APOBEC3C explained

DNA dC->dU-editing enzyme APOBEC-3C is a protein that in humans is encoded by the APOBEC3C gene.^{[1] [2]}

A3C belong to the A3 family of cytidine deaminases that act as restriction factors against diverse retroviruses. A3C was reported to inhibit simian immunodeficiency deficiency virus potently rather than HIV-1, in absence of viral infectivity factor, Vif.^[3] Enhancing A3C's catalytic activity had only a marginal effect on HIV-1 replication (in absence of Vif), the counteractive viral mechanism is unclear.^[4] A3C was also shown to inhibit other viruses.^{[5] [6] [7] [8] [9]}

Function

This gene is a member of the cytidine deaminase gene family. It is one of seven related genes or pseudogenes found in a cluster thought to result from gene duplication, on chromosome 22. Members of the cluster encode proteins that are structurally and functionally related to the C to U RNA-editing cytidine deaminase APOBEC1. Conversely, A3 proteins enzymatically convert cytidine to uridine present in the single stranded DNA.^{[10] [11] [12] [13] [14]} Two residues in loop 1 of A3C were demonstrated to determine its antiviral activity against HIV-1.^[15]

Structure

The crystal structure of A3C suggests a putative HIV-1 vif binding region.^{[16] [17]} A3C was found to inhibit LINE-1 elements by directly interacting with ORF1p proteins, in a deaminase-independent manner.^[18]

Further reading

• Wedekind JE, Dance GS, Sowden MP, Smith HC . Messenger RNA editing in mammals: new members of the APOBEC family seeking roles in the family business . Trends in Genetics . 19 . 4 . 207–16 . April 2003 . 12683974 . 10.1016/S0168-9525(03)00054-4 .
• Cullen BR . Role and mechanism of action of the APOBEC3 family of antiretroviral resistance factors . Journal of Virology . 80 . 3 . 1067–76 . February 2006 . 16414984 . 1346961 . 10.1128/JVI.80.3.1067-1076.2006 .
• Vasudevan AA, Smits SH, Höppner A, Häussinger D, Koenig BW, Münk C . Structural features of antiviral DNA cytidine deaminases . Biological Chemistry . 394 . 11 . 1357–70 . November 2013 . 23787464 . 10.1515/hsz-2013-0165 . 4151961 .
• Haché G, Mansky LM, Harris RS . Human APOBEC3 proteins, retrovirus restriction, and HIV drug resistance . AIDS Reviews . 8 . 3 . 148–57 . 2006 . 17078485 .
• Madsen P, Anant S, Rasmussen HH, Gromov P, Vorum H, Dumanski JP, Tommerup N, Collins JE, Wright CL, Dunham I, MacGinnitie AJ, Davidson NO, Celis JE . Psoriasis upregulated phorbolin-1 shares structural but not functional similarity to the mRNA-editing protein apobec-1 . The Journal of Investigative Dermatology . 113 . 2 . 162–9 . August 1999 . 10469298 . 10.1046/j.1523-1747.1999.00682.x . free .
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP . The DNA sequence of human chromosome 22 . Nature . 402 . 6761 . 489–95 . December 1999 . 10591208 . 10.1038/990031 . 1999Natur.402..489D . free .
• Mariani R, Chen D, Schröfelbauer B, Navarro F, König R, Bollman B, Münk C, Nymark-McMahon H, Landau NR . Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif . Cell . 114 . 1 . 21–31 . July 2003 . 12859895 . 10.1016/S0092-8674(03)00515-4 . free .
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I . A genome annotation-driven approach to cloning the human ORFeome . Genome Biology . 5 . 10 . R84 . 2005 . 15461802 . 545604 . 10.1186/gb-2004-5-10-r84 . free .
• Yu Q, Chen D, König R, Mariani R, Unutmaz D, Landau NR . APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication . The Journal of Biological Chemistry . 279 . 51 . 53379–86 . December 2004 . 15466872 . 10.1074/jbc.M408802200 . free.
• Langlois MA, Beale RC, Conticello SG, Neuberger MS . Mutational comparison of the single-domained APOBEC3C and double-domained APOBEC3F/G anti-retroviral cytidine deaminases provides insight into their DNA target site specificities . Nucleic Acids Research . 33 . 6 . 1913–23 . 2005 . 15809227 . 1074398 . 10.1093/nar/gki343 .
• Pope SN, Lee IR . Yeast two-hybrid identification of prostatic proteins interacting with human sex hormone-binding globulin . The Journal of Steroid Biochemistry and Molecular Biology . 94 . 1–3 . 203–8 . February 2005 . 15862967 . 10.1016/j.jsbmb.2005.01.007 . 9746088 .
• Doehle BP, Schäfer A, Wiegand HL, Bogerd HP, Cullen BR . Differential sensitivity of murine leukemia virus to APOBEC3-mediated inhibition is governed by virion exclusion . Journal of Virology . 79 . 13 . 8201–7 . July 2005 . 15956565 . 1143768 . 10.1128/JVI.79.13.8201-8207.2005 .
• Rose KM, Marin M, Kozak SL, Kabat D . Regulated production and anti-HIV type 1 activities of cytidine deaminases APOBEC3B, 3F, and 3G . AIDS Research and Human Retroviruses . 21 . 7 . 611–9 . July 2005 . 16060832 . 10.1089/aid.2005.21.611 .
• Muckenfuss H, Hamdorf M, Held U, Perkovic M, Löwer J, Cichutek K, Flory E, Schumann GG, Münk C . APOBEC3 proteins inhibit human LINE-1 retrotransposition . The Journal of Biological Chemistry . 281 . 31 . 22161–72 . August 2006 . 16735504 . 10.1074/jbc.M601716200 . free .
• Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D . Large-scale mapping of human protein-protein interactions by mass spectrometry . Molecular Systems Biology . 3 . 1 . 89 . 2007 . 17353931 . 1847948 . 10.1038/msb4100134 .
• Kinomoto M, Kanno T, Shimura M, Ishizaka Y, Kojima A, Kurata T, Sata T, Tokunaga K . All APOBEC3 family proteins differentially inhibit LINE-1 retrotransposition . Nucleic Acids Research . 35 . 9 . 2955–64 . 2007 . 17439959 . 1888823 . 10.1093/nar/gkm181 .

