DDRGK1: A Key Regulator of UFMylation and Ribosome Quality Control
Comprehensive genomic and proteomic analysis of DDRGK1, a UFM1-specific E3 ligase component involved in ER stress, bone development, and cancer.
Gene Information Card
| Symbol | DDRGK1 |
|---|---|
| Full Name | DDRGK domain containing 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p13 |
| NCBI Gene ID | 65982 ncbi.nlm.nih.gov/gene/65982 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | Q96HY6 |
| OMIM ID | 614177 |
| HGNC ID | 16110 |
| Aliases | C20orf116, dJ1181N3.1, UFBP1, UFM1-binding protein 1 |
Description
DDRGK1 (DDRGK domain containing 1), also known as UFBP1, encodes a protein that serves as a component of the UFM1-specific E3 ligase complex. It is essential for UFMylation, a post-translational modification that targets ribosomes and regulates ribosome-associated quality control, ER stress response, and hematopoiesis. Mutations in DDRGK1 cause Shoji syndrome (spondyloepimetaphyseal dysplasia with joint laxity), and altered expression is implicated in various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Shoji syndrome (spondyloepimetaphyseal dysplasia with joint laxity) | Loss-of-function mutations impair UFMylation, leading to defective ribosome quality control and skeletal dysplasia. | OMIM #614177; PMID: 28132693 |
| Hepatocellular carcinoma | DDRGK1 overexpression promotes tumor growth via UFMylation of ribosomal proteins and activation of NF-κB signaling. | COSMIC; PMID: 31527837 |
| Breast cancer | DDRGK1 upregulation correlates with poor prognosis; UFMylation of 60S ribosomal proteins enhances translation of oncogenic mRNAs. | COSMIC; PMID: 32084332 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 28.5 | High |
| Liver | 22.1 | High |
| Kidney | 18.7 | Medium |
| Heart | 12.3 | Medium |
| Brain | 6.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver cancer) | 32.4 | High expression; consistent with liver tissue data |
| MCF7 (breast cancer) | 25.1 | Elevated compared to normal breast tissue |
| HEK293 (embryonic kidney) | 19.8 | Moderate expression |
| K562 (leukemia) | 10.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.502C>T (p.Arg168Trp) | Missense | Rare (0.0004) | Loss of UFM1 binding; associated with Shoji syndrome |
| c.1A>G (p.Met1Val) | Start loss | Very rare | Complete loss of protein; severe skeletal dysplasia |
| c.832G>A (p.Gly278Arg) | Missense | Somatic (0.2% in COSMIC) | Gain of function?; reported in colorectal cancer |
Mutation functional classification
Loss of Function (LOF)
Homozygous missense (p.Arg168Trp) and start-loss (p.Met1Val) mutations abolish UFM1 binding or protein expression, leading to defective UFMylation and Shoji syndrome.
Gain of Function (GOF)
Somatic missense mutations (e.g., p.Gly278Arg) in cancer may enhance UFMylation activity or alter substrate specificity, promoting oncogenic translation.
Dominant Negative (DN)
No dominant-negative mutations currently reported in ClinVar or literature.
View complete mutation data：
Gene Ontology (GO)
Pathways
• UFMylation pathway (R-HSA-8868773)
• Ribosome quality control (R-HSA-9759567)
• ER stress response (R-HSA-381119)
Protein Summary
DDRGK1 (UFBP1) is a 369-amino-acid protein containing a conserved DDRGK domain. It functions as a scaffold for the UFM1-conjugating enzyme UFC1 and the E3 ligase UFL1, facilitating UFMylation of ribosomal proteins (e.g., RPL26). This modification regulates ribosome stalling, translation fidelity, and ER homeostasis. The protein localizes to the endoplasmic reticulum and nucleus. Structural studies show that the DDRGK domain mediates interaction with UFM1 and is critical for complex assembly.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DDRGK1 Knockout HEK293 Cell Line | EDJ-KQ13111 | Human | 65992 | Details Get a Quote |
| DDRGK1 Knockout HCT 116 Cell Line | EDJ-KQ41187 | Human | 65992 | Details Get a Quote |
| DDRGK1 Knockout A-549 Cell Line | EDJ-KQ42418 | Human | 65992 | Details Get a Quote |
| DDRGK1 Knockout HeLa Cell Line | EDJ-KQ42419 | Human | 65992 | Details Get a Quote |
