Apolipoprotein C-I Explained

Symbol:	ApoC-I
ApoC-I
Pfam:	PF04691
Interpro:	IPR006781
Scop:	1ale

Apolipoprotein C-I is a protein component of lipoproteins that in humans is encoded by the APOC1 gene.^{[1] [2]}

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.^[3]

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.^{[4] [5] [6]}

Further reading

• Shulman RS, Herbert PN, Wehrly K, Fredrickson DS . Thf complete amino acid sequence of C-I (apoLp-Ser), an apolipoprotein from human very low density lipoproteins . The Journal of Biological Chemistry . 250 . 1 . 182–90 . January 1975 . 10.1016/S0021-9258(19)41998-4 . 166984 . free .
• Lauer SJ, Walker D, Elshourbagy NA, Reardon CA, Levy-Wilson B, Taylor JM . Two copies of the human apolipoprotein C-I gene are linked closely to the apolipoprotein E gene . The Journal of Biological Chemistry . 263 . 15 . 7277–86 . May 1988 . 10.1016/S0021-9258(18)68638-7 . 2835369 . free .
• Smit M, van der Kooij-Meijs E, Woudt LP, Havekes LM, Frants RR . 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 . May 1988 . 2897845 . 10.1016/S0006-291X(88)80424-8 .
• Davison PJ, Norton P, Wallis SC, Gill L, Cook M, Williamson R, Humphries SE . 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 . May 1986 . 3013172 . 10.1016/0006-291X(86)90414-6 .
• Myklebost O, Rogne S . 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 . August 1986 . 3017837 . 10.1007/BF00279087 . 11662593 .
• Jackson RL, Sparrow JT, Baker HN, Morrisett JD, Taunton OD, Gotto AM . The primary structure of apolopoprotein-serine . The Journal of Biological Chemistry . 249 . 16 . 5308–13 . August 1974 . 10.1016/S0021-9258(19)42365-X . 4369340 . free .
• Knott TJ, Robertson ME, Priestley LM, Urdea M, Wallis S, Scott J . Characterisation of mRNAs encoding the precursor for human apolipoprotein CI . Nucleic Acids Research . 12 . 9 . 3909–15 . May 1984 . 6328444 . 318798 . 10.1093/nar/12.9.3909 .
• Servillo L, Brewer HB, Osborne JC . Evaluation of the mixed interaction between apolipoproteins A-II and C-I equilibrium sedimentation . Biophysical Chemistry . 13 . 1 . 29–38 . February 1981 . 6789904 . 10.1016/0301-4622(81)80022-1 .
• Curry MD, McConathy WJ, Fesmire JD, Alaupovic P . Quantitative determination of apolipoproteins C-I and C-II in human plasma by separate electroimmunoassays . Clinical Chemistry . 27 . 4 . 543–8 . April 1981 . 7471419 . 10.1093/clinchem/27.4.543. free .
• Rozek A, Buchko GW, Cushley RJ . 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 . June 1995 . 7779782 . 10.1021/bi00022a013 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Trask B, Fertitta A, Christensen M, Youngblom J, Bergmann A, Copeland A, de Jong P, Mohrenweiser H, Olsen A, Carrano A . 6 . Fluorescence in situ hybridization mapping of human chromosome 19: cytogenetic band location of 540 cosmids and 70 genes or DNA markers . Genomics . 15 . 1 . 133–45 . January 1993 . 8432525 . 10.1006/geno.1993.1021 .
• Kamino K, Yoshiiwa A, Nishiwaki Y, Nagano K, Yamamoto H, Kobayashi T, Nonomura Y, Yoneda H, Sakai T, Imagawa M, Miki T, Ogihara T . 6 . Genetic association study between senile dementia of Alzheimer's type and APOE/C1/C2 gene cluster . Gerontology . 42 . 12–9 . 1996 . Suppl 1 . 8804993 . 10.1159/000213820 .
• Rozek A, Buchko GW, Kanda P, Cushley RJ . Conformational studies of the N-terminal lipid-associating domain of human apolipoprotein C-I by CD and 1H NMR spectroscopy . Protein Science . 6 . 9 . 1858–68 . September 1997 . 9300485 . 2143781 . 10.1002/pro.5560060906 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–56 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A . 6 . Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis . Nature Genetics . 22 . 3 . 239–47 . July 1999 . 10391210 . 10.1038/10297 . 4636523 .
• Freitas EM, Zhang WJ, Lalonde JP, Tay GK, Gaudieri S, Ashworth LK, Van Bockxmeer FM, Dawkins RL . 6 . Sequencing of 42kb of the APO E-C2 gene cluster reveals a new gene: PEREC1 . DNA Sequence . 9 . 2 . 89–100 . 1999 . 10520737 . 10.3109/10425179809086433 .
• Gautier T, Masson D, de Barros JP, Athias A, Gambert P, Aunis D, Metz-Boutigue MH, Lagrost L . 6 . Human apolipoprotein C-I accounts for the ability of plasma high density lipoproteins to inhibit the cholesteryl ester transfer protein activity . The Journal of Biological Chemistry . 275 . 48 . 37504–9 . December 2000 . 10978346 . 10.1074/jbc.M007210200 . free .
• Hartley JL, Temple GF, Brasch MA . DNA cloning using in vitro site-specific recombination . Genome Research . 10 . 11 . 1788–95 . November 2000 . 11076863 . 310948 . 10.1101/gr.143000 .

External links

• • PDBe-KB provides an overview of all the structure information available in the PDB for Human Apolipoprotein C-I

Notes and References

1. Tata F, Henry I, Markham AF, Wallis SC, Weil D, Grzeschik KH, Junien C, Williamson R, Humphries SE . 6 . 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 . 1985 . 2985493 . 10.1007/BF00291654 . 32767041 .
2. Smit M, van der Kooij-Meijs E, Frants RR, Havekes L, Klasen EC . 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 . January 1988 . 2892779 . 10.1007/BF00291243 . 22711986 .
3. Web site: Entrez Gene: APOC1 apolipoprotein C-I.
4. Puppione DL, Ryan CM, Bassilian S, Souda P, Xiao X, Ryder OA, Whitelegge JP . Detection of two distinct forms of apoC-I in great apes . Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics . 5 . 1 . 73–9 . March 2010 . 20209111 . 2830554 . 10.1016/j.cbd.2009.12.003 .
5. Puppione D, Whitelegge JP . Proteogenomic Review of the Changes in Primate apoC-I during Evolution . Frontiers in Biology . 8 . 5 . 533–548 . October 2013 . 28757862 . 5528196 . 10.1007/s11515-013-1278-7 .
6. Puppione DL . 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 . September 2014 . 25160599 . 10.1016/j.cbd.2014.08.001 .