Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P04070 (PROC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 196. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Vitamin K-dependent protein C

EC=3.4.21.69
Alternative name(s):
Anticoagulant protein C
Autoprothrombin IIA
Blood coagulation factor XIV
Gene names
Name:PROC
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length461 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

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. Ref.2 Ref.13 Ref.16

The iron and 2-oxoglutarate dependent 3-hydroxylation of aspartate and asparagine is (R) stereospecific within EGF domains.

May be phosphorylated on a Ser or Thr in a region (AA 25-30) of the propeptide.

Involvement in disease

Thrombophilia due to protein C deficiency, autosomal dominant (THPH3) [MIM:176860]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.20 Ref.21 Ref.22 Ref.23 Ref.26 Ref.27 Ref.31 Ref.32 Ref.33 Ref.37 Ref.40 Ref.41 Ref.42

Thrombophilia due to protein C deficiency, autosomal recessive (THPH4) [MIM:612304]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

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.

Sequence caution

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

Ontologies

Keywords
   Biological processBlood coagulation
Hemostasis
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Thrombophilia
   DomainEGF-like domain
Repeat
Signal
   LigandCalcium
   Molecular functionHydrolase
Protease
Serine protease
   PTMCleavage on pair of basic residues
Disulfide bond
Gamma-carboxyglutamic acid
Glycoprotein
Hydroxylation
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processblood coagulation

Traceable author statement. Source: Reactome

cellular protein metabolic process

Traceable author statement. Source: Reactome

leukocyte migration

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 12563316. Source: UniProtKB

negative regulation of blood coagulation

Traceable author statement PubMed 15005336. Source: UniProtKB

peptidyl-glutamic acid carboxylation

Traceable author statement. Source: Reactome

post-translational protein modification

Traceable author statement. Source: Reactome

proteolysis

Non-traceable author statement PubMed 12052963. Source: UniProtKB

   Cellular_componentGolgi lumen

Traceable author statement. Source: Reactome

endoplasmic reticulum lumen

Traceable author statement. Source: Reactome

extracellular region

Non-traceable author statement PubMed 14718574. Source: UniProtKB

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

protein binding

Inferred from physical interaction PubMed 15248212. Source: IntAct

serine-type endopeptidase activity

Traceable author statement PubMed 15005336. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MMP15P515112EBI-1383018,EBI-1383043

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P04070-1)

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.
Isoform 2 (identifier: P04070-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Propeptide19 – 4224
PRO_0000028107
Chain43 – 461419Vitamin K-dependent protein C
PRO_0000028108
Chain43 – 197155Vitamin K-dependent protein C light chain
PRO_0000028109
Chain200 – 461262Vitamin K-dependent protein C heavy chain
PRO_0000028110
Peptide200 – 21112Activation peptide
PRO_0000028111

Regions

Domain43 – 8846Gla
Domain97 – 13236EGF-like 1
Domain136 – 17641EGF-like 2
Domain212 – 450239Peptidase S1

Sites

Active site2531Charge relay system
Active site2991Charge relay system
Active site4021Charge relay system
Site211 – 2122Cleavage; by thrombin

Amino acid modifications

Modified residue4814-carboxyglutamate Ref.2
Modified residue4914-carboxyglutamate Ref.2
Modified residue5614-carboxyglutamate Ref.2
Modified residue5814-carboxyglutamate Ref.2
Modified residue6114-carboxyglutamate Ref.2
Modified residue6214-carboxyglutamate Ref.2
Modified residue6714-carboxyglutamate Ref.2
Modified residue6814-carboxyglutamate Ref.2
Modified residue7114-carboxyglutamate Ref.2
Modified residue1131(3R)-3-hydroxyaspartate
Glycosylation191O-linked (GalNAc...) Ref.16
Glycosylation1391N-linked (GlcNAc...)
Glycosylation2901N-linked (GlcNAc...) Ref.2 Ref.15
Glycosylation3551N-linked (GlcNAc...) Ref.2
Glycosylation3711N-linked (GlcNAc...); partial; atypical Ref.2 Ref.13
Disulfide bond59 ↔ 64
Disulfide bond92 ↔ 111
Disulfide bond101 ↔ 106
Disulfide bond105 ↔ 120
Disulfide bond122 ↔ 131
Disulfide bond140 ↔ 151
Disulfide bond147 ↔ 160
Disulfide bond162 ↔ 175
Disulfide bond183 ↔ 319Interchain (between light and heavy chains)
Disulfide bond238 ↔ 254
Disulfide bond373 ↔ 387
Disulfide bond398 ↔ 426

Natural variations

Alternative sequence11M → MAAGRRTCSISTTRPCASAS RM in isoform 2.
VSP_054393
Alternative sequence1331R → RGEGERWMLAGGGAGLGPGW GRGTSTSCPRPPLPA in isoform 2.
VSP_054394
Natural variant141W → G in patients with PROC deficiency. Ref.30 Ref.35
VAR_006634
Natural variant321R → C in THPH3. Ref.41
VAR_006635
Natural variant381R → W in patients with PROC deficiency. Ref.29
VAR_006636
Natural variant421R → C in patients with PROC deficiency. Ref.29
VAR_006638
Natural variant421R → H in Malakoff; low anticoagulant activity. Ref.29
VAR_006637
Natural variant421R → S in THPH3; type II; Osaka-10; alters proteolytic processing so that S-42 is the N-terminus of the mature protein. Ref.9
VAR_055074
Natural variant431A → T. Ref.40
VAR_006639
Natural variant491E → D in patients with PROC deficiency. Ref.38
VAR_006640
Natural variant511R → C in patients with PROC deficiency.
VAR_006641
Natural variant571R → G in Yonago; defective anticoagulant activity. Ref.10
VAR_006643
Natural variant571R → Q in patients with PROC deficiency.
VAR_006644
Natural variant571R → W in THPH3. Ref.31 Ref.40
VAR_006642
Natural variant621E → A in THPH3; Vermont-1. Ref.23
VAR_006645
Natural variant761V → M in THPH3; Vermont-1. Ref.23
VAR_006646
Natural variant891G → C in patients with PROC deficiency. Ref.39
VAR_006647
Natural variant1081H → N in patients with PROC deficiency; La Jolla-1.
VAR_006648
Natural variant1091G → R in patients with PROC deficiency.
VAR_006649
Natural variant114 – 1185Missing in patients with PROC deficiency.
VAR_006650
Natural variant1141G → R in THPH3. Ref.40
VAR_006651
Natural variant1181F → L in patients with PROC deficiency.
VAR_006652
Natural variant119 – 1246Missing in patients with PROC deficiency; St Louis-2.
VAR_006653
Natural variant120 – 1256Missing in patients with PROC deficiency; St Louis-3.
VAR_006654
Natural variant144 – 1452NG → K in THPH4; neonatal purpura fulminans.
VAR_006655
Natural variant1451G → R in THPH3. Ref.32
VAR_006656
Natural variant1471C → Y in patients with PROC deficiency.
VAR_006657
Natural variant1491H → P in patients with PROC deficiency.
VAR_006658
Natural variant1611S → R in patients with PROC deficiency.
VAR_006659
Natural variant1781A → P in THPH4; Clamart. Ref.12
VAR_006660
Natural variant1831C → R in patients with PROC deficiency.
VAR_006661
Natural variant1891R → W in patients with PROC deficiency; La Jolla-3.
Corresponds to variant rs146922325 [ dbSNP | Ensembl ].
VAR_006662
Natural variant1941R → C in patients with PROC deficiency.
VAR_006663
Natural variant2101P → L in THPH3. Ref.32
VAR_006664
Natural variant2111R → Q in patients with PROC deficiency. Ref.30
Corresponds to variant rs28933987 [ dbSNP | Ensembl ].
VAR_006666
Natural variant2111R → W in THPH3; London-1/Tochigi. Ref.21 Ref.32
Corresponds to variant rs28933986 [ dbSNP | Ensembl ].
VAR_006665
Natural variant2201R → P in patients with PROC deficiency. Ref.39
VAR_006667
Natural variant2201R → Q in THPH3; Vermont-3. Ref.26 Ref.27 Ref.42
VAR_006669
Natural variant2201R → W in THPH3. Ref.26
VAR_006668
Natural variant2261Q → H in patients with PROC deficiency.
VAR_006670
Natural variant2431I → T in THPH3. Ref.32
VAR_006671
Natural variant2441H → Y in patients with PROC deficiency. Ref.30
VAR_006672
Natural variant2531H → Q in patients with PROC deficiency. Ref.30
VAR_006673
Natural variant2651L → F in patients with PROC deficiency.
VAR_006674
Natural variant2711R → Q in Marseille; low anticoagulant activity. Ref.29
VAR_006675
Natural variant2711R → W in patients with PROC deficiency.
VAR_006676
Natural variant2721R → C in THPH3. Ref.22
VAR_006677
Natural variant2811D → DLD in patients with PROC deficiency.
VAR_006678
Natural variant2891P → L in THPH4. Ref.25
VAR_006679
Natural variant2941S → N in Paris; low anticoagulant activity. Ref.29
VAR_006680
Natural variant2981N → D in patients with PROC deficiency.
VAR_006681
Natural variant3011A → T in patients with PROC deficiency. Ref.39
VAR_006682
Natural variant3011A → V in patients with PROC deficiency.
VAR_006683
Natural variant3091A → T in patients with PROC deficiency.
VAR_006684
Natural variant3121S → L in patients with PROC deficiency.
VAR_006685
Natural variant3121S → P in a patient with PROC deficiency; sporadic case. Ref.34
VAR_006686
Natural variant3211P → L in THPH3. Ref.30 Ref.32
VAR_006687
Natural variant3241G → R in THPH3. Ref.40
VAR_006688
Natural variant3281R → C in THPH3. Ref.30 Ref.40
VAR_006689
Natural variant3281R → H in THPH4; Muenchen. Ref.12
VAR_006690
Natural variant3341G → S in THPH4. Ref.28
VAR_006691
Natural variant3401T → M in THPH3; Vermont-2. Ref.32 Ref.42
VAR_006692
Natural variant3431G → D in patients with PROC deficiency.
VAR_006693
Natural variant3631Missing in patients with PROC deficiency.
VAR_006694
Natural variant3671V → A in THPH4; neonatal purpura fulminans. Ref.36
VAR_006695
Natural variant3691P → L in THPH3; Osaka-6. Ref.37 Ref.40
VAR_006696
Natural variant3851M → I in patients with PROC deficiency. Ref.30
VAR_006697
Natural variant3881A → T in patients with PROC deficiency. Ref.30
VAR_006698
Natural variant3881A → V in patients with PROC deficiency. Ref.30
VAR_006699
Natural variant3921G → R in THPH3; Osaka-9. Ref.37
VAR_006700
Natural variant3941R → W in patients with PROC deficiency.
VAR_006701
Natural variant4011D → N in THPH3; La Jolla-2/Osaka-7 and -8. Ref.37
VAR_006702
Natural variant4181G → D in THPH4; Hong Kong-2. Ref.24
VAR_006703
Natural variant4231G → S in THPH3. Ref.33
VAR_006704
Natural variant4261C → Y in THPH3. Ref.32
VAR_006705
Natural variant4331G → S in patients with PROC deficiency; Purmerend.
VAR_006706
Natural variant4361T → N in THPH3. Ref.41
VAR_006707
Natural variant4411Y → H in THPH3; Osaka-4. Ref.37
VAR_006708
Natural variant4441W → C in THPH3. Ref.20
VAR_006709
Natural variant4451I → M in patients with PROC deficiency.
VAR_006710

Experimental info

Sequence conflict1061C → Q in AAA60164. Ref.11
Sequence conflict4451I → IL in AAA60165. Ref.3

Secondary structure

........................................................................ 461
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 1, 1986. Version 1.
Checksum: 3531B0AE5345B39A

FASTA46152,071
        10         20         30         40         50         60 
MWQLTSLLLF VATWGISGTP APLDSVFSSS ERAHQVLRIR KRANSFLEEL RHSSLERECI 

        70         80         90        100        110        120 
EEICDFEEAK EIFQNVDDTL AFWSKHVDGD QCLVLPLEHP CASLCCGHGT CIDGIGSFSC 

       130        140        150        160        170        180 
DCRSGWEGRF CQREVSFLNC SLDNGGCTHY CLEEVGWRRC SCAPGYKLGD DLLQCHPAVK 

       190        200        210        220        230        240 
FPCGRPWKRM EKKRSHLKRD TEDQEDQVDP RLIDGKMTRR GDSPWQVVLL DSKKKLACGA 

       250        260        270        280        290        300 
VLIHPSWVLT AAHCMDESKK LLVRLGEYDL RRWEKWELDL DIKEVFVHPN YSKSTTDNDI 

       310        320        330        340        350        360 
ALLHLAQPAT LSQTIVPICL PDSGLAEREL NQAGQETLVT GWGYHSSREK EAKRNRTFVL 

       370        380        390        400        410        420 
NFIKIPVVPH NECSEVMSNM VSENMLCAGI LGDRQDACEG DSGGPMVASF HGTWFLVGLV 

       430        440        450        460 
SWGEGCGLLH NYGVYTKVSR YLDWIHGHIR DKEAPQKSWA P 

« Hide

Isoform 2 [UniParc].

Checksum: 6F21DD7C17317C88
Show »

FASTA51657,556

References

« Hide 'large scale' references
[1]"The structure and evolution of a 461 amino acid human protein C precursor and its messenger RNA, based upon the DNA sequence of cloned human liver cDNAs."
Beckmann R.J., Schmidt R.J., Santerre R.F., Plutzky J., Crabtree G.R., Long G.L.
Nucleic Acids Res. 13:5233-5247(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"The nucleotide sequence of the gene for human protein C."
Foster D.C., Yoshitake S., Davie E.W.
Proc. Natl. Acad. Sci. U.S.A. 82:4673-4677(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], HYDROXYLATION AT ASP-113, GLYCOSYLATION AT ASN-290; ASN-355 AND ASN-371, GAMMA-CARBOXYGLUTAMATION AT GLU-48; GLU-49; GLU-56; GLU-58; GLU-61; GLU-62; GLU-67; GLU-68 AND GLU-71.
[3]"Evolution and organization of the human protein C gene."
Plutzky J., Hoskins J.A., Long G.L., Crabtree G.R.
Proc. Natl. Acad. Sci. U.S.A. 83:546-550(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]SeattleSNPs variation discovery resource
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Liver.
[6]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] (ISOFORM 1).
Tissue: Colon.
[9]"Protein C Osaka 10 with aberrant propeptide processing: loss of anticoagulant activity due to an amino acid substitution in the protein C precursor."
Miyata T., Zheng Y.-Z., Sakata T., Kato H.
Thromb. Haemost. 74:1003-1008(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 42-57, VARIANT THPH3 SER-42.
Tissue: Blood.
[10]"An abnormal protein C (protein C Yonago) with an amino acid substitution of Gly for Arg-15 caused by a single base mutation of C to G in codon 57 (CGG-->GGG). Deteriorated calcium-dependent conformation of the gamma-carboxyglutamic acid domain relevant to a thrombotic tendency."
Mimuro J., Muramatsu S., Kaneko M., Yoshitake S., Iijima K., Nakamura K., Sakata Y., Matsuda M.
Int. J. Hematol. 57:9-14(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 43-64, VARIANT PROC DEFICIENCY GLY-57.
[11]"Characterization of a cDNA coding for human protein C."
Foster D.C., Davie E.W.
Proc. Natl. Acad. Sci. U.S.A. 81:4766-4770(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 106-461 (ISOFORM 1).
[12]"Homozygous type I protein C deficiency in two unrelated families exhibiting thrombophilia related to Ala136-->Pro or Arg286-->His mutations."
Long G.L., Tomczak J.A., Rainville I.R., Dreyfus M., Schramm W., Schwarz H.P.
Thromb. Haemost. 72:526-533(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 134-178 AND 267-332, VARIANTS THPH4 PRO-178 AND HIS-328.
[13]"Beta protein C is not glycosylated at asparagine 329. The rate of translation may influence the frequency of usage at asparagine-X-cysteine sites."
Miletich J.P., Broze G.J. Jr.
J. Biol. Chem. 265:11397-11404(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT ASN-371.
[14]"O-linked fucose is present in the first epidermal growth factor domain of factor XII but not protein C."
Harris R.J., Ling V.T., Spellman M.W.
J. Biol. Chem. 267:5102-5107(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: HYDROXYLATION.
[15]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-290.
Tissue: Plasma.
[16]"Human urinary glycoproteomics; attachment site specific analysis of N-and O-linked glycosylations by CID and ECD."
Halim A., Nilsson J., Ruetschi U., Hesse C., Larson G.
Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT THR-19, STRUCTURE OF CARBOHYDRATES, IDENTIFICATION BY MASS SPECTROMETRY.
[17]"Models of the serine protease domain of the human antithrombotic plasma factor activated protein C and its zymogen."
Fisher C.L., Greengard J.S., Griffin J.H.
Protein Sci. 3:588-599(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: 3D-STRUCTURE MODELING OF 175-450.
[18]"The 2.8 A crystal structure of Gla-domainless activated protein C."
Mather T., Oganessyan V., Hof P., Huber R., Foundling S., Esmon C., Bode W.
EMBO J. 15:6822-6831(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 84-461.
[19]"Protein C deficiency: a database of mutations."
Reitsma P.H., Poort S.R., Bernardi F., Gandrille S., Long G.L., Sala N., Cooper D.N.
Thromb. Haemost. 69:77-84(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON PROC VARIANTS.
[20]"Hereditary thrombophilia: identification of nonsense and missense mutations in the protein C gene."
Romeo G., Hassan H.J., Staempfli S., Roncuzzi L., Cianetti L., Leonardi A., Vicente V., Mannucci P.M., Bertina R.M., Peschle C., Cortese R.
Proc. Natl. Acad. Sci. U.S.A. 84:2829-2832(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH3 CYS-444.
[21]"Protein C London 1: recurrent mutation at Arg-169 (CGG-->TGG) in the protein C gene causing thrombosis."
Grundy C.B., Chitolie A., Talbot S., Bevan D., Kakkar V.V., Cooper D.N.
Nucleic Acids Res. 17:10513-10513(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH3 TRP-211.
[22]"The spectrum of genetic defects in a panel of 40 Dutch families with symptomatic protein C deficiency type I: heterogeneity and founder effects."
Reitsma P.H., Poort S.R., Allaart C.F., Briet E., Bertina R.M.
Blood 78:890-894(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH3 CYS-272.
[23]"Protein CVermont: symptomatic type II protein C deficiency associated with two GLA domain mutations."
Bovill E.G., Tomczak J.A., Grant B., Bhushan F., Pillemer E., Rainville I.R., Long G.L.
Blood 79:1456-1465(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THPH3 ALA-62 AND MET-76.
[24]"Protein C deficiency Hong Kong 1 and 2: hereditary protein C deficiency caused by two mutant alleles, a 5-nucleotide deletion and a missense mutation."
Sugahara Y., Miura O., Yuen P., Aoki N.
Blood 80:126-133(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH4 ASP-418.
[25]"A novel homozygous missense mutation in the protein C (PROC) gene causing recurrent venous thrombosis."
Grundy C.B., Chisholm M., Kakkar V.V., Cooper D.N.
Hum. Genet. 89:683-684(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH4 LEU-289.
[26]"Two different missense mutations at Arg 178 of the protein C (PROC) gene causing recurrent venous thrombosis."
Grundy C.B., Schulman S., Tengborn L., Kakkar V.V., Cooper D.N.
Hum. Genet. 89:685-686(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THPH3 GLN-220 AND TRP-220.
[27]"Two novel mutations responsible for hereditary type I protein C deficiency: characterization by denaturing gradient gel electrophoresis."
Gandrille S., Vidaud M., Aiach M., Alhenc-Gelas M., Fischer A.M., Gouault-Heilman M., Toulon P., Fiessinger J.-N., Goossens M.
Hum. Mutat. 1:491-500(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH3 GLN-220.
[28]"Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C."
Yamamoto K., Matsushita T., Sugiura I., Takamatsu J., Iwasaki E., Wada H., Deguchi K., Shirakawa S., Saito H.
J. Lab. Clin. Med. 119:682-689(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH4 SER-334.
[29]"Five novel mutations located in exons III and IX of the protein C gene in patients presenting with defective protein C anticoagulant activity."
Gandrille S., Alhenc-Gelas M., Gaussem P., Aillaud M.-F., Dupuy E., Juhan-Vague I., Aiach M.
Blood 82:159-168(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TRP-38; CYS-42; HIS-42; GLN-271 AND ASN-294.
[30]"Twelve novel and two recurrent mutations in 14 Austrian families with hereditary protein C deficiency."
Poort S.R., Pabinger-Fasching I., Mannhalter C., Reitsma P.H., Bertina R.M.
Blood Coagul. Fibrinolysis 4:273-280(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLY-14; GLN-211; TYR-244; GLN-253; LEU-321; CYS-328; ILE-385; THR-388 AND VAL-388.
[31]"A Gla domain mutation (Arg 15-->Trp) in the protein C (PROC) gene causing type 2 protein C deficiency and recurrent venous thrombosis."
Millar D.S., Grundy C.B., Bignell P., Moffat E.H., Martin R., Kakkar V.V., Cooper D.N.
Blood Coagul. Fibrinolysis 4:345-347(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH3 TRP-57.
[32]"Genetic mutations in ten unrelated American patients with symptomatic type 1 protein C deficiency."
Tsay W., Greengard J.S., Montgomery R.R., McPherson R.A., Fucci J.C., Koerper M.A., Coughlin J., Griffin J.H.
Blood Coagul. Fibrinolysis 4:791-796(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THPH3 ARG-145; LEU-210; TRP-211; THR-243; LEU-321; MET-340 AND TYR-426.
[33]"Symptomatic type II protein C deficiency caused by a missense mutation (Gly 381-->Ser) in the substrate-binding pocket."
Marchetti G., Patracchini P., Gemmati D., Castaman G., Rodeghiero F., Wacey A., Cooper D.N., Tuddenham E.G., Bernardi F.
Br. J. Haematol. 84:285-289(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH3 SER-423.
[34]"First de novo mutations in the protein C gene of two patients with type I deficiency: a missense mutation and a splice site deletion."
Gandrille S., Jude B., Alhenc-Gelas M., Emmerich J., Aiach M.
Blood 84:2566-2570(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PRO-312.
[35]"A homozygous deletion/insertion mutation in the protein C (PROC) gene causing neonatal Purpura fulminans: prenatal diagnosis in an at-risk pregnancy."
Millar D.S., Allgrove J., Rodeck C., Kakkar V.V., Cooper D.N.
Blood Coagul. Fibrinolysis 5:647-649(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH4 144-ASN-GLY-145 DELINS LYS.
[36]"A novel homozygous missense mutation (Val 325-->Ala) in the protein C gene causing neonatal purpura fulminans."
Witt I., Beck S., Seydewitz H.H., Tasangil C., Schenck W.
Blood Coagul. Fibrinolysis 5:651-653(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THPH4 ALA-367.
[37]"Six missense mutations associated with type I and type II protein C deficiency and implications obtained from molecular modelling."
Zheng Y.-Z., Sakata T., Matsusue T., Umeyama H., Kato H., Miyata T.
Blood Coagul. Fibrinolysis 5:687-696(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THPH3 LEU-369; ARG-392; ASN-401 AND HIS-441.
[38]"Influence of six mutations of the protein C gene on the Gla domain conformation and calcium affinity."
Gaussem P., Gandrille S., Duchemin J., Emmerich J., Alhenc-Gelas M., Aillaud M.-F., Aiach M.
Thromb. Haemost. 71:748-754(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASP-49.
[39]"Three novel mutations in the protein C (PROC) gene causing venous thrombosis."
Millar D.S., Bevan D., Chitolie A., Reynaud J., Chisholm M., Kakkar V.V., Cooper D.N.
Blood Coagul. Fibrinolysis 6:138-140(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CYS-89; PRO-220 AND THR-301.
[40]"Six different point mutations in seven Danish families with symptomatic protein C deficiency."
Lind B., Schwartz M., Thorsen S.
Thromb. Haemost. 73:186-193(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THPH3 TRP-57; ARG-114; ARG-324; CYS-328 AND LEU-369, VARIANT THR-43.
[41]"Two novel (R(-11)C; T394D) and two repeat missense mutations in the protein C gene associated with venous thrombosis in six kindreds."
Ireland H.A., Boisclair M.D., Taylor J., Thompson E., Thein S.L., Girolami A., de Caterina M., Scopacasa F., de Stefano V., Leone G., Finazzi G., Cohen H., Lane D.A.
Hum. Mutat. 7:176-179(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THPH3 CYS-32 AND ASN-436.
[42]"Type I protein C deficiency in French Canadians: evidence of a founder effect and association of specific protein C gene mutations with plasma protein C levels."
Couture P., Demers C., Morissette J., Delage R., Jomphe M., Couture L., Simard J.
Thromb. Haemost. 80:551-556(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS THPH3 GLN-220 AND MET-340.
+Additional computationally mapped references.

Web resources

Wikipedia

Protein C entry

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X02750 mRNA. Translation: CAA26528.1.
M11228 Genomic DNA. Translation: AAA60166.1.
M12712 expand/collapse EMBL AC list , 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.
CCDSCCDS2145.1.
PIRKXHU. A22331.
RefSeqNP_000303.1. NM_000312.3. [P04070-1]
XP_005263773.1. XM_005263716.2. [P04070-2]
UniGeneHs.224698.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP04070.
SMRP04070. Positions 43-451.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111608. 5 interactions.
IntActP04070. 3 interactions.
MINTMINT-8247437.
STRING9606.ENSP00000234071.

Chemistry

BindingDBP04070.
ChEMBLCHEMBL4444.
DrugBankDB00025. Antihemophilic Factor.
DB00055. Drotrecogin alfa.
DB00170. Menadione.
DB00464. Sodium Tetradecyl Sulfate.

Protein family/group databases

MEROPSS01.218.

PTM databases

PhosphoSiteP04070.
UniCarbKBP04070.

Polymorphism databases

DMDM131067.

Proteomic databases

MaxQBP04070.
PaxDbP04070.
PeptideAtlasP04070.
PRIDEP04070.

Protocols and materials databases

DNASU5624.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000234071; ENSP00000234071; ENSG00000115718.
ENST00000422777; ENSP00000409543; ENSG00000115718.
ENST00000453608; ENSP00000404030; ENSG00000115718.
GeneID5624.
KEGGhsa:5624.
UCSCuc002tok.3. human. [P04070-1]

Organism-specific databases

CTD5624.
GeneCardsGC02P128176.
HGNCHGNC:9451. PROC.
HPACAB016721.
CAB016792.
HPA005550.
MIM176860. phenotype.
612283. gene.
612304. phenotype.
neXtProtNX_P04070.
Orphanet745. Hereditary thrombophilia due to congenital protein C deficiency.
PharmGKBPA33799.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251821.
HOVERGENHBG013304.
KOK01344.
PhylomeDBP04070.
TreeFamTF327329.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
REACT_604. Hemostasis.

Gene expression databases

ArrayExpressP04070.
BgeeP04070.
CleanExHS_PROC.
GenevestigatorP04070.

Family and domain databases

Gene3D4.10.740.10. 1 hit.
InterProIPR017857. 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]
PfamPF00594. Gla. 1 hit.
PF00089. Trypsin. 1 hit.
[Graphical view]
PIRSFPIRSF001143. Factor_X. 1 hit.
PRINTSPR00722. CHYMOTRYPSIN.
PR00001. GLABLOOD.
SMARTSM00181. EGF. 1 hit.
SM00179. EGF_CA. 1 hit.
SM00069. GLA. 1 hit.
SM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
SSF57630. SSF57630. 1 hit.
PROSITEPS00010. 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]
ProtoNetSearch...

Other

EvolutionaryTraceP04070.
GeneWikiProtein_C.
GenomeRNAi5624.
NextBio21860.
PMAP-CutDBP04070.
PROP04070.
SOURCESearch...

Entry information

Entry namePROC_HUMAN
AccessionPrimary (citable) accession number: P04070
Secondary accession number(s): B4DPQ7 expand/collapse secondary AC list , Q15189, Q15190, Q16001, Q53S74, Q9UC55
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: July 9, 2014
This is version 196 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM