Reviewed, UniProtKB/Swiss-Prot P33587 (PROC_MOUSE)

Names and origin

Protein names

Recommended name:
    Vitamin K-dependent protein C
    EC=3.4.21.69
Alternative name(s):
    Autoprothrombin IIA
    Anticoagulant protein C
    Blood coagulation factor XIV
Cleaved into the following 3 chains:
    1- Recommended name:
            Vitamin K-dependent protein C light chain
    2- Recommended name:
            Vitamin K-dependent protein C heavy chain
    3- Recommended name:
            Activation peptide

Gene names

Name:

Proc

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	460 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	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.
Catalytic activity	Degradation of blood coagulation factors Va and VIIIa.
Subunit structure	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.
Tissue specificity	Plasma; synthesized in the liver.
Post-translational modification	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.
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.
Sequence similarities	Belongs to the peptidase S1 family. Contains 2 EGF-like domains. Contains 1 Gla (gamma-carboxy-glutamate) domain. Contains 1 peptidase S1 domain.

Ontologies

Keywords
Biological process	Blood coagulation
Domain	EGF-like domain Repeat Signal
Ligand	Calcium
Molecular function	Hydrolase Protease Serine protease
PTM	Cleavage on pair of basic residues Disulfide bond Gamma-carboxyglutamic acid Glycoprotein Hydroxylation Zymogen
Gene Ontology (GO)
Biological process	blood coagulation Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of apoptosis Non-traceable author statement. Source: UniProtKB negative regulation of blood coagulation Inferred from direct assay. Source: MGI proteolysis Inferred from electronic annotation. Source: InterPro
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW serine-type endopeptidase activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 33	33	By similarity
	Propeptide	34 – 41	8	By similarity		PRO_0000028112
	Chain	42 – 460	419	Vitamin K-dependent protein C		PRO_0000028113
	Chain	42 – 196	155	Vitamin K-dependent protein C light chain By similarity		PRO_0000028114
	Chain	199 – 460	262	Vitamin K-dependent protein C heavy chain By similarity		PRO_0000028115
	Peptide	199 – 212	14	Activation peptide By similarity		PRO_0000028116
Regions
	Domain	42 – 87	46	Gla
	Domain	96 – 131	36	EGF-like 1
	Domain	135 – 175	41	EGF-like 2
	Domain	213 – 449	237	Peptidase S1
Sites
	Active site	253	1	Charge relay system
	Active site	299	1	Charge relay system
	Active site	401	1	Charge relay system
	Site	212 – 213	2	Cleavage; by thrombin By similarity
Amino acid modifications
	Modified residue	47	1	4-carboxyglutamate By similarity
	Modified residue	48	1	4-carboxyglutamate By similarity
	Modified residue	55	1	4-carboxyglutamate By similarity
	Modified residue	57	1	4-carboxyglutamate By similarity
	Modified residue	60	1	4-carboxyglutamate By similarity
	Modified residue	61	1	4-carboxyglutamate By similarity
	Modified residue	66	1	4-carboxyglutamate By similarity
	Modified residue	67	1	4-carboxyglutamate By similarity
	Modified residue	70	1	4-carboxyglutamate By similarity
	Modified residue	112	1	(3R)-3-hydroxyaspartate By similarity
	Glycosylation	214	1	N-linked (GlcNAc...) Ref.6
	Glycosylation	290	1	N-linked (GlcNAc...) Potential
	Glycosylation	354	1	N-linked (GlcNAc...) Potential
	Disulfide bond	58 ↔ 63		By similarity
	Disulfide bond	91 ↔ 110		By similarity
	Disulfide bond	100 ↔ 105		By similarity
	Disulfide bond	104 ↔ 119		By similarity
	Disulfide bond	121 ↔ 130		By similarity
	Disulfide bond	139 ↔ 150		By similarity
