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P04070

- PROC_HUMAN

UniProt

P04070 - PROC_HUMAN

Protein

Vitamin K-dependent protein C

Gene

PROC

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 198 (01 Oct 2014)
      Sequence version 1 (01 Nov 1986)
      Previous versions | rss
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    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.

    Catalytic activityi

    Degradation of blood coagulation factors Va and VIIIa.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei211 – 2122Cleavage; by thrombin
    Active sitei253 – 2531Charge relay system
    Active sitei299 – 2991Charge relay system
    Active sitei402 – 4021Charge relay system

    GO - Molecular functioni

    1. calcium ion binding Source: InterPro
    2. protein binding Source: IntAct
    3. serine-type endopeptidase activity Source: UniProtKB

    GO - Biological processi

    1. blood coagulation Source: Reactome
    2. cellular protein metabolic process Source: Reactome
    3. leukocyte migration Source: Reactome
    4. negative regulation of apoptotic process Source: UniProtKB
    5. negative regulation of blood coagulation Source: UniProtKB
    6. peptidyl-glutamic acid carboxylation Source: Reactome
    7. post-translational protein modification Source: Reactome
    8. proteolysis Source: UniProtKB

    Keywords - Molecular functioni

    Hydrolase, Protease, Serine protease

    Keywords - Biological processi

    Blood coagulation, Hemostasis

    Keywords - Ligandi

    Calcium

    Enzyme and pathway databases

    ReactomeiREACT_1050. Gamma-carboxylation of protein precursors.
    REACT_12051. Cell surface interactions at the vascular wall.
    REACT_1439. Common Pathway.
    REACT_1906. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
    REACT_733. Removal of aminoterminal propeptides from gamma-carboxylated proteins.

    Protein family/group databases

    MEROPSiS01.218.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Vitamin K-dependent protein C (EC:3.4.21.69)
    Alternative name(s):
    Anticoagulant protein C
    Autoprothrombin IIA
    Blood coagulation factor XIV
    Cleaved into the following 3 chains:
    Gene namesi
    Name:PROC
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:9451. PROC.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum lumen Source: Reactome
    2. extracellular region Source: UniProtKB
    3. Golgi lumen Source: Reactome
    4. plasma membrane Source: Reactome

    Pathology & Biotechi

    Involvement in diseasei

    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.14 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti32 – 321R → C in THPH3. 1 Publication
    VAR_006635
    Natural varianti42 – 421R → S in THPH3; type II; Osaka-10; alters proteolytic processing so that S-42 is the N-terminus of the mature protein. 1 Publication
    VAR_055074
    Natural varianti57 – 571R → W in THPH3. 2 Publications
    VAR_006642
    Natural varianti62 – 621E → A in THPH3; Vermont-1. 1 Publication
    VAR_006645
    Natural varianti76 – 761V → M in THPH3; Vermont-1. 1 Publication
    VAR_006646
    Natural varianti114 – 1141G → R in THPH3. 1 Publication
    VAR_006651
    Natural varianti145 – 1451G → R in THPH3. 1 Publication
    VAR_006656
    Natural varianti210 – 2101P → L in THPH3. 1 Publication
    VAR_006664
    Natural varianti211 – 2111R → W in THPH3; London-1/Tochigi. 2 Publications
    Corresponds to variant rs28933986 [ dbSNP | Ensembl ].
    VAR_006665
    Natural varianti220 – 2201R → Q in THPH3; Vermont-3. 3 Publications
    VAR_006669
    Natural varianti220 – 2201R → W in THPH3. 1 Publication
    VAR_006668
    Natural varianti243 – 2431I → T in THPH3. 1 Publication
    VAR_006671
    Natural varianti272 – 2721R → C in THPH3. 1 Publication
    VAR_006677
    Natural varianti321 – 3211P → L in THPH3. 2 Publications
    VAR_006687
    Natural varianti324 – 3241G → R in THPH3. 1 Publication
    VAR_006688
    Natural varianti328 – 3281R → C in THPH3. 2 Publications
    VAR_006689
    Natural varianti340 – 3401T → M in THPH3; Vermont-2. 2 Publications
    VAR_006692
    Natural varianti369 – 3691P → L in THPH3; Osaka-6. 2 Publications
    VAR_006696
    Natural varianti392 – 3921G → R in THPH3; Osaka-9. 1 Publication
    VAR_006700
    Natural varianti401 – 4011D → N in THPH3; La Jolla-2/Osaka-7 and -8. 1 Publication
    VAR_006702
    Natural varianti423 – 4231G → S in THPH3. 1 Publication
    VAR_006704
    Natural varianti426 – 4261C → Y in THPH3. 1 Publication
    VAR_006705
    Natural varianti436 – 4361T → N in THPH3. 1 Publication
    VAR_006707
    Natural varianti441 – 4411Y → H in THPH3; Osaka-4. 1 Publication
    VAR_006708
    Natural varianti444 – 4441W → C in THPH3. 1 Publication
    VAR_006709
    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.6 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti144 – 1452NG → K in THPH4; neonatal purpura fulminans. 1 Publication
    VAR_006655
    Natural varianti178 – 1781A → P in THPH4; Clamart. 1 Publication
    VAR_006660
    Natural varianti289 – 2891P → L in THPH4. 1 Publication
    VAR_006679
    Natural varianti328 – 3281R → H in THPH4; Muenchen. 1 Publication
    VAR_006690
    Natural varianti334 – 3341G → S in THPH4. 1 Publication
    VAR_006691
    Natural varianti367 – 3671V → A in THPH4; neonatal purpura fulminans. 1 Publication
    VAR_006695
    Natural varianti418 – 4181G → D in THPH4; Hong Kong-2. 1 Publication
    VAR_006703

    Keywords - Diseasei

    Disease mutation, Thrombophilia

    Organism-specific databases

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

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Propeptidei19 – 4224PRO_0000028107Add
    BLAST
    Chaini43 – 461419Vitamin K-dependent protein CPRO_0000028108Add
    BLAST
    Chaini43 – 197155Vitamin K-dependent protein C light chainPRO_0000028109Add
    BLAST
    Chaini200 – 461262Vitamin K-dependent protein C heavy chainPRO_0000028110Add
    BLAST
    Peptidei200 – 21112Activation peptidePRO_0000028111Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi19 – 191O-linked (GalNAc...)1 Publication
    Modified residuei48 – 4814-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Modified residuei49 – 4914-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Modified residuei56 – 5614-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Modified residuei58 – 5814-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Disulfide bondi59 ↔ 64
    Modified residuei61 – 6114-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Modified residuei62 – 6214-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Modified residuei67 – 6714-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Modified residuei68 – 6814-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Modified residuei71 – 7114-carboxyglutamate1 PublicationPROSITE-ProRule annotation
    Disulfide bondi92 ↔ 111
    Disulfide bondi101 ↔ 106
    Disulfide bondi105 ↔ 120
    Modified residuei113 – 1131(3R)-3-hydroxyaspartate2 Publications
    Disulfide bondi122 ↔ 131
    Glycosylationi139 – 1391N-linked (GlcNAc...)
    Disulfide bondi140 ↔ 151
    Disulfide bondi147 ↔ 160
    Disulfide bondi162 ↔ 175
    Disulfide bondi183 ↔ 319Interchain (between light and heavy chains)
    Disulfide bondi238 ↔ 254
    Glycosylationi290 – 2901N-linked (GlcNAc...)2 Publications
    Glycosylationi355 – 3551N-linked (GlcNAc...)1 Publication
    Glycosylationi371 – 3711N-linked (GlcNAc...); partial; atypical2 Publications
    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.

    Keywords - PTMi

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

    Proteomic databases

    MaxQBiP04070.
    PaxDbiP04070.
    PeptideAtlasiP04070.
    PRIDEiP04070.

    PTM databases

    PhosphoSiteiP04070.
    UniCarbKBiP04070.

    Miscellaneous databases

    PMAP-CutDBP04070.

    Expressioni

    Tissue specificityi

    Plasma; synthesized in the liver.

    Gene expression databases

    ArrayExpressiP04070.
    BgeeiP04070.
    CleanExiHS_PROC.
    GenevestigatoriP04070.

    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. 5 interactions.
    IntActiP04070. 3 interactions.
    MINTiMINT-8247437.
    STRINGi9606.ENSP00000234071.

    Structurei

    Secondary structure

    1
    461
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi48 – 503
    Helixi55 – 595
    Helixi66 – 738
    Beta strandi100 – 1034
    Turni104 – 1074
    Beta strandi108 – 1114
    Beta strandi120 – 1223
    Beta strandi126 – 1283
    Beta strandi137 – 1426
    Helixi143 – 1464
    Beta strandi148 – 1536
    Beta strandi155 – 1617
    Beta strandi166 – 1683
    Beta strandi175 – 1773
    Beta strandi179 – 1813
    Beta strandi226 – 2305
    Beta strandi236 – 2449
    Beta strandi247 – 2504
    Helixi252 – 2543
    Beta strandi255 – 2573
    Beta strandi262 – 2665
    Beta strandi269 – 2724
    Beta strandi278 – 28710
    Turni293 – 2964
    Beta strandi301 – 3077
    Helixi323 – 3286
    Turni329 – 3313
    Beta strandi336 – 3416
    Beta strandi357 – 3593
    Beta strandi361 – 3688
    Helixi370 – 3767
    Beta strandi385 – 3884
    Beta strandi405 – 4106
    Beta strandi413 – 42210
    Beta strandi424 – 4274
    Beta strandi433 – 4364
    Helixi438 – 4403
    Helixi442 – 4498

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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. Positions 43-451.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP04070.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini43 – 8846GlaPROSITE-ProRule annotationAdd
    BLAST
    Domaini97 – 13236EGF-like 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini136 – 17641EGF-like 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini212 – 450239Peptidase S1PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase S1 family.PROSITE-ProRule annotation
    Contains 2 EGF-like domains.PROSITE-ProRule annotation
    Contains 1 Gla (gamma-carboxy-glutamate) domain.PROSITE-ProRule annotation
    Contains 1 peptidase S1 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    EGF-like domain, Repeat, Signal

    Phylogenomic databases

    eggNOGiCOG5640.
    HOGENOMiHOG000251821.
    HOVERGENiHBG013304.
    KOiK01344.
    PhylomeDBiP04070.
    TreeFamiTF327329.

    Family and domain databases

    Gene3Di4.10.740.10. 1 hit.
    InterProiIPR017857. Coagulation_fac_subgr_Gla_dom.
    IPR000742. EG-like_dom.
    IPR001881. EGF-like_Ca-bd_dom.
    IPR013032. EGF-like_CS.
    IPR000152. EGF-type_Asp/Asn_hydroxyl_site.
    IPR018097. EGF_Ca-bd_CS.
    IPR000294. GLA_domain.
    IPR012224. Pept_S1A_FX.
    IPR001254. Peptidase_S1.
    IPR018114. Peptidase_S1_AS.
    IPR001314. Peptidase_S1A.
    IPR009003. Trypsin-like_Pept_dom.
    [Graphical view]
    PfamiPF00594. Gla. 1 hit.
    PF00089. Trypsin. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001143. Factor_X. 1 hit.
    PRINTSiPR00722. CHYMOTRYPSIN.
    PR00001. GLABLOOD.
    SMARTiSM00181. EGF. 1 hit.
    SM00179. EGF_CA. 1 hit.
    SM00069. GLA. 1 hit.
    SM00020. Tryp_SPc. 1 hit.
    [Graphical view]
    SUPFAMiSSF50494. SSF50494. 1 hit.
    SSF57630. SSF57630. 1 hit.
    PROSITEiPS00010. ASX_HYDROXYL. 1 hit.
    PS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 2 hits.
    PS50026. EGF_3. 1 hit.
    PS01187. EGF_CA. 1 hit.
    PS00011. GLA_1. 1 hit.
    PS50998. GLA_2. 1 hit.
    PS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view]

    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. Align

    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

    MWQLTSLLLF VATWGISGTP APLDSVFSSS ERAHQVLRIR KRANSFLEEL    50
    RHSSLERECI EEICDFEEAK EIFQNVDDTL AFWSKHVDGD QCLVLPLEHP 100
    CASLCCGHGT CIDGIGSFSC DCRSGWEGRF CQREVSFLNC SLDNGGCTHY 150
    CLEEVGWRRC SCAPGYKLGD DLLQCHPAVK FPCGRPWKRM EKKRSHLKRD 200
    TEDQEDQVDP RLIDGKMTRR GDSPWQVVLL DSKKKLACGA VLIHPSWVLT 250
    AAHCMDESKK LLVRLGEYDL RRWEKWELDL DIKEVFVHPN YSKSTTDNDI 300
    ALLHLAQPAT LSQTIVPICL PDSGLAEREL NQAGQETLVT GWGYHSSREK 350
    EAKRNRTFVL NFIKIPVVPH NECSEVMSNM VSENMLCAGI LGDRQDACEG 400
    DSGGPMVASF HGTWFLVGLV SWGEGCGLLH NYGVYTKVSR YLDWIHGHIR 450
    DKEAPQKSWA P 461
    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.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti106 – 1061C → Q in AAA60164. (PubMed:6589623)Curated
    Sequence conflicti445 – 4451I → IL in AAA60165. (PubMed:3511471)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti14 – 141W → G in patients with PROC deficiency. 1 Publication
    VAR_006634
    Natural varianti32 – 321R → C in THPH3. 1 Publication
    VAR_006635
    Natural varianti38 – 381R → W in patients with PROC deficiency. 1 Publication
    VAR_006636
    Natural varianti42 – 421R → C in patients with PROC deficiency. 1 Publication
    VAR_006638
    Natural varianti42 – 421R → H in Malakoff; low anticoagulant activity. 1 Publication
    VAR_006637
    Natural varianti42 – 421R → S in THPH3; type II; Osaka-10; alters proteolytic processing so that S-42 is the N-terminus of the mature protein. 1 Publication
    VAR_055074
    Natural varianti43 – 431A → T.1 Publication
    VAR_006639
    Natural varianti49 – 491E → D in patients with PROC deficiency. 1 Publication
    VAR_006640
    Natural varianti51 – 511R → C in patients with PROC deficiency.
    VAR_006641
    Natural varianti57 – 571R → G in Yonago; defective anticoagulant activity. 1 Publication
    VAR_006643
    Natural varianti57 – 571R → Q in patients with PROC deficiency.
    VAR_006644
    Natural varianti57 – 571R → W in THPH3. 2 Publications
    VAR_006642
    Natural varianti62 – 621E → A in THPH3; Vermont-1. 1 Publication
    VAR_006645
    Natural varianti76 – 761V → M in THPH3; Vermont-1. 1 Publication
    VAR_006646
    Natural varianti89 – 891G → C in patients with PROC deficiency. 1 Publication
    VAR_006647
    Natural varianti108 – 1081H → N in patients with PROC deficiency; La Jolla-1.
    VAR_006648
    Natural varianti109 – 1091G → R in patients with PROC deficiency.
    VAR_006649
    Natural varianti114 – 1185Missing in patients with PROC deficiency.
    VAR_006650
    Natural varianti114 – 1141G → R in THPH3. 1 Publication
    VAR_006651
    Natural varianti118 – 1181F → L in patients with PROC deficiency.
    VAR_006652
    Natural varianti119 – 1246Missing in patients with PROC deficiency; St Louis-2.
    VAR_006653
    Natural varianti120 – 1256Missing in patients with PROC deficiency; St Louis-3.
    VAR_006654
    Natural varianti144 – 1452NG → K in THPH4; neonatal purpura fulminans. 1 Publication
    VAR_006655
    Natural varianti145 – 1451G → R in THPH3. 1 Publication
    VAR_006656
    Natural varianti147 – 1471C → Y in patients with PROC deficiency.
    VAR_006657
    Natural varianti149 – 1491H → P in patients with PROC deficiency.
    VAR_006658
    Natural varianti161 – 1611S → R in patients with PROC deficiency.
    VAR_006659
    Natural varianti178 – 1781A → P in THPH4; Clamart. 1 Publication
    VAR_006660
    Natural varianti183 – 1831C → R in patients with PROC deficiency.
    VAR_006661
    Natural varianti189 – 1891R → W in patients with PROC deficiency; La Jolla-3.
    Corresponds to variant rs146922325 [ dbSNP | Ensembl ].
    VAR_006662
    Natural varianti194 – 1941R → C in patients with PROC deficiency.
    VAR_006663
    Natural varianti210 – 2101P → L in THPH3. 1 Publication
    VAR_006664
    Natural varianti211 – 2111R → Q in patients with PROC deficiency. 1 Publication
    Corresponds to variant rs28933987 [ dbSNP | Ensembl ].
    VAR_006666
    Natural varianti211 – 2111R → W in THPH3; London-1/Tochigi. 2 Publications
    Corresponds to variant rs28933986 [ dbSNP | Ensembl ].
    VAR_006665
    Natural varianti220 – 2201R → P in patients with PROC deficiency. 1 Publication
    VAR_006667
    Natural varianti220 – 2201R → Q in THPH3; Vermont-3. 3 Publications
    VAR_006669
    Natural varianti220 – 2201R → W in THPH3. 1 Publication
    VAR_006668
    Natural varianti226 – 2261Q → H in patients with PROC deficiency.
    VAR_006670
    Natural varianti243 – 2431I → T in THPH3. 1 Publication
    VAR_006671
    Natural varianti244 – 2441H → Y in patients with PROC deficiency. 1 Publication
    VAR_006672
    Natural varianti253 – 2531H → Q in patients with PROC deficiency. 1 Publication
    VAR_006673
    Natural varianti265 – 2651L → F in patients with PROC deficiency.
    VAR_006674
    Natural varianti271 – 2711R → Q in Marseille; low anticoagulant activity. 1 Publication
    VAR_006675
    Natural varianti271 – 2711R → W in patients with PROC deficiency.
    VAR_006676
    Natural varianti272 – 2721R → C in THPH3. 1 Publication
    VAR_006677
    Natural varianti281 – 2811D → DLD in patients with PROC deficiency.
    VAR_006678
    Natural varianti289 – 2891P → L in THPH4. 1 Publication
    VAR_006679
    Natural varianti294 – 2941S → N in Paris; low anticoagulant activity. 1 Publication
    VAR_006680
    Natural varianti298 – 2981N → D in patients with PROC deficiency.
    VAR_006681
    Natural varianti301 – 3011A → T in patients with PROC deficiency. 1 Publication
    VAR_006682
    Natural varianti301 – 3011A → V in patients with PROC deficiency.
    VAR_006683
    Natural varianti309 – 3091A → T in patients with PROC deficiency.
    VAR_006684
    Natural varianti312 – 3121S → L in patients with PROC deficiency.
    VAR_006685
    Natural varianti312 – 3121S → P in a patient with PROC deficiency; sporadic case. 1 Publication
    VAR_006686
    Natural varianti321 – 3211P → L in THPH3. 2 Publications
    VAR_006687
    Natural varianti324 – 3241G → R in THPH3. 1 Publication
    VAR_006688
    Natural varianti328 – 3281R → C in THPH3. 2 Publications
    VAR_006689
    Natural varianti328 – 3281R → H in THPH4; Muenchen. 1 Publication
    VAR_006690
    Natural varianti334 – 3341G → S in THPH4. 1 Publication
    VAR_006691
    Natural varianti340 – 3401T → M in THPH3; Vermont-2. 2 Publications
    VAR_006692
    Natural varianti343 – 3431G → D in patients with PROC deficiency.
    VAR_006693
    Natural varianti363 – 3631Missing in patients with PROC deficiency.
    VAR_006694
    Natural varianti367 – 3671V → A in THPH4; neonatal purpura fulminans. 1 Publication
    VAR_006695
    Natural varianti369 – 3691P → L in THPH3; Osaka-6. 2 Publications
    VAR_006696
    Natural varianti385 – 3851M → I in patients with PROC deficiency. 1 Publication
    VAR_006697
    Natural varianti388 – 3881A → T in patients with PROC deficiency. 1 Publication
    VAR_006698
    Natural varianti388 – 3881A → V in patients with PROC deficiency. 1 Publication
    VAR_006699
    Natural varianti392 – 3921G → R in THPH3; Osaka-9. 1 Publication
    VAR_006700
    Natural varianti394 – 3941R → W in patients with PROC deficiency.
    VAR_006701
    Natural varianti401 – 4011D → N in THPH3; La Jolla-2/Osaka-7 and -8. 1 Publication
    VAR_006702
    Natural varianti418 – 4181G → D in THPH4; Hong Kong-2. 1 Publication
    VAR_006703
    Natural varianti423 – 4231G → S in THPH3. 1 Publication
    VAR_006704
    Natural varianti426 – 4261C → Y in THPH3. 1 Publication
    VAR_006705
    Natural varianti433 – 4331G → S in patients with PROC deficiency; Purmerend.
    VAR_006706
    Natural varianti436 – 4361T → N in THPH3. 1 Publication
    VAR_006707
    Natural varianti441 – 4411Y → H in THPH3; Osaka-4. 1 Publication
    VAR_006708
    Natural varianti444 – 4441W → C in THPH3. 1 Publication
    VAR_006709
    Natural varianti445 – 4451I → M in patients with PROC deficiency.
    VAR_006710

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 11M → MAAGRRTCSISTTRPCASAS RM in isoform 2. 1 PublicationVSP_054393
    Alternative sequencei133 – 1331R → RGEGERWMLAGGGAGLGPGW GRGTSTSCPRPPLPA in isoform 2. 1 PublicationVSP_054394

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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]
    XP_005263773.1. XM_005263716.2. [P04070-2]
    UniGeneiHs.224698.

    Genome annotation databases

    EnsembliENST00000234071; ENSP00000234071; ENSG00000115718. [P04070-1]
    GeneIDi5624.
    KEGGihsa:5624.
    UCSCiuc002tok.3. human. [P04070-1]

    Polymorphism databases

    DMDMi131067.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    Protein C entry

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.
    CCDSi CCDS2145.1. [P04070-1 ]
    PIRi A22331. KXHU.
    RefSeqi NP_000303.1. NM_000312.3. [P04070-1 ]
    XP_005263773.1. XM_005263716.2. [P04070-2 ]
    UniGenei Hs.224698.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1AUT X-ray 2.80 C 212-461 [» ]
    L 84-197 [» ]
    1LQV X-ray 1.60 C/D 43-75 [» ]
    1PCU model - A 175-450 [» ]
    2PCT model - A 175-450 [» ]
    3F6U X-ray 2.80 H 212-451 [» ]
    L 91-188 [» ]
    3JTC X-ray 1.60 C/D 43-75 [» ]
    4DT7 X-ray 1.90 E/F 204-223 [» ]
    ProteinModelPortali P04070.
    SMRi P04070. Positions 43-451.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111608. 5 interactions.
    IntActi P04070. 3 interactions.
    MINTi MINT-8247437.
    STRINGi 9606.ENSP00000234071.

    Chemistry

    BindingDBi P04070.
    ChEMBLi CHEMBL4444.
    DrugBanki DB00025. Antihemophilic Factor.
    DB00055. Drotrecogin alfa.
    DB00170. Menadione.
    DB00464. Sodium Tetradecyl Sulfate.

    Protein family/group databases

    MEROPSi S01.218.

    PTM databases

    PhosphoSitei P04070.
    UniCarbKBi P04070.

    Polymorphism databases

    DMDMi 131067.

    Proteomic databases

    MaxQBi P04070.
    PaxDbi P04070.
    PeptideAtlasi P04070.
    PRIDEi P04070.

    Protocols and materials databases

    DNASUi 5624.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000234071 ; ENSP00000234071 ; ENSG00000115718 . [P04070-1 ]
    GeneIDi 5624.
    KEGGi hsa:5624.
    UCSCi uc002tok.3. human. [P04070-1 ]

    Organism-specific databases

    CTDi 5624.
    GeneCardsi GC02P128176.
    HGNCi HGNC:9451. PROC.
    HPAi CAB016721.
    CAB016792.
    HPA005550.
    MIMi 176860. phenotype.
    612283. gene.
    612304. phenotype.
    neXtProti NX_P04070.
    Orphaneti 745. Hereditary thrombophilia due to congenital protein C deficiency.
    PharmGKBi PA33799.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5640.
    HOGENOMi HOG000251821.
    HOVERGENi HBG013304.
    KOi K01344.
    PhylomeDBi P04070.
    TreeFami TF327329.

    Enzyme and pathway databases

    Reactomei REACT_1050. Gamma-carboxylation of protein precursors.
    REACT_12051. Cell surface interactions at the vascular wall.
    REACT_1439. Common Pathway.
    REACT_1906. Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus.
    REACT_733. Removal of aminoterminal propeptides from gamma-carboxylated proteins.

    Miscellaneous databases

    EvolutionaryTracei P04070.
    GeneWikii Protein_C.
    GenomeRNAii 5624.
    NextBioi 21860.
    PMAP-CutDB P04070.
    PROi P04070.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P04070.
    Bgeei P04070.
    CleanExi HS_PROC.
    Genevestigatori P04070.

    Family and domain databases

    Gene3Di 4.10.740.10. 1 hit.
    InterProi IPR017857. 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 ]
    Pfami PF00594. Gla. 1 hit.
    PF00089. Trypsin. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001143. Factor_X. 1 hit.
    PRINTSi PR00722. CHYMOTRYPSIN.
    PR00001. GLABLOOD.
    SMARTi SM00181. EGF. 1 hit.
    SM00179. EGF_CA. 1 hit.
    SM00069. GLA. 1 hit.
    SM00020. Tryp_SPc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF50494. SSF50494. 1 hit.
    SSF57630. SSF57630. 1 hit.
    PROSITEi PS00010. ASX_HYDROXYL. 1 hit.
    PS00022. EGF_1. 1 hit.
    PS01186. EGF_2. 2 hits.
    PS50026. EGF_3. 1 hit.
    PS01187. EGF_CA. 1 hit.
    PS00011. GLA_1. 1 hit.
    PS50998. GLA_2. 1 hit.
    PS50240. TRYPSIN_DOM. 1 hit.
    PS00134. TRYPSIN_HIS. 1 hit.
    PS00135. TRYPSIN_SER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. 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.
      , 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.
      , 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. 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.

    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: October 1, 2014
    This is version 198 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

    External Data

    Dasty 3