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P05154 (IPSP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 168. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Plasma serine protease inhibitor
Alternative name(s):
Acrosomal serine protease inhibitor
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, PLANH3, PROCI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length406 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. Ref.12 Ref.13 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.30 Ref.33

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. Ref.20

Subcellular location

Secretedextracellular space. 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. Ref.15 Ref.17 Ref.19 Ref.22 Ref.23 Ref.33

Tissue specificity

Predominantly expressed in the epithelium of seminal vesicles. Expressed in the proximal tubular epithelium of the kidney. Expressed in the superficial and more differentiated epidermal keratinocytes of the skin. Expressed in megakaryocytes and platelets. Expressed poorly in kidney tumor cells compared to non tumor kidney tissues. Expressed in spermatozoa. Present in very high concentration in seminal plasma. Present in high concentration in plasma, synovial and Graaf follicle fluids. Present in low concentration in breast milk and in amniotic fluids. Present in very low concentration in urine, cerebrospinal fluids, saliva and tears (at protein level). Strongly expressed in liver. Expressed in kidney, spleen, pancreas, skeletal muscle, heart, testes, ovary, interstitial Leydig cells, epididymal glands, seminal vesicles and prostate. Ref.16 Ref.22 Ref.23 Ref.26 Ref.28 Ref.32 Ref.33

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.

Post-translational modification

N- and O-glycosylated. N-glycosylation consists 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 with core 1 or possibly core 8 glycans. Further modified with 2 sialic acid residues. Ref.33 Ref.35 Ref.36 Ref.38

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. Proteolytically cleaved at the N-terminus; inhibits slightly the heparin- and thrombomodulin-enhanced rates of thrombin inhibition. Ref.27 Ref.33

Sequence similarities

Belongs to the serpin family.

Ontologies

Keywords
   Biological processFertilization
Lipid transport
Transport
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   LigandHeparin-binding
   Molecular functionProtease inhibitor
Serine protease inhibitor
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processfusion of sperm to egg plasma membrane

Non-traceable author statement Ref.22. Source: UniProtKB

lipid transport

Inferred from electronic annotation. Source: UniProtKB-KW

negative 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 sequence or structural similarity. Source: UniProtKB

   Cellular_componentacrosomal membrane

Inferred from direct assay Ref.17Ref.22. Source: UniProtKB

external side of plasma membrane

Inferred from direct assay Ref.23. Source: UniProtKB

extracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

extracellular space

Inferred from direct assay Ref.24Ref.15Ref.19. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 21557262. Source: UniProtKB

membrane

Inferred from direct assay Ref.17. Source: UniProtKB

platelet alpha granule

Inferred from direct assay Ref.23. Source: UniProtKB

platelet dense tubular network

Inferred from direct assay Ref.23. Source: UniProtKB

protein C inhibitor-KLK3 complex

Inferred from direct assay Ref.15. Source: UniProtKB

protein C inhibitor-PLAT complex

Inferred from direct assay Ref.24. Source: UniProtKB

protein C inhibitor-PLAU complex

Inferred from direct assay Ref.24Ref.13Ref.19. Source: UniProtKB

protein C inhibitor-TMPRSS11E complex

Inferred from direct assay Ref.27. Source: UniProtKB

protein C inhibitor-TMPRSS7 complex

Inferred from direct assay Ref.30. Source: UniProtKB

protein C inhibitor-coagulation factor V complex

Inferred from direct assay Ref.12. Source: UniProtKB

protein C inhibitor-coagulation factor XI complex

Inferred from direct assay Ref.14. Source: UniProtKB

protein C inhibitor-coagulation factor Xa complex

Inferred from direct assay Ref.12. Source: UniProtKB

protein C inhibitor-plasma kallikrein complex

Inferred from direct assay Ref.14Ref.19. Source: UniProtKB

protein C inhibitor-thrombin complex

Inferred from direct assay Ref.12. Source: UniProtKB

protein complex

Inferred from direct assay Ref.17. Source: UniProtKB

   Molecular_functionacrosin binding

Inferred from physical interaction Ref.17. Source: UniProtKB

glycosaminoglycan binding

Traceable author statement PubMed 8796266. Source: UniProtKB

heparin binding

Traceable author statement PubMed 11120760. Source: UniProtKB

phosphatidylcholine binding

Inferred from direct assay Ref.23. Source: UniProtKB

protease binding

Inferred from physical interaction Ref.24Ref.26Ref.30Ref.15Ref.14Ref.13Ref.12Ref.17Ref.23. Source: UniProtKB

retinoic acid binding

Inferred from direct assay Ref.25. Source: UniProtKB

serine-type endopeptidase inhibitor activity

Inferred from direct assay Ref.24Ref.30Ref.15Ref.14Ref.13Ref.12Ref.17Ref.19Ref.22Ref.23. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Ref.11
Propeptide20 – 256Removed in mature form
PRO_0000414091
Chain26 – 406381Plasma serine protease inhibitor
PRO_0000032427

Sites

Site373 – 3742Reactive bond

Amino acid modifications

Glycosylation391O-linked (GalNAc...) Ref.35 Ref.36
Glycosylation2491N-linked (GlcNAc...) Ref.29 Ref.33
Glycosylation2621N-linked (GlcNAc...) Ref.31 Ref.33 Ref.38
Glycosylation3381N-linked (GlcNAc...) Ref.31 Ref.33

Natural variations

Natural variant441S → G. Ref.6
Corresponds to variant rs2069975 [ dbSNP | Ensembl ].
VAR_013080
Natural variant551A → V in allele PCI*B. Ref.5 Ref.6 Ref.41
Corresponds to variant rs6118 [ dbSNP | Ensembl ].
VAR_007100
Natural variant641S → N. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.41
Corresponds to variant rs6115 [ dbSNP | Ensembl ].
VAR_013081
Natural variant941G → V. Ref.6
Corresponds to variant rs2069976 [ dbSNP | Ensembl ].
VAR_013082
Natural variant1051K → E in allele PCI*B. Ref.5 Ref.6 Ref.41
Corresponds to variant rs6119 [ dbSNP | Ensembl ].
VAR_007101
Natural variant1151L → P. Ref.6
Corresponds to variant rs2069999 [ dbSNP | Ensembl ].
VAR_013083
Natural variant1211P → A. Ref.41
Corresponds to variant rs6120 [ dbSNP | Ensembl ].
VAR_013900
Natural variant2171G → R. Ref.6 Ref.41
Corresponds to variant rs6114 [ dbSNP | Ensembl ].
VAR_013084

Experimental info

Mutagenesis2481R → E: Does not change the rate of thrombin or activated protein C/F5 inhibition in the presence or absence of heparin. Strongly reduces the rate of thrombin inhibition in the presence of heparin. Ref.40
Mutagenesis2531R → E: Inhibits strongly thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34
Mutagenesis2721E → K: Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34
Mutagenesis2741K → E: Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34
Mutagenesis2851K → E: Does not change the rate of thrombin or activated protein C/F5 inhibition in the presence or absence of heparin. Slightly reduces the rate of thrombin inhibition in the presence of heparin. Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34 Ref.40
Mutagenesis2881R → E: Does not change the rate of thrombin or activated protein C/F5 inhibition in the presence or absence of heparin. Slightly reduces the rate of thrombin inhibition in the presence of heparin. Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34 Ref.40
Mutagenesis2891K → E: Does not change the rate of thrombin or activated protein C/F5 inhibition in the presence or absence of heparin. Slightly reduces the rate of thrombin inhibition in the presence of heparin. Inhibits weakly thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34 Ref.40
Mutagenesis2921K → E: Does not change the rate of thrombin or activated protein C/F5 inhibition in the presence or absence of heparin. Slightly reduces the rate of thrombin inhibition in the presence of heparin. Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34 Ref.40
Mutagenesis3601T → R: Inhibits heterodimer formation with TMPRSS11E. Ref.27
Mutagenesis3711T → R: Increases inhibition of activated protein C/F5 and factor XI/F11 activities. Decreases inhibition of thrombin activity. Ref.18
Mutagenesis3721F → P or G: Increases inhibition of thrombin activity. Ref.18
Mutagenesis3731R → P: Increases inhibition of thrombin activity. Inhibits heterodimer formation with TMPRSS11E. Ref.18 Ref.27
Mutagenesis3761R → P: Does not change inhibition of thrombin, activated protein C/F5 and factor XI/F11 activities. Ref.18
Mutagenesis3811R → E: Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34
Sequence conflict281K → E in CAB45766. Ref.10
Sequence conflict2211Q → L in AAB26244. Ref.9
Sequence conflict3351G → R in AAA35688. Ref.1
Sequence conflict3351G → R in AAB26244. Ref.9
Sequence conflict3841F → S in AAB26244. Ref.9

Secondary structure

......................................................... 406
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P05154 [UniParc].

