SERINC5
Serine incorporator 5 is a protein that in humans is encoded by the SERINC5 gene.[1]
Properties
[edit]SERINC5 is a protein belonging to the serine incorporator (SERINC) family, in the predicted membrane proteins class.[6] It is believed that SERINC5 proteins help incorporate serine into certain lipid bilayer membranes; however, scientists are unsure of their primary function and physiology.[7][8] Of the five proteins in the human SERINC family, their topologies are strikingly similar. Approximately 17% of amino acids are shared amongst these proteins.[8]
C-terminal Transmembrane Domain
[edit]SERINC proteins have about 10 to 11 transmembrane domains. For SERINC5 to localize itself to the plasma membrane to inhibit infectivity by viruses, an extra c-terminal transmembrane domain is required.[7] This extra transmembrane domain allows the protein to express itself stably.
Antagonistic Relationships
[edit]
Nef, glycoGag, and S2 viral proteins are located throughout HIV-1 virions that aid in the facilitation of retrovirus release. When present, SERINC5, in the absence of certain virulence factors, prohibits HIV retrovirus particles from fusing to the cell membrane and incorporating their genetic information into target cells.[9] Because SERINC5 is primarily localized via the plasma membrane, and attaches to vesicles carrying virus particles, the restriction factor has the ability to greatly decrease viral infectivity in the early stages of infection.[10] It has been observed in past experiments that the highest SERINC5 concentration, regardless the expression of Nef, decreased infectivity approximately 250-fold.[8] Although poorly understood, it is believed that Nef is a primary cause for the destruction of SERINC5 and other restriction factors. When in the presence of virulence factors, specifically Nef, both SERINC5 and CD4 cells are downregulated through lysosomal degradation via the AP-2 endocytic pathway.[10] This causes rapid infectivity, and an increase in viral load.
References
[edit]- ^ "SERINC5 (Gene)". GeneCards. Retrieved April 24, 2019.
- ^ a b c GRCh38: Ensembl release 89: ENSG00000164300 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021703 – Ensembl, May 2017
- ^ "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.
- ^ "SERINC5". The Human Protein Atlas.
- ^ a b Zhang, Xianfeng; Zhou, Tao; Yang, Jie; Lin, Yumei; Shi, Jing; Zhang, Xihe; Frabutt, Dylan A.; Zeng, Xiangwei; Li, Sunan (February 2017). Ross, Susan (ed.). "Identification of SERINC5-001 as the Predominant Spliced Isoform for HIV-1 Restriction". Journal of Virology. 91 (10): 1–13. doi:10.1128/JVI.00137-17. PMC 5411613. PMID 28275190 – via American Society for Microbiology.
- ^ a b c Rosa, Annachiara; Chande, Ajit; Ziglio, Serena; De Sanctis, Veronica; Bertorelli, Roberto; Goh, Shih Lin; McCauley, Sean M.; Nowosielska, Anetta; Antonarakis, Stylianos E. (October 2015). "HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation". Nature. 526 (7572): 212–217. doi:10.1038/nature15399. PMC 4861059. PMID 26416734.
- ^ Kluge, Silvia F. (October 2015). "SnapShot: Antiviral Restriction Factors" (PDF). Cell. 163 (3): 774–774.e1. doi:10.1016/j.cell.2015.10.019. PMID 26496613. S2CID 32924308.
- ^ a b Zheng, Yong-Hui; Shi, Jing; Xiong, Ran; Zhou, Tao; Su, Peiyi; Zhang, Xihe; Qiu, Xusheng; Li, Hongmei; Li, Sunan (March 2018). "HIV-1 Nef Antagonizes SERINC5 Restriction by Downregulation of SERINC5 via the Endosome/Lysosome System". Journal of Virology. 92 (11): 16. doi:10.1128/JVI.00196-18. PMC 5952139. PMID 29514909 – via American Society for Microbiology.