APOBEC3C

Last updated
APOBEC3C
Available structures
PDB Human UniProt search: PDBe RCSB
Identifiers
Aliases APOBEC3C , A3C, APOBEC1L, ARDC2, ARDC4, ARP5, PBI, bK150C2.3, apolipoprotein B mRNA editing enzyme catalytic subunit 3C
External IDs OMIM: 607750 HomoloGene: 129856 GeneCards: APOBEC3C
Orthologs
SpeciesHumanMouse
Entrez

27350

n/a

Ensembl

ENSG00000244509

n/a

UniProt

Q9NRW3

n/a

RefSeq (mRNA)

NM_014508

n/a

RefSeq (protein)

NP_055323

n/a

Location (UCSC) Chr 22: 39.01 – 39.02 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

DNA dC->dU-editing enzyme APOBEC-3C is a protein that in humans is encoded by the APOBEC3C gene. [3] [4]

Contents

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. [5] Enhancing A3C's catalytic activity had only a marginal effect on HIV-1 replication (in absence of Vif), the counteractive viral mechanism is unclear. [6] A3C was also shown to inhibit other viruses. [7] [8] [9] [10] [11]

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. [12] [13] [14] [15] [16] Two residues in loop 1 of A3C were demonstrated to determine its antiviral activity against HIV-1. [17]

Structure

The crystal structure of A3C suggests a putative HIV-1 vif binding region. [18] [19] A3C was found to inhibit LINE-1 elements by directly interacting with ORF1p proteins, in a deaminase-independent manner. [20]

Related Research Articles

<span class="mw-page-title-main">Viral infectivity factor</span> Protein found in lentiviruses

Viral infectivity factor, or Vif, is an accessory protein found in HIV and other lentiviruses. Its role is to disrupt the antiviral activity of the human enzyme APOBEC by targeting it for ubiquitination and cellular degradation. APOBEC is a cytidine deaminase enzyme that mutates viral nucleic acids.

Human foamy virus (HFV) is a retrovirus and specifically belongs to the genus Spumavirus. The spumaviruses are complex and significantly different from the other six genera of retroviruses in several ways. The foamy viruses derive their name from the characteristic ‘foamy’ appearance of the cytopathic effect (CPE) induced in the cells. Foamy virus in humans occurs only as a result of zoonotic infection.

<span class="mw-page-title-main">APOBEC3G</span> Protein and coding gene in humans

APOBEC3G is a human enzyme encoded by the APOBEC3G gene that belongs to the APOBEC superfamily of proteins. This family of proteins has been suggested to play an important role in innate anti-viral immunity. APOBEC3G belongs to the family of cytidine deaminases that catalyze the deamination of cytidine to uridine in the single stranded DNA substrate. The C-terminal domain of A3G renders catalytic activity, several NMR and crystal structures explain the substrate specificity and catalytic activity.

<span class="mw-page-title-main">PSMD8</span> Enzyme found in humans

26S proteasome non-ATPase regulatory subunit 8 is an enzyme that in humans is encoded by the PSMD8 gene.

<span class="mw-page-title-main">PSMD3</span> Enzyme found in humans

26S proteasome non-ATPase regulatory subunit 3 is an enzyme that in humans is encoded by the PSMD3 gene.

<span class="mw-page-title-main">PSMD6</span> Enzyme found in humans

26S proteasome non-ATPase regulatory subunit 6 is an enzyme that in humans is encoded by the PSMD6 gene.

<span class="mw-page-title-main">PSME4</span> Protein found in humans

Proteasome activator complex subunit 4 is a protein that in humans is encoded by the PSME4 gene.

<span class="mw-page-title-main">APOBEC1</span> Protein-coding gene in the species Homo sapiens

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 also known as C->U-editing enzyme APOBEC-1 is a protein that in humans is encoded by the APOBEC1 gene.

<span class="mw-page-title-main">APOBEC3F</span> Protein-coding gene in the species Homo sapiens

DNA dC->dU-editing enzyme APOBEC-3F is a protein that in humans is encoded by the APOBEC3F gene.

<span class="mw-page-title-main">APOBEC3A</span> Protein-coding gene in the species Homo sapiens

Apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A, also known as APOBEC3A, or A3A is a gene of the APOBEC3 family found in humans, non-human primates, and some other mammals. It is a single-domain DNA cytidine deaminase with antiviral effects. While other members of the family such as APOBEC3G are believed to act by editing ssDNA by removing an amino group from cytosine in DNA, introducing a cytosine to uracil change which can ultimately lead to a cytosine to thymine mutation, one study suggests that APOBEC3A can inhibit parvoviruses by another mechanism. The cellular function of APOBEC3A is likely to be the destruction of foreign DNA through extensive deamination of cytosine.Stenglein MD, Burns MB, Li M, Lengyel J, Harris RS. "APOBEC3 proteins mediate the clearance of foreign DNA from human cells". Nature Structural & Molecular Biology. 17 (2): 222–9. doi:10.1038/nsmb.1744. PMC 2921484. PMID 20062055.

<span class="mw-page-title-main">APOBEC3B</span> Protein-coding gene in the species Homo sapiens

Probable DNA dC->dU-editing enzyme APOBEC-3B is a protein that in humans is encoded by the APOBEC3B gene.

<span class="mw-page-title-main">APOBEC3D</span> Protein-coding gene in the species Homo sapiens

Probable DNA dC->dU-editing enzyme APOBEC-3D is a protein that in humans is encoded by the APOBEC3D gene.

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<span class="mw-page-title-main">APOBEC</span> Enzyme involved in messenger RNA editing

APOBEC is a family of evolutionarily conserved cytidine deaminases.

<span class="mw-page-title-main">APOBEC3H</span> Protein-coding gene in the species Homo sapiens

DNA dC->dU-editing enzyme APOBEC-3H, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3H or APOBEC-related protein 10, is a protein that in humans is encoded by the APOBEC3H gene.

<span class="mw-page-title-main">APOBEC4</span> Protein-coding gene in the species Homo sapiens

C->U-editing enzyme APOBEC-4, also known as Apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 4, is a protein that in humans is encoded by the APOBEC4 gene. It is primarily expressed in testis and found in mammals, chicken, but not fishes.

<span class="mw-page-title-main">Kataegis</span>

In molecular biology, kataegis describes a pattern of localized hypermutations identified in some cancer genomes, in which a large number of highly patterned basepair mutations occur in a small region of DNA. The mutational clusters are usually several hundred basepairs long, alternating between a long range of C→T substitutional pattern and a long range of G→A substitutional pattern. This suggests that kataegis is carried out on only one of the two template strands of DNA during replication. Compared to other cancer-related mutations, such as chromothripsis, kataegis is more commonly seen; it is not an accumulative process but likely happens during one cycle of replication.

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<span class="mw-page-title-main">Harold Smith (scientist)</span>

Harold C. Smith Jr. is an American scientist, researcher, professor, founder and CEO of OyaGen. Smith has written over 100 publications on his research in RNA editing, AIDS, oncology, and immunodeficiency, among others.

Viviana Simon is a Professor of Microbiology at the Icahn School of Medicine at Mount Sinai (ISMMS). She is a member of the ISMMS Global Health and Emerging Pathogens Institute. Her research considers viral-host interactions and the mode of action of retroviral restriction factors. During the COVID-19 pandemic, Simon developed an antibody test that can determine immunity to Coronavirus disease 2019.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000244509 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ Jarmuz A, Chester A, Bayliss J, Gisbourne J, Dunham I, Scott J, Navaratnam N (March 2002). "An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22". Genomics. 79 (3): 285–96. doi:10.1006/geno.2002.6718. PMID   11863358.
  4. ↑ "Entrez Gene: APOBEC3C apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3C".
  5. ↑ Yu Q, Chen D, König R, Mariani R, Unutmaz D, Landau NR (December 2004). "APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication". The Journal of Biological Chemistry. 279 (51): 53379–86. doi:10.1074/jbc.M408802200. PMID   15466872.
  6. ↑ Jaguva Vasudevan AA, Hofmann H, Willbold D, Häussinger D, Koenig BW, Münk C (April 2017). "Enhancing the Catalytic Deamination Activity of APOBEC3C Is Insufficient to Inhibit Vif-Deficient HIV-1". Journal of Molecular Biology. 429 (8): 1171–1191. doi:10.1016/j.jmb.2017.03.015. PMID   28315663.
  7. ↑ Baumert TF, Rösler C, Malim MH, von Weizsäcker F (September 2007). "Hepatitis B virus DNA is subject to extensive editing by the human deaminase APOBEC3C". Hepatology. 46 (3): 682–9. doi: 10.1002/hep.21733 . PMID   17625792. S2CID   9029300.
  8. ↑ Suspène R, Aynaud MM, Koch S, Pasdeloup D, Labetoulle M, Gaertner B, Vartanian JP, Meyerhans A, Wain-Hobson S (August 2011). "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. doi:10.1128/JVI.00290-11. PMC   3147940 . PMID   21632763.
  9. ↑ Köck J, Blum HE (May 2008). "Hypermutation of hepatitis B virus genomes by APOBEC3G, APOBEC3C and APOBEC3H". The Journal of General Virology. 89 (Pt 5): 1184–91. doi: 10.1099/vir.0.83507-0 . PMID   18420796.
  10. ↑ Li D, Liu J, Kang F, Guan W, Gao X, Wang Y, Sun D (October 2011). "Core-APOBEC3C chimerical protein inhibits hepatitis B virus replication". Journal of Biochemistry. 150 (4): 371–4. doi:10.1093/jb/mvr086. PMID   21746770.
  11. ↑ 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 (February 2015). "APOBEC3A and 3C decrease human papillomavirus 16 pseudovirion infectivity". Biochemical and Biophysical Research Communications. 457 (3): 295–9. doi:10.1016/j.bbrc.2014.12.103. hdl: 2297/44628 . PMID   25576866.
  12. ↑ Yu Q, König R, Pillai S, Chiles K, Kearney M, Palmer S, Richman D, Coffin JM, Landau NR (May 2004). "Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV genome". Nature Structural & Molecular Biology. 11 (5): 435–42. doi:10.1038/nsmb758. PMID   15098018. S2CID   24306371.
  13. ↑ Harris RS, Petersen-Mahrt SK, Neuberger MS (November 2002). "RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators". Molecular Cell. 10 (5): 1247–53. doi: 10.1016/s1097-2765(02)00742-6 . PMID   12453430.
  14. ↑ Harris RS, Sheehy AM, Craig HM, Malim MH, Neuberger MS (July 2003). "DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses". Nature Immunology. 4 (7): 641–3. doi:10.1038/ni0703-641. PMID   12830140. S2CID   5549252.
  15. ↑ Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH (June 2003). "DNA deamination mediates innate immunity to retroviral infection". Cell. 113 (6): 803–9. doi: 10.1016/s0092-8674(03)00423-9 . PMID   12809610.
  16. ↑ Yu Q, Chen D, König R, Mariani R, Unutmaz D, Landau NR (December 2004). "APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication". The Journal of Biological Chemistry. 279 (51): 53379–86. doi:10.1074/jbc.M408802200. PMID   15466872.
  17. ↑ 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): 6200–6227. doi:10.1016/j.jmb.2020.10.014. PMID   33068636. S2CID   224318971.
  18. ↑ Kitamura S, Ode H, Nakashima M, Imahashi M, Naganawa Y, Kurosawa T, Yokomaku Y, Yamane T, Watanabe N, Suzuki A, Sugiura W, Iwatani Y (October 2012). "The APOBEC3C crystal structure and the interface for HIV-1 Vif binding". Nature Structural & Molecular Biology. 19 (10): 1005–10. doi:10.1038/nsmb.2378. PMID   23001005. S2CID   7871310.
  19. ↑ 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 (November 2016). "Vif Proteins from Diverse Human Immunodeficiency Virus/Simian Immunodeficiency Virus Lineages Have Distinct Binding Sites in A3C". Journal of Virology. 90 (22): 10193–10208. doi:10.1128/JVI.01497-16. PMC   5105656 . PMID   27581978.
  20. ↑ 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 (January 2014). "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. doi:10.1093/nar/gkt898. PMC   3874205 . PMID   24101588.

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