The reference OMIM entry for this protein is 603743

Apolipoprotein l-i; apol1
Apol
Apol-i

DESCRIPTION

The APOL1 gene encodes apolipoprotein L-I (apoL-I), a human-specific serum apolipoprotein bound to high-density lipoprotein (HDL) particles (summary by Perez-Morga et al., 2005). This apolipoprotein kills the African trypanosome Trypanosoma brucei brucei, except subspecies adapted to humans (T. b. rhodesiense, T. b. gambiense). Genovese et al. (2010) found that APOL1 carrying African population-specific mutations can lyse T. b. rhodesiense; these mutations were also associated with increased susceptibility to focal segmental glomerulosclerosis in African Americans (see FSGS4, 612551).

CLONING

Based on peptide sequences of a novel high density lipoprotein, Duchateau et al. (1997) cloned cDNAs encoding APOL. The cDNA encodes a 383-amino acid polypeptide that includes a 12-amino acid secretory signal peptide. Northern blot analysis detected a 1.3-kb APOL transcript in the pancreas but not in any other human tissues. Affinity immunosorption showed that APOL is not free in the plasma, but is associated with lipoproteins containing APOA1 (107680). APOL was found in high density lipoprotein fractions. By sequencing a number of APOL1 clones, Duchateau et al. (2001) identified a minor splice variant that includes exon 2. This variant predicts a protein that contains a 43-residue signal peptide. The more common transcript, lacking exon 2, predicts a protein with a 27-residue signal peptide. By mRNA dot blot analysis, they found APOL1 expressed in a wide variety of tissues, the only exception being fetal brain. Quantitative RT-PCR, reflecting the sum of both splice variants, revealed highest expression in lung. By genomic sequence analysis, Page et al. (2001) identified APOL1 within the APOL gene cluster. The predicted 398-amino acid protein has a calculated molecular mass of 43.9 kD. They noted that the APOL proteins share significant identity within the predicted amphipathic alpha helices. Semiquantitative RT-PCR revealed ubiquitous expression of APOL1, with highest levels in lung, spleen, prostate, and placenta, and weak expression in fetal brain and pancreas. In situ hybridization of human placenta revealed expression in all 3 tissue layers, including the basal plate, cytiotrophoblast, and chorionic plate. By Northern blot analysis, Monajemi et al. (2002) detected highest expression of a 3-kb APOL1 transcript in placenta, lung, and liver, with low expression in heart and minimal expression in pancreas. In situ hybridization of human vascular tissue showed APOL1 expression in endothelial cells and possibly in macrophages.

GENE STRUCTURE

Duchateau et al. (2001) determined that the APOL1 gene contains 7 exons and spans 14 kb. The promoter regions of the APOL1, APOL2, APOL3 (607253), and APOL4 genes have at least 1 SP1 (189906) site, a number of AP1 (165160) and AP4 (600743) sites, at least 1 GC box, multiple zinc finger-binding sites, and at least 1 sterol regulatory element-binding protein (see 184756) site. Each contains at least 2 conserved initiator sequences. The most commonly used promoter regions are TATA-less with multiple transcription initiation sites. Noting homology within intronic sequences, Monajemi et al. (2002) concluded that the APOL1, APOL2, APOL3, and APOL4 gene cluster is the result of tandem gene duplication, whereas APOL5 (607255) and APOL6 (607256) are more distantly related.

MAPPING

By genomic sequence analysis, Duchateau et al. (2001) mapped APOL1 to chromosome 22q12 ... More on the omim web site

Subscribe to this protein entry history

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 APOL1

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603743 was added.