IPSP_BOVIN
ID IPSP_BOVIN Reviewed; 404 AA.
AC Q9N2I2; A7E3W0;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Plasma serine protease inhibitor;
DE AltName: Full=Protein C inhibitor;
DE Short=PCI;
DE AltName: Full=Serpin A5;
DE Flags: Precursor;
GN Name=SERPINA5;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=10739384;
RA Yuasa H., Tanaka H., Hayashi T., Wakita T., Nakamura H., Nishioka J.,
RA Kawarada Y., Suzuki K.;
RT "Bovine protein C inhibitor has a unique reactive site and can transiently
RT inhibit plasmin.";
RL Thromb. Haemost. 83:262-267(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Crossbred X Angus; TISSUE=Liver;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 20-68, FUNCTION, AND GLYCOSYLATION.
RX PubMed=2160449; DOI=10.1093/oxfordjournals.jbchem.a123054;
RA Suzuki K., Kusumoto H., Nishioka J., Komiyama Y.;
RT "Bovine plasma protein C inhibitor with structural and functional
RT homologous properties to human plasma protein C inhibitor.";
RL J. Biochem. 107:381-388(1990).
RN [5]
RP GLYCOSYLATION AT THR-35 AND THR-36, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=19674964; DOI=10.1074/mcp.m900211-mcp200;
RA Darula Z., Medzihradszky K.F.;
RT "Affinity enrichment and characterization of mucin core-1 type
RT glycopeptides from bovine serum.";
RL Mol. Cell. Proteomics 8:2515-2526(2009).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 42-404 IN COMPLEX WITH F2 AND
RP SYNTHETIC HEPARIN.
RX PubMed=18362344; DOI=10.1073/pnas.0711055105;
RA Li W., Adams T.E., Nangalia J., Esmon C.T., Huntington J.A.;
RT "Molecular basis of thrombin recognition by protein C inhibitor revealed by
RT the 1.6-A structure of the heparin-bridged complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:4661-4666(2008).
CC -!- FUNCTION: Heparin-dependent serine protease inhibitor acting in body
CC fluids and secretions. Inactivates serine proteases by binding
CC irreversibly to their serine activation site. Involved in the
CC regulation of intravascular and extravascular proteolytic activities.
CC Plays hemostatic roles in the blood plasma. Acts as a procoagulant and
CC pro-inflammatory factor by inhibiting the anticoagulant activated
CC protein C factor as well as the generation of activated protein C
CC factor by the thrombin/thrombomodulin complex. Acts as an anticoagulant
CC factor by inhibiting blood coagulation factors like prothrombin, factor
CC XI, factor Xa, plasma kallikrein and fibrinolytic enzymes such as
CC tissue- and urinary-type plasminogen activators. In seminal plasma,
CC inactivates several serine proteases implicated in the reproductive
CC system. Inhibits the serpin acrosin; indirectly protects component of
CC the male genital tract from being degraded by excessive released
CC acrosin. Inhibits tissue- and urinary-type plasminogen activator,
CC prostate-specific antigen and kallikrein activities; has a control on
CC the sperm motility and fertilization. Inhibits the activated protein C-
CC catalyzed degradation of SEMG1 and SEMG2; regulates the degradation of
CC semenogelin during the process of transfer of spermatozoa from the male
CC reproductive tract into the female tract. In urine, inhibits urinary-
CC type plasminogen activator and kallikrein activities. Inactivates
CC membrane-anchored serine proteases activities such as MPRSS7 and
CC TMPRSS11E. Inhibits urinary-type plasminogen activator-dependent tumor
CC cell invasion and metastasis. May also play a non-inhibitory role in
CC seminal plasma and urine as a hydrophobic hormone carrier by its
CC binding to retinoic acid (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:10739384, ECO:0000269|PubMed:2160449}.
CC -!- ACTIVITY REGULATION: Its inhibitory activity is greatly enhanced in the
CC presence of glycosaminoglycans, heparin, thrombomodulin and
CC phospholipids vesicles. {ECO:0000250}.
CC -!- SUBUNIT: Forms protease inhibiting heterodimers in extracellular body
CC fluids with serine proteases such as activated protein C/coagulation
CC factor V/F5, acrosin/ACR, chymotrypsinogen B/CTRB1, prothrombin/F2,
CC factor Xa/F10, factor XI/F11, kallikrein/KLKB1, tissue kallikrein,
CC trypsin/PRSS1, prostate specific antigen/KLK3, tissue plasminogen
CC activator/PLAT and urinary plasminogen activator/PLAU. Forms membrane-
CC anchored serine proteases inhibiting heterodimers with TMPRSS7 and
CC TMPRSS11E. Interacts with SEMG2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space {ECO:0000250}.
CC Note=Localized on the plasma membrane overlying the acrosomal head of
CC spermatozoa of ependymal spermatozoa and ejaculated sperm. Localized at
CC the equatorial segment of acrosome-reacted spermatozoa. Localized in
CC alpha granules in resting platelets and on the external plasma membrane
CC and within the surface-connected cannalicular system in activated
CC platelets (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed strongly in the liver, and moderately in
CC the kidney and testis, but not in other tissues tested.
CC {ECO:0000269|PubMed:10739384}.
CC -!- DOMAIN: The reactive center loop (RCL) extends out from the body of the
CC protein and directs binding to the target protease. The protease
CC cleaves the serpin at the reactive site within the RCL, establishing a
CC covalent linkage between the carboxyl group of the serpin reactive site
CC and the serine hydroxyl of the protease. The resulting inactive serpin-
CC protease complex is highly stable (By similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylated; glycans consist of a mixture of sialylated
CC bi- (including sialyl-Lewis X epitopes), tri- and tetra-antennary
CC complex-type chains; affects the maximal heparin- and thrombomodulin-
CC enhanced rates of thrombin inhibition. O-glycosylated; further modified
CC with 2 sialic acid residues. Proteolytically cleaved at the N-terminus;
CC inhibits slightly the heparin- and thrombomodulin-enhanced rates of
CC thrombin inhibition (By similarity). N- and O-glycosylated.
CC {ECO:0000250, ECO:0000269|PubMed:2160449}.
CC -!- PTM: Proteolytically cleaved. Inhibition of proteases is accompanied by
CC formation of a stable enzyme-inhibitor complex and by degradation of
CC the serpin to lower molecular weight derivatives.
CC -!- SIMILARITY: Belongs to the serpin family. {ECO:0000305}.
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DR EMBL; AB026444; BAA93451.1; -; mRNA.
DR EMBL; BT030731; ABS45047.1; -; mRNA.
DR EMBL; BC109553; AAI09554.1; -; mRNA.
DR PIR; PX0029; PX0029.
DR RefSeq; NP_788819.1; NM_176646.3.
DR PDB; 3B9F; X-ray; 1.60 A; I=42-404.
DR PDBsum; 3B9F; -.
DR AlphaFoldDB; Q9N2I2; -.
DR SMR; Q9N2I2; -.
DR STRING; 9913.ENSBTAP00000005307; -.
DR MEROPS; I04.004; -.
DR GlyConnect; 819; 2 O-Linked glycans (2 sites).
DR iPTMnet; Q9N2I2; -.
DR PaxDb; Q9N2I2; -.
DR PRIDE; Q9N2I2; -.
DR GeneID; 338050; -.
DR KEGG; bta:338050; -.
DR CTD; 5104; -.
DR eggNOG; KOG2392; Eukaryota.
DR HOGENOM; CLU_023330_2_1_1; -.
DR InParanoid; Q9N2I2; -.
DR OrthoDB; 1124079at2759; -.
DR TreeFam; TF343201; -.
DR SABIO-RK; Q9N2I2; -.
DR EvolutionaryTrace; Q9N2I2; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0002080; C:acrosomal membrane; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR GO; GO:0031091; C:platelet alpha granule; ISS:UniProtKB.
DR GO; GO:0031094; C:platelet dense tubular network; ISS:UniProtKB.
DR GO; GO:0097181; C:protein C inhibitor-coagulation factor V complex; ISS:UniProtKB.
DR GO; GO:0097182; C:protein C inhibitor-coagulation factor Xa complex; ISS:UniProtKB.
DR GO; GO:0097183; C:protein C inhibitor-coagulation factor XI complex; ISS:UniProtKB.
DR GO; GO:0036029; C:protein C inhibitor-KLK3 complex; ISS:UniProtKB.
DR GO; GO:0036030; C:protein C inhibitor-plasma kallikrein complex; ISS:UniProtKB.
DR GO; GO:0036026; C:protein C inhibitor-PLAT complex; ISS:UniProtKB.
DR GO; GO:0036027; C:protein C inhibitor-PLAU complex; ISS:UniProtKB.
DR GO; GO:0036028; C:protein C inhibitor-thrombin complex; ISS:UniProtKB.
DR GO; GO:0036025; C:protein C inhibitor-TMPRSS11E complex; ISS:UniProtKB.
DR GO; GO:0036024; C:protein C inhibitor-TMPRSS7 complex; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0031210; F:phosphatidylcholine binding; ISS:UniProtKB.
DR GO; GO:0001972; F:retinoic acid binding; ISS:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0006869; P:lipid transport; IEA:UniProtKB-KW.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IBA:GO_Central.
DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR InterPro; IPR036186; Serpin_sf.
DR InterPro; IPR042178; Serpin_sf_1.
DR InterPro; IPR042185; Serpin_sf_2.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Fertilization; Glycoprotein;
KW Heparin-binding; Lipid transport; Protease inhibitor; Reference proteome;
KW Secreted; Serine protease inhibitor; Signal; Transport.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:2160449"
FT PROPEP 20..24
FT /note="Removed in mature form"
FT /evidence="ECO:0000250"
FT /id="PRO_0000414093"
FT CHAIN 25..404
FT /note="Plasma serine protease inhibitor"
FT /id="PRO_0000244409"
FT SITE 369..370
FT /note="Reactive bond"
FT CARBOHYD 35
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:19674964"
FT CARBOHYD 36
FT /note="O-linked (GalNAc...) threonine"
FT /evidence="ECO:0000269|PubMed:19674964"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 334
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT HELIX 44..55
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 61..63
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 65..75
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 76..78
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 81..90
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 100..113
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 123..132
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 139..149
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 161..175
FT /evidence="ECO:0007829|PDB:3B9F"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 192..201
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:3B9F"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 215..224
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 226..243
FT /evidence="ECO:0007829|PDB:3B9F"
FT TURN 244..247
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 248..258
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 271..277
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 280..289
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 291..300
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 302..309
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 310..312
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 314..317
FT /evidence="ECO:0007829|PDB:3B9F"
FT HELIX 321..323
FT /evidence="ECO:0007829|PDB:3B9F"
FT TURN 330..332
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 341..351
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 365..367
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 376..379
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 384..392
FT /evidence="ECO:0007829|PDB:3B9F"
FT STRAND 395..402
FT /evidence="ECO:0007829|PDB:3B9F"
SQ SEQUENCE 404 AA; 45297 MW; 548872756C16FF9B CRC64;
MRLCLFLCLV LLGPRMATLR RSQKKKIQEV PPAVTTAPPG SRDFVFDLYR ALAAAAPAQN
IFFSPLSITV SLAMLSLGAQ SNTKAQILEG LGIGPGEGSE EELHSASQRL LRELQQPQDS
LQLSLGNALF TKPRLPIQEA FLGAMRTLYL ADTFPTNFED PEGAKKKIND YVAKQTKGKI
VDLIKSLDGT QVMVMVNYIF FKAKWETSFN LKSTHEQDFY VTPETVVRVP MMKQQDQFYY
LLDRNLSCKV VGVPYQGNAT AFFILPREGE MEQVENGLKE KTLKKWLRMP MKRRLELYLP
KFSIEGSYQL EEVLPKLGIR DIFTSDADLT GISNHSSIRV SEMVHKAVVE VDESGTQAAA
ATGMVITFKS ARLGSQRIVF NRPFLVLIVK NSKHILFLGK VTRP
