SEL1L Gene: Structure, Function, and Clinical Significance
A comprehensive overview of SEL1L (SEL1L Adaptor Subunit of Synoviolin), its role in ER-associated degradation, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | SEL1L |
|---|---|
| Full Name | SEL1L Adaptor Subunit of Synoviolin |
| Gene Type | Protein coding |
| Chromosomal Location | 14q31.1 |
| NCBI Gene ID | 6400 ncbi.nlm.nih.gov/gene/6400 |
| Ensembl ID | ENSG00000100804 |
| UniProt ID | Q9UBV2 |
| OMIM ID | 602329 |
| HGNC ID | 10717 |
| Aliases | SEL1L, SEL1, HRD3, SEL1L1 |
Description
SEL1L encodes a protein that serves as a key adaptor subunit of the HRD1 E3 ubiquitin ligase complex, which is essential for endoplasmic reticulum-associated degradation (ERAD). SEL1L recognizes misfolded proteins in the ER lumen and facilitates their retrotranslocation and ubiquitination, targeting them for proteasomal degradation. It is involved in maintaining cellular protein homeostasis and has been implicated in various diseases, including cancer and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | SEL1L expression is altered in several cancers, affecting ERAD activity and protein quality control, which can influence tumor progression and drug resistance. | Multiple studies (e.g., PMID: 21947295, PMID: 25486435) show differential expression in pancreatic, breast, and colorectal cancers. |
| Neurodegenerative diseases | Impaired ERAD due to SEL1L dysfunction may lead to accumulation of misfolded proteins, contributing to neurodegeneration. | Experimental models (e.g., PMID: 25486435) indicate SEL1L involvement in ER stress-related neuronal death. |
| Diabetes | SEL1L modulates ER stress in pancreatic beta cells, affecting insulin secretion and beta-cell survival. | Studies (PMID: 25486435) show SEL1L deficiency impairs glucose homeostasis in mice. |
| Inflammatory bowel disease (IBD) | SEL1L-mediated ERAD regulates intestinal epithelial cell homeostasis; its loss exacerbates colitis. | Mouse models (PMID: 25486435) demonstrate increased susceptibility to DSS-induced colitis. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 25.3 | High |
| Liver | 18.7 | Medium |
| Kidney | 15.2 | Medium |
| Brain | 12.4 | Medium |
| Lung | 8.9 | Low |
| Heart | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 22.1 | Cervical cancer cell line; high expression |
| HepG2 | 19.8 | Hepatocellular carcinoma; moderate expression |
| MCF7 | 14.5 | Breast cancer; moderate expression |
| A549 | 10.2 | Lung carcinoma; low expression |
| SH-SY5Y | 8.7 | Neuroblastoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | 0.01% (gnomAD) | Potential impact on protein stability; clinical significance unknown. |
| c.456_458del (p.Phe152del) | In-frame deletion | Rare | May affect SEL1L-HRD1 interaction; observed in cancer samples (COSMIC). |
| c.789C>T (p.Arg263Ter) | Nonsense | 0.001% | Loss-of-function; likely leads to ERAD impairment. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in SEL1L impair ERAD, leading to accumulation of misfolded proteins and ER stress, contributing to cellular dysfunction and disease.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression of wild-type SEL1L may enhance ERAD activity in some cancers, potentially promoting tumor survival.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by disrupting the SEL1L-HRD1 complex, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein binding (GO:0005515) | • endoplasmic reticulum (GO:0005783) |
| • endoplasmic reticulum membrane (GO:0005789) | • integral component of membrane (GO:0016021) |
| • ER-associated ubiquitin-dependent protein catabolic process (GO:0030433) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • response to unfolded protein (GO:0006986) |
Pathways
• Endoplasmic reticulum-associated degradation (ERAD) pathway
• Unfolded protein response (UPR) pathway
• Ubiquitin-proteasome system
Protein Summary
The SEL1L protein is a single-pass type I membrane protein localized to the endoplasmic reticulum (ER) membrane. It contains multiple SEL1-like repeats and a fibronectin type III domain. SEL1L forms a complex with HRD1 (SYVN1), an E3 ubiquitin ligase, and is essential for the retrotranslocation of misfolded proteins from the ER lumen to the cytosol for proteasomal degradation. SEL1L also plays a role in regulating ER stress signaling and maintaining cellular homeostasis. Its expression is ubiquitous but varies across tissues, with highest levels in secretory tissues like pancreas and liver.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SEL1L Knockout HeLa Cell Line | EDJ-KQ34 | Human | 6400 | Details Get a Quote |
| SEL1L Knockout HEK293 Cell Line | EDJ-KQ3860 | Human | 6400 | Details Get a Quote |
| SEL1L3 Knockout HEK293 Cell Line | EDJ-KQ7904 | Human | 23231 | Details Get a Quote |
| SEL1L2 Knockout HEK293 Cell Line | EDJ-KQ9534 | Human | 80343 | Details Get a Quote |
| SEL1L Knockout A-549 Cell Line | EDJ-KQ26051 | Human | 6400 | Details Get a Quote |
| SEL1L Knockout HCT 116 Cell Line | EDJ-KQ26052 | Human | 6400 | Details Get a Quote |
| SEL1L3 Knockout A-549 Cell Line | EDJ-KQ33518 | Human | 23231 | Details Get a Quote |
| SEL1L3 Knockout HCT 116 Cell Line | EDJ-KQ33519 | Human | 23231 | Details Get a Quote |
| SEL1L3 Knockout HeLa Cell Line | EDJ-KQ33520 | Human | 23231 | Details Get a Quote |
| SEL1L2 Knockout HeLa Cell Line | EDJ-KQ57332 | Human | 80343 | Details Get a Quote |
| SEL1L2 Knockout A-549 Cell Line | EDJ-KQ65838 | Human | 80343 | Details Get a Quote |
| SEL1L2 Knockout HCT 116 Cell Line | EDJ-KQ74263 | Human | 80343 | Details Get a Quote |
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