P70458 (IPSP_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Serpina5
Synonyms:	Pci

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	405 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 By similarity.
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 By similarity.
Subcellular location	Secreted › extracellular 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.
Tissue specificity	Not detected in blood plasma (at protein level). Expressed in testis, epididymis, seminal vesicles, prostate and ovaries. Ref.6
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 By similarity.
Post-translational modification	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. 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.
Disruption phenotype	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. Ref.5
Sequence similarities	Belongs to the serpin family.
Caution	According to Ref.5 it is not detectable in blood plasma.

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of proteolysis Inferred from electronic annotation. Source: Compara regulation of proteolysis Inferred from Biological aspect of Ancestor. Source: RefGenome spermatogenesis Inferred from mutant phenotype Ref.5. Source: UniProtKB
Cellular_component	acrosomal membrane Inferred from sequence or structural similarity. Source: UniProtKB external side of plasma membrane Inferred from electronic annotation. Source: Compara extracellular space Inferred from sequence or structural similarity. Source: UniProtKB platelet alpha granule Inferred from sequence or structural similarity. Source: UniProtKB platelet dense tubular network Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-KLK3 complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-PLAT complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-PLAU complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-TMPRSS11E complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-TMPRSS7 complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-coagulation factor V complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-coagulation factor XI complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-coagulation factor Xa complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-plasma kallikrein complex Inferred from sequence or structural similarity. Source: UniProtKB protein C inhibitor-thrombin complex Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	phosphatidylcholine binding Inferred from sequence or structural similarity. Source: UniProtKB retinoic acid binding Inferred from sequence or structural similarity. Source: UniProtKB serine-type endopeptidase inhibitor activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Tmprss11e	Q5S248	2	EBI-490966,EBI-490889

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Propeptide	20 – 24	5	Removed in mature form By similarity		PRO_0000414092
	Chain	25 – 405	381	Plasma serine protease inhibitor		PRO_0000032428
Sites
	Site	372 – 373	2	Reactive bond
Amino acid modifications
	Glycosylation	247	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	55	1	V → A in AAC53063. Ref.1
	Sequence conflict	55	1	V → A in AAH90981. Ref.4
	Sequence conflict	185	1	F → L in AAC53063. Ref.1
	Sequence conflict	185	1	F → L in AAH90981. Ref.4
	Sequence conflict	227 – 230	4	RTTQ → KTIR in AAC53063. Ref.1
	Sequence conflict	227 – 230	4	RTTQ → KTIR in AAH90981. Ref.4
	Sequence conflict	239	1	G → E in AAC53063. Ref.1
	Sequence conflict	239	1	G → E in AAH90981. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P70458 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 0E7377A3F8C1A464	FASTA	405	45,600
	10 20 30 40 50 60 MRFFPILCLV LFISHGVASR RHSHSKKKKA KESSVGAVGP PSSKDFAFRL YRALVSESPG 70 80 90 100 110 120 QNVFFSPLSV SMSLGMLSLG AGLKTKTQIL DGLGLSLQQG QEDKLHKGFQ QLLQRFRQPS 130 140 150 160 170 180 DGLQLSLGSA LFKDPAVHIR DDFLSAMKTL YMSDTFSTNF GNPEIAKKQI NNYVAKQTKG 190 200 210 220 230 240 KIVDFIKDLD STHVMIVVNY IFFKAKWQTA FSETNTHKMD FHVTPKRTTQ VPMMNREDGY 250 260 270 280 290 300 SYYLDQNISC TVVGIPYQGN AIALFILPSE GKMKQVEDGL DERTLRNWLK MFTKRRLDLY 310 320 330 340 350 360 LPKFSIEATY KLENVLPKLG IQDVFTTHAD LSGITDHTNI KLSEMVHKSM MEVEESGTTA 370 380 390 400 AAITGAIFTF RSARPSSLKI EFTRPFLLTL MEDSHILFVG KVTRP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U67878 Genomic DNA. Translation: AAC53063.1. AK087714 mRNA. Translation: BAC39979.1. CH466549 Genomic DNA. Translation: EDL18804.1. BC090981 mRNA. Translation: AAH90981.1.
IPI	IPI00109339.
RefSeq	NP_766541.2. NM_172953.3.
UniGene	Mm.73172.
3D structure databases
HSSP	HSSP built from PDB template 1LQ8 based on UniProtKB P05154.
ProteinModelPortal	P70458.
SMR	P70458. Positions 44-405.
ModBase	Search...
Protein-protein interaction databases
IntAct	P70458. 1 interaction.
PTM databases
PhosphoSite	P70458.
Proteomic databases
PRIDE	P70458.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000021495; ENSMUSP00000021495; ENSMUSG00000041550.
GeneID	268591.
KEGG	mmu:268591.
Organism-specific databases
CTD	5104.
MGI	MGI:107817. Serpina5.
Phylogenomic databases
eggNOG	COG4826.
GeneTree	ENSGT00700000104184.
HOGENOM	HOG000238521.
HOVERGEN	HBG005957.
InParanoid	Q5BKQ8.
KO	K03913.
OMA	QRIVFNR.
OrthoDB	EOG4P5K98.
Gene expression databases
Bgee	P70458.
Genevestigator	P70458.
GermOnline	ENSMUSG00000041550. Mus musculus.
Family and domain databases
InterPro	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. False negative. [Graphical view]
ProtoNet	Search...
Other
NextBio	392397.
SOURCE	Search...

Entry information

Entry name

IPSP_MOUSE

Accession

Primary (citable) accession number: P70458
Secondary accession number(s): Q5BKQ8, Q8BU50

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	July 27, 2011
Last modified:	April 3, 2013
This is version 93 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program