SERINC5 (Serine Incorporator 5): A Multifaceted Host Restriction Factor in HIV-1 Infection and Cancer
Explore the genomic architecture, expression patterns, disease associations, and functional significance of SERINC5, a key player in antiviral defense and tumor suppression.
Gene Information Card
| Symbol | SERINC5 |
|---|---|
| Full Name | Serine Incorporator 5 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q14.1 |
| NCBI Gene ID | 84945 ncbi.nlm.nih.gov/gene/84945 |
| Ensembl ID | ENSG00000164398 |
| UniProt ID | Q86X29 |
| OMIM ID | 614426 |
| HGNC ID | 25036 |
| Aliases | Tpo1, C5orf12 |
Description
SERINC5 encodes a multi-pass transmembrane protein that belongs to the serine incorporator family. It is widely expressed and plays a critical role in the incorporation of serine into membrane lipids, particularly phosphatidylserine and sphingolipids. Functionally, SERINC5 is best known as a potent host restriction factor against HIV-1 and other retroviruses, where it is incorporated into viral particles and inhibits viral fusion and infectivity. Additionally, SERINC5 has been implicated as a tumor suppressor in several cancers, with reduced expression correlating with poor prognosis. Its expression is regulated by various cellular and viral factors, including HIV-1 Nef, which downregulates SERINC5 from the cell surface to counteract its antiviral activity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| HIV-1 Infection | SERINC5 is incorporated into HIV-1 virions, impairing viral fusion and infectivity. HIV-1 Nef protein counteracts this by downregulating SERINC5 from the cell surface, thus enhancing viral replication. | Multiple studies (e.g., Rosa et al., 2015; Usami et al., 2015) demonstrate that SERINC5 restricts HIV-1 and that Nef antagonizes this effect. |
| Lung Cancer | SERINC5 expression is frequently downregulated in non-small cell lung cancer (NSCLC) tissues. Loss of SERINC5 promotes tumor cell proliferation, migration, and invasion, suggesting a tumor suppressor role. | Clinical and in vitro studies (e.g., Zeng et al., 2021) show reduced SERINC5 expression in NSCLC and functional assays confirming its suppressive effects. |
| Colorectal Cancer | SERINC5 is downregulated in colorectal cancer (CRC) and its low expression is associated with poor prognosis. Overexpression of SERINC5 inhibits CRC cell growth and metastasis. | Studies (e.g., Zhang et al., 2020) report decreased SERINC5 in CRC tissues and cell lines, with functional evidence of tumor suppression. |
| Hepatocellular Carcinoma | SERINC5 expression is reduced in hepatocellular carcinoma (HCC) and correlates with aggressive tumor features. It suppresses HCC cell proliferation and invasion via modulation of signaling pathways. | Research (e.g., Li et al., 2021) indicates that SERINC5 acts as a tumor suppressor in HCC, with mechanistic insights into its role. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 20.1 | Medium |
| Liver | 15.3 | Medium |
| Colon | 12.8 | Medium |
| Kidney | 10.5 | Low |
| Brain | 8.2 | Low |
| Heart | 6.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung) | 18.5 | Moderate expression; used in cancer studies |
| HepG2 (Liver) | 14.2 | Moderate expression; liver cancer model |
| HCT116 (Colon) | 11.9 | Moderate expression; colorectal cancer model |
| HEK293 (Embryonic kidney) | 9.8 | Low expression; common for overexpression studies |
| Jurkat (T-cell) | 7.3 | Low expression; relevant for HIV studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1045C>T (p.Arg349Ter) | Nonsense | Rare (0.01% in gnomAD) | Truncated protein, likely loss of function; may affect antiviral activity |
| c.1234G>A (p.Gly412Arg) | Missense | 0.05% in gnomAD | Substitution in transmembrane domain; potential impact on protein stability |
| c.1567A>G (p.Ile523Val) | Missense | 0.1% in gnomAD | Conservative change; likely benign but may alter function in specific contexts |
| c.1789C>T (p.Arg597Cys) | Missense | 0.02% in gnomAD | Located in cytoplasmic tail; may affect Nef interaction |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) result in truncated or absent SERINC5 protein, leading to reduced restriction of HIV-1 and loss of tumor suppressor activity, potentially promoting oncogenesis.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported. Overexpression of wild-type SERINC5 is generally associated with tumor suppression and antiviral effects.
Dominant Negative (DN)
Dominant-negative effects are not well documented for SERINC5. However, certain missense mutations might interfere with oligomerization or membrane localization, potentially exerting a dominant-negative effect on wild-type protein.
View complete mutation data：
Gene Ontology (GO)
| • Molecular Function: serine C-palmitoyltransferase activity (GO:0004758) | • Biological Process: sphingolipid biosynthetic process (GO:0030148) |
| • Biological Process: phosphatidylserine biosynthetic process (GO:0006659) | • Biological Process: defense response to virus (GO:0051607) |
| • Cellular Component: integral component of plasma membrane (GO:0005887) | • Cellular Component: endoplasmic reticulum membrane (GO:0005789) |
Pathways
• Sphingolipid metabolism (Reactome: R-HSA-428157)
• HIV-1 Nef-mediated evasion of host restriction (Reactome: R-HSA-162587)
• Tumor suppressor pathways (not yet fully characterized)
Protein Summary
SERINC5 is a 10-transmembrane domain protein localized primarily to the plasma membrane and endosomes. It functions as a serine incorporator, facilitating the synthesis of phosphatidylserine and sphingolipids, which are essential for membrane integrity and signaling. In the context of HIV-1, SERINC5 is incorporated into budding virions, where it blocks viral fusion by interfering with the viral envelope glycoprotein. HIV-1 Nef counteracts this by binding to SERINC5 and promoting its internalization and degradation. In cancer, SERINC5 acts as a tumor suppressor by inhibiting cell proliferation, migration, and invasion, likely through modulation of signaling pathways such as PI3K/AKT and Wnt/β-catenin. Its expression is frequently downregulated in tumors, and restoration of SERINC5 may offer therapeutic potential.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SERINC5 Knockout HEK293 Cell Line | EDJ-KQ11852 | Human | 256987 | Details Get a Quote |
| SERINC5 Knockout A-549 Cell Line | EDJ-KQ40278 | Human | 256987 | Details Get a Quote |
| SERINC5 Knockout HCT 116 Cell Line | EDJ-KQ40279 | Human | 256987 | Details Get a Quote |
| SERINC5 Knockout HeLa Cell Line | EDJ-KQ40280 | Human | 256987 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
