Apolipoprotein C-I is a protein component of lipoproteins that in humans is encoded by the APOC1gene.[5][6]
Function
The protein encoded by this gene is a member of the apolipoprotein C family. This gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. Alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined.[7]
Apolipoprotein C-I has a length of 57 amino acids normally found in plasma and responsible for the activation of esterified lecithin cholesterol with an important role in the exchange of esterified cholesterol between lipoproteins and in removal of cholesterol from tissues. Its main function is inhibition of cholesteryl ester transfer protein (CETP), probably by altering the electric charge of HDL molecules.
During fasting (like other apolipoprotein C), it is found primarily within HDL, while after a meal it is found on the surface of other lipoproteins. When proteins rich in triglycerides like chylomicrons and VLDL are broken down, this apoprotein is transferred again to HDL. It is one of the most positively charged proteins in the human body.
Pseudogene
A pseudogene of this gene is located 4 kb downstream from the apoC-I gene in the same orientation on chromosome 19, where both reside within an apolipoprotein gene cluster. This pseudogene, which was also reported to have been present in Denisovans and Neandertals, originated from two separate events. Following the divergence of New World monkeys from the human lineage, the apoC-I gene was duplicated. Old World monkeys and great apes other than humans have been shown to have two active genes. One of the duplicates encodes a basic protein designated apoC-IB that is orthologous to human apolipoprotein C-I. The other encodes an acidic protein, apoC-IA, that is orthologous to the virtual protein encoded by the pseudogene. The pseudogenization event occurred sometime between the divergence of bonobos and chimpanzees from the human lineage and the arrival of Denisovans and Neandertals. The pseudogene is due to a change in a single nucleotide in the codon for the penultimate amino acid, i.e. glutamine, in the signal sequence, resulting in a stop codon.[8][9][10]
Interactive pathway map
Click on genes, proteins and metabolites below to link to respective articles.[§ 1]
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^Tata F, Henry I, Markham AF, Wallis SC, Weil D, Grzeschik KH, et al. (1985). "Isolation and characterisation of a cDNA clone for human apolipoprotein CI and assignment of the gene to chromosome 19". Human Genetics. 69 (4): 345–9. doi:10.1007/BF00291654. PMID2985493. S2CID32767041.
^Smit M, van der Kooij-Meijs E, Frants RR, Havekes L, Klasen EC (January 1988). "Apolipoprotein gene cluster on chromosome 19. Definite localization of the APOC2 gene and the polymorphic Hpa I site associated with type III hyperlipoproteinemia". Human Genetics. 78 (1): 90–3. doi:10.1007/BF00291243. PMID2892779. S2CID22711986.
^Puppione DL (September 2014). "Higher primates, but not New World monkeys, have a duplicate set of enhancers flanking their apoC-I genes". Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics. 11: 45–8. doi:10.1016/j.cbd.2014.08.001. PMID25160599.
Smit M, van der Kooij-Meijs E, Woudt LP, Havekes LM, Frants RR (May 1988). "Exact localization of the familial dysbetalipoproteinemia associated HpaI restriction site in the promoter region of the APOC1 gene". Biochemical and Biophysical Research Communications. 152 (3): 1282–8. doi:10.1016/S0006-291X(88)80424-8. PMID2897845.
Davison PJ, Norton P, Wallis SC, Gill L, Cook M, Williamson R, Humphries SE (May 1986). "There are two gene sequences for human apolipoprotein CI (apo CI) on chromosome 19, one of which is 4 kb from the gene for apo E". Biochemical and Biophysical Research Communications. 136 (3): 876–84. doi:10.1016/0006-291X(86)90414-6. PMID3013172.
Myklebost O, Rogne S (August 1986). "The gene for human apolipoprotein CI is located 4.3 kilobases away from the apolipoprotein E gene on chromosome 19". Human Genetics. 73 (4): 286–9. doi:10.1007/BF00279087. PMID3017837. S2CID11662593.
Rozek A, Buchko GW, Cushley RJ (June 1995). "Conformation of two peptides corresponding to human apolipoprotein C-I residues 7-24 and 35-53 in the presence of sodium dodecyl sulfate by CD and NMR spectroscopy". Biochemistry. 34 (22): 7401–8. doi:10.1021/bi00022a013. PMID7779782.
Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Kamino K, Yoshiiwa A, Nishiwaki Y, Nagano K, Yamamoto H, Kobayashi T, et al. (1996). "Genetic association study between senile dementia of Alzheimer's type and APOE/C1/C2 gene cluster". Gerontology. 42 (Suppl 1): 12–9. doi:10.1159/000213820. PMID8804993.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, et al. (July 1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis". Nature Genetics. 22 (3): 239–47. doi:10.1038/10297. PMID10391210. S2CID4636523.
Freitas EM, Zhang WJ, Lalonde JP, Tay GK, Gaudieri S, Ashworth LK, et al. (1999). "Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1". DNA Sequence. 9 (2): 89–100. doi:10.3109/10425179809086433. PMID10520737.
