UFL1: UFM1-Specific Ligase 1
A key component of the UFMylation system involved in endoplasmic reticulum stress response and protein homeostasis.
Gene Information Card
| Symbol | UFL1 |
|---|---|
| Full Name | UFM1 Specific Ligase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q16.1 |
| NCBI Gene ID | 23376 ncbi.nlm.nih.gov/gene/23376 |
| Ensembl ID | ENSG00000112210 |
| UniProt ID | Q94874 |
| OMIM ID | 613372 |
| HGNC ID | 29565 |
| Aliases | RCAD, NLBP, UFM1 ligase 1, UFL1a, UFL1b |
Description
UFL1 encodes the E3 ligase for UFM1 (ubiquitin-fold modifier 1), catalyzing the final step of UFMylation. This post-translational modification targets proteins such as DDRGK1 and is critical for endoplasmic reticulum (ER) homeostasis, unfolded protein response, and hematopoiesis. UFL1 is widely expressed and its dysfunction is linked to developmental disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Developmental and epileptic encephalopathy 107 (DEE107) | Loss-of-function mutations in UFL1 impair UFMylation, leading to ER stress and neuronal dysfunction. | ClinVar, OMIM |
| Bone marrow failure syndrome 6 (BMFS6) | Biallelic UFL1 mutations disrupt hematopoietic stem cell maintenance via defective UFMylation. | ClinVar, OMIM |
| Colorectal cancer | UFL1 overexpression promotes tumor growth through enhanced UFMylation of β-catenin. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 10.2 | High |
| Brain | 6.8 | Medium |
| Heart | 5.1 | Medium |
| Lung | 4.3 | Medium |
| Skeletal muscle | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.3 | High expression |
| HepG2 | 11.7 | High expression |
| SH-SY5Y | 7.4 | Medium expression |
| A549 | 5.9 | Medium expression |
| K562 | 3.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.676C>T (p.Arg226*) | Nonsense | Rare (0.0001) | Loss of function; truncation of UFL1 protein |
| c.1024G>A (p.Gly342Arg) | Missense | Rare (0.0002) | Impaired UFM1 ligase activity |
| c.1450_1451del (p.Leu484fs) | Frameshift | Rare (0.00005) | Loss of function; premature termination |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg226*, p.Leu484fs) cause complete or partial loss of UFM1 ligase activity, leading to ER stress and disease.
Gain of Function (GOF)
Not reported in UFL1.
Dominant Negative (DN)
Not reported in UFL1.
View complete mutation data：
Gene Ontology (GO)
| • UFM1 ligase activity (GO:0061659) | • Protein ufmylation (GO:0071569) |
| • Endoplasmic reticulum (GO:0005783) | • Response to endoplasmic reticulum stress (GO:0034976) |
| • Protein homeostasis (GO:0030163) |
Pathways
• UFMylation pathway (R-HSA-8866654)
• Unfolded Protein Response (UPR) (R-HSA-381119)
Protein Summary
UFL1 is a 794-amino acid protein that functions as the E3 ligase in the UFM1 conjugation system. It localizes to the endoplasmic reticulum membrane and mediates the attachment of UFM1 to target proteins such as DDRGK1, regulating ER stress responses and protein quality control. The protein contains a conserved UFL1 domain essential for ligase activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| UFL1 Knockout HEK293 Cell Line | EDJ-KQ2091 | Human | 23376 | Details Get a Quote |
| UFL1 Knockout A-549 Cell Line | EDJ-KQ22184 | Human | 23376 | Details Get a Quote |
| UFL1 Knockout HCT 116 Cell Line | EDJ-KQ22185 | Human | 23376 | Details Get a Quote |
| UFL1 Knockout HeLa Cell Line | EDJ-KQ22186 | Human | 23376 | Details Get a Quote |
