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Protein

Vitamin K-dependent protein C

Gene

PROC

Organism
Homo sapiens (Human)
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 (PubMed:25618265). Exerts a protective effect on the endothelial cell barrier function (PubMed:25651845).2 Publications

Catalytic activityi

Degradation of blood coagulation factors Va and VIIIa.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei253Charge relay system1
Active sitei299Charge relay system1
Active sitei402Charge relay system1

GO - Molecular functioni

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

GO - Biological processi

  • blood coagulation Source: Reactome
  • ER to Golgi vesicle-mediated transport Source: Reactome
  • leukocyte migration Source: Reactome
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of blood coagulation Source: UniProtKB
  • negative regulation of coagulation Source: UniProtKB
  • negative regulation of inflammatory response Source: UniProtKB
  • peptidyl-glutamic acid carboxylation Source: Reactome
  • positive regulation of establishment of endothelial barrier Source: UniProtKB
  • proteolysis Source: UniProtKB
  • signal peptide processing Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Serine protease

Keywords - Biological processi

Blood coagulation, Hemostasis

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:HS03931-MONOMER.
BRENDAi3.4.21.69. 2681.
ReactomeiR-HSA-140837. Intrinsic Pathway of Fibrin Clot Formation.
R-HSA-140875. Common Pathway of Fibrin Clot Formation.
R-HSA-159740. Gamma-carboxylation of protein precursors.
R-HSA-159763. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
R-HSA-159782. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
R-HSA-202733. Cell surface interactions at the vascular wall.
SABIO-RKP04070.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:9451. PROC.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • endoplasmic reticulum lumen Source: Reactome
  • extracellular region Source: UniProtKB
  • extracellular space Source: GO_Central
  • Golgi apparatus Source: UniProtKB
  • Golgi lumen Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Secreted