Notes and References

1. Jarmuz A, Chester A, Bayliss J, Gisbourne J, Dunham I, Scott J, Navaratnam N . An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22 . Genomics . 79 . 3 . 285–96 . March 2002 . 11863358 . 10.1006/geno.2002.6718 .
2. Web site: Entrez Gene: APOBEC3C apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3C.
3. Yu Q, Chen D, König R, Mariani R, Unutmaz D, Landau NR . APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication . The Journal of Biological Chemistry . 279 . 51 . 53379–86 . December 2004 . 15466872 . 10.1074/jbc.M408802200 . free.
4. Jaguva Vasudevan AA, Hofmann H, Willbold D, Häussinger D, Koenig BW, Münk C . Enhancing the Catalytic Deamination Activity of APOBEC3C Is Insufficient to Inhibit Vif-Deficient HIV-1 . Journal of Molecular Biology . 429 . 8 . 1171–1191 . April 2017 . 28315663 . 10.1016/j.jmb.2017.03.015 .
5. Baumert TF, Rösler C, Malim MH, von Weizsäcker F . Hepatitis B virus DNA is subject to extensive editing by the human deaminase APOBEC3C . Hepatology . 46 . 3 . 682–9 . September 2007 . 17625792 . 10.1002/hep.21733 . 9029300 . free .
6. Suspène R, Aynaud MM, Koch S, Pasdeloup D, Labetoulle M, Gaertner B, Vartanian JP, Meyerhans A, Wain-Hobson S . Genetic editing of herpes simplex virus 1 and Epstein-Barr herpesvirus genomes by human APOBEC3 cytidine deaminases in culture and in vivo . Journal of Virology . 85 . 15 . 7594–602 . August 2011 . 21632763 . 3147940 . 10.1128/JVI.00290-11 .
7. Köck J, Blum HE . Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H . The Journal of General Virology . 89 . Pt 5 . 1184–91 . May 2008 . 18420796 . 10.1099/vir.0.83507-0 . free .
8. Li D, Liu J, Kang F, Guan W, Gao X, Wang Y, Sun D . Core-APOBEC3C chimerical protein inhibits hepatitis B virus replication . Journal of Biochemistry . 150 . 4 . 371–4 . October 2011 . 21746770 . 10.1093/jb/mvr086 .
9. Ahasan MM, Wakae K, Wang Z, Kitamura K, Liu G, Koura M, Imayasu M, Sakamoto N, Hanaoka K, Nakamura M, Kyo S, Kondo S, Fujiwara H, Yoshizaki T, Mori S, Kukimoto I, Muramatsu M . APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity . Biochemical and Biophysical Research Communications . 457 . 3 . 295–9 . February 2015 . 25576866 . 10.1016/j.bbrc.2014.12.103 . 2297/44628 . free .
10. Yu Q, König R, Pillai S, Chiles K, Kearney M, Palmer S, Richman D, Coffin JM, Landau NR . Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome . Nature Structural & Molecular Biology . 11 . 5 . 435–42 . May 2004 . 15098018 . 10.1038/nsmb758 . 24306371 .
11. Harris RS, Petersen-Mahrt SK, Neuberger MS . RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators . Molecular Cell . 10 . 5 . 1247–53 . November 2002 . 12453430 . 10.1016/s1097-2765(02)00742-6. free .
12. Harris RS, Sheehy AM, Craig HM, Malim MH, Neuberger MS . DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses . Nature Immunology . 4 . 7 . 641–3 . July 2003 . 12830140 . 10.1038/ni0703-641 . 5549252 .
13. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH . DNA deamination mediates innate immunity to retroviral infection . Cell . 113 . 6 . 803–9 . June 2003 . 12809610 . 10.1016/s0092-8674(03)00423-9. free .
14. Yu Q, Chen D, König R, Mariani R, Unutmaz D, Landau NR . APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication . The Journal of Biological Chemistry . 279 . 51 . 53379–86 . December 2004 . 15466872 . 10.1074/jbc.M408802200 . free.
15. Ayyappan Jaguva Vasudevan. Ananda. Balakrishnan. Kannan. G. W. Gertzen. Christoph. Borvető. Fanni. Zhang. Zeli. Sangwiman. Anucha. Held. Ulrike. Küstermann. Caroline. Banerjee. Sharmistha. Schumann. Gerald G.. Häussinger. Dieter. October 2020. Loop 1 of APOBEC3C regulates its antiviral activity against HIV-1. Journal of Molecular Biology. 432 . 23 . en. 6200–6227. 10.1016/j.jmb.2020.10.014. 33068636 . 224318971 .
16. Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Kurosawa T, Yokomaku Y, Yamane T, Watanabe N, Suzuki A, Sugiura W, Iwatani Y . The APOBEC3C crystal structure and the interface for HIV-1 Vif binding . Nature Structural & Molecular Biology . 19 . 10 . 1005–10 . October 2012 . 23001005 . 10.1038/nsmb.2378 . 7871310 .
17. Zhang Z, Gu Q, Jaguva Vasudevan AA, Jeyaraj M, Schmidt S, Zielonka J, Perković M, Heckel JO, Cichutek K, Häussinger D, Smits SH, Münk C . Vif Proteins from Diverse Human Immunodeficiency Virus/Simian Immunodeficiency Virus Lineages Have Distinct Binding Sites in A3C . Journal of Virology . 90 . 22 . 10193–10208 . November 2016 . 27581978 . 10.1128/JVI.01497-16 . 5105656.
18. Horn AV, Klawitter S, Held U, Berger A, Vasudevan AA, Bock A, Hofmann H, Hanschmann KM, Trösemeier JH, Flory E, Jabulowsky RA, Han JS, Löwer J, Löwer R, Münk C, Schumann GG . Human LINE-1 restriction by APOBEC3C is deaminase independent and mediated by an ORF1p interaction that affects LINE reverse transcriptase activity . Nucleic Acids Research . 42 . 1 . 396–416 . January 2014 . 24101588 . 10.1093/nar/gkt898 . 3874205.