	Disulfide bond	146 ↔ 159		By similarity
	Disulfide bond	161 ↔ 174		By similarity
	Disulfide bond	182 ↔ 319		Interchain (between light and heavy chains) By similarity
	Disulfide bond	238 ↔ 254		By similarity
	Disulfide bond	372 ↔ 386		By similarity
	Disulfide bond	397 ↔ 425		By similarity
Natural variations
	Natural variant	327	1	Q → QQ in strain: BALB/c.
	Natural variant	392	1	D → N in strain: BALB/c.
Experimental info
	Sequence conflict	65	1	F → L in AAK07918. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P33587-1 [UniParc]. Last modified June 7, 2004. Version 2. Checksum: 0117F26E68FCC274	FASTA	460	51,818
	10 20 30 40 50 60 MWQFRVFLLL MSTWGISSIP AHPDPVFSSS EHAHQVLRVR RANSFLEEMR PGSLERECME 70 80 90 100 110 120 EICDFEEAQE IFQNVEDTLA FWIKYFDGDQ CSAPPLDHQC DSPCCGHGTC IDGIGSFSCS 130 140 150 160 170 180 CDKGWEGKFC QQELRFQDCR VNNGGCLHYC LEESNGRRCA CAPGYELADD HMRCKSTVNF 190 200 210 220 230 240 PCGKLGRWIE KKRKILKRDT DLEDELEPDP RIVNGTLTKQ GDSPWQAILL DSKKKLACGG 250 260 270 280 290 300 VLIHTSWVLT AAHCVEGTKK LTVRLGEYDL RRRDHWELDL DIKEILVHPN YTRSSSDNDI 310 320 330 340 350 360 ALLRLAQPAT LSKTIVPICL PNNGLAQELT QAGQETVVTG WGYQSDRIKD GRRNRTFILT 370 380 390 400 410 420 FIRIPLVARN ECVEVMKNVV SENMLCAGII GDTRDACDGD SGGPMVVFFR GTWFLVGLVS 430 440 450 460 WGEGCGHTNN YGIYTKVGSY LKWIHSYIGE KGVSLKSQKL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 1618739] [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: 9493582] [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: 15489334] [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: 8043441] [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: 16944957] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-214, MASS SPECTROMETRY. Tissue: Plasma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00113750.
PIR	JX0210.
RefSeq	NP_001036232.1. NP_001036233.1. NP_032960.2.
UniGene	Mm.2786
3D structure databases
HSSP	HSSP built from PDB template 1AUT based on UniProtKB P04070.
SMR	P33587. Positions 212-448.
ModBase	Search...
Protein family/group databases
MEROPS	S01.218.
Genome annotation databases
Ensembl	ENSMUSG00000024386. Mus musculus. [Contig view]
GeneID	19123.
KEGG	mmu:19123.
NMPDR	fig|10090.3.peg.3736.
Organism-specific databases
MGI	MGI:97771. Proc.
Phylogenomic databases
HOGENOM	P33587.
HOVERGEN	P33587.
OMA	P33587. TVVTGWG.
Enzyme and pathway databases
BRENDA	3.4.21.69. 244.
Gene expression databases
ArrayExpress	P33587.
Bgee	P33587.
CleanEx	MM_PROC.
GermOnline	ENSMUSG00000024386. Mus musculus.
Family and domain databases
InterPro	IPR002383. Coagulation_factor_Gla. IPR006209. EGF. IPR006210. EGF-like. IPR013032. EGF-like_reg_CS. IPR000152. EGF-type_Asp/Asn_hydroxyl_CS. IPR000742. EGF_3. IPR001881. EGF_Ca_bd. IPR018097. EGF_Ca_bd_CS. IPR000294. GLA_domain. IPR012224. Pept_S1A_FX. IPR018114. Peptidase_S1/S6_AS. IPR001254. Peptidase_S1_S6. IPR001314. Peptidase_S1A. [Graphical view]
Pfam	PF00008. EGF. 2 hits. PF00594. Gla. 1 hit. PF00089. Trypsin. 1 hit. [Graphical view]
PIRSF	PIRSF001143. Factor_X. 1 hit.
PRINTS	PR00722. CHYMOTRYPSIN. PR00001. GLABLOOD.
SMART	SM00181. EGF. 1 hit. SM00179. EGF_CA. 1 hit. SM00069. GLA. 1 hit. SM00020. Tryp_SPc. 1 hit. [Graphical view]
PROSITE	PS00010. 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]
ProtoNet	Search...
Other Resources
NextBio	295718.
SOURCE	Search...

Entry information

Entry name

PROC_MOUSE

Accession

Primary (citable) accession number: P33587
Secondary accession number(s): O35498, Q91WN8, Q99PC6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	June 7, 2004
Last modified:	June 16, 2009
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)