P05154 (IPSP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	406 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Secreted › extracellular 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 process	Fertilization Lipid transport Transport
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Heparin-binding
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	fusion 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 proteolysis Inferred from electronic annotation. Source: Compara regulation of proteolysis Inferred from Biological aspect of Ancestor. Source: RefGenome spermatogenesis Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	acrosomal membrane Inferred from direct assay Ref.17Ref.22. Source: UniProtKB external side of plasma membrane Inferred from direct assay Ref.23. 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 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
Molecular_function	heparin binding Traceable author statement PubMed 11120760. Source: UniProtKB phosphatidylcholine binding Inferred from direct assay Ref.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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.11

Propeptide

20 – 25

6

Removed in mature form

PRO_0000414091

Chain

26 – 406

381

Plasma serine protease inhibitor

PRO_0000032427

Sites

Site

373 – 374

2

Reactive bond

Amino acid modifications

Glycosylation

39

1

O-linked (GalNAc...) Ref.35 Ref.36

Glycosylation

249

1

N-linked (GlcNAc...) Ref.29 Ref.33

Glycosylation

262

1

N-linked (GlcNAc...) Ref.31 Ref.33 Ref.38

Glycosylation

338

1

N-linked (GlcNAc...) Ref.31 Ref.33

Natural variations

Natural variant

44

1

S → G. Ref.6
Corresponds to variant rs2069975 [ dbSNP | Ensembl ].

VAR_013080

Natural variant

55

1

A → V in allele PCI*B. Ref.5 Ref.6 Ref.41
Corresponds to variant rs6118 [ dbSNP | Ensembl ].

VAR_007100

Natural variant

64

1

S → 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 variant

94

1

G → V. Ref.6
Corresponds to variant rs2069976 [ dbSNP | Ensembl ].

VAR_013082

Natural variant

105

1

K → E in allele PCI*B. Ref.5 Ref.6 Ref.41
Corresponds to variant rs6119 [ dbSNP | Ensembl ].

VAR_007101

Natural variant

115

1

L → P. Ref.6
Corresponds to variant rs2069999 [ dbSNP | Ensembl ].

VAR_013083

Natural variant

121

1

P → A. Ref.41
Corresponds to variant rs6120 [ dbSNP | Ensembl ].

VAR_013900

Natural variant

217

1

G → R. Ref.6 Ref.41
Corresponds to variant rs6114 [ dbSNP | Ensembl ].

VAR_013084

Experimental info

Mutagenesis

248

1

R → 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

Mutagenesis

253

1

R → E: Inhibits strongly thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34

Mutagenesis

272

1

E → K: Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34

Mutagenesis

274

1

K → E: Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34

Mutagenesis

285

1

K → 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

Mutagenesis

288

1

R → 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

Mutagenesis

289

1

K → 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

Mutagenesis

292

1

K → 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

Mutagenesis

360

1

T → R: Inhibits heterodimer formation with TMPRSS11E. Ref.27

Mutagenesis

371

1

T → R: Increases inhibition of activated protein C/F5 and factor XI/F11 activities. Decreases inhibition of thrombin activity. Ref.18

Mutagenesis

372

1

F → P or G: Increases inhibition of thrombin activity. Ref.18

Mutagenesis

373

1

R → P: Increases inhibition of thrombin activity. Inhibits heterodimer formation with TMPRSS11E. Ref.18 Ref.27

Mutagenesis

376

1

R → P: Does not change inhibition of thrombin, activated protein C/F5 and factor XI/F11 activities. Ref.18

Mutagenesis

381

1

R → E: Does not inhibit thrombomodulin-enhanced rate of thrombin inhibition in presence of heparin. Ref.34

Sequence conflict

28

1

K → E in CAB45766. Ref.10

Sequence conflict

221

1

Q → L in AAB26244. Ref.9

Sequence conflict

335

1

G → R in AAA35688. Ref.1

Sequence conflict

335

1

G → R in AAB26244. Ref.9

Sequence conflict

384

1

F → S in AAB26244. Ref.9

Secondary structure

1

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406

Helix Strand Turn

Details...

