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P70458

- IPSP_MOUSE

UniProt

P70458 - IPSP_MOUSE

Protein

Plasma serine protease inhibitor

Gene

Serpina5

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 106 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    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. protein binding Source: IntAct
    3. retinoic acid binding Source: UniProtKB
    4. 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

    Keywords - Molecular functioni

    Protease inhibitor, Serine protease inhibitor

    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

    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.
    GeneTreeiENSGT00740000115120.
    HOGENOMiHOG000238521.
    HOVERGENiHBG005957.
    InParanoidiQ5BKQ8.
    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

    MRFFPILCLV LFISHGVASR RHSHSKKKKA KESSVGAVGP PSSKDFAFRL    50
    YRALVSESPG QNVFFSPLSV SMSLGMLSLG AGLKTKTQIL DGLGLSLQQG 100
    QEDKLHKGFQ QLLQRFRQPS DGLQLSLGSA LFKDPAVHIR DDFLSAMKTL 150
    YMSDTFSTNF GNPEIAKKQI NNYVAKQTKG KIVDFIKDLD STHVMIVVNY 200
    IFFKAKWQTA FSETNTHKMD FHVTPKRTTQ VPMMNREDGY SYYLDQNISC 250
    TVVGIPYQGN AIALFILPSE GKMKQVEDGL DERTLRNWLK MFTKRRLDLY 300
    LPKFSIEATY KLENVLPKLG IQDVFTTHAD LSGITDHTNI KLSEMVHKSM 350
    MEVEESGTTA AAITGAIFTF RSARPSSLKI EFTRPFLLTL MEDSHILFVG 400
    KVTRP 405
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 ENSGT00740000115120.
    HOGENOMi HOG000238521.
    HOVERGENi HBG005957.
    InParanoidi Q5BKQ8.
    KOi K03913.
    OMAi NFRDSAG.
    OrthoDBi EOG7QC7W9.
    TreeFami TF343201.

    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

    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: October 1, 2014
    This is version 106 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