SEC61G: The Essential Translocon Subunit in Protein Translocation and Disease
A comprehensive overview of SEC61G, a core component of the SEC61 translocon complex, its role in protein biogenesis, associated pathologies, and expression profiles.
Gene Information Card
| Symbol | SEC61G |
|---|---|
| Full Name | SEC61 translocon subunit gamma |
| Gene Type | protein coding |
| Chromosomal Location | 7p11.2 |
| NCBI Gene ID | 23480 ncbi.nlm.nih.gov/gene/23480 |
| Ensembl ID | ENSG00000132432 |
| UniProt ID | P60059 |
| OMIM ID | 609214 |
| HGNC ID | 16992 |
| Aliases | SSR-gamma, SEC61GAMMA |
Description
SEC61G encodes the gamma subunit of the SEC61 complex, a highly conserved heterotrimeric channel essential for the translocation of nascent secretory and membrane proteins into the endoplasmic reticulum (ER). The SEC61 complex, composed of alpha, beta, and gamma subunits, forms a ribosome receptor and a protein-conducting channel. The gamma subunit is a small, non-glycosylated protein that is crucial for the structural stability and function of the complex. It plays a fundamental role in co-translational protein translocation, maintaining cellular protein homeostasis, and is implicated in various physiological and pathological processes, including cancer and immune responses.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | SEC61G is overexpressed in several cancers, potentially enhancing the translocation of growth factor receptors and other oncogenic proteins to the cell surface, promoting tumor progression. | COSMIC; PubMed studies showing upregulation in breast, lung, and colorectal cancers. |
| Immunodeficiency | Defects in SEC61G can impair the translocation of proteins, including MHC class I molecules, leading to altered immune responses and potential susceptibility to infections. | ClinVar; Studies on SEC61 complex deficiencies. |
| Developmental Disorders | Mutations affecting the SEC61 complex can disrupt protein secretion during development, potentially leading to syndromic phenotypes, though specific SEC61G-related syndromes are rare. | OMIM; Literature on SEC61 complex mutations. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 38.2 | High |
| Liver | 25.1 | High |
| Kidney | 22.8 | High |
| Lung | 18.5 | Medium |
| Brain | 12.3 | Medium |
| Heart | 10.9 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical cancer) | 45.0 | High expression, consistent with active protein secretion. |
| HepG2 (liver cancer) | 38.5 | High expression, reflecting its role in secretory tissues. |
| A549 (lung cancer) | 30.2 | High expression, potentially linked to oncogenic signaling. |
| MCF7 (breast cancer) | 28.7 | High expression, may support tumor growth. |
| K562 (leukemia) | 15.4 | Moderate expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.157C>T (p.Arg53Trp) | Missense | Rare (<0.01%) | May affect protein stability or interaction with other translocon subunits, potentially impairing translocation efficiency. |
| c.224A>G (p.Asn75Ser) | Missense | Rare (<0.01%) | Located in a conserved region; predicted to be possibly damaging, may alter complex assembly. |
| c.1-16C>T | 5' UTR variant | Unknown | Could affect mRNA stability or translation efficiency, leading to altered SEC61G protein levels. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SEC61G are rare and may lead to reduced translocon activity, causing ER stress and impaired secretion of key proteins. This could manifest as cellular dysfunction and potentially contribute to developmental or immune-related pathologies.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented for SEC61G. However, gene amplification or overexpression, often seen in cancers, can be considered a functional gain, enhancing protein translocation capacity and supporting rapid cell proliferation.
Dominant Negative (DN)
A dominant-negative effect is possible if a mutant SEC61G protein integrates into the translocon complex and disrupts its function, even in the presence of the wild-type allele. This could severely impair protein translocation, but specific disease-associated dominant-negative mutations have not been extensively characterized.
View complete mutation data：
Gene Ontology (GO)
| • protein transport | • ER to Golgi vesicle-mediated transport |
| • cotranslational protein targeting to membrane | • SRP-dependent cotranslational protein targeting to membrane |
| • protein targeting to ER | • translocon complex |
| • endoplasmic reticulum membrane | • integral component of membrane |
| • protein channel activity |
Pathways
• Protein processing in endoplasmic reticulum
• SRP-dependent cotranslational protein targeting to membrane
• Post-translational protein modification
• Metabolism of proteins
Protein Summary
The SEC61 gamma subunit is a small, integral membrane protein of 68 amino acids. It is a component of the heterotrimeric SEC61 complex, which forms the core of the translocon. While the alpha subunit forms the main channel pore, the gamma subunit is essential for the structural integrity and stability of the entire complex. It is localized in the endoplasmic reticulum (ER) membrane and plays a critical role in the co-translational translocation of proteins into the ER lumen. This process is fundamental for the proper folding, modification, and delivery of secretory and membrane proteins. The protein is highly conserved across species, underscoring its essential cellular function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SEC61G Knockout HEK293 Cell Line | EDJ-KQ51110 | Human | 23480 | Details Get a Quote |
| SEC61G Knockout HeLa Cell Line | EDJ-KQ55748 | Human | 23480 | Details Get a Quote |
| SEC61G Knockout A-549 Cell Line | EDJ-KQ64246 | Human | 23480 | Details Get a Quote |
| SEC61G Knockout HCT 116 Cell Line | EDJ-KQ72692 | Human | 23480 | Details Get a Quote |
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