Coagulation factor IX (F9)
The protein contains 461 amino acids for an estimated molecular weight of 51778 Da.
Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa. (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Blood coagulation
Blood coagulation, extrinsic pathway
Blood coagulation, intrinsic pathway
Cellular protein metabolic process
Endoplasmic reticulum to Golgi vesicle-mediated transport
Peptidyl-glutamic acid carboxylation
Post-translational protein modification
Proteolysis
Signal peptide processing
Zymogen activation
The reference OMIM entry for this protein is 300746
Coagulation factor ix; f9
Factor ix
Plasma thromboplastin component; ptc
DESCRIPTION
The F9 gene encodes coagulation factor IX, which circulates as an inactive zymogen until proteolytic release of its activation peptide allows it to assume the conformation of an active serine protease (Davie and Fujikawa, 1975). Its role in the blood coagulation cascade is to activate factor X (F10; 227600) through interactions with calcium, membrane phospholipids, and factor VIII (F8; 300841). Factor IX and factor X both consist of 2 polypeptide chains referred to as the L (light) and H (heavy) chains. The H chain bears a structural resemblance to the polypeptide chain of the pancreatic serine protease trypsin (PRSS1; 276000). The L chain is covalently linked to the H chain by a single disulfide bond (Fujikawa et al., 1974).CLONING
Kurachi and Davie (1982) isolated and characterized a cDNA coding for the human factor IX gene. The deduced 416-residue protein contains a 46-residue leader sequence that includes both a signal sequence and a pro-sequence for the mature protein that circulates in plasma. The amino-terminal region contains 12 glutamic acid residues that are converted to gamma-carboxyglutamic acid in the mature protein. The arginyl peptide bonds that are cleaved in the conversion of human factor IX to factor IXa by factor XIa (F11; 264900) were identified as Arg145-Ala146 and Arg180-Val181. The cleavage of these 2 internal peptide bonds results in the formation of a 35-residue activation peptide and factor IXa, a serine protease composed of a 145-residue light chain and a 236-residue heavy chain that are held together by a disulfide bond. The homology in the amino acid sequence between human and bovine factor IX was found to be 83%. Choo et al. (1982) isolated clones corresponding to the human factor IX gene from a human cDNA library. The deduced human protein showed 78% homology with the bovine protein. Jagadeeswaran et al. (1984) used the peptide sequence of bovine F9 to develop a probe to screen a human liver cDNA library. They identified a recombinant clone corresponding to 70% of the coding region of human factor IX. This F9 cDNA was used to probe restriction endonuclease digested polymorphism, as well as to verify that the haploid genome contains a single copy of the gene. Anson et al. (1984) isolated clones corresponding to the full sequence of the human factor IX gene from a human liver cDNA library. The gene encodes a mature 415-residue protein.GENE STRUCTURE
Anson et al. (1984) determined that the F9 gene contains 8 exons and spans about 34 kb. Introns accounted for 92% of the gene length. Exons conformed roughly to previously designated protein regions but the catalytic region of the protein appeared to be coded by 2 separate exons, which differed from the arrangement in other characterized serine protease genes.GENE FUNCTION
Factor IXa activates factor X as part of an intrinsic activating complex that also consists of factor VIIIa. Using several chimeric and mutant F9 proteins in coagulation assays, Wilkinson et al. (2002) determined that residues 88 to 109, excluding arg94, within the second epidermal growth factor-like domain of factor IX are important for phospholipid surface assembly of the factor X activating complex. Rusconi et al. (2002) demonstrated that protein-binding oligonucleotides (aptamers) against coagulation factor IXa are potent anticoagulants. They also showed that oligonucleotides complementary to these aptamers could act as antidotes ca ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for F9
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 300746 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed