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Protein

Vitamin K-dependent protein C

Gene

PROC

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

Functioni

Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids. Exerts a protective effect on the endothelial cell barrier function.By similarity

Catalytic activityi

Degradation of blood coagulation factors Va and VIIIa.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei252 – 2521Charge relay system
Active sitei298 – 2981Charge relay system
Active sitei397 – 3971Charge relay system

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Blood coagulation, Hemostasis

Keywords - Ligandi

Calcium

Protein family/group databases

MEROPSiS01.218.

Names & Taxonomyi

Protein namesi
Recommended name:
Vitamin K-dependent protein C (EC:3.4.21.69)
Alternative name(s):
Anticoagulant protein C
Autoprothrombin IIA
Blood coagulation factor XIV
Cleaved into the following 3 chains:
Gene namesi
Name:PROC
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Secreted By similarity
  • Golgi apparatus By similarity
  • Endoplasmic reticulum By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei‹1 – 15›15Sequence analysisAdd
BLAST
Propeptidei16 – 39241 PublicationPRO_0000028098Add
BLAST
Chaini40 – 456417Vitamin K-dependent protein CPRO_0000028099Add
BLAST
Chaini40 – 194155Vitamin K-dependent protein C light chainPRO_0000028100Add
BLAST
Chaini197 – 456260Vitamin K-dependent protein C heavy chainPRO_0000028101Add
BLAST
Peptidei197 – 21014Activation peptidePRO_0000028102Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei45 – 4514-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei46 – 4614-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei53 – 5314-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei55 – 5514-carboxyglutamatePROSITE-ProRule annotation1 Publication
Disulfide bondi56 ↔ 61By similarity
Modified residuei58 – 5814-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei59 – 5914-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei62 – 6214-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei64 – 6414-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei65 – 6514-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei68 – 6814-carboxyglutamatePROSITE-ProRule annotation1 Publication
Modified residuei74 – 7414-carboxyglutamatePROSITE-ProRule annotation1 Publication
Disulfide bondi89 ↔ 108By similarity
Disulfide bondi98 ↔ 103By similarity
Disulfide bondi102 ↔ 117By similarity
Modified residuei110 – 1101(3R)-3-hydroxyaspartate1 Publication
Disulfide bondi119 ↔ 128By similarity
Glycosylationi136 – 1361N-linked (GlcNAc...)1 Publication
Disulfide bondi137 ↔ 148By similarity
Disulfide bondi144 ↔ 157By similarity
Disulfide bondi159 ↔ 172By similarity
Disulfide bondi180 ↔ 318Interchain (between light and heavy chains)
Disulfide bondi237 ↔ 253
Glycosylationi289 – 2891N-linked (GlcNAc...)1 Publication
Glycosylationi350 – 3501N-linked (GlcNAc...)1 Publication
Glycosylationi366 – 3661N-linked (GlcNAc...); atypical; partial1 Publication
Disulfide bondi368 ↔ 382
Disulfide bondi393 ↔ 421

Post-translational modificationi

The vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind calcium.
The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Gamma-carboxyglutamic acid, Glycoprotein, Hydroxylation, Zymogen

Proteomic databases

PaxDbiP00745.
PRIDEiP00745.

Miscellaneous databases

PMAP-CutDBP00745.

Expressioni

Tissue specificityi

Plasma; synthesized in the liver.

Interactioni

Subunit structurei

Synthesized as a single chain precursor, which is cleaved into a light chain and a heavy chain held together by a disulfide bond. The enzyme is then activated by thrombin, which cleaves a tetradecapeptide from the amino end of the heavy chain; this reaction, which occurs at the surface of endothelial cells, is strongly promoted by thrombomodulin.

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000005163.

Structurei

3D structure databases

ProteinModelPortaliP00745.
SMRiP00745. Positions 41-85, 88-183, 211-445.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini40 – 8546GlaPROSITE-ProRule annotationAdd
BLAST
Domaini94 – 12936EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini133 – 17341EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini211 – 445235Peptidase S1PROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase S1 family.PROSITE-ProRule annotation
Contains 2 EGF-like domains.PROSITE-ProRule annotation
Contains 1 Gla (gamma-carboxy-glutamate) domain.PROSITE-ProRule annotation
Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IJRM. Eukaryota.
COG5640. LUCA.
HOGENOMiHOG000251821.
HOVERGENiHBG013304.
InParanoidiP00745.
OrthoDBiEOG75B84T.

Family and domain databases

Gene3Di4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR012224. Pept_S1A_FX.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00594. Gla. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001143. Factor_X. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
SMARTiSM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00069. GLA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57630. SSF57630. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 1 hit.
PS01187. EGF_CA. 1 hit.
PS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

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

P00745-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
XTSLLLFVTI WGISSTPAPP DSVFSSSQRA HQVLRIRKRA NSFLEELRPG
60 70 80 90 100
NVERECSEEV CEFEEAREIF QNTEDTMAFW SFYSDGDQCE DRPSGSPCDL
110 120 130 140 150
PCCGRGKCID GLGGFRCDCA EGWEGRFCLH EVRFSNCSAE NGGCAHYCME
160 170 180 190 200
EEGRRHCSCA PGYRLEDDHQ LCVSKVTFPC GRLGKRMEKK RKTLKRDTNQ
210 220 230 240 250
VDQKDQLDPR IVDGQEAGWG ESPWQAVLLD SKKKLVCGAV LIHVSWVLTV
260 270 280 290 300
AHCLDSRKKL IVRLGEYDMR RWESWEVDLD IKEVIIHPNY TKSTSDNDIA
310 320 330 340 350
LLRLAKPATL SQTIVPICLP DSGLSERKLT QVGQETVVTG WGYRDETKRN
360 370 380 390 400
RTFVLSFIKV PVVPYNACVH AMENKISENM LCAGILGDPR DACEGDSGGP
410 420 430 440 450
MVTFFRGTWF LVGLVSWGEG CGRLYNYGVY TKVSRYLDWI YGHIKAQEAP

LESQVP
Length:456
Mass (Da):51,409
Last modified:August 13, 1987 - v1
Checksum:iCAAF6833F894C209
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11
Sequence conflicti455 – 4562VP → PV AA sequence (PubMed:6896877).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti82 – 821F → K.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02435 mRNA. Translation: AAA30685.1.
PIRiA26250. KXBO.
UniGeneiBt.49146.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02435 mRNA. Translation: AAA30685.1.
PIRiA26250. KXBO.
UniGeneiBt.49146.

3D structure databases

ProteinModelPortaliP00745.
SMRiP00745. Positions 41-85, 88-183, 211-445.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000005163.

Protein family/group databases

MEROPSiS01.218.

Proteomic databases

PaxDbiP00745.
PRIDEiP00745.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiENOG410IJRM. Eukaryota.
COG5640. LUCA.
HOGENOMiHOG000251821.
HOVERGENiHBG013304.
InParanoidiP00745.
OrthoDBiEOG75B84T.

Miscellaneous databases

PMAP-CutDBP00745.

Family and domain databases

Gene3Di4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000742. EGF-like_dom.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR012224. Pept_S1A_FX.
IPR009003. Peptidase_S1_PA.
IPR001314. Peptidase_S1A.
IPR001254. Trypsin_dom.
IPR033116. TRYPSIN_SER.
[Graphical view]
PfamiPF00008. EGF. 1 hit.
PF00594. Gla. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001143. Factor_X. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
SMARTiSM00181. EGF. 2 hits.
SM00179. EGF_CA. 1 hit.
SM00069. GLA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMiSSF50494. SSF50494. 1 hit.
SSF57630. SSF57630. 1 hit.
PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
PS00022. EGF_1. 1 hit.
PS01186. EGF_2. 2 hits.
PS50026. EGF_3. 1 hit.
PS01187. EGF_CA. 1 hit.
PS00011. GLA_1. 1 hit.
PS50998. GLA_2. 1 hit.
PS50240. TRYPSIN_DOM. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Cloning and sequencing of liver cDNA coding for bovine protein C."
    Long G.L., Balagaje R.M., McGillivray R.T.A.
    Proc. Natl. Acad. Sci. U.S.A. 81:5653-5656(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Amino acid sequence of the light chain of bovine protein C."
    Fernlund P., Stenflo J.
    J. Biol. Chem. 257:12170-12179(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 40-194, GLYCOSYLATION AT ASN-136, HYDROXYLATION AT ASP-110, GAMMA-CARBOXYGLUTAMATION AT GLU-45; GLU-46; GLU-53; GLU-55; GLU-58; GLU-59; GLU-62; GLU-64; GLU-65; GLU-68 AND GLU-74.
  3. Cited for: SEQUENCE REVISION TO 110.
  4. "Amino acid sequence of the heavy chain of bovine protein C."
    Stenflo J., Fernlund P.
    J. Biol. Chem. 257:12180-12190(1982) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 197-456, GLYCOSYLATION AT ASN-289; ASN-350 AND ASN-366.
  5. "Proteolytic formation and properties of gamma-carboxyglutamic acid-domainless protein C."
    Esmon N.L., Debault L.E., Esmon C.T.
    J. Biol. Chem. 258:5548-5553(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING, CALCIUM-BINDING.
  6. "Structural changes required for activation of protein C are induced by Ca2+ binding to a high affinity site that does not contain gamma-carboxyglutamic acid."
    Johnson A.E., Esmon N.L., Laue T.M., Esmon C.T.
    J. Biol. Chem. 258:5554-5560(1983) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING, CALCIUM-BINDING DATA.

Entry informationi

Entry nameiPROC_BOVIN
AccessioniPrimary (citable) accession number: P00745
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: August 13, 1987
Last modified: May 11, 2016
This is version 147 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Calcium also binds, with stronger affinity to another site, beyond the GLA domain. This GLA-independent binding site is necessary for the recognition of the thrombin-thrombomodulin complex.

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  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.