Ask about this productRelated genes to: SERINC3 antibody
- Gene:
- SERINC3 NIH gene
- Name:
- serine incorporator 3
- Previous symbol:
- TDE1
- Synonyms:
- DIFF33, TDE, SBBI99, TMS-1, AIGP1
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 1999-12-07
- Date modifiied:
- 2014-11-19
Related products to: SERINC3 antibody
Related articles to: SERINC3 antibody
- Human transmembrane proteins Serinc3 and Serinc5 are antiviral restriction factors that inhibit HIV-1 infectivity. In the absence of viral antagonism, Serinc3 and Serinc5 incorporate into the envelopes of nascent virions and inhibit the fusion of virions to the target cells. The HIV-1 virus counteracts the restriction of Serinc3 by downregulating it from the cell surface and thus excluding it from budding virions. This is orchestrated by the viral accessory protein Nef and involves hijacking of the clathrin adaptor protein complex 2 (AP2)-dependent endocytosis. The mechanistic details of Nef-mediated Serinc3 downregulation, however, have been enigmatic. In this work, we investigated and revealed the molecular determinants of Serinc3 modulation by Nef. Our results show that Nef recruits Serinc3 by binding to its N-terminal cytosolic tail. Furthermore, Nef residues important for Serinc3-binding in vitro, and for the exclusion of Serinc3 from virions, overlap with those required for Nef-mediated CD4 downregulation, suggesting great mechanistic similarities between the two functions of Nef. In addition to shedding light on the mechanism of Serinc3 antagonism, our work also highlights the conserved substrate-binding pocket of Nef as a molecular hotspot for inhibitor development and antiretroviral drug discovery. - Source: PubMed
Publication date: 2025/12/19
Karimian Shamsabadi MohammadStoneham CharlotteDe Leon AmaliaFares TonyGuatelli JohnJia Xiaofei - The HIV-1 restriction factor, hSERINC3, functions as a lipid scramblase, translocating lipids across the bilayer in reconstituted proteoliposomes and the viral envelope. Phosphatidylserine(PS) scrambling and exposure at the outer leaflet are recognized to play important roles in several biological processes. To understand the mechanistic basis for hSERINC3-mediated PS lipid scrambling at atomistic resolution, we implemented the transition-tempered metadynamics (TTMetaD) enhanced sampling method. Our simulations sampled close-to-open hSERINC3 conformational transition during PS scrambling and demonstrated that while other non-ATP-dependent lipid transporters with similar architecture transport lipid following a "trap-and-flip" mechanism, hSERINC3 adopts a "credit card" mechanism of lipid scrambling and does not follow the classical "alternating access" mechanism. Notably, we observe unfolding of the H8 NTD, consistent with the cryo-EM density map of WT-hSERINC3, mediates PS scrambling. A cluster of hydrophilic residues in the hSERINC3 central cavity, forming central gates and interacting with the PS headgroup, stabilizes the intermediate state of inner-groove scrambling and is also observed in the AlphaFold2 model of hSERINC5 that exhibits the highest viral restriction activity. Surprisingly, our simulations reveal distinct pathways for lipid translocation and pathway-dependent alterations of hSERINC3 central cavity, providing direct evidence for a non-canonical, closed-state out-of-groove PS scrambling in a complex membrane environment. - Source: PubMed
Publication date: 2025/11/13
Banerjee PujaYeager MarkVoth Gregory A - Phylogenetic reconstruction is indispensable for inferring evolutionary trajectories of novel traits and historical biogeography of extant species. However, resolving phylogenetic relationships remains particularly challenging during episodes of rapid radiation, as exemplified by Rhinolophus-the second-largest genus of Chiroptera. This Old World bat lineage underwent rapid diversification, resulting in persistent ambiguities in its species-level phylogeny. To date, limited taxonomic sampling and insufficient molecular markers have precluded robust identification of the ancestral clade within Rhinolophus. Here, we address this knowledge gap using genome-wide nuclear datasets with comprehensive taxon sampling. Phylogenetic reconstructions integrating concatenation and coalescent-based approaches robustly recovered two strongly supported sister clades within Rhinolophus-the Afro-Palaearctic clade and the Asian clade-and resolved R. hipposideros