IPSP_MOUSE
ID IPSP_MOUSE Reviewed; 405 AA.
AC P70458; Q5BKQ8; Q8BU50;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Plasma serine protease inhibitor;
DE AltName: Full=Plasminogen activator inhibitor 3;
DE Short=PAI-3;
DE Short=PAI3;
DE AltName: Full=Protein C inhibitor;
DE Short=PCI;
DE AltName: Full=Serpin A5;
DE Flags: Precursor;
GN Name=Serpina5; Synonyms=Pci;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=BALB/cJ; TISSUE=Liver, and Testis;
RX PubMed=9047345; DOI=10.1016/s0378-1119(96)00681-6;
RA Zechmeister-Machhart M., Hufnagl P., Uhrin P., Korschineck I., Binder B.R.,
RA Geiger M.;
RT "Molecular cloning and sequence analysis of the mouse protein C inhibitor
RT gene.";
RL Gene 186:61-66(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Ovary;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=11120760; DOI=10.1172/jci10768;
RA Uhrin P., Dewerchin M., Hilpert M., Chrenek P., Schofer C.,
RA Zechmeister-Machhart M., Kronke G., Vales A., Carmeliet P., Binder B.R.,
RA Geiger M.;
RT "Disruption of the protein C inhibitor gene results in impaired
RT spermatogenesis and male infertility.";
RL J. Clin. Invest. 106:1531-1539(2000).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=15140131; DOI=10.1111/j.1538-7836.2004.00733.x;
RA Hayashi T., Nishioka J., Kamada H., Asanuma K., Kondo H., Gabazza E.C.,
RA Ido M., Suzuki K.;
RT "Characterization of a novel human protein C inhibitor (PCI) gene
RT transgenic mouse useful for studying the role of PCI in physiological and
RT pathological conditions.";
RL J. Thromb. Haemost. 2:949-961(2004).
CC -!- FUNCTION: Heparin-dependent serine protease inhibitor acting in body
CC fluids and secretions. Inactivates serine proteases by binding
CC irreversibly to their serine activation site. Involved in the
CC regulation of intravascular and extravascular proteolytic activities.
CC Plays hemostatic roles in the blood plasma. Acts as a procoagulant and
CC pro-inflammatory factor by inhibiting the anticoagulant activated
CC protein C factor as well as the generation of activated protein C
CC factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant
CC factor by inhibiting blood coagulation factors like prothrombin, factor
CC XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as
CC tissue- and urinary-type plasminogen activators. In seminal plasma,
CC inactivates several serine proteases implicated in the reproductive
CC system. Inhibits the serpin acrosin; indirectly protects component of
CC the male genital tract from being degraded by excessive released
CC acrosin. Inhibits tissue- and urinary-type plasminogen activator,
CC prostate-specific antigen and kallikrein activities; has a control on
CC the sperm motility and fertilization. Inhibits the activated protein C-
CC catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of
CC semenogelin during the process of transfer of spermatozoa from the male
CC reproductive tract into the female tract. In urine, inhibits urinary-
CC type plasminogen activator and kallikrein activities. Inactivates
CC membrane-anchored serine proteases activities such as MPRSS7 and
CC TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor
CC cell invasion and metastasis. May also play a non-inhibitory role in
CC seminal plasma and urine as a hydrophobic hormone carrier by its
CC binding to retinoic acid (By similarity). {ECO:0000250}.
CC -!- ACTIVITY REGULATION: Its inhibitory activity is greatly enhanced in the
CC presence of glycosaminoglycans, heparin, thrombomodulin and
CC phospholipids vesicles.
CC -!- SUBUNIT: Forms protease inhibiting heterodimers in extracellular body
CC fluids with serine proteases such as activated protein C/coagulation
CC factor V/F5, acrosin/ACR, chymotrypsinogen B/CTRB1, prothrombin/F2,
CC factor Xa/F10, factor XI/F11, kallikrein/KLKB1, tissue kallikrein,
CC trypsin/PRSS1, prostate specific antigen/KLK3, tissue plasminogen
CC activator/PLAT and urinary plasminogen activator/PLAU. Forms membrane-
CC anchored serine proteases inhibiting heterodimers with TMPRSS7 and
CC TMPRSS11E. Interacts with SEMG2 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC P70458; Q5S248: Tmprss11e; NbExp=2; IntAct=EBI-490966, EBI-490889;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}.
CC Note=Localized on the plasma membrane overlying the acrosomal head of
CC spermatozoa of ependymal spermatozoa and ejaculated sperm. Localized at
CC the equatorial segment of acrosome-reacted spermatozoa. Localized in
CC alpha granules in resting platelets and on the external plasma membrane
CC and within the surface-connected cannalicular system in activated
CC platelets (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Not detected in blood plasma (at protein level).
CC Expressed in testis, epididymis, seminal vesicles, prostate and
CC ovaries. {ECO:0000269|PubMed:15140131}.
CC -!- DOMAIN: The reactive center loop (RCL) extends out from the body of the
CC protein and directs binding to the target protease. The protease
CC cleaves the serpin at the reactive site within the RCL, establishing a
CC covalent linkage between the carboxyl group of the serpin reactive site
CC and the serine hydroxyl of the protease. The resulting inactive serpin-
CC protease complex is highly stable (By similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated; glycans consist of a mixture of sialylated
CC bi- (including sialyl-Lewis X epitopes), tri- and tetra-antennary
CC complex-type chains; affects the maximal heparin- and thrombomodulin-
CC enhanced rates of thrombin inhibition. O-glycosylated; further modified
CC with 2 sialic acid residues. Proteolytically cleaved at the N-terminus;
CC inhibits slightly the heparin- and thrombomodulin-enhanced rates of
CC thrombin inhibition (By similarity). {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved. Inhibition of proteases is accompanied by
CC formation of a stable enzyme-inhibitor complex and by degradation of
CC the serpin to lower molecular weight derivatives (By similarity).
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are healthy but males are infertile;
CC spermatozoa are morphologically abnormal, most lacked tails and
CC malformed heads. The lumina of the seminiferous tubules are filled with
CC cells in different stages of spermatogenesis and are sometimes
CC necrotic. The cytoplasm of Sertoli cells contained vacuoles and
CC appeared necrotic. The Sertoli cell barrier appeared disrupted.
CC {ECO:0000269|PubMed:11120760}.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
CC -!- CAUTION: According to PubMed:11120760 it is not detectable in blood
CC plasma. {ECO:0000305}.
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DR EMBL; U67878; AAC53063.1; -; Genomic_DNA.
DR EMBL; AK087714; BAC39979.1; -; mRNA.
DR EMBL; CH466549; EDL18804.1; -; Genomic_DNA.
DR EMBL; BC090981; AAH90981.1; -; mRNA.
DR CCDS; CCDS26146.1; -.
DR RefSeq; NP_766541.2; NM_172953.3.
DR RefSeq; XP_006515979.1; XM_006515916.2.
DR AlphaFoldDB; P70458; -.
DR SMR; P70458; -.
DR BioGRID; 234523; 1.
DR IntAct; P70458; 1.
DR STRING; 10090.ENSMUSP00000021495; -.
DR MEROPS; I04.004; -.
DR GlyGen; P70458; 1 site.
DR iPTMnet; P70458; -.
DR PhosphoSitePlus; P70458; -.
DR PaxDb; P70458; -.
DR PRIDE; P70458; -.
DR ProteomicsDB; 268985; -.
DR Antibodypedia; 27096; 541 antibodies from 34 providers.
DR DNASU; 268591; -.
DR Ensembl; ENSMUST00000021495; ENSMUSP00000021495; ENSMUSG00000041550.
DR GeneID; 268591; -.
DR KEGG; mmu:268591; -.
DR UCSC; uc007ows.1; mouse.
DR CTD; 5104; -.
DR MGI; MGI:107817; Serpina5.
DR VEuPathDB; HostDB:ENSMUSG00000041550; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000162217; -.
DR HOGENOM; CLU_023330_2_1_1; -.
DR InParanoid; P70458; -.
DR OMA; YYYFLDR; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; P70458; -.
DR TreeFam; TF343201; -.
DR Reactome; R-MMU-140837; Intrinsic Pathway of Fibrin Clot Formation.
DR Reactome; R-MMU-140875; Common Pathway of Fibrin Clot Formation.
