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P70458

- IPSP_MOUSE

UniProt

P70458 - IPSP_MOUSE

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Protein

Plasma serine protease inhibitor

Gene

Serpina5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- 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

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei372 – 3732Reactive bond

GO - Molecular functioni

  1. phosphatidylcholine binding Source: UniProtKB
  2. retinoic acid binding Source: UniProtKB
  3. serine-type endopeptidase inhibitor activity Source: UniProtKB

GO - Biological processi

  1. negative regulation of endopeptidase activity Source: RefGenome
  2. negative regulation of proteolysis Source: Ensembl
  3. regulation of proteolysis Source: RefGenome
  4. spermatogenesis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Enzyme and pathway databases

ReactomeiREACT_239392. Intrinsic Pathway.
REACT_259461. Common Pathway.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 12

Organism-specific databases

MGIiMGI:107817. Serpina5.

Subcellular locationi

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).By similarity

GO - Cellular componenti

  1. acrosomal membrane Source: UniProtKB
  2. external side of plasma membrane Source: Ensembl
  3. extracellular region Source: RefGenome
  4. extracellular space Source: UniProtKB
  5. extracellular vesicular exosome Source: Ensembl
  6. platelet alpha granule Source: UniProtKB
  7. platelet dense tubular network Source: UniProtKB
  8. protein C inhibitor-coagulation factor V complex Source: UniProtKB
  9. protein C inhibitor-coagulation factor Xa complex Source: UniProtKB
  10. protein C inhibitor-coagulation factor XI complex Source: UniProtKB
  11. protein C inhibitor-KLK3 complex Source: UniProtKB
  12. protein C inhibitor-plasma kallikrein complex Source: UniProtKB
  13. protein C inhibitor-PLAT complex Source: UniProtKB
  14. protein C inhibitor-PLAU complex Source: UniProtKB
  15. protein C inhibitor-thrombin complex Source: UniProtKB
  16. protein C inhibitor-TMPRSS11E complex Source: UniProtKB
  17. protein C inhibitor-TMPRSS7 complex Source: UniProtKB
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence AnalysisAdd
BLAST
Propeptidei20 – 245Removed in mature formBy similarityPRO_0000414092
Chaini25 – 405381Plasma serine protease inhibitorPRO_0000032428Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi247 – 2471N-linked (GlcNAc...)Sequence Analysis

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

PRIDEiP70458.

PTM databases

PhosphoSiteiP70458.

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

BgeeiP70458.
GenevestigatoriP70458.

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

Protein-protein interaction databases

BioGridi234523. 1 interaction.
IntActiP70458. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliP70458.
SMRiP70458. Positions 44-405.
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

eggNOGiCOG4826.
GeneTreeiENSGT00760000118839.
HOGENOMiHOG000238521.
HOVERGENiHBG005957.
InParanoidiP70458.
KOiK03913.
OMAiNFRDSAG.
OrthoDBiEOG7QC7W9.
TreeFamiTF343201.

Family and domain databases

InterProiIPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiPF00079. Serpin. 1 hit.
[Graphical view]
SMARTiSM00093. SERPIN. 1 hit.
[Graphical view]
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti55 – 551V → A in AAC53063. (PubMed:9047345)Curated
Sequence conflicti55 – 551V → A in AAH90981. (PubMed:15489334)Curated
Sequence conflicti185 – 1851F → L in AAC53063. (PubMed:9047345)Curated
Sequence conflicti185 – 1851F → L in AAH90981. (PubMed:15489334)Curated
Sequence conflicti227 – 2304RTTQ → KTIR in AAC53063. (PubMed:9047345)Curated
Sequence conflicti227 – 2304RTTQ → KTIR in AAH90981. (PubMed:15489334)Curated
Sequence conflicti239 – 2391G → E in AAC53063. (PubMed:9047345)Curated
Sequence conflicti239 – 2391G → E in AAH90981. (PubMed:15489334)Curated

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_006515916.1.
UniGeneiMm.73172.

Genome annotation databases

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

Cross-referencesi

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 .
CCDSi CCDS26146.1.
RefSeqi NP_766541.2. NM_172953.3.
XP_006515979.1. XM_006515916.1.
UniGenei Mm.73172.

3D structure databases

ProteinModelPortali P70458.
SMRi P70458. Positions 44-405.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 234523. 1 interaction.
IntActi P70458. 1 interaction.

Protein family/group databases

MEROPSi I04.004.

PTM databases

PhosphoSitei P70458.

Proteomic databases

PRIDEi P70458.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000021495 ; ENSMUSP00000021495 ; ENSMUSG00000041550 .
GeneIDi 268591.
KEGGi mmu:268591.
UCSCi uc007ows.1. mouse.

Organism-specific databases

CTDi 5104.
MGIi MGI:107817. Serpina5.

Phylogenomic databases

eggNOGi COG4826.
GeneTreei ENSGT00760000118839.
HOGENOMi HOG000238521.
HOVERGENi HBG005957.
InParanoidi P70458.
KOi K03913.
OMAi NFRDSAG.
OrthoDBi EOG7QC7W9.
TreeFami TF343201.

Enzyme and pathway databases

Reactomei REACT_239392. Intrinsic Pathway.
REACT_259461. Common Pathway.

Miscellaneous databases

NextBioi 392397.
PROi P70458.
SOURCEi Search...

Gene expression databases

Bgeei P70458.
Genevestigatori P70458.

Family and domain databases

InterProi IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view ]
PANTHERi PTHR11461. PTHR11461. 1 hit.
Pfami PF00079. Serpin. 1 hit.
[Graphical view ]
SMARTi SM00093. SERPIN. 1 hit.
[Graphical view ]
SUPFAMi SSF56574. SSF56574. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiIPSP_MOUSE
AccessioniPrimary (citable) accession number: P70458
Secondary accession number(s): Q5BKQ8, Q8BU50
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: July 27, 2011
Last modified: November 26, 2014
This is version 108 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

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

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

External Data

Dasty 3