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Protein

Plasma serine protease inhibitor

Gene

SERPINA5

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Heparin-dependent serine protease inhibitor acting in body fluids and secretions. Inactivates serine proteases by binding irreversibly to their serine activation site. Involved in the regulation of intravascular and extravascular proteolytic activities. Plays hemostatic roles in the blood plasma. Acts as a procoagulant and proinflammatory factor by inhibiting the anticoagulant activated protein C factor as well as the generation of activated protein C factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant factor by inhibiting blood coagulation factors like prothrombin, factor XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as tissue- and urinary-type plasminogen activators. In seminal plasma, inactivates several serine proteases implicated in the reproductive system. Inhibits the serpin acrosin; indirectly protects component of the male genital tract from being degraded by excessive released acrosin. Inhibits tissue-and urinary-type plasminogen activator, prostate-specific antigen and kallikrein activities; has a control on the sperm motility and fertilization. Inhibits the activated protein C-catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of semenogelin during the process of transfer of spermatozoa from the male reproductive tract into the female tract. In urine, inhibits urinary-type plasminogen activator and kallikrein activities. Inactivates membrane-anchored serine proteases activities such as MPRSS7 and TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor cell invasion and metastasis. May also play a non-inhibitory role in seminal plasma and urine as a hydrophobic hormone carrier by its binding to retinoic acid (By similarity).By similarity2 Publications

Enzyme regulationi

Its inhibitory activity is greatly enhanced in the presence of glycosaminoglycans, heparin, thrombomodulin and phospholipids vesicles.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei369 – 3702Reactive bond

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Fertilization, Lipid transport, Transport

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiR-BTA-140837. Intrinsic Pathway of Fibrin Clot Formation.
R-BTA-140875. Common Pathway of Fibrin Clot Formation.

Protein family/group databases

MEROPSiI04.004.

Names & Taxonomyi

Protein namesi
Recommended name:
Plasma serine protease inhibitor
Alternative name(s):
Protein C inhibitor
Short name:
PCI
Serpin A5
Gene namesi
Name:SERPINA5
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 21

Subcellular locationi

  • Secretedextracellular space By similarity

  • Note: Localized on the plasma membrane overlying the acrosomal head of spermatozoa of ependymal spermatozoa and ejaculated sperm. Localized at the equatorial segment of acrosome-reacted spematozoa. Localized in alpha granules in resting platelets and on the external plasma membrane and within the surface-connected cannalicular system in activated platelets (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 19191 PublicationAdd
BLAST
Propeptidei20 – 245Removed in mature formBy similarityPRO_0000414093
Chaini25 – 404380Plasma serine protease inhibitorPRO_0000244409Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi35 – 351O-linked (GalNAc...)1 Publication
Glycosylationi36 – 361O-linked (GalNAc...)1 Publication
Glycosylationi245 – 2451N-linked (GlcNAc...)Sequence analysis
Glycosylationi258 – 2581N-linked (GlcNAc...)Sequence analysis
Glycosylationi334 – 3341N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylated; glycans consist of a mixture of sialylated bi- (including sialyl-Lewis X epitopes), tri- and tetra-antennary complex-type chains; affects the maximal heparin- and thrombomodulin-enhanced rates of thrombin inhibition. O-glycosylated; further modified with 2 sialic acid residues. Proteolytically cleaved at the N-terminus; inhibits slightly the heparin- and thrombomodulin-enhanced rates of thrombin inhibition (By similarity). N- and O-glycosylated.By similarity1 Publication
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.

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9N2I2.
PRIDEiQ9N2I2.

PTM databases

UniCarbKBiQ9N2I2.

Expressioni

Tissue specificityi

Expressed strongly in the liver, and moderately in the kidney and testis, but not in other tissues tested.1 Publication

Interactioni

Subunit structurei

Forms protease inhibiting heterodimers in extracellular body fluids with serine proteases such as activated protein C/coagulation factor V/F5, acrosin/ACR, chymotrypsinogen B/CTRB1, prothrombin/F2, factor Xa/F10, factor XI/F11, kallikrein/KLKB1, tissue kallikrein, trypsin/PRSS1, prostate specific antigen/KLK3, tissue plasminogen activator/PLAT and urinary plasminogen activator/PLAU. Forms membrane-anchored serine proteases inhibiting heterodimers with TMPRSS7 and TMPRSS11E. Interacts with SEMG2 (By similarity).By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000005307.

Structurei

Secondary structure

1
404
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi44 – 5512Combined sources
Beta strandi61 – 633Combined sources
Helixi65 – 7511Combined sources
Helixi76 – 783Combined sources
Helixi81 – 9010Combined sources
Helixi100 – 11314Combined sources
Beta strandi123 – 13210Combined sources
Helixi139 – 14911Combined sources
Beta strandi152 – 1565Combined sources
Helixi161 – 17515Combined sources
Turni176 – 1783Combined sources
Beta strandi192 – 20110Combined sources
Beta strandi205 – 2073Combined sources
Turni211 – 2133Combined sources
Beta strandi215 – 22410Combined sources
Beta strandi226 – 24318Combined sources
Turni244 – 2474Combined sources
Beta strandi248 – 25811Combined sources
Beta strandi260 – 2667Combined sources
Helixi271 – 2777Combined sources
Helixi280 – 28910Combined sources
Beta strandi291 – 30010Combined sources
Beta strandi302 – 3098Combined sources
Helixi310 – 3123Combined sources
Helixi314 – 3174Combined sources
Helixi321 – 3233Combined sources
Turni330 – 3323Combined sources
Beta strandi341 – 35111Combined sources
Beta strandi355 – 3573Combined sources
Beta strandi365 – 3673Combined sources
Beta strandi376 – 3794Combined sources
Beta strandi384 – 3918Combined sources
Beta strandi394 – 4029Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3B9FX-ray1.60I42-404[»]
ProteinModelPortaliQ9N2I2.
SMRiQ9N2I2. Positions 43-404.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9N2I2.

Family & Domainsi

Domaini

The reactive center loop (RCL) extends out from the body of the protein and directs binding to the target protease. The protease cleaves the serpin at the reactive site within the RCL, establishing a covalent linkage between the carboxyl group of the serpin reactive site and the serine hydroxyl of the protease. The resulting inactive serpin-protease complex is highly stable (By similarity).By similarity

Sequence similaritiesi

Belongs to the serpin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG2392. Eukaryota.
COG4826. LUCA.
GeneTreeiENSGT00760000118839.
HOGENOMiHOG000238521.
HOVERGENiHBG005957.
InParanoidiQ9N2I2.
KOiK03913.
OMAiQRIVFNR.
OrthoDBiEOG7QC7W9.
TreeFamiTF343201.

Family and domain databases

InterProiIPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiPF00079. Serpin. 1 hit.
[Graphical view]
SMARTiSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiPS00284. SERPIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9N2I2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLCLFLCLV LLGPRMATLR RSQKKKIQEV PPAVTTAPPG SRDFVFDLYR
60 70 80 90 100
ALAAAAPAQN IFFSPLSITV SLAMLSLGAQ SNTKAQILEG LGIGPGEGSE
110 120 130 140 150
EELHSASQRL LRELQQPQDS LQLSLGNALF TKPRLPIQEA FLGAMRTLYL
160 170 180 190 200
ADTFPTNFED PEGAKKKIND YVAKQTKGKI VDLIKSLDGT QVMVMVNYIF
210 220 230 240 250
FKAKWETSFN LKSTHEQDFY VTPETVVRVP MMKQQDQFYY LLDRNLSCKV
260 270 280 290 300
VGVPYQGNAT AFFILPREGE MEQVENGLKE KTLKKWLRMP MKRRLELYLP
310 320 330 340 350
KFSIEGSYQL EEVLPKLGIR DIFTSDADLT GISNHSSIRV SEMVHKAVVE
360 370 380 390 400
VDESGTQAAA ATGMVITFKS ARLGSQRIVF NRPFLVLIVK NSKHILFLGK

VTRP
Length:404
Mass (Da):45,297
Last modified:October 1, 2000 - v1
Checksum:i548872756C16FF9B
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB026444 mRNA. Translation: BAA93451.1.
BT030731 mRNA. Translation: ABS45047.1.
BC109553 mRNA. Translation: AAI09554.1.
PIRiPX0029.
RefSeqiNP_788819.1. NM_176646.3.
UniGeneiBt.2712.

Genome annotation databases

EnsembliENSBTAT00000005307; ENSBTAP00000005307; ENSBTAG00000004063.
GeneIDi338050.
KEGGibta:338050.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB026444 mRNA. Translation: BAA93451.1.
BT030731 mRNA. Translation: ABS45047.1.
BC109553 mRNA. Translation: AAI09554.1.
PIRiPX0029.
RefSeqiNP_788819.1. NM_176646.3.
UniGeneiBt.2712.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3B9FX-ray1.60I42-404[»]
ProteinModelPortaliQ9N2I2.
SMRiQ9N2I2. Positions 43-404.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000005307.

Protein family/group databases

MEROPSiI04.004.

PTM databases

UniCarbKBiQ9N2I2.

Proteomic databases

PaxDbiQ9N2I2.
PRIDEiQ9N2I2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000005307; ENSBTAP00000005307; ENSBTAG00000004063.
GeneIDi338050.
KEGGibta:338050.

Organism-specific databases

CTDi5104.

Phylogenomic databases

eggNOGiKOG2392. Eukaryota.
COG4826. LUCA.
GeneTreeiENSGT00760000118839.
HOGENOMiHOG000238521.
HOVERGENiHBG005957.
InParanoidiQ9N2I2.
KOiK03913.
OMAiQRIVFNR.
OrthoDBiEOG7QC7W9.
TreeFamiTF343201.

Enzyme and pathway databases

ReactomeiR-BTA-140837. Intrinsic Pathway of Fibrin Clot Formation.
R-BTA-140875. Common Pathway of Fibrin Clot Formation.

Miscellaneous databases

EvolutionaryTraceiQ9N2I2.
NextBioi20812501.

Family and domain databases

InterProiIPR023795. Serpin_CS.
IPR023796. Serpin_dom.
IPR000215. Serpin_fam.
[Graphical view]
PANTHERiPTHR11461. PTHR11461. 1 hit.
PfamiPF00079. Serpin. 1 hit.
[Graphical view]
SMARTiSM00093. SERPIN. 1 hit.
[Graphical view]
SUPFAMiSSF56574. SSF56574. 1 hit.
PROSITEiPS00284. SERPIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Bovine protein C inhibitor has a unique reactive site and can transiently inhibit plasmin."
    Yuasa H., Tanaka H., Hayashi T., Wakita T., Nakamura H., Nishioka J., Kawarada Y., Suzuki K.
    Thromb. Haemost. 83:262-267(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. NIH - Mammalian Gene Collection (MGC) project
    Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Crossbred X Angus.
    Tissue: Liver.
  4. "Bovine plasma protein C inhibitor with structural and functional homologous properties to human plasma protein C inhibitor."
    Suzuki K., Kusumoto H., Nishioka J., Komiyama Y.
    J. Biochem. 107:381-388(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 20-68, FUNCTION, GLYCOSYLATION.
  5. "Affinity enrichment and characterization of mucin core-1 type glycopeptides from bovine serum."
    Darula Z., Medzihradszky K.F.
    Mol. Cell. Proteomics 8:2515-2526(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION AT THR-35 AND THR-36, IDENTIFICATION BY MASS SPECTROMETRY.
  6. "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: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 42-404 IN COMPLEX WITH F2 AND SYNTHETIC HEPARIN.

Entry informationi

Entry nameiIPSP_BOVIN
AccessioniPrimary (citable) accession number: Q9N2I2
Secondary accession number(s): A7E3W0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 27, 2006
Last sequence update: October 1, 2000
Last modified: May 11, 2016
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.