Pathology & Biotechi

Involvement in diseasei

Thrombophilia due to protein C deficiency, autosomal dominant (THPH3)16 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. Individuals with decreased amounts of protein C are classically referred to as having type I protein C deficiency and those with normal amounts of a functionally defective protein as having type II deficiency.
See also OMIM:176860
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00663532R → C in THPH3. 1 Publication1
Natural variantiVAR_05507442R → S in THPH3; type II; Osaka-10; alters proteolytic processing so that S-42 is the N-terminus of the mature protein. 1 Publication1
Natural variantiVAR_00664257R → W in THPH3. 2 PublicationsCorresponds to variant rs757583846dbSNPEnsembl.1
Natural variantiVAR_00664562E → A in THPH3; Vermont-1. 1 PublicationCorresponds to variant rs121918148dbSNPEnsembl.1
Natural variantiVAR_00664676V → M in THPH3; Vermont-1. 1 PublicationCorresponds to variant rs121918149dbSNPEnsembl.1
Natural variantiVAR_006651114G → R in THPH3. 1 PublicationCorresponds to variant rs374476971dbSNPEnsembl.1
Natural variantiVAR_006656145G → R in THPH3. 1 Publication1
Natural variantiVAR_073147163A → V in THPH3; drastically reduced secretion; colocalizes with 26S proteasome. 1 Publication1
Natural variantiVAR_006664210P → L in THPH3. 1 PublicationCorresponds to variant rs121918145dbSNPEnsembl.1
Natural variantiVAR_006665211R → W in THPH3; London-1/Tochigi. 2 PublicationsCorresponds to variant rs28933986dbSNPEnsembl.1
Natural variantiVAR_006669220R → Q in THPH3; Vermont-3. 3 PublicationsCorresponds to variant rs121918153dbSNPEnsembl.1
Natural variantiVAR_006668220R → W in THPH3. 2 PublicationsCorresponds to variant rs121918152dbSNPEnsembl.1
Natural variantiVAR_006671243I → T in THPH3. 1 PublicationCorresponds to variant rs774584131dbSNPEnsembl.1
Natural variantiVAR_006677272R → C in THPH3. 1 PublicationCorresponds to variant rs121918154dbSNPEnsembl.1
Natural variantiVAR_074303297D → H in THPH3; also found in patients with PROC deficiency; decrease in vitamin-K dependent serine protease activity; decreased Golgi localization. 2 PublicationsCorresponds to variant rs199469471dbSNPEnsembl.1
Natural variantiVAR_006687321P → L in THPH3. 2 Publications1
Natural variantiVAR_006688324G → R in THPH3. 1 Publication1
Natural variantiVAR_006689328R → C in THPH3. 2 PublicationsCorresponds to variant rs201907715dbSNPEnsembl.1
Natural variantiVAR_006692340T → M in THPH3; Vermont-2. 2 PublicationsCorresponds to variant rs766261022dbSNPEnsembl.1
Natural variantiVAR_006696369P → L in THPH3; Osaka-6. 2 Publications1
Natural variantiVAR_006700392G → R in THPH3; Osaka-9. 1 PublicationCorresponds to variant rs756467027dbSNPEnsembl.1
Natural variantiVAR_006702401D → N in THPH3; La Jolla-2/Osaka-7 and -8. 1 PublicationCorresponds to variant rs142742242dbSNPEnsembl.1
Natural variantiVAR_074307420V → L in THPH3; also found in patients with PROC deficiency; decrease in vitamin-K dependent serine protease activity. 2 PublicationsCorresponds to variant rs199469472dbSNPEnsembl.1
Natural variantiVAR_006704423G → S in THPH3. 1 Publication1
Natural variantiVAR_006705426C → Y in THPH3. 1 Publication1
Natural variantiVAR_006707436T → N in THPH3. 1 Publication1
Natural variantiVAR_006708441Y → H in THPH3; Osaka-4. 1 PublicationCorresponds to variant rs753436021dbSNPEnsembl.1
Natural variantiVAR_006709444W → C in THPH3. 1 PublicationCorresponds to variant rs121918142dbSNPEnsembl.1
Thrombophilia due to protein C deficiency, autosomal recessive (THPH4)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA hemostatic disorder characterized by impaired regulation of blood coagulation and a tendency to recurrent venous thrombosis. It results in a thrombotic condition that can manifest as a severe neonatal disorder or as a milder disorder with late-onset thrombophilia. The severe form leads to neonatal death through massive neonatal venous thrombosis. Often associated with ecchymotic skin lesions which can turn necrotic called purpura fulminans, this disorder is very rare.
See also OMIM:612304
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07314577D → G in THPH4; no effect on secretion; no effect on catalytic activity in vitro. 1 Publication1
Natural variantiVAR_006655144 – 145NG → K in THPH4; neonatal purpura fulminans. 1 Publication2
Natural variantiVAR_073146163A → E in THPH4; drastically reduced secretion; colocalizes with 26S proteasome. 1 Publication1
Natural variantiVAR_006660178A → P in THPH4; Clamart. 1 Publication1
Natural variantiVAR_006679289P → L in THPH4. 1 PublicationCorresponds to variant rs121918151dbSNPEnsembl.1
Natural variantiVAR_006690328R → H in THPH4; Muenchen. 1 Publication1
Natural variantiVAR_006691334G → S in THPH4. 1 PublicationCorresponds to variant rs121918150dbSNPEnsembl.1
Natural variantiVAR_006695367V → A in THPH4; neonatal purpura fulminans. 1 PublicationCorresponds to variant rs767730328dbSNPEnsembl.1
Natural variantiVAR_006703418G → D in THPH4; Hong Kong-2. 1 Publication1

Keywords - Diseasei

Disease mutation, Thrombophilia

Organism-specific databases

DisGeNETi5624.
MalaCardsiPROC.
MIMi176860. phenotype.
612304. phenotype.
OpenTargetsiENSG00000115718.
Orphaneti745. Hereditary thrombophilia due to congenital protein C deficiency.
PharmGKBiPA33799.

Chemistry databases

ChEMBLiCHEMBL4444.
DrugBankiDB00025. Antihemophilic Factor (Recombinant).
DB00170. Menadione.
DB00464. Sodium Tetradecyl Sulfate.
GuidetoPHARMACOLOGYi2396.

Polymorphism and mutation databases

BioMutaiPROC.
DMDMi131067.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
PropeptideiPRO_000002810719 – 42Add BLAST24
ChainiPRO_000002810843 – 461Vitamin K-dependent protein CAdd BLAST419
ChainiPRO_000002810943 – 197Vitamin K-dependent protein C light chainAdd BLAST155
ChainiPRO_0000028110200 – 461Vitamin K-dependent protein C heavy chainAdd BLAST262
PeptideiPRO_0000028111200 – 211Activation peptideAdd BLAST12

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi19O-linked (GalNAc...)1 Publication1
Modified residuei484-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei494-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei564-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei584-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Disulfide bondi59 ↔ 64
Modified residuei614-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei624-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei674-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei684-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Modified residuei714-carboxyglutamatePROSITE-ProRule annotation1 Publication1
Disulfide bondi92 ↔ 111
Disulfide bondi101 ↔ 106
Disulfide bondi105 ↔ 120
Modified residuei113(3R)-3-hydroxyaspartate1 Publication1
Disulfide bondi122 ↔ 131
Glycosylationi139N-linked (GlcNAc...)1
Disulfide bondi140 ↔ 151
Disulfide bondi147 ↔ 160
Disulfide bondi162 ↔ 175
Disulfide bondi183 ↔ 319Interchain (between light and heavy chains)
Disulfide bondi238 ↔ 254
Glycosylationi290N-linked (GlcNAc...)2 Publications1
Modified residuei347Phosphoserine; by FAM20C1 Publication1
Glycosylationi355N-linked (GlcNAc...)1 Publication1
Glycosylationi371N-linked (GlcNAc...); atypical; partial2 Publications1
Disulfide bondi373 ↔ 387
Disulfide bondi398 ↔ 426

Post-translational modificationi

The vitamin K-dependent, enzymatic carboxylation of some Glu residues allows the modified protein to bind calcium.
N- and O-glycosylated. Partial (70%) N-glycosylation of Asn-371 with an atypical N-X-C site produces a higher molecular weight form referred to as alpha. The lower molecular weight form, not N-glycosylated at Asn-371, is beta. O-glycosylated with core 1 or possibly core 8 glycans.4 Publications
The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.2 Publications
May be phosphorylated on a Ser or Thr in a region (AA 25-30) of the propeptide.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei211 – 212Cleavage; by thrombin2

Keywords - PTMi

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

Proteomic databases

MaxQBiP04070.
PaxDbiP04070.
PeptideAtlasiP04070.
PRIDEiP04070.

PTM databases

iPTMnetiP04070.
PhosphoSitePlusiP04070.
UniCarbKBiP04070.

Miscellaneous databases

PMAP-CutDBP04070.

Expressioni

Tissue specificityi

Plasma; synthesized in the liver.

Gene expression databases

BgeeiENSG00000115718.
CleanExiHS_PROC.
ExpressionAtlasiP04070. baseline and differential.
GenevisibleiP04070. HS.

Organism-specific databases

HPAiCAB016721.
CAB016792.
HPA005550.

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.

Binary interactionsi

WithEntry#Exp.IntActNotes
MMP15P515112EBI-1383018,EBI-1383043

Protein-protein interaction databases

BioGridi111608. 11 interactors.
IntActiP04070. 3 interactors.
MINTiMINT-8247437.
STRINGi9606.ENSP00000234071.

Chemistry databases

BindingDBiP04070.

