Gene: [13q34/F7] coagulation factor VII (serum prothrombin conversion accelerator); hypoproconvertinemia (factor VII deficiency);
GEN | [1] The
gene length is 12.8 kb. Exons: 9 (1a= 110 bp, 1b= 66, 2= 161, 3= 25, 4=
139, 5= 141, 6= 110, 7= 124, 8= 1600); introns: 8 (A1=1067 bp, A2= 2574, B=
1919, C= 68, D= 1908, E= 971, F= 595, G= 816). Exons 1a and 1b, as well as
a 5'-third of exon 2 code for preproleader peptide. Exon 1b is facultative;
it is able to be processed along with flanking introns thus determining
signal peptide length polymorphism. Normal liver mRNA is enriched with a
shorter transcript, which does not contain exon 1b (coding for a 22-amino
acid insert within the prepropeptide, between -18(ala)|-17(val), in the
short 38-amino acid form). Exon 6 codes for activation (splitting into L
and H chains) domain, which the most variable one in the group of related
proteins. Almost two thirds of exon 8 represent the 3'-utl (untranslated)
region, which consists (after the stop codon tag/980 bp) poly(A) signal
[2] Five regions (r1-r5, denoted at the diagram) contain prolonged, tandem, imperfect minisatellite repeats (r1= 747 bp, r2= 871, r3= 894, r4= 222, r5= 364 bp). (r1-r4) take up 27% of the total length of introns; (r5) takes up 35.5% of the 3'-utl region length of exon 8. The monomer lengths in the satellites vary within 14-20 bp, number of copies in a tandem being 6-52. Polymorphism with respect to number of copies in r4, as well as periodicity of a higher order have been revealed (e.g., an 82 bp duplication in r3: monomers 12-15 are identical to monomers 41-44). In terms of the Stanford code, the consensus monomer (18 bp: cykcacncncjcaggdca) contains tetranucleotide |
FUN | Coagulation factor VII is a glycoprotein (vitamin K-dependent). It is synthesized in liver and secreted into the blood flow (its level being 100-500 ng/ml) as a single-stranded inactive protein (50 kD). Its convertion into an active form, VIIa, is catalyzed by other coagulation factors, IXa, Xa (both or one of them), XIIa, and thrombin (the external pathway of so called coagulation cascade). Factor VIIa, in the presence of membrane-bound thromboplastin (GEM:01p2/F3) and Ca ions, converts inactive factor X to the active form, Xa (the external and the internal cascade pathways meet at this stage). Moreover, complex VIIa+F3 activates factor X also indirectly, through the internal pathway, by participating in factor IX convertion into the active form, IXa (in the presence of Ca ions and factor XIa)." |
MOP | [1] The primary translated peptide has two forms.
They differ in the length of the N-terminal preproleader peptide (60 and 38
amino acid residues), which contain tetrapeptide Arg-Arg-Arg-Arg at the
C-end and is splitted by signal peptidase at position -1,+1 (Arg-Ala). The
mature inactive protein contains 406 amino acids. Activation (performed by
proteases such as factor Xa) consists in the splitting of inactive factor
VII at position 152-153 (Arg-Ile) with the formation of double-chained
molecule of active VIIa. [2] The light L-chain (1-152) contains 10 Glu in the N-terminal region (potential sites for vitamin K-dependent gamma-carboxylation), which form domain [3] The heavy H-chain (30 kD, 254 amino acids, the N-end: Ile-Val-Gly-Gly..) contains in the middle part a catalytic (serine protease) region, including three amino acid residues that play a key role in catalysis (His-41, Asp-90, Ser-192), as well as potential glycosilation site, Asn-170. [4] L- and H-chains form a disulfide link Cys(L/135)-Cys(H/110) analogous to that in other vitamin K-dependent proteins. The total MM of the two polypeptide chains is 45.5 kD; two carbohydrate chains (after L-,H-glycosilation) add 4.5 kD. The degree of homology with other serum proteins (prothrombin, factors IX and X, C protein) varies from 25 to 40%, that is the evidence in favor of their origin from a single ancestor gene." |
FAG | It is possible that chr 8 contains a gene regulator (repressor) of F7 activity, as follows from the data on 50% decreased factor VII activity in several mosaics for trisomy 8 (see Reference in GEM:08p23/F7R)." |
LIN | F7 gene is closely linked to F10 (GEM:13q34/F10). |
PRO | [1] Probe 7M1 is a 12
kb EcoRI insert covering 85% of F7 gene 5'-part. The clone was obtained
from the genomic library (in phage lambda Charon 4A). [2]Probe 7DC1 is a 8 kb BamHI insert covering 80% of F7 gene 3'-part. The clone was obtained from the genomic library (in phage lambda L47.1)." |
REF | HIS,PAT,FOG
"Alexander &: J Clin Invest, 30, 596-?, 1951 PRO,SEQ,MOP "Berkner &: Cold Spring Harbor Symp, 51, (Part 1), 531-541, 1986 LOC,FAG "De Grouchy J &: Hum Genet, 66, 230-233, 1984 HIS,PAT,FOG "De Vries &: Blood, 4, 247-?, 1949 HIS,PAT,FOG "Dische, Benfield: Acta Haematol, 21, 257-?, 1959 FUN,MEB "Fay, Walker: BBA, 994, 142-148, 1989 PHE,MGC,CAG "Fukushima &: Jpn J Hum Genet, 32, 91-96, 1987 LOC,FAG "Gilgenkrantz &: Ann Genet, 29, 32-35, 1986 PRO,SEQ,MOP "Hagen FS &: PNAS, 83, N8, 2412-2416, 1986 HIS,PAT,FOG "Hougie &: J Clin Invest, 36, 485-?, 1957 HIS,PAT,FOG "Koller &: Acta Haematol, 6, 1-?, 1951 HIS,PAT,FOG "Kupfer &: Blood, 15, 146-163, 1960 HIS,PAT,FOG "Mann, Hurn: Am J Physiol, 164, 105-?, 1951 HIS,PAT,FOG "Marder, Shulman: Am J Med, 37, 182-194, 1964 PHE,MGC,CAG "Mariani &: Brit J Haematol, 48, 7-14, 1981 GEN,MOP,FAG "Murray &: NAR, 16, N9, 4166, 1988 GEN,MAF "O'Hara PJ, Grant: Gene, 66, 147-158, 1988 GEN,SEQ,EXP,PRO "O'Hara PJ &: PNAS, 84, N15, 5158-5162, 1987 LOC,FAG "Ott R, Pfeiffer: Hum Hered, 34, 123-126, 1984 HIS,PAT,FOG "Owren PA: Scand J Lab Invest, 3, 168-?, 1951 LOC,FAG "Pfeiffer RA &: Hum Genet, 69, N2, 192, 1985 LOC,FAG "Pfeiffer RA &: Hum Genet, 62, 358-360, 1982 PHE,MGC,CAG "Ragni &: Am J Hematol, 10, 79-88, 1981 FUN,MEB "Rao, Rapaport: PNAS, 85, N18, 6687-6691, 1988 HIS,PAT,FOG "Stefanini M: Am J Med, 14, 64-?, 1953 PHE,MGC,CAG "Triplett &: Blood, 66, 1284-1287, 1985 HIS,PAT,FOG "Voss, Waaler: Thromb Diath Haemorrah, 3, 375-?, 1959 HIS,PAT,FOG "Yoshioka &: J Nara Med Ass, 20, N6, 462-473, 1969 |
SWI | SWISSPROT: P08709 |
KEY | hem, clot |
CLA | coding, basic |
LOC | 13 q34 |
MIM | MIM: 227500 |
EZN | ENZYME: 3.4.21.21 |
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