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Protein

Vitamin K-dependent protein C

Gene

Proc

Organism
Mus musculus (Mouse)
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.By similarity

Catalytic activityi

Degradation of blood coagulation factors Va and VIIIa.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei212 – 2132Cleavage; by thrombinBy similarity
Active sitei253 – 2531Charge relay system
Active sitei299 – 2991Charge relay system
Active sitei401 – 4011Charge relay system

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • peptidase activity Source: MGI
  • serine-type endopeptidase activity Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Blood coagulation, Hemostasis

Keywords - Ligandi

Calcium

Enzyme and pathway databases

ReactomeiREACT_278886. Cell surface interactions at the vascular wall.
REACT_281620. Gamma-carboxylation of protein precursors.
REACT_286713. Common Pathway of Fibrin Clot Formation.
REACT_340184. Intrinsic Pathway of Fibrin Clot Formation.
REACT_351509. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
REACT_352087. Removal of aminoterminal propeptides from gamma-carboxylated proteins.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:97771. Proc.

Subcellular locationi

  • Secreted By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Propeptidei19 – 4123By similarityPRO_0000028112Add
BLAST
Chaini42 – 460419Vitamin K-dependent protein CPRO_0000028113Add
BLAST
Chaini42 – 196155Vitamin K-dependent protein C light chainBy similarityPRO_0000028114Add
BLAST
Chaini199 – 460262Vitamin K-dependent protein C heavy chainBy similarityPRO_0000028115Add
BLAST
Peptidei199 – 21214Activation peptideBy similarityPRO_0000028116Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei47 – 4714-carboxyglutamatePROSITE-ProRule annotation
Modified residuei48 – 4814-carboxyglutamatePROSITE-ProRule annotation
Modified residuei55 – 5514-carboxyglutamatePROSITE-ProRule annotation
Modified residuei57 – 5714-carboxyglutamatePROSITE-ProRule annotation
Disulfide bondi58 ↔ 63By similarity
Modified residuei60 – 6014-carboxyglutamatePROSITE-ProRule annotation
Modified residuei61 – 6114-carboxyglutamatePROSITE-ProRule annotation
Modified residuei66 – 6614-carboxyglutamatePROSITE-ProRule annotation
Modified residuei67 – 6714-carboxyglutamatePROSITE-ProRule annotation
Modified residuei70 – 7014-carboxyglutamatePROSITE-ProRule annotation
Modified residuei76 – 7614-carboxyglutamatePROSITE-ProRule annotation
Disulfide bondi91 ↔ 110By similarity
Disulfide bondi100 ↔ 105By similarity
Disulfide bondi104 ↔ 119By similarity
Modified residuei112 – 1121(3R)-3-hydroxyaspartateBy similarity
Disulfide bondi121 ↔ 130By similarity
Disulfide bondi139 ↔ 150By similarity
Disulfide bondi146 ↔ 159By similarity
Disulfide bondi161 ↔ 174By similarity
Disulfide bondi182 ↔ 319Interchain (between light and heavy chains)PROSITE-ProRule annotation
Glycosylationi214 – 2141N-linked (GlcNAc...)1 Publication
Disulfide bondi238 ↔ 254By similarity
Glycosylationi290 – 2901N-linked (GlcNAc...)Sequence Analysis
Glycosylationi354 – 3541N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi372 ↔ 386By similarity
Disulfide bondi397 ↔ 425By similarity

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.By similarity

Keywords - PTMi

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

Proteomic databases

MaxQBiP33587.
PaxDbiP33587.
PRIDEiP33587.

PTM databases

PhosphoSiteiP33587.

Expressioni

Tissue specificityi

Plasma; synthesized in the liver.

Gene expression databases

BgeeiP33587.
CleanExiMM_PROC.
GenevisibleiP33587. MM.

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

STRINGi10090.ENSMUSP00000132226.

Structurei

3D structure databases

ProteinModelPortaliP33587.
SMRiP33587. Positions 46-87, 90-184, 212-448.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini42 – 8746GlaPROSITE-ProRule annotationAdd
BLAST
Domaini96 – 13136EGF-like 1PROSITE-ProRule annotationAdd
BLAST
Domaini135 – 17541EGF-like 2PROSITE-ProRule annotationAdd
BLAST
Domaini213 – 449237Peptidase 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

eggNOGiCOG5640.
GeneTreeiENSGT00760000118890.
HOGENOMiHOG000251821.
HOVERGENiHBG013304.
InParanoidiP33587.
KOiK01344.
OMAiPNYSKST.
OrthoDBiEOG75B84T.
PhylomeDBiP33587.
TreeFamiTF327329.

Family and domain databases

Gene3Di4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR012224. Pept_S1A_FX.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF00594. Gla. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001143. Factor_X. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
SMARTiSM00181. EGF. 1 hit.
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.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P33587-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWQFRVFLLL MSTWGISSIP AHPDPVFSSS EHAHQVLRVR RANSFLEEMR
60 70 80 90 100
PGSLERECME EICDFEEAQE IFQNVEDTLA FWIKYFDGDQ CSAPPLDHQC
110 120 130 140 150
DSPCCGHGTC IDGIGSFSCS CDKGWEGKFC QQELRFQDCR VNNGGCLHYC
160 170 180 190 200
LEESNGRRCA CAPGYELADD HMRCKSTVNF PCGKLGRWIE KKRKILKRDT
210 220 230 240 250
DLEDELEPDP RIVNGTLTKQ GDSPWQAILL DSKKKLACGG VLIHTSWVLT
260 270 280 290 300
AAHCVEGTKK LTVRLGEYDL RRRDHWELDL DIKEILVHPN YTRSSSDNDI
310 320 330 340 350
ALLRLAQPAT LSKTIVPICL PNNGLAQELT QAGQETVVTG WGYQSDRIKD
360 370 380 390 400
GRRNRTFILT FIRIPLVARN ECVEVMKNVV SENMLCAGII GDTRDACDGD
410 420 430 440 450
SGGPMVVFFR GTWFLVGLVS WGEGCGHTNN YGIYTKVGSY LKWIHSYIGE
460
KGVSLKSQKL
Length:460
Mass (Da):51,818
Last modified:June 7, 2004 - v2
Checksum:i0117F26E68FCC274
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti65 – 651F → L in AAK07918 (Ref. 3) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti327 – 3271Q → QQ in strain: BALB/c.
Natural varianti392 – 3921D → N in strain: BALB/c.

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10445 mRNA. Translation: BAA01235.1.
AF034569 Genomic DNA. Translation: AAC33795.1.
AF318182 mRNA. Translation: AAK07918.1.
BC013896 mRNA. Translation: AAH13896.1.
D43755 Genomic DNA. Translation: BAA07812.1.
CCDSiCCDS29116.1.
PIRiJX0210.
RefSeqiNP_001036232.1. NM_001042767.2.
NP_001036233.2. NM_001042768.2.
NP_032960.3. NM_008934.3.
XP_011245159.1. XM_011246857.1.
UniGeneiMm.2786.
Mm.489734.

Genome annotation databases

EnsembliENSMUST00000171765; ENSMUSP00000132226; ENSMUSG00000024386.
GeneIDi19123.
KEGGimmu:19123.
UCSCiuc008eiz.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D10445 mRNA. Translation: BAA01235.1.
AF034569 Genomic DNA. Translation: AAC33795.1.
AF318182 mRNA. Translation: AAK07918.1.
BC013896 mRNA. Translation: AAH13896.1.
D43755 Genomic DNA. Translation: BAA07812.1.
CCDSiCCDS29116.1.
PIRiJX0210.
RefSeqiNP_001036232.1. NM_001042767.2.
NP_001036233.2. NM_001042768.2.
NP_032960.3. NM_008934.3.
XP_011245159.1. XM_011246857.1.
UniGeneiMm.2786.
Mm.489734.

3D structure databases

ProteinModelPortaliP33587.
SMRiP33587. Positions 46-87, 90-184, 212-448.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000132226.

Protein family/group databases

MEROPSiS01.218.

PTM databases

PhosphoSiteiP33587.

Proteomic databases

MaxQBiP33587.
PaxDbiP33587.
PRIDEiP33587.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000171765; ENSMUSP00000132226; ENSMUSG00000024386.
GeneIDi19123.
KEGGimmu:19123.
UCSCiuc008eiz.1. mouse.

Organism-specific databases

CTDi5624.
MGIiMGI:97771. Proc.

Phylogenomic databases

eggNOGiCOG5640.
GeneTreeiENSGT00760000118890.
HOGENOMiHOG000251821.
HOVERGENiHBG013304.
InParanoidiP33587.
KOiK01344.
OMAiPNYSKST.
OrthoDBiEOG75B84T.
PhylomeDBiP33587.
TreeFamiTF327329.

Enzyme and pathway databases

ReactomeiREACT_278886. Cell surface interactions at the vascular wall.
REACT_281620. Gamma-carboxylation of protein precursors.
REACT_286713. Common Pathway of Fibrin Clot Formation.
REACT_340184. Intrinsic Pathway of Fibrin Clot Formation.
REACT_351509. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
REACT_352087. Removal of aminoterminal propeptides from gamma-carboxylated proteins.

Miscellaneous databases

ChiTaRSiProc. mouse.
NextBioi295718.
PROiP33587.
SOURCEiSearch...

Gene expression databases

BgeeiP33587.
CleanExiMM_PROC.
GenevisibleiP33587. MM.

Family and domain databases

Gene3Di4.10.740.10. 1 hit.
InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
IPR018097. EGF_Ca-bd_CS.
IPR000294. GLA_domain.
IPR012224. Pept_S1A_FX.
IPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamiPF00594. Gla. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFiPIRSF001143. Factor_X. 1 hit.
PRINTSiPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
SMARTiSM00181. EGF. 1 hit.
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.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Isolation and characterization of a mouse protein C cDNA."
    Tada N., Sato M., Tsujimura A., Iwase R., Hashimoto-Gotoh T.
    J. Biochem. 111:491-495(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
    Tissue: Liver.
  2. "Nucleotide structure and characterization of the murine gene encoding anticoagulant protein C."
    Jalbert L.R., Rosen E.D., Lissens A., Carmeliet P., Collen D., Castellino F.J.
    Thromb. Haemost. 79:310-316(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129/SvJ.
  3. "Complete sequence of UC72A01."
    Korf I.
    Submitted (NOV-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE.
    Strain: C57BL/6.
  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: Liver.
  5. "A comparative study of partial primary structures of the catalytic region of mammalian protein C."
    Murakawa M., Okamura T., Kamura T., Kuroiwa M., Harada M., Niho Y.
    Br. J. Haematol. 86:590-600(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 274-433.
    Strain: BALB/c.
  6. "Proteome-wide characterization of N-glycosylation events by diagonal chromatography."
    Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.
    J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-214.
    Strain: C57BL/6.
    Tissue: Plasma.

Entry informationi

Entry nameiPROC_MOUSE
AccessioniPrimary (citable) accession number: P33587
Secondary accession number(s): O35498, Q91WN8, Q99PC6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: June 7, 2004
Last modified: July 22, 2015
This is version 158 of the entry and version 2 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, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.