Structurei

Secondary structure

1461
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi48 – 50Combined sources3
Helixi55 – 59Combined sources5
Helixi66 – 73Combined sources8
Beta strandi100 – 103Combined sources4
Turni104 – 107Combined sources4
Beta strandi108 – 111Combined sources4
Beta strandi120 – 122Combined sources3
Beta strandi126 – 128Combined sources3
Beta strandi137 – 142Combined sources6
Helixi143 – 146Combined sources4
Beta strandi148 – 153Combined sources6
Beta strandi155 – 161Combined sources7
Beta strandi166 – 168Combined sources3
Beta strandi175 – 177Combined sources3
Beta strandi179 – 181Combined sources3
Beta strandi226 – 230Combined sources5
Beta strandi236 – 244Combined sources9
Beta strandi247 – 250Combined sources4
Helixi252 – 254Combined sources3
Beta strandi255 – 257Combined sources3
Beta strandi262 – 266Combined sources5
Beta strandi269 – 272Combined sources4
Beta strandi278 – 287Combined sources10
Turni293 – 296Combined sources4
Beta strandi301 – 307Combined sources7
Helixi323 – 328Combined sources6
Turni329 – 331Combined sources3
Beta strandi336 – 341Combined sources6
Beta strandi357 – 359Combined sources3
Beta strandi361 – 368Combined sources8
Helixi370 – 376Combined sources7
Beta strandi385 – 388Combined sources4
Beta strandi405 – 410Combined sources6
Beta strandi413 – 422Combined sources10
Beta strandi424 – 427Combined sources4
Beta strandi433 – 436Combined sources4
Helixi438 – 440Combined sources3
Helixi442 – 449Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AUTX-ray2.80C212-461[»]
L84-197[»]
1LQVX-ray1.60C/D43-75[»]
1PCUmodel-A175-450[»]
2PCTmodel-A175-450[»]
3F6UX-ray2.80H212-451[»]
L91-188[»]
3JTCX-ray1.60C/D43-75[»]
4DT7X-ray1.90E/F204-223[»]
ProteinModelPortaliP04070.
SMRiP04070.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04070.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini43 – 88GlaPROSITE-ProRule annotationAdd BLAST46
Domaini97 – 132EGF-like 1PROSITE-ProRule annotationAdd BLAST36
Domaini136 – 176EGF-like 2PROSITE-ProRule annotationAdd BLAST41
Domaini212 – 450Peptidase S1PROSITE-ProRule annotationAdd BLAST239

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.
GeneTreeiENSGT00760000118890.
HOGENOMiHOG000251821.
HOVERGENiHBG013304.
InParanoidiP04070.
KOiK01344.
PhylomeDBiP04070.
TreeFamiTF327329.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
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.
IPR018114. TRYPSIN_HIS.
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.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P04070-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MWQLTSLLLF VATWGISGTP APLDSVFSSS ERAHQVLRIR KRANSFLEEL
60 70 80 90 100
RHSSLERECI EEICDFEEAK EIFQNVDDTL AFWSKHVDGD QCLVLPLEHP
110 120 130 140 150
CASLCCGHGT CIDGIGSFSC DCRSGWEGRF CQREVSFLNC SLDNGGCTHY
160 170 180 190 200
CLEEVGWRRC SCAPGYKLGD DLLQCHPAVK FPCGRPWKRM EKKRSHLKRD
210 220 230 240 250
TEDQEDQVDP RLIDGKMTRR GDSPWQVVLL DSKKKLACGA VLIHPSWVLT
260 270 280 290 300
AAHCMDESKK LLVRLGEYDL RRWEKWELDL DIKEVFVHPN YSKSTTDNDI
310 320 330 340 350
ALLHLAQPAT LSQTIVPICL PDSGLAEREL NQAGQETLVT GWGYHSSREK
360 370 380 390 400
EAKRNRTFVL NFIKIPVVPH NECSEVMSNM VSENMLCAGI LGDRQDACEG
410 420 430 440 450
DSGGPMVASF HGTWFLVGLV SWGEGCGLLH NYGVYTKVSR YLDWIHGHIR
460
DKEAPQKSWA P
Length:461
Mass (Da):52,071
Last modified:November 1, 1986 - v1
Checksum:i3531B0AE5345B39A
GO
Isoform 2 (identifier: P04070-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MAAGRRTCSISTTRPCASASRM
     133-133: R → RGEGERWMLAGGGAGLGPGWGRGTSTSCPRPPLPA

Note: No experimental confirmation available.
Show »
Length:516
Mass (Da):57,556
Checksum:i6F21DD7C17317C88
GO

Sequence cautioni

The sequence S76088 differs from that shown. Reason: Erroneous termination at position 151. Translated as Cys.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti106C → Q in AAA60164 (PubMed:6589623).Curated1
Sequence conflicti445I → IL in AAA60165 (PubMed:3511471).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00663414W → G in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_00663532R → C in THPH3. 1 Publication1
Natural variantiVAR_00663638R → W in patients with PROC deficiency. 1 PublicationCorresponds to variant rs769900251dbSNPEnsembl.1
Natural variantiVAR_00663842R → C in patients with PROC deficiency. 1 PublicationCorresponds to variant rs774572099dbSNPEnsembl.1
Natural variantiVAR_00663742R → H in Malakoff; low anticoagulant activity. 1 PublicationCorresponds to variant rs369504169dbSNPEnsembl.1
Natural variantiVAR_05507442R → S in THPH3; type II; Osaka-10; alters proteolytic processing so that S-42 is the N-terminus of the mature protein. 1 Publication1
Natural variantiVAR_00663943A → T.1 PublicationCorresponds to variant rs767626189dbSNPEnsembl.1
Natural variantiVAR_00664049E → D in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_00664151R → C in patients with PROC deficiency. Corresponds to variant rs764546127dbSNPEnsembl.1
Natural variantiVAR_00664357R → G in Yonago; defective anticoagulant activity. 1 Publication1
Natural variantiVAR_00664457R → Q in patients with PROC deficiency. Corresponds to variant rs574949343dbSNPEnsembl.1
Natural variantiVAR_00664257R → W in THPH3. 2 PublicationsCorresponds to variant rs757583846dbSNPEnsembl.1
Natural variantiVAR_00664562E → A in THPH3; Vermont-1. 1 PublicationCorresponds to variant rs121918148dbSNPEnsembl.1
Natural variantiVAR_07429670K → E in patients with PROC deficiency. 1 PublicationCorresponds to variant rs199469481dbSNPEnsembl.1
Natural variantiVAR_00664676V → M in THPH3; Vermont-1. 1 PublicationCorresponds to variant rs121918149dbSNPEnsembl.1
Natural variantiVAR_07314577D → G in THPH4; no effect on secretion; no effect on catalytic activity in vitro. 1 Publication1
Natural variantiVAR_00664789G → C in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_074297106C → G in patients with PROC deficiency. 1 PublicationCorresponds to variant rs199469479dbSNPEnsembl.1
Natural variantiVAR_006648108H → N in patients with PROC deficiency; La Jolla-1. Corresponds to variant rs200234655dbSNPEnsembl.1
Natural variantiVAR_006649109G → R in patients with PROC deficiency. 1
Natural variantiVAR_006650114 – 118Missing in patients with PROC deficiency. 5
Natural variantiVAR_006651114G → R in THPH3. 1 PublicationCorresponds to variant rs374476971dbSNPEnsembl.1
Natural variantiVAR_074298118F → A in patients with PROC deficiency; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_006652118F → L in patients with PROC deficiency. 1
Natural variantiVAR_006653119 – 124Missing in patients with PROC deficiency; St Louis-2. 6
Natural variantiVAR_006654120 – 125Missing in patients with PROC deficiency; St Louis-3. 6
Natural variantiVAR_006655144 – 145NG → K in THPH4; neonatal purpura fulminans. 1 Publication2
Natural variantiVAR_006656145G → R in THPH3. 1 Publication1
Natural variantiVAR_006657147C → Y in patients with PROC deficiency. 1
Natural variantiVAR_006658149H → P in patients with PROC deficiency. Corresponds to variant rs121918159dbSNPEnsembl.1
Natural variantiVAR_006659161S → R in patients with PROC deficiency. 1
Natural variantiVAR_073146163A → E in THPH4; drastically reduced secretion; colocalizes with 26S proteasome. 1 Publication1
Natural variantiVAR_073147163A → V in THPH3; drastically reduced secretion; colocalizes with 26S proteasome. 1 Publication1
Natural variantiVAR_074299175C → Y in patients with PROC deficiency. 1 PublicationCorresponds to variant rs199469474dbSNPEnsembl.1
Natural variantiVAR_006660178A → P in THPH4; Clamart. 1 Publication1
Natural variantiVAR_074300181F → V in patients with PROC deficiency. 1 PublicationCorresponds to variant rs199469470dbSNPEnsembl.1
Natural variantiVAR_006661183C → R in patients with PROC deficiency. Corresponds to variant rs748920874dbSNPEnsembl.1
Natural variantiVAR_006662189R → W in patients with PROC deficiency; La Jolla-3. 1 PublicationCorresponds to variant rs146922325dbSNPEnsembl.1
Natural variantiVAR_006663194R → C in patients with PROC deficiency. Corresponds to variant rs371071104dbSNPEnsembl.1
Natural variantiVAR_006664210P → L in THPH3. 1 PublicationCorresponds to variant rs121918145dbSNPEnsembl.1
Natural variantiVAR_006666211R → Q in patients with PROC deficiency. 2 PublicationsCorresponds to variant rs28933987dbSNPEnsembl.1
Natural variantiVAR_006665211R → W in THPH3; London-1/Tochigi. 2 PublicationsCorresponds to variant rs28933986dbSNPEnsembl.1
Natural variantiVAR_006667220R → P in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006669220R → Q in THPH3; Vermont-3. 3 PublicationsCorresponds to variant rs121918153dbSNPEnsembl.1
Natural variantiVAR_006668220R → W in THPH3. 2 PublicationsCorresponds to variant rs121918152dbSNPEnsembl.1
Natural variantiVAR_074301223S → R in patients with PROC deficiency. 1 PublicationCorresponds to variant rs199469483dbSNPEnsembl.1
Natural variantiVAR_006670226Q → H in patients with PROC deficiency. Corresponds to variant rs121918155dbSNPEnsembl.1
Natural variantiVAR_074302240A → G in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006671243I → T in THPH3. 1 PublicationCorresponds to variant rs774584131dbSNPEnsembl.1
Natural variantiVAR_006672244H → Y in patients with PROC deficiency. 1 PublicationCorresponds to variant rs759557871dbSNPEnsembl.1
Natural variantiVAR_006673253H → Q in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006674265L → F in patients with PROC deficiency. Corresponds to variant rs121918156dbSNPEnsembl.1
Natural variantiVAR_006675271R → Q in Marseille; low anticoagulant activity. 1 Publication1
Natural variantiVAR_006676271R → W in patients with PROC deficiency. Corresponds to variant rs767112991dbSNPEnsembl.1
Natural variantiVAR_006677272R → C in THPH3. 1 PublicationCorresponds to variant rs121918154dbSNPEnsembl.1
Natural variantiVAR_006678281D → DLD in patients with PROC deficiency. 1
Natural variantiVAR_006679289P → L in THPH4. 1 PublicationCorresponds to variant rs121918151dbSNPEnsembl.1
Natural variantiVAR_006680294S → N in Paris; low anticoagulant activity. 1 PublicationCorresponds to variant rs200721675dbSNPEnsembl.1
Natural variantiVAR_074303297D → H in THPH3; also found in patients with PROC deficiency; decrease in vitamin-K dependent serine protease activity; decreased Golgi localization. 2 PublicationsCorresponds to variant rs199469471dbSNPEnsembl.1
Natural variantiVAR_006681298N → D in patients with PROC deficiency. 1
Natural variantiVAR_006682301A → T in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006683301A → V in patients with PROC deficiency. Corresponds to variant rs121918144dbSNPEnsembl.1
Natural variantiVAR_006684309A → T in patients with PROC deficiency. Corresponds to variant rs121918146dbSNPEnsembl.1
Natural variantiVAR_006685312S → L in patients with PROC deficiency. 1 PublicationCorresponds to variant rs121918160dbSNPEnsembl.1
Natural variantiVAR_006686312S → P in a patient with PROC deficiency; sporadic case. 1 Publication1
Natural variantiVAR_074304317P → S in patients with PROC deficiency; abolishes Golgi localization. 1 Publication1
Natural variantiVAR_006687321P → L in THPH3. 2 Publications1
Natural variantiVAR_006688324G → R in THPH3. 1 Publication1
Natural variantiVAR_074305327E → V in patients with PROC deficiency. 1 PublicationCorresponds to variant rs199469480dbSNPEnsembl.1
Natural variantiVAR_006689328R → C in THPH3. 2 PublicationsCorresponds to variant rs201907715dbSNPEnsembl.1
Natural variantiVAR_006690328R → H in THPH4; Muenchen. 1 Publication1
Natural variantiVAR_006691334G → S in THPH4. 1 PublicationCorresponds to variant rs121918150dbSNPEnsembl.1
Natural variantiVAR_006692340T → M in THPH3; Vermont-2. 2 PublicationsCorresponds to variant rs766261022dbSNPEnsembl.1
Natural variantiVAR_006693343G → D in patients with PROC deficiency. 1
Natural variantiVAR_074306357T → A Gain of function mutation; abolishes glycosylation at N-313; decreases its catalytic activity; significant loss of its protective effect on endothelial barrier function; increased activation by thrombin. 1 Publication1
Natural variantiVAR_006694363Missing in patients with PROC deficiency. 1
Natural variantiVAR_006695367V → A in THPH4; neonatal purpura fulminans. 1 PublicationCorresponds to variant rs767730328dbSNPEnsembl.1
Natural variantiVAR_006696369P → L in THPH3; Osaka-6. 2 Publications1
Natural variantiVAR_006697385M → I in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006698388A → T in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006699388A → V in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006700392G → R in THPH3; Osaka-9. 1 PublicationCorresponds to variant rs756467027dbSNPEnsembl.1
Natural variantiVAR_006701394R → W in patients with PROC deficiency. Corresponds to variant rs759316085dbSNPEnsembl.1
Natural variantiVAR_006702401D → N in THPH3; La Jolla-2/Osaka-7 and -8. 1 PublicationCorresponds to variant rs142742242dbSNPEnsembl.1
Natural variantiVAR_006703418G → D in THPH4; Hong Kong-2. 1 Publication1
Natural variantiVAR_074307420V → L in THPH3; also found in patients with PROC deficiency; decrease in vitamin-K dependent serine protease activity. 2 PublicationsCorresponds to variant rs199469472dbSNPEnsembl.1
Natural variantiVAR_006704423G → S in THPH3. 1 Publication1
Natural variantiVAR_006705426C → Y in THPH3. 1 Publication1
Natural variantiVAR_006706433G → S in patients with PROC deficiency; Purmerend. 1
Natural variantiVAR_006707436T → N in THPH3. 1 Publication1
Natural variantiVAR_006708441Y → H in THPH3; Osaka-4. 1 PublicationCorresponds to variant rs753436021dbSNPEnsembl.1
Natural variantiVAR_006709444W → C in THPH3. 1 PublicationCorresponds to variant rs121918142dbSNPEnsembl.1
Natural variantiVAR_006710445I → M in patients with PROC deficiency. Corresponds to variant rs121918157dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0543931M → MAAGRRTCSISTTRPCASAS RM in isoform 2. 1 Publication1
Alternative sequenceiVSP_054394133R → RGEGERWMLAGGGAGLGPGW GRGTSTSCPRPPLPA in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02750 mRNA. Translation: CAA26528.1.
M11228 Genomic DNA. Translation: AAA60166.1.
M12712
, M12683, M12684, M12685, M12686, M12687 Genomic DNA. Translation: AAA60165.1.
AF378903 Genomic DNA. Translation: AAK56377.1.
AK298454 mRNA. Translation: BAG60669.1.
AC068282 Genomic DNA. Translation: AAY15044.1.
CH471103 Genomic DNA. Translation: EAW95320.1.
BC034377 mRNA. Translation: AAH34377.1.
S58668 Genomic DNA. Translation: AAB26335.1.
K02059 mRNA. Translation: AAA60164.1.
S76088 Genomic DNA. No translation available.
S76090 Genomic DNA. No translation available.
CCDSiCCDS2145.1. [P04070-1]
PIRiA22331. KXHU.
RefSeqiNP_000303.1. NM_000312.3. [P04070-1]
UniGeneiHs.224698.