DR BioGRID-ORCS; 268591; 1 hit in 75 CRISPR screens.
DR PRO; PR:P70458; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P70458; protein.
DR Bgee; ENSMUSG00000041550; Expressed in spermatocyte and 40 other tissues.
DR Genevisible; P70458; MM.
DR GO; GO:0002080; C:acrosomal membrane; ISS:UniProtKB.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0070062; C:extracellular exosome; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0031091; C:platelet alpha granule; ISS:UniProtKB.
DR GO; GO:0031094; C:platelet dense tubular network; ISS:UniProtKB.
DR GO; GO:0097181; C:protein C inhibitor-coagulation factor V complex; ISS:UniProtKB.
DR GO; GO:0097182; C:protein C inhibitor-coagulation factor Xa complex; ISS:UniProtKB.
DR GO; GO:0097183; C:protein C inhibitor-coagulation factor XI complex; ISS:UniProtKB.
DR GO; GO:0036029; C:protein C inhibitor-KLK3 complex; ISS:UniProtKB.
DR GO; GO:0036030; C:protein C inhibitor-plasma kallikrein complex; ISS:UniProtKB.
DR GO; GO:0036026; C:protein C inhibitor-PLAT complex; ISS:UniProtKB.
DR GO; GO:0036027; C:protein C inhibitor-PLAU complex; ISS:UniProtKB.
DR GO; GO:0036028; C:protein C inhibitor-thrombin complex; ISS:UniProtKB.
DR GO; GO:0036025; C:protein C inhibitor-TMPRSS11E complex; ISS:UniProtKB.
DR GO; GO:0036024; C:protein C inhibitor-TMPRSS7 complex; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0032190; F:acrosin binding; ISO:MGI.
DR GO; GO:0031210; F:phosphatidylcholine binding; ISS:UniProtKB.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0001972; F:retinoic acid binding; ISS:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0051346; P:negative regulation of hydrolase activity; ISO:MGI.
DR GO; GO:0045861; P:negative regulation of proteolysis; ISO:MGI.
DR GO; GO:0061107; P:seminal vesicle development; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IMP:UniProtKB.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR InterPro; IPR036186; Serpin_sf.
DR InterPro; IPR042178; Serpin_sf_1.
DR InterPro; IPR042185; Serpin_sf_2.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..24
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000414092"
FT CHAIN 25..405
FT /note="Plasma serine protease inhibitor"
FT /id="PRO_0000032428"
FT SITE 372..373
FT /note="Reactive bond"
FT CARBOHYD 247
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 55
FT /note="V -> A (in Ref. 1; AAC53063 and 4; AAH90981)"
FT /evidence="ECO:0000305"
FT CONFLICT 185
FT /note="F -> L (in Ref. 1; AAC53063 and 4; AAH90981)"
FT /evidence="ECO:0000305"
FT CONFLICT 227..230
FT /note="RTTQ -> KTIR (in Ref. 1; AAC53063 and 4; AAH90981)"
FT /evidence="ECO:0000305"
FT CONFLICT 239
FT /note="G -> E (in Ref. 1; AAC53063 and 4; AAH90981)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 405 AA; 45600 MW; 0E7377A3F8C1A464 CRC64;
MRFFPILCLV LFISHGVASR RHSHSKKKKA KESSVGAVGP PSSKDFAFRL YRALVSESPG
QNVFFSPLSV SMSLGMLSLG AGLKTKTQIL DGLGLSLQQG QEDKLHKGFQ QLLQRFRQPS
DGLQLSLGSA LFKDPAVHIR DDFLSAMKTL YMSDTFSTNF GNPEIAKKQI NNYVAKQTKG
KIVDFIKDLD STHVMIVVNY IFFKAKWQTA FSETNTHKMD FHVTPKRTTQ VPMMNREDGY
SYYLDQNISC TVVGIPYQGN AIALFILPSE GKMKQVEDGL DERTLRNWLK MFTKRRLDLY
LPKFSIEATY KLENVLPKLG IQDVFTTHAD LSGITDHTNI KLSEMVHKSM MEVEESGTTA
AAITGAIFTF RSARPSSLKI EFTRPFLLTL MEDSHILFVG KVTRP
