Belongs to the serpin family.

Caution

According to Ref.5 it is not detectable in blood plasma.

Ontologies

Keywords
   Cellular componentSecreted
   DomainSignal
   Molecular functionProtease inhibitor
Serine protease inhibitor
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative regulation of endopeptidase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of proteolysis

Inferred from electronic annotation. Source: Ensembl

regulation of proteolysis

Inferred from Biological aspect of Ancestor. Source: RefGenome

spermatogenesis

Inferred from mutant phenotype Ref.5. Source: UniProtKB

   Cellular_componentacrosomal membrane

Inferred from sequence or structural similarity. Source: UniProtKB

external side of plasma membrane

Inferred from electronic annotation. Source: Ensembl

extracellular region

Inferred from Biological aspect of Ancestor. Source: RefGenome

extracellular space

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular vesicular exosome

Inferred from electronic annotation. Source: Ensembl

platelet alpha granule

Inferred from sequence or structural similarity. Source: UniProtKB

platelet dense tubular network

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-KLK3 complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-PLAT complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-PLAU complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-TMPRSS11E complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-TMPRSS7 complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-coagulation factor V complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-coagulation factor XI complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-coagulation factor Xa complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-plasma kallikrein complex

Inferred from sequence or structural similarity. Source: UniProtKB

protein C inhibitor-thrombin complex

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionphosphatidylcholine binding

Inferred from sequence or structural similarity. Source: UniProtKB

retinoic acid binding

Inferred from sequence or structural similarity. Source: UniProtKB

serine-type endopeptidase inhibitor activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Tmprss11eQ5S2482EBI-490966,EBI-490889

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Propeptide20 – 245Removed in mature form By similarity
PRO_0000414092
Chain25 – 405381Plasma serine protease inhibitor
PRO_0000032428

Sites

Site372 – 3732Reactive bond

Amino acid modifications

Glycosylation2471N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict551V → A in AAC53063. Ref.1
Sequence conflict551V → A in AAH90981. Ref.4
Sequence conflict1851F → L in AAC53063. Ref.1
Sequence conflict1851F → L in AAH90981. Ref.4
Sequence conflict227 – 2304RTTQ → KTIR in AAC53063. Ref.1
Sequence conflict227 – 2304RTTQ → KTIR in AAH90981. Ref.4
Sequence conflict2391G → E in AAC53063. Ref.1
Sequence conflict2391G → E in AAH90981. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P70458 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 0E7377A3F8C1A464

FASTA40545,600
        10         20         30         40         50         60 
MRFFPILCLV LFISHGVASR RHSHSKKKKA KESSVGAVGP PSSKDFAFRL YRALVSESPG 

        70         80         90        100        110        120 
QNVFFSPLSV SMSLGMLSLG AGLKTKTQIL DGLGLSLQQG QEDKLHKGFQ QLLQRFRQPS 

       130        140        150        160        170        180 
DGLQLSLGSA LFKDPAVHIR DDFLSAMKTL YMSDTFSTNF GNPEIAKKQI NNYVAKQTKG 

       190        200        210        220        230        240 
KIVDFIKDLD STHVMIVVNY IFFKAKWQTA FSETNTHKMD FHVTPKRTTQ VPMMNREDGY 

       250        260        270        280        290        300 
SYYLDQNISC TVVGIPYQGN AIALFILPSE GKMKQVEDGL DERTLRNWLK MFTKRRLDLY 

       310        320        330        340        350        360 
LPKFSIEATY KLENVLPKLG IQDVFTTHAD LSGITDHTNI KLSEMVHKSM MEVEESGTTA 

       370        380        390        400 
AAITGAIFTF RSARPSSLKI EFTRPFLLTL MEDSHILFVG KVTRP 

« Hide

References

« Hide 'large scale' references
[1]"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].
Strain: BALB/c.
Tissue: Liver and Testis.
[2]"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. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Ovary.
[3]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].
[4]"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].
Tissue: Testis.
[5]"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.
[6]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U67878 Genomic DNA. Translation: AAC53063.1.
AK087714 mRNA. Translation: BAC39979.1.
CH466549 Genomic DNA. Translation: EDL18804.1.
BC090981 mRNA. Translation: AAH90981.1.
RefSeqNP_766541.2. NM_172953.3.
XP_006515979.1. XM_006515916.1.
UniGeneMm.73172.

3D structure databases

ProteinModelPortalP70458.
SMRP70458. Positions 44-405.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid234523. 1 interaction.
IntActP70458. 1 interaction.

Protein family/group databases

MEROPSI04.004.

PTM databases

PhosphoSiteP70458.

Proteomic databases

PRIDEP70458.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000021495; ENSMUSP00000021495; ENSMUSG00000041550.
GeneID268591.
KEGGmmu:268591.
UCSCuc007ows.1. mouse.

Organism-specific databases

CTD5104.
MGIMGI:107817. Serpina5.

Phylogenomic databases

eggNOGCOG4826.
GeneTreeENSGT00740000115120.
HOGENOMHOG000238521.
HOVERGENHBG005957.
InParanoidQ5BKQ8.
KOK03913.
OMAWETSFNH.
OrthoDBEOG7QC7W9.
TreeFamTF343201.

Gene expression databases

BgeeP70458.
GenevestigatorP70458.

Family and domain databases

InterProIPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERPTHR11461. PTHR11461. 1 hit.
PfamPF00079. Serpin. 1 hit.
[Graphical view]
SMARTSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMSSF56574. SSF56574. 1 hit.
ProtoNetSearch...

Other

NextBio392397.
PROP70458.
SOURCESearch...

Entry information

Entry nameIPSP_MOUSE
AccessionPrimary (citable) accession number: P70458
Secondary accession number(s): Q5BKQ8, Q8BU50
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 102 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot