Apolipoprotein(a) (LPA)
The protein contains 4548 amino acids for an estimated molecular weight of 501319 Da.
Apo(a) is the main constituent of lipoprotein(a) (Lp(a)). It has serine proteinase activity and is able of autoproteolysis. Inhibits tissue-type plasminogen activator 1. Lp(a) may be a ligand for megalin/Gp 330. (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.
(right-click above to access to more options from the contextual menu)
The reference OMIM entry for this protein is 152200
Apolipoprotein(a); lpa lipoprotein(a), included; lp(a), included
Lipoprotein types--lp system lp(a) hyperlipoproteinemia, included
Sinking pre-beta-lipoprotein, included; spb, included
Lipoprotein(a) deficiency, congenital, included
Lp(a) def
Berg and Mohr (1963) discovered a new serum protein system, called Lp (for lipoprotein), by the intravenous injection of rabbits with human serum beta-lipoprotein isolated from 1 individual. The resulting antibody distinguishes 2 distinct types of human beta-lipoprotein. Berg and Mohr (1963) demonstrated regular dominant inheritance. The Lp(a) allele has a frequency of 0.19 in Norwegians. The authors concluded that this system is independent of the Ag system of Blumberg (which subsequently proved to be a variation in the APOB gene; see 107730). Berg (1967) suggested that at least 4 lipoprotein systems exist: Ag, Lp, Ld, and Lt. Schultz and Shreffler (1972) espoused a polygenic determination of Lp antigen, whereas Berg (1972) defended his monolocus hypothesis. Dahlen and Berg (1976) found that over a period of time mean fasting cholesterol and triglyceride concentrations in blood rose in Lp(a+) persons but not in Lp(a-) persons. Berg et al. (1979) found an association between phenotype Lp(a+) and coronary heart disease. Hewitt et al. (1982) confirmed the correlation between the Lp(a) antigen and the presence of a sinking pre-beta component of low density lipoprotein fraction of serum cholesterol (Breckenridge and Maguire, 1981). Studying a large Utah pedigree, Hasstedt et al. (1983) concluded that 'a dominant major gene with polygenic background' determines the quantitative plasma Lp(a) level. The Lp(a) glycoprotein is joined to apoB-100 (APOB) by one or more disulfide bridges. Utermann et al. (1987) studied the glycoprotein directly by sodium dodecyl sulfate-gel electrophoresis. Family studies were compatible with the concept that Lp(a) glycoprotein phenotypes are controlled by a series of autosomal alleles at a single locus. A highly significant association was found between electrophoretic phenotype and concentration of Lp(a) lipoprotein. This suggested that the same gene locus is involved in determining the Lp(a) glycoprotein phenotypes and the Lp(a) lipoprotein concentrations in plasma and was the first indication for structural differences underlying the quantitative genetic Lp(a)-trait. Because in other respects it resembles LDL, the atherogenicity of Lp(a) is probably due to the presence of the apolipoprotein(a) component (apoa). Kane and Havel (1989) discussed Lp(a) hyperlipoproteinemia as a separate disorder. Also see Utermann (1989). Namboodiri et al. (1977) concluded that Lp and esterase D (ESD; 133280) are closely linked; the maximum lod score was 2.32 at a recombination fraction of 0.0. Ott and Falk (1982), however, reanalyzed the data of Namboodiri et al. (1977) in connection with a theoretic consideration of the confounding effects of epistatic association on linkage. Namboodiri et al. (1977) had noted a strong association between the phenotypes a- and a+ at the Lp locus and the phenotypes 2-1 and 1-1 at the ESD locus (no 2-2 persons were found in the pedigree). The reanalysis resulted in a considerable drop in the lod score for linkage. Greger et al. (1988) excluded linkage of LPA not only with ESD but also with the retinoblastoma locus (RB; 180200), which is closely situated on chromosome 13. McLean et al. (1987) sequenced a cloned human LPA cDNA and showed striking similarities to human plasminogen (PLG; 173350). Consistent with this close similarity in nucleotide sequence and amino acid sequence is the finding of close linkage of the LPA locus and the PLG locus on 6q26-q27 in family studies (Weitkamp et al., 1988). Th ... 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
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for LPA
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 152200 was added.