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Literature summary for 3.4.21.21 extracted from

  • Persson, E.; Bolt, G.; Steenstrup, T.D.; Ezban, M.
    Recombinant coagulation factor VIIa--from molecular to clinical aspects of a versatile haemostatic agent (2010), Thromb. Res., 125, 483-489.
    View publication on PubMed

Application

Application Comment Organism
medicine the therapeutic efficacy and safety of recombinant factor VIIa in haemophilia patients with inhibitors is established in a number of clinical trials which also forms the basis for regulatory approval Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
for expression as a recombinant protein in baby hamster kidney cells cDNA comprising the entire FVII open reading frame encoding signal peptide, propeptide and the mature FVII protein is inserted into an expression plasmid containing the elements required to direct transcription of the FVII cDNA in mammalian cells. The endogenous signal peptide and propeptide of FVII are necessary for intracellular transport and processing of FVII in the producer cells but are both removed prior to secretion Homo sapiens

Protein Variants

Protein Variants Comment Organism
306X mutation studies show that the interaction between protein cofactor tissue factor and methionine-306 in the serine protease domain of FVIIa triggers the activation process and suggested some ensuing steps on the pathway to the active conformation Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ Ca2+ ions constitute an important cofactor for FVIIa and bind to a total of nine sites, seven in the N-terminal gamma-carboxyglutamic acid (Gla) domain and one each in the first EGF-like and protease domains Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Homo sapiens complex formation with the essential protein cofactor tissue factor ?
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?

Organism

Organism UniProt Comment Textmining
Homo sapiens P08709
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-

Posttranslational Modification

Posttranslational Modification Comment Organism
proteolytic modification FVII is secreted as a single-chain polypeptide and a peptide bond cleavage (after arginine 152) results in the enzymatically active form FVIIa. The two polypeptide chains are referred to as light (152 residues) and heavy (254 residues). The light chain contains an N-terminal gamma-carboxyglutamic acid (Gla) domain, in which all ten Glu residues are posttranslationally-carboxylated Homo sapiens

Purification (Commentary)

Purification (Comment) Organism
purification process starts with pH adjustment of the clarified medium, which is loaded onto an anion-exchange column. Detergent is added to the eluate in order to inactivate enveloped viruses. Subsequently, FVII and FVIIa are affinity purified on a column with a monoclonal antibody recognizing the FVII Gla domain in its functional conformation. Only FVII/FVIIa without propetide and with a functional and sufficiently gamma-carboxylated Gla domain is captured and purified. The eluate from the affinity column is subjected to two anion-exchange chromatography steps Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
liver
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Homo sapiens
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plasma
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Homo sapiens
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Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information complex formation with the essential protein cofactor tissue factor Homo sapiens ?
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?

Synonyms

Synonyms Comment Organism
factor VIIa
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Homo sapiens

Cofactor

Cofactor Comment Organism Structure
additional information complex formation with the essential protein cofactor tissue factor Homo sapiens