Last modified February 8, 2011. Version 3.
Checksum: 2A8FF3DC33C77E04

FASTA40645,675
        10         20         30         40         50         60 
MQLFLLLCLV LLSPQGASLH RHHPREMKKR VEDLHVGATV APSSRRDFTF DLYRALASAA 

        70         80         90        100        110        120 
PSQSIFFSPV SISMSLAMLS LGAGSSTKMQ ILEGLGLNLQ KSSEKELHRG FQQLLQELNQ 

       130        140        150        160        170        180 
PRDGFQLSLG NALFTDLVVD LQDTFVSAMK TLYLADTFPT NFRDSAGAMK QINDYVAKQT 

       190        200        210        220        230        240 
KGKIVDLLKN LDSNAVVIMV NYIFFKAKWE TSFNHKGTQE QDFYVTSETV VRVPMMSRED 

       250        260        270        280        290        300 
QYHYLLDRNL SCRVVGVPYQ GNATALFILP SEGKMQQVEN GLSEKTLRKW LKMFKKRQLE 

       310        320        330        340        350        360 
LYLPKFSIEG SYQLEKVLPS LGISNVFTSH ADLSGISNHS NIQVSEMVHK AVVEVDESGT 

       370        380        390        400 
RAAAATGTIF TFRSARLNSQ RLVFNRPFLM FIVDNNILFL GKVNRP 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of a cDNA for human protein C inhibitor. A new member of the plasma serine protease inhibitor superfamily."
Suzuki K., Deyashiki Y., Nishioka J., Kurachi K., Akira M., Yamamoto S., Hashimoto S.
J. Biol. Chem. 262:611-616(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ASN-64.
[2]"Evidence for a glycine residue at position 316 in human protein C inhibitor."
Meijers J.C.M., Chung D.W.
Thromb. Res. 59:389-393(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-64.
[3]"Organization of the gene coding for human protein C inhibitor (plasminogen activator inhibitor-3). Assignment of the gene to chromosome 14."
Meijers J.C.M., Chung D.W.
J. Biol. Chem. 266:15028-15034(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ASN-64.
[4]"Gene organization of human protein C inhibitor, a member of SERPIN family proteins encoded in five exons."
Hayashi T., Suzuki K.
Int. J. Hematol. 58:213-224(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"A two-allele polymorphism in protein C inhibitor with varying frequencies in different ethnic populations."
Radtke K.-P., Greengard J.S., Fernandez J.A., Villoutreix B.O., Griffin J.H.
Thromb. Haemost. 75:62-69(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-55; ASN-64 AND GLU-105.
Tissue: Liver.
[6]SeattleSNPs variation discovery resource
Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-44; VAL-55; ASN-64; VAL-94; GLU-105; PRO-115 AND ARG-217.
[7]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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], VARIANT ASN-64.
Tissue: Skin.
[9]"Human sperm-egg binding is inhibited by peptides corresponding to core region of an acrosomal serine protease inhibitor."
Moore A., Penfold L.M., Johnson J.L., Latchman D.S., Moore H.D.
Mol. Reprod. Dev. 34:280-291(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 27-406, VARIANT ASN-64.
Tissue: Testis.
[10]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 28-406, VARIANT ASN-64.
Tissue: Testis.
[11]"Protein C inhibitor from human plasma: characterization of native and cleaved inhibitor and demonstration of inhibitor complexes with plasma kallikrein."
Laurell M., Stenflo J.
Thromb. Haemost. 62:885-891(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-39.
[12]"Mechanism of inhibition of activated protein C by protein C inhibitor."
Suzuki K., Nishioka J., Kusumoto H., Hashimoto S.
J. Biochem. 95:187-195(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN BLOOD PLASMA SERINE PROTEASE INHIBITION, HETERODIMER WITH F2; F5 AND F10.
[13]"Inhibition of urokinase by protein C-inhibitor (PCI). Evidence for identity of PCI and plasminogen activator inhibitor 3."
Stief T.W., Radtke K.P., Heimburger N.
Biol. Chem. Hoppe-Seyler 368:1427-1433(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN BLOOD PLASMA PLAU INHIBITION, HETERODIMER WITH PLAU.
[14]"Inactivation of human plasma kallikrein and factor XIa by protein C inhibitor."
Meijers J.C., Kanters D.H., Vlooswijk R.A., van Erp H.E., Hessing M., Bouma B.N.
Biochemistry 27:4231-4237(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN BLOOD PLASMA SERINE PROTEASE INHIBITION, HETERODIMER WITH F5; F11 AND KLKB1.
[15]"Functionally active protein C inhibitor/plasminogen activator inhibitor-3 (PCI/PAI-3) is secreted in seminal vesicles, occurs at high concentrations in human seminal plasma and complexes with prostate-specific antigen."
Espana F., Gilabert J., Estelles A., Romeu A., Aznar J., Cabo A.
Thromb. Res. 64:309-320(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SEMINAL PLASMA KLK3 INHIBITION, HETERODIMER WITH KLK3, SUBCELLULAR LOCATION.
[16]"Protein C inhibitor in human body fluids. Seminal plasma is rich in inhibitor antigen deriving from cells throughout the male reproductive system."
Laurell M., Christensson A., Abrahamsson P.A., Stenflo J., Lilja H.
J. Clin. Invest. 89:1094-1101(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[17]"Inhibition of acrosin by protein C inhibitor and localization of protein C inhibitor to spermatozoa."
Zheng X., Geiger M., Ecke S., Bielek E., Donner P., Eberspacher U., Schleuning W.D., Binder B.R.
Am. J. Physiol. 267:C466-C472(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SEMINAL PLASMA ACR INHIBITION, HETERODIMER WITH ACR, SUBCELLULAR LOCATION.
[18]"Intermolecular interactions between protein C inhibitor and coagulation proteases."
Cooper S.T., Whinna H.C., Jackson T.P., Boyd J.M., Church F.C.
Biochemistry 34:12991-12997(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SERINE PROTEASE INHIBITION, MUTAGENESIS OF THR-371; PHE-372; ARG-373 AND ARG-376.
[19]"Complexes of tissue kallikrein with protein C inhibitor in human semen and urine."
Espana F., Fink E., Sanchez-Cuenca J., Gilabert J., Estelles A., Witzgall K.
Eur. J. Biochem. 234:641-649(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SEMINAL PLASMA AND URINE KALLIKREIN INHIBITION, HETERODIMER WITH TISSUE KALLIKREIN, SUBCELLULAR LOCATION.
[20]"Characterization of semenogelin II and its molecular interaction with prostate-specific antigen and protein C inhibitor."
Kise H., Nishioka J., Kawamura J., Suzuki K.
Eur. J. Biochem. 238:88-96(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SEMINAL PLASMA KLK3 INHIBITION, HETERODIMER WITH F5, INTERACTION WITH SEMG2.
[21]"Protein C inhibitor acts as a procoagulant by inhibiting the thrombomodulin-induced activation of protein C in human plasma."
Elisen M.G., von dem Borne P.A., Bouma B.N., Meijers J.C.
Blood 91:1542-1547(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN BLOOD PLASMA F5 INHIBITION.
[22]"Protein C inhibitor may modulate human sperm-oocyte interactions."
Elisen M.G., van Kooij R.J., Nolte M.A., Marquart J.A., Lock T.M., Bouma B.N., Meijers J.C.
Biol. Reprod. 58:670-677(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN FERTILIZATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[23]"Protein C inhibitor secreted from activated platelets efficiently inhibits activated protein C on phosphatidylethanolamine of platelet membrane and microvesicles."
Nishioka J., Ning M., Hayashi T., Suzuki K.
J. Biol. Chem. 273:11281-11287(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN BLOOD PLASMA F5 INHIBITION, HETERODIMER WITH F5, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[24]"Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility."
He S., Lin Y.L., Liu Y.X.
Mol. Hum. Reprod. 5:513-519(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN SEMINAL PLASMA SERINE PROTEASES INHIBITION, HETERODIMER WITH PLAT AND PLAU.
[25]"Binding of retinoic acid by the inhibitory serpin protein C inhibitor."
Jerabek I., Zechmeister-Machhart M., Binder B.R., Geiger M.
Eur. J. Biochem. 268:5989-5996(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RETINOIC ACID TRANSPORT.
[26]"Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma."
Wakita T., Hayashi T., Nishioka J., Tamaru H., Akita N., Asanuma K., Kamada H., Gabazza E.C., Ido M., Kawamura J., Suzuki K.
Int. J. Cancer 108:516-523(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS REGULATOR OF TUMOR CELL INVASION, HETERODIMER WITH PLAU, TISSUE SPECIFICITY.
[27]"Mouse DESC1 is located within a cluster of seven DESC1-like genes and encodes a type II transmembrane serine protease that forms serpin inhibitory complexes."
Hobson J.P., Netzel-Arnett S., Szabo R., Rehault S.M., Church F.C., Strickland D.K., Lawrence D.A., Antalis T.M., Bugge T.H.
J. Biol. Chem. 279:46981-46994(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MEMBRANE-ANCHORED SERINE PROTEASE TMPRSS11E INHIBITION, HETERODIMER WITH TMPRSS11E, PROTEOLYTIC CLEAVAGE, MUTAGENESIS OF THR-360 AND ARG-373.
[28]"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: FUNCTION IN BLOOD PLASMA F5 INHIBITION, HETERODIMER WITH F5, TISSUE SPECIFICITY.
[29]"Screening for N-glycosylated proteins by liquid chromatography mass spectrometry."
Bunkenborg J., Pilch B.J., Podtelejnikov A.V., Wisniewski J.R.
Proteomics 4:454-465(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-249.
Tissue: Plasma.