Genome annotation databases

EnsembliENST00000234071; ENSP00000234071; ENSG00000115718. [P04070-1]
GeneIDi5624.
KEGGihsa:5624.
UCSCiuc002tok.4. human. [P04070-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

Protein C entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02750 mRNA. Translation: CAA26528.1.
M11228 Genomic DNA. Translation: AAA60166.1.
M12712
, M12683, M12684, M12685, M12686, M12687 Genomic DNA. Translation: AAA60165.1.
AF378903 Genomic DNA. Translation: AAK56377.1.
AK298454 mRNA. Translation: BAG60669.1.
AC068282 Genomic DNA. Translation: AAY15044.1.
CH471103 Genomic DNA. Translation: EAW95320.1.
BC034377 mRNA. Translation: AAH34377.1.
S58668 Genomic DNA. Translation: AAB26335.1.
K02059 mRNA. Translation: AAA60164.1.
S76088 Genomic DNA. No translation available.
S76090 Genomic DNA. No translation available.
CCDSiCCDS2145.1. [P04070-1]
PIRiA22331. KXHU.
RefSeqiNP_000303.1. NM_000312.3. [P04070-1]
UniGeneiHs.224698.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1AUTX-ray2.80C212-461[»]
L84-197[»]
1LQVX-ray1.60C/D43-75[»]
1PCUmodel-A175-450[»]
2PCTmodel-A175-450[»]
3F6UX-ray2.80H212-451[»]
L91-188[»]
3JTCX-ray1.60C/D43-75[»]
4DT7X-ray1.90E/F204-223[»]
ProteinModelPortaliP04070.
SMRiP04070.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111608. 11 interactors.
IntActiP04070. 3 interactors.
MINTiMINT-8247437.
STRINGi9606.ENSP00000234071.

Chemistry databases

BindingDBiP04070.
ChEMBLiCHEMBL4444.
DrugBankiDB00025. Antihemophilic Factor (Recombinant).
DB00170. Menadione.
DB00464. Sodium Tetradecyl Sulfate.
GuidetoPHARMACOLOGYi2396.

Protein family/group databases

MEROPSiS01.218.

PTM databases

iPTMnetiP04070.
PhosphoSitePlusiP04070.
UniCarbKBiP04070.

Polymorphism and mutation databases

BioMutaiPROC.
DMDMi131067.

Proteomic databases

MaxQBiP04070.
PaxDbiP04070.
PeptideAtlasiP04070.
PRIDEiP04070.

Protocols and materials databases

DNASUi5624.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000234071; ENSP00000234071; ENSG00000115718. [P04070-1]
GeneIDi5624.
KEGGihsa:5624.
UCSCiuc002tok.4. human. [P04070-1]

Organism-specific databases

CTDi5624.
DisGeNETi5624.
GeneCardsiPROC.
HGNCiHGNC:9451. PROC.
HPAiCAB016721.
CAB016792.
HPA005550.
MalaCardsiPROC.
MIMi176860. phenotype.
612283. gene.
612304. phenotype.
neXtProtiNX_P04070.
OpenTargetsiENSG00000115718.
Orphaneti745. Hereditary thrombophilia due to congenital protein C deficiency.
PharmGKBiPA33799.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJRM. Eukaryota.
COG5640. LUCA.
GeneTreeiENSGT00760000118890.
HOGENOMiHOG000251821.
HOVERGENiHBG013304.
InParanoidiP04070.
KOiK01344.
PhylomeDBiP04070.
TreeFamiTF327329.

Enzyme and pathway databases

BioCyciZFISH:HS03931-MONOMER.
BRENDAi3.4.21.69. 2681.
ReactomeiR-HSA-140837. Intrinsic Pathway of Fibrin Clot Formation.
R-HSA-140875. Common Pathway of Fibrin Clot Formation.
R-HSA-159740. Gamma-carboxylation of protein precursors.
R-HSA-159763. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
R-HSA-159782. Removal of aminoterminal propeptides from gamma-carboxylated proteins.
R-HSA-202733. Cell surface interactions at the vascular wall.
SABIO-RKP04070.

Miscellaneous databases

EvolutionaryTraceiP04070.
GeneWikiiProtein_C.
GenomeRNAii5624.
PMAP-CutDBP04070.
PROiP04070.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115718.
CleanExiHS_PROC.
ExpressionAtlasiP04070. baseline and differential.
GenevisibleiP04070. HS.

Family and domain databases

CDDicd00190. Tryp_SPc. 1 hit.
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.
IPR018114. TRYPSIN_HIS.
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.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPROC_HUMAN
AccessioniPrimary (citable) accession number: P04070
Secondary accession number(s): B4DPQ7
, Q15189, Q15190, Q16001, Q53S74, Q9UC55
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: November 2, 2016
This is version 219 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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

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

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.