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UniProtKB - P04070 (PROC_HUMAN)

Protein

Vitamin K-dependent protein C

Gene

PROC

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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.

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
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Protease, Serine protease
Biological processBlood coagulation, Hemostasis
LigandCalcium

Enzyme and pathway databases

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
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
SABIO-RKiP04070

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:
Vitamin K-dependent protein C light chain
Vitamin K-dependent protein C heavy chain
Activation peptide
Gene namesi
Name:PROC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000115718.17
HGNCiHGNC:9451 PROC
MIMi612283 gene
neXtProtiNX_P04070

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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 dbSNP:rs757583846EnsemblClinVar.1
Natural variantiVAR_00664562E → A in THPH3; Vermont-1. 1 PublicationCorresponds to variant dbSNP:rs121918148EnsemblClinVar.1
Natural variantiVAR_00664676V → M in THPH3; Vermont-1. 1 PublicationCorresponds to variant dbSNP:rs121918149EnsemblClinVar.1
Natural variantiVAR_006651114G → R in THPH3. 1 PublicationCorresponds to variant dbSNP:rs374476971EnsemblClinVar.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 dbSNP:rs121918145EnsemblClinVar.1
Natural variantiVAR_006665211R → W in THPH3; London-1/Tochigi. 2 PublicationsCorresponds to variant dbSNP:rs121918143EnsemblClinVar.1
Natural variantiVAR_006669220R → Q in THPH3; Vermont-3. 3 PublicationsCorresponds to variant dbSNP:rs121918153EnsemblClinVar.1
Natural variantiVAR_006668220R → W in THPH3. 2 PublicationsCorresponds to variant dbSNP:rs121918152EnsemblClinVar.1
Natural variantiVAR_006671243I → T in THPH3. 1 PublicationCorresponds to variant dbSNP:rs774584131Ensembl.1
Natural variantiVAR_006677272R → C in THPH3. 1 PublicationCorresponds to variant dbSNP:rs121918154EnsemblClinVar.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 dbSNP:rs199469471Ensembl.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 dbSNP:rs201907715Ensembl.1
Natural variantiVAR_006692340T → M in THPH3; Vermont-2. 2 PublicationsCorresponds to variant dbSNP:rs766261022Ensembl.1
Natural variantiVAR_006696369P → L in THPH3; Osaka-6. 2 Publications1
Natural variantiVAR_006700392G → R in THPH3; Osaka-9. 1 PublicationCorresponds to variant dbSNP:rs756467027EnsemblClinVar.1
Natural variantiVAR_006702401D → N in THPH3; La Jolla-2/Osaka-7 and -8. 1 PublicationCorresponds to variant dbSNP:rs142742242EnsemblClinVar.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 dbSNP:rs199469472Ensembl.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 dbSNP:rs753436021Ensembl.1
Natural variantiVAR_006709444W → C in THPH3. 1 PublicationCorresponds to variant dbSNP:rs121918142EnsemblClinVar.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 dbSNP:rs121918151EnsemblClinVar.1
Natural variantiVAR_006690328R → H in THPH4; Muenchen. 1 Publication1
Natural variantiVAR_006691334G → S in THPH4. 1 PublicationCorresponds to variant dbSNP:rs121918150EnsemblClinVar.1
Natural variantiVAR_006695367V → A in THPH4; neonatal purpura fulminans. 1 PublicationCorresponds to variant dbSNP:rs767730328Ensembl.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
Orphaneti64738 NON RARE IN EUROPE: Non rare thrombophilia
745 Severe 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...) threonine1 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...) asparagine1
Disulfide bondi140 ↔ 151
Disulfide bondi147 ↔ 160
Disulfide bondi162 ↔ 175
Disulfide bondi183 ↔ 319Interchain (between light and heavy chains)
Disulfide bondi238 ↔ 254
Glycosylationi290N-linked (GlcNAc...) asparagine2 Publications1
Modified residuei347Phosphoserine; by FAM20C1 Publication1
Glycosylationi355N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi371N-linked (GlcNAc...) asparagine; 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
ProteomicsDBi51646

PTM databases

GlyConnecti620
iPTMnetiP04070
PhosphoSitePlusiP04070
UniCarbKBiP04070

Miscellaneous databases

PMAP-CutDBiP04070

Expressioni

Tissue specificityi

Plasma; synthesized in the liver.

Gene expression databases

BgeeiENSG00000115718 Expressed in 94 organ(s), highest expression level in right lobe of liver
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
ELMiP04070
IntActiP04070, 4 interactors
MINTiP04070
STRINGi9606.ENSP00000234071

Chemistry databases

BindingDBiP04070

Structurei

Secondary structure

1461
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
InterProiView protein in InterPro
IPR017857 Coagulation_fac-like_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
IPR035972 GLA-like_dom_SF
IPR000294 GLA_domain
IPR012224 Pept_S1A_FX
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PF00594 Gla, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001143 Factor_X, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
PR00001 GLABLOOD
SMARTiView protein in SMART
SM00181 EGF, 2 hits
SM00179 EGF_CA, 1 hit
SM00069 GLA, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57630 SSF57630, 1 hit
PROSITEiView protein in 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

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

This entry has 2 described isoforms and 6 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7END6E7END6_HUMAN
Vitamin K-dependent protein C
PROC
495Annotation score:
E7ENR9E7ENR9_HUMAN
Vitamin K-dependent protein C
PROC
175Annotation score:
E7EVH6E7EVH6_HUMAN
Vitamin K-dependent protein C
PROC
126Annotation score:
E7EU72E7EU72_HUMAN
Vitamin K-dependent protein C
PROC
116Annotation score:
H7BYX9H7BYX9_HUMAN
Vitamin K-dependent protein C
PROC
236Annotation score:
F2Z2A0F2Z2A0_HUMAN
Vitamin K-dependent protein C
PROC
52Annotation score:

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 dbSNP:rs769900251Ensembl.1
Natural variantiVAR_00663842R → C in patients with PROC deficiency. 1 PublicationCorresponds to variant dbSNP:rs774572099Ensembl.1
Natural variantiVAR_00663742R → H in Malakoff; low anticoagulant activity. 1 PublicationCorresponds to variant dbSNP:rs369504169EnsemblClinVar.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 → T1 PublicationCorresponds to variant dbSNP:rs767626189Ensembl.1
Natural variantiVAR_00664049E → D in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_00664151R → C in patients with PROC deficiency. Corresponds to variant dbSNP:rs764546127Ensembl.1
Natural variantiVAR_00664357R → G in Yonago; defective anticoagulant activity. 1 Publication1
Natural variantiVAR_00664457R → Q in patients with PROC deficiency. Corresponds to variant dbSNP:rs574949343Ensembl.1
Natural variantiVAR_00664257R → W in THPH3. 2 PublicationsCorresponds to variant dbSNP:rs757583846EnsemblClinVar.1
Natural variantiVAR_00664562E → A in THPH3; Vermont-1. 1 PublicationCorresponds to variant dbSNP:rs121918148EnsemblClinVar.1
Natural variantiVAR_07429670K → E in patients with PROC deficiency. 1 PublicationCorresponds to variant dbSNP:rs199469481Ensembl.1
Natural variantiVAR_00664676V → M in THPH3; Vermont-1. 1 PublicationCorresponds to variant dbSNP:rs121918149EnsemblClinVar.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 dbSNP:rs199469479Ensembl.1
Natural variantiVAR_006648108H → N in patients with PROC deficiency; La Jolla-1. Corresponds to variant dbSNP:rs200234655EnsemblClinVar.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 dbSNP:rs374476971EnsemblClinVar.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 dbSNP:rs121918159EnsemblClinVar.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 dbSNP:rs199469474Ensembl.1
Natural variantiVAR_006660178A → P in THPH4; Clamart. 1 Publication1
Natural variantiVAR_074300181F → V in patients with PROC deficiency. 1 PublicationCorresponds to variant dbSNP:rs199469470Ensembl.1
Natural variantiVAR_006661183C → R in patients with PROC deficiency. Corresponds to variant dbSNP:rs748920874Ensembl.1
Natural variantiVAR_006662189R → W in patients with PROC deficiency; La Jolla-3. 1 PublicationCorresponds to variant dbSNP:rs146922325EnsemblClinVar.1
Natural variantiVAR_006663194R → C in patients with PROC deficiency. Corresponds to variant dbSNP:rs371071104EnsemblClinVar.1
Natural variantiVAR_006664210P → L in THPH3. 1 PublicationCorresponds to variant dbSNP:rs121918145EnsemblClinVar.1
Natural variantiVAR_006666211R → Q in patients with PROC deficiency. 2 PublicationsCorresponds to variant dbSNP:rs199469476Ensembl.1
Natural variantiVAR_006665211R → W in THPH3; London-1/Tochigi. 2 PublicationsCorresponds to variant dbSNP:rs121918143EnsemblClinVar.1
Natural variantiVAR_006667220R → P in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006669220R → Q in THPH3; Vermont-3. 3 PublicationsCorresponds to variant dbSNP:rs121918153EnsemblClinVar.1
Natural variantiVAR_006668220R → W in THPH3. 2 PublicationsCorresponds to variant dbSNP:rs121918152EnsemblClinVar.1
Natural variantiVAR_074301223S → R in patients with PROC deficiency. 1 PublicationCorresponds to variant dbSNP:rs199469483Ensembl.1
Natural variantiVAR_006670226Q → H in patients with PROC deficiency. Corresponds to variant dbSNP:rs121918155EnsemblClinVar.1
Natural variantiVAR_074302240A → G in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006671243I → T in THPH3. 1 PublicationCorresponds to variant dbSNP:rs774584131Ensembl.1
Natural variantiVAR_006672244H → Y in patients with PROC deficiency. 1 PublicationCorresponds to variant dbSNP:rs759557871Ensembl.1
Natural variantiVAR_006673253H → Q in patients with PROC deficiency. 1 Publication1
Natural variantiVAR_006674265L → F in patients with PROC deficiency. Corresponds to variant dbSNP:rs121918156EnsemblClinVar.1
Natural variantiVAR_006675271R → Q in Marseille; low anticoagulant activity. 1 Publication1
Natural variantiVAR_006676271R → W in patients with PROC deficiency. Corresponds to variant dbSNP:rs767112991EnsemblClinVar.1
Natural variantiVAR_006677272R → C in THPH3. 1 PublicationCorresponds to variant dbSNP:rs121918154EnsemblClinVar.1
Natural variantiVAR_006678281D → DLD in patients with PROC deficiency. 1
Natural variantiVAR_006679289P → L in THPH4. 1 PublicationCorresponds to variant dbSNP:rs121918151EnsemblClinVar.1
Natural variantiVAR_006680294S → N in Paris; low anticoagulant activity. 1 PublicationCorresponds to variant dbSNP:rs200721675Ensembl.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 dbSNP:rs199469471Ensembl.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 dbSNP:rs121918144EnsemblClinVar.1
Natural variantiVAR_006684309A → T in patients with PROC deficiency. Corresponds to variant dbSNP:rs121918146EnsemblClinVar.1
Natural variantiVAR_006685312S → L in patients with PROC deficiency. 1 PublicationCorresponds to variant dbSNP:rs121918160EnsemblClinVar.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 dbSNP:rs199469480Ensembl.1
Natural variantiVAR_006689328R → C in THPH3. 2 PublicationsCorresponds to variant dbSNP:rs201907715Ensembl.1
Natural variantiVAR_006690328R → H in THPH4; Muenchen. 1 Publication1
Natural variantiVAR_006691334G → S in THPH4. 1 PublicationCorresponds to variant dbSNP:rs121918150EnsemblClinVar.1
Natural variantiVAR_006692340T → M in THPH3; Vermont-2. 2 PublicationsCorresponds to variant dbSNP:rs766261022Ensembl.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 dbSNP:rs767730328Ensembl.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 PublicationCorresponds to variant dbSNP:rs769277939Ensembl.1
Natural variantiVAR_006700392G → R in THPH3; Osaka-9. 1 PublicationCorresponds to variant dbSNP:rs756467027EnsemblClinVar.1
Natural variantiVAR_006701394R → W in patients with PROC deficiency. Corresponds to variant dbSNP:rs759316085Ensembl.1
Natural variantiVAR_006702401D → N in THPH3; La Jolla-2/Osaka-7 and -8. 1 PublicationCorresponds to variant dbSNP:rs142742242EnsemblClinVar.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 dbSNP:rs199469472Ensembl.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 dbSNP:rs753436021Ensembl.1
Natural variantiVAR_006709444W → C in THPH3. 1 PublicationCorresponds to variant dbSNP:rs121918142EnsemblClinVar.1
Natural variantiVAR_006710445I → M in patients with PROC deficiency. Corresponds to variant dbSNP:rs121918157EnsemblClinVar.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

Similar proteinsi

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
ELMiP04070
IntActiP04070, 4 interactors
MINTiP04070
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

GlyConnecti620
iPTMnetiP04070
PhosphoSitePlusiP04070
UniCarbKBiP04070

Polymorphism and mutation databases

BioMutaiPROC
DMDMi131067

Proteomic databases

MaxQBiP04070
PaxDbiP04070
PeptideAtlasiP04070
PRIDEiP04070
ProteomicsDBi51646

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
EuPathDBiHostDB:ENSG00000115718.17
GeneCardsiPROC
HGNCiHGNC:9451 PROC
HPAiCAB016721
CAB016792
HPA005550
MalaCardsiPROC
MIMi176860 phenotype
612283 gene
612304 phenotype
neXtProtiNX_P04070
OpenTargetsiENSG00000115718
Orphaneti64738 NON RARE IN EUROPE: Non rare thrombophilia
745 Severe 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

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
R-HSA-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-8957275 Post-translational protein phosphorylation
SABIO-RKiP04070

Miscellaneous databases

ChiTaRSiPROC human
EvolutionaryTraceiP04070
GeneWikiiProtein_C
GenomeRNAii5624
PMAP-CutDBiP04070
PROiPR:P04070
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115718 Expressed in 94 organ(s), highest expression level in right lobe of liver
CleanExiHS_PROC
ExpressionAtlasiP04070 baseline and differential
GenevisibleiP04070 HS

Family and domain databases

CDDicd00190 Tryp_SPc, 1 hit
Gene3Di4.10.740.10, 1 hit
InterProiView protein in InterPro
IPR017857 Coagulation_fac-like_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
IPR035972 GLA-like_dom_SF
IPR000294 GLA_domain
IPR012224 Pept_S1A_FX
IPR009003 Peptidase_S1_PA
IPR001314 Peptidase_S1A
IPR001254 Trypsin_dom
IPR018114 TRYPSIN_HIS
IPR033116 TRYPSIN_SER
PfamiView protein in Pfam
PF00008 EGF, 1 hit
PF00594 Gla, 1 hit
PF00089 Trypsin, 1 hit
PIRSFiPIRSF001143 Factor_X, 1 hit
PRINTSiPR00722 CHYMOTRYPSIN
PR00001 GLABLOOD
SMARTiView protein in SMART
SM00181 EGF, 2 hits
SM00179 EGF_CA, 1 hit
SM00069 GLA, 1 hit
SM00020 Tryp_SPc, 1 hit
SUPFAMiSSF50494 SSF50494, 1 hit
SSF57630 SSF57630, 1 hit
PROSITEiView protein in 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
ProtoNetiSearch...

Entry informationi

Entry nameiPROC_HUMAN
AccessioniPrimary (citable) accession number: P04070
Secondary accession number(s): B4DPQ7
, Q15189, Q15190, Q16001, Q53S74, Q9UC55
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: November 7, 2018
This is version 237 of the entry and version 1 of the sequence. See 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

Keywords - Technical termi

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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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