[30]"Matriptase-3 is a novel phylogenetically preserved membrane-anchored serine protease with broad serpin reactivity."
Szabo R., Netzel-Arnett S., Hobson J.P., Antalis T.M., Bugge T.H.
Biochem. J. 390:231-242(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN MEMBRANE-ANCHORED SERINE PROTEASE TMPRSS7 INHIBITION, HETERODIMER WITH TMPRSS7.
[31]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-262 AND ASN-338.
Tissue: Plasma.
[32]"Immunolocalization of protein C inhibitor in differentiation of human epidermal keratinocytes."
Zhang C., Li X., Lian X., Wang Y., Zeng Y., Yang K., Yu J., Gao Q., Yang T.
Acta Histochem. 109:461-467(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[33]"N-glycans and the N terminus of protein C inhibitor affect the cofactor-enhanced rates of thrombin inhibition."
Sun W., Parry S., Panico M., Morris H.R., Kjellberg M., Engstrom A., Dell A., Schedin-Weiss S.
J. Biol. Chem. 283:18601-18611(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PROTEOLYTIC CLEAVAGE, GLYCOSYLATION AT ASN-249; ASN-262 AND ASN-338, STRUCTURE OF CARBOHYDRATES, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION BY MASS SPECTROMETRY.
[34]"Molecular basis of thrombin recognition by protein C inhibitor revealed by the 1.6-A structure of the heparin-bridged complex."
Li W., Adams T.E., Nangalia J., Esmon C.T., Huntington J.A.
Proc. Natl. Acad. Sci. U.S.A. 105:4661-4666(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-253; GLU-272; LYS-274; LYS-285; ARG-288; LYS-289; LYS-292 AND ARG-381.
[35]"Further insight into the roles of the glycans attached to human blood protein C inhibitor."
Sun W., Parry S., Ubhayasekera W., Engstrom A., Dell A., Schedin-Weiss S.
Biochem. Biophys. Res. Commun. 403:198-202(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT THR-39, IDENTIFICATION BY MASS SPECTROMETRY.
[36]"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD."
Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.
Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT THR-39, STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY.
[37]"Elucidating the structural chemistry of glycosaminoglycan recognition by protein C inhibitor."
Kuhn L.A., Griffin J.H., Fisher C.L., Greengard J.S., Bouma B.N., Espana F., Tainer J.A.
Proc. Natl. Acad. Sci. U.S.A. 87:8506-8510(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING.
[38]"Crystal structure of protein C inhibitor provides insights into hormone binding and heparin activation."
Huntington J.A., Kjellberg M., Stenflo J.
Structure 11:205-215(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 30-406, GLYCOSYLATION AT ASN-262.
[39]"Structure of native protein C inhibitor provides insight into its multiple functions."
Li W., Adams T.E., Kjellberg M., Stenflo J., Huntington J.A.
J. Biol. Chem. 282:13759-13768(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 36-406.
[40]"The heparin binding site of protein C inhibitor is protease-dependent."
Li W., Huntington J.A.
J. Biol. Chem. 283:36039-36045(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 37-406 IN COMPLEX WITH SYNTHETIC HEPARIN, HEPARIN-BINDING SITES, MUTAGENESIS OF ARG-248; LYS-285; ARG-288; LYS-289 AND LYS-292.
[41]"Characterization of single-nucleotide polymorphisms in coding regions of human genes."
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 22:231-238(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-55; ASN-64; GLU-105; ALA-121 AND ARG-217.
[42]Erratum
Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S.
Nat. Genet. 23:373-373(1999)
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J02639 mRNA. Translation: AAA35688.1.
M68516 Genomic DNA. Translation: AAA02811.1.
S69366 expand/collapse EMBL AC list , S69364, S69574, S69365 Genomic DNA. Translation: AAB30461.1.
U35464 mRNA. Translation: AAB60386.1.
AF361796 Genomic DNA. Translation: AAK27240.1.
AL049839 Genomic DNA. No translation available.
BC008915 mRNA. Translation: AAH08915.1.
S58545 mRNA. Translation: AAB26244.2.
AL080185 mRNA. Translation: CAB45766.1.
CCDSCCDS9928.1.
PIRA39339.
RefSeqNP_000615.3. NM_000624.5.
UniGeneHs.159628.
Hs.741309.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1LQ8X-ray2.40A/C/E/G30-375[»]
B/D/F/H376-406[»]
1PAImodel-A20-373[»]
B374-406[»]
2HI9X-ray2.30A/B/C44-406[»]
2OL2X-ray2.00A/B36-406[»]
2PAImodel-A20-373[»]
B374-406[»]
3DY0X-ray1.55A37-372[»]
B379-406[»]
ProteinModelPortalP05154.
SMRP05154. Positions 47-406.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111135. 12 interactions.
DIPDIP-29869N.
IntActP05154. 6 interactions.
MINTMINT-1386269.
STRING9606.ENSP00000333203.