as the ancestral lineage of the Afro-Palaearctic clade. This topology received further validation from PhyloNet analyses accounting for gene flow. Notably, mitochondrial phylogenomics exhibited significant topological discordance with nuclear DNA, suggesting widespread mito-nuclear discordance attributable to historical introgression. Genome-scale introgression analyses revealed pervasive cross-lineage nuclear gene flow, occurring not only among sister taxa but also between distantly related lineages. Crucially, highly introgressed genes (RANBP2 and SERINC3) functionally associated with antiviral defence mechanisms were previously shown to be under positive selection in bats. This pattern supports the occurrence of adaptive introgression facilitating viral resistance across the genus. Overall, our findings demonstrate the power of genome-scale data in resolving deep evolutionary relationships within rapidly radiating groups and underscore the importance of hybridization and introgression as key mechanisms in mammal diversification. - Source: PubMed
Publication date: 2025/11/18
Yang ShanxiuZhang HaixinXie JinjinMao Xiuguang - The viral accessory protein Nef is a major determinant of HIV-1 pathogenicity in vivo. Nef is a multifunctional, immunomodulatory protein that downmodulates cell surface proteins, including CD4 and MHC class I (MHC-I), which are important for T cell-mediated immunity. In addition, Nef also regulates cell-intrinsic immunity-Nef boosts the infectivity of virions produced and released from HIV-infected cells, at least in part, by counteracting the antiviral activity of transmembrane proteins SERINC3 and SERINC5. Here, we show that Nef proteins derived from many primary isolates of HIV-1 restore infectivity in interferon-treated cells and confer resistance to the antiviral protein interferon-induced transmembrane protein 3 (IFITM3) in a SERINC3/5-independent manner. Using Nef derived from primary HIV-1 clade C infection, we found that Nef interacts with IFITM3 in membranes, reduces IFITM3 incorporation into HIV-1 virions, and restores HIV-1 fusion with target cells. Our findings reveal a previously unrecognized immunomodulatory role for Nef in the setting of the interferon-induced antiviral state during HIV-1 infection. - Source: PubMed
Publication date: 2025/10/01
Agarwal MaheshLai Kin KuiWilt IsaiahMajdoul SalihaJolley Abigail ALewinski MaryCompton Alex A - The viral accessory protein Nef is a major determinant of HIV-1 pathogenicity in vivo. Nef is a multifunctional, immunomodulatory protein that downmodulates cell surface proteins, including CD4 and MHC class I (MHC-I) important for T-cell-mediated immunity. In addition, Nef also regulates cell-intrinsic immunity-Nef boosts the infectivity of virions produced and released from HIV-infected cells, at least in part, by counteracting the antiviral activity of transmembrane proteins SERINC3 and SERINC5. However, it has been reported that the enhancement of HIV-1 infectivity by Nef persists in certain cell lines deficient for SERINC3/5, revealing the existence of other Nef-sensitive host factors that impact HIV-1 infectivity. Here, we show that Nef proteins, especially those derived from many primary isolates of HIV-1, restore infectivity in interferon-treated cells and confer resistance to interferon-induced transmembrane protein 3 (IFITM3). IFITM3 is a restriction factor that reduces retroviral infectivity by incorporating into virions, inhibiting Envelope glycoprotein function, and reducing entry into cells. Using a primary isolate of Nef derived from HIV-1 clade C, we found that Nef interacts with IFITM3 in membranes and uses the endocytic adaptor protein AP-2 to counteract it. Furthermore, Nef reduced IFITM3 cell surface levels, increased IFITM3 levels in early endosomes, and reduced IFITM3 incorporation into HIV-1 virions. Nef also impaired IFITM3 oligomerization and restored membrane fluidity in IFITM3-expressing cells. The antiviral activity of IFITM3 and its inhibition by Nef were unaffected by SERINC5 knockdown, suggesting that the counteraction of IFITM3 represents a unique function of Nef. Our findings reveal a previously unrecognized immunomodulatory role for Nef in the setting of the interferon-induced antiviral state during HIV-1 infection. - Source: PubMed
Publication date: 2025/05/15
Agarwal MaheshLai Kin KuiWilt IsaiahMajdoul SalihaJolley Abigail ALewinski MaryCompton Alex A