Helix

48 – 59

12

Beta strand

65 – 67

3

Helix

69 – 79

11

Helix

80 – 82

3

Helix

85 – 95

11

Helix

99 – 101

3

Helix

105 – 118

14

Beta strand

126 – 138

13

Helix

143 – 153

11

Beta strand

156 – 160

5

Helix

165 – 179

15

Turn

180 – 182

3

Beta strand

197 – 206

10

Beta strand

209 – 211

3

Beta strand

219 – 228

10

Beta strand

230 – 247

18

Turn

248 – 251

4

Beta strand

252 – 262

11

Beta strand

264 – 270

7

Helix

275 – 281

7

Helix

284 – 293

10

Beta strand

295 – 304

10

Beta strand

306 – 313

8

Helix

314 – 316

3

Helix

318 – 321

4

Helix

325 – 327

3

Turn

334 – 336

3

Beta strand

345 – 355

11

Beta strand

359 – 361

3

Beta strand

372 – 375

4

Beta strand

380 – 383

4

Beta strand

388 – 404

17

Sequences

	Sequence		Length	Mass (Da)
	P05154 [UniParc]. Last modified February 8, 2011. Version 3. Checksum: 2A8FF3DC33C77E04	FASTA	406	45,675
	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

References

	« Hide 'large scale' referencesShow '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. , 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, MASS SPECTROMETRY. 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, MASS SPECTROMETRY. 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, 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, 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, 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

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J02639 mRNA. Translation: AAA35688.1.
M68516 Genomic DNA. Translation: AAA02811.1.
S69366 , 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.

IPI

IPI00007221.

PIR

A39339.

RefSeq

NP_000615.3. NM_000624.5.

UniGene

Hs.159628.
Hs.741309.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1LQ8	X-ray	2.40	A/C/E/G	30-375	[»]
			B/D/F/H	376-406	[»]
1PAI	model	-	A	20-373	[»]
			B	374-406	[»]
2HI9	X-ray	2.30	A/B/C	44-406	[»]
2OL2	X-ray	2.00	A/B	36-406	[»]
2PAI	model	-	A	20-373	[»]
			B	374-406	[»]
3DY0	X-ray	1.55	A	37-372	[»]
			B	379-406	[»]

ProteinModelPortal

P05154.

SMR

P05154. Positions 47-406.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29869N.

IntAct

P05154. 6 interactions.

MINT

MINT-1386269.

STRING

9606.ENSP00000333203.

Protein family/group databases

MEROPS

I04.004.

PTM databases

PhosphoSite

P05154.

Polymorphism databases

DMDM

400068.

Proteomic databases

PaxDb

P05154.

PRIDE

P05154.

Protocols and materials databases

DNASU

5104.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000329597; ENSP00000333203; ENSG00000188488.
ENST00000553780; ENSP00000450837; ENSG00000188488.
ENST00000554276; ENSP00000451610; ENSG00000188488.
ENST00000554866; ENSP00000451126; ENSG00000188488.

GeneID

5104.

KEGG

hsa:5104.

UCSC

uc001ydm.2. human.

Organism-specific databases

CTD

5104.

GeneCards

GC14P095047.

H-InvDB

HIX0079547.

HGNC

HGNC:8723. SERPINA5.

MIM

601841. gene.

neXtProt

NX_P05154.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4826.

HOGENOM

HOG000238521.

HOVERGEN

HBG005957.

InParanoid

P05154.

KO

K03913.

OMA

QRIVFNR.

OrthoDB

EOG4P5K98.

PhylomeDB

P05154.

Gene expression databases

ArrayExpress

P05154.

Bgee

P05154.

CleanEx

HS_SERPINA5.

Genevestigator

P05154.

GermOnline

ENSG00000188488. Homo sapiens.

Family and domain databases

InterPro

IPR023795. Protease_inhib_I4_serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]

PANTHER

PTHR11461. PTHR11461. 1 hit.

Pfam

PF00079. Serpin. 1 hit.
[Graphical view]

SMART

SM00093. SERPIN. 1 hit.
[Graphical view]

SUPFAM

SSF56574. Prot_inh_serpin. 1 hit.

PROSITE

PS00284. SERPIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SERPINA5. human.

DrugBank

DB00055. Drotrecogin alfa.
DB00013. Urokinase.

EvolutionaryTrace

P05154.

GenomeRNAi

5104.

NextBio

19698.

PMAP-CutDB

P05154.

SOURCE

Search...

Entry information

Entry name

IPSP_HUMAN

Accession

Primary (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:	April 3, 2013
This is version 157 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.