Chemistry

DrugBankDB00055. Drotrecogin alfa.
DB00013. Urokinase.

Protein family/group databases

MEROPSI04.004.

PTM databases

PhosphoSiteP05154.

Polymorphism databases

DMDM322510122.

Proteomic databases

MaxQBP05154.
PaxDbP05154.
PRIDEP05154.

Protocols and materials databases

DNASU5104.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329597; ENSP00000333203; ENSG00000188488.
ENST00000553780; ENSP00000450837; ENSG00000188488.
ENST00000554276; ENSP00000451610; ENSG00000188488.
ENST00000554866; ENSP00000451126; ENSG00000188488.
GeneID5104.
KEGGhsa:5104.
UCSCuc001ydm.3. human.

Organism-specific databases

CTD5104.
GeneCardsGC14P095047.
H-InvDBHIX0079547.
HGNCHGNC:8723. SERPINA5.
HPAHPA056919.
HPA061957.
MIM601841. gene.
neXtProtNX_P05154.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4826.
HOGENOMHOG000238521.
HOVERGENHBG005957.
InParanoidP05154.
KOK03913.
OMANFRDSAG.
PhylomeDBP05154.
TreeFamTF343201.

Gene expression databases

ArrayExpressP05154.
BgeeP05154.
CleanExHS_SERPINA5.
GenevestigatorP05154.

Family and domain databases

InterProIPR023795. Serpin_CS.
IPR023796. 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.
PROSITEPS00284. SERPIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSERPINA5. human.
EvolutionaryTraceP05154.
GeneWikiProtein_C_inhibitor.
GenomeRNAi5104.
NextBio19698.
PMAP-CutDBP05154.
PROP05154.
SOURCESearch...

Entry information

Entry nameIPSP_HUMAN
AccessionPrimary (citable) accession number: P05154
Secondary accession number(s): Q07616, Q9UG30
Entry history
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: February 8, 2011
Last modified: July 9, 2014
This is version 168 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM