Gene: [0Xq271/F9] coagulation factor IX (plasma thromboplastic component); hemophilia B (Christmas disease; coagulation factor IX deficiency);

FUN

 [1] Converts coagulation factor X to Xa.
[2] Systematic name: not known.
[3] Catalyzes hydrolysis one arg-|-ile bond in factor X to form factor Xa."

MOP

 The molecular product is a serum glycoprotein (MM 56 kD). It is synthesized by hepatocytes as a single-strand polypeptide. N-terminal region of the primary translation product contains 46 amino acids and two domains: the signal peptide (28 amino acids), which is necessary for transferring the protein through membrane, and the (Thr...Arg) propeptide (18 amino acids), which serves for post-translational modification and (PTM) and the consequent secretion of inactive F(IX) into the blood flow. The PTM occurs after the splitting of the signal peptide and includes the vitamin K-dependent gamma-carboxylation of the first 12 Glu in the catalytical peptide, beta-carboxylation of Asp in position <64>, and propeptide splitting. The mature enzyme consists of two peptide chains, light and heavy (L and H) ones, which arises from the splitting of the inactive catalytic polypeptide."

MUT

 The mutant forms include F(IX)-Chapel Hill (substitution of Arg for Hys at position 145 (Noyes-1983), that prevents the peptide splitting and hence the enzyme activation), F(IX)-Alabama (substitution of Asp for Gly at position 47 (Davis-1984)), 'splicing' mutations (see Rees-1985), large deletions (see Giannelli-1983 and Hassan-1985), and F(IX)-Campbridge (substitution of Arg (codon ag) for Ser (codons ag or ag) at position <-1>, see Diuguid-1986 and a similar example in Bentley-1986: substitution of Arg for Glu in position <-4>). As for the latter case, the mutation does not prevent the signal peptide splitting at position <-19,-18> but makes it impossible to split the propeptide from the catalytic one, F(IX), at position <-1,+1>, thus disturbing the F(IX) processing. As a result, the F(IX)-Campbridge is 18 amino acids longer than the normal protein and has only seven of 12 gamma-carboxylated Asp."

REF

 MUT "Bentley AK &: Cell, 45, (May), 343-348, 1986
LOC "Boyd &: Ann Hum Genet, 48, 145-152, 1984
LOC,POL "Camerino &: PNAS, 81, 498-502, 1984
CLO,SEQ "Choo KH &: Nature, 299, (9 Sep), 178-180, 1982
POL,PND "Connor &: J Med Genet, 22, 441-446, 1985
MUT "Davis &: Blood, 64, (Suppl), 262, 1984
MUT,POG "de la Salle C &: Clin Genet, 38, N6, 434-440, 1990
MUT "Diuguid &: PNAS, 83, N16, 5803-5807, 1986
POL,PND "Giannelli F &: Lancet, 1, N8371, 239-241, 1984
MUT "Giannelli F &: Nature, 303, (12 May), 181-182, 1983
MUT "Hassan &: Blood, 66, N3, 728-730, 1985
POL,PND "Hay CW &: Blood, 67, N5, 1508-1511, 1986
SEQ,POL "Jagadeeswaran P &: Somat Cell Mol Genet, 10, N5, 465-473, 1984
SEQ,PEP "Kurachi K, Davie: PNAS, 79, 6461-6464, 1982
POL,PND "Lillicrap &: Brit J Haematol, 62, 557-565, 1986
POL,PND "Lubahn DB &: AJHG, 40, 527-536, 1987
POL,PND "Mulligan L &: Hum Genet, 75, 381-383, 1987
EXP,PND "Nisen &: New Engl J Med, 315, N18, 1139-1142, 1986
MUT "Noyes CM &: PNAS, 80, 4200-4202, 1983
LOC "Purrello M &: EMBO J, 4, 725-729, 1985
LOC "Quirk S &: CCG, 39, 121-124, 1985
MOP,EXP,EVO "Rees DJ &: EMBO J, 7, N7, 2053-2061, 1988
MUT "Rees DJ &: Nature, 316, 643-645, 1985
EVO,MAM,GEN,MOP,SEQ "Sarkar &: Genomics, 6, N1, 133-143, 1990
LOC "Schwartz &: Hum Genet, 76, 64-67, 1987
ENG,EXP "Simpson PJ &: Gene, 61, 373-383, 1987

KEY

 hem, clot

CLA

 coding, basic

LOC

 0X q27.1

MIM

 MIM: 306900

EZN

 ENZYME: 3.4.21.22

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