SUMO4: Small Ubiquitin Like Modifier 4
A key regulator of protein SUMOylation involved in immune response and diabetes susceptibility
Gene Information Card
| Symbol | SUMO4 |
|---|---|
| Full Name | Small Ubiquitin Like Modifier 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 6q25.1 |
| NCBI Gene ID | 387082 ncbi.nlm.nih.gov/gene/387082 |
| Ensembl ID | ENSG00000198211 |
| UniProt ID | Q6EEV6 |
| OMIM ID | 608833 |
| HGNC ID | 21182 |
| Aliases | SMT3H4, SUMO-4, dJ281H8.1 |
Description
SUMO4 encodes a member of the small ubiquitin-like modifier (SUMO) protein family. SUMO4 is involved in post-translational modification of target proteins through SUMOylation, a process that regulates protein stability, localization, and transcriptional activity. Unlike other SUMO paralogs, SUMO4 is predominantly expressed in immune tissues and plays a critical role in modulating NF-κB signaling and immune responses. A common missense variant (M55V) has been associated with susceptibility to type 1 diabetes and other autoimmune diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Type 1 Diabetes | The M55V variant (rs237025) impairs SUMO4-mediated inhibition of NF-κB, leading to increased pro-inflammatory cytokine production and beta-cell autoimmunity. | OMIM 608833; NCBI Gene; ClinVar |
| Systemic Lupus Erythematosus | SUMO4 M55V variant may contribute to altered immune regulation and increased inflammatory responses. | OMIM 608833; PubMed studies |
| Rheumatoid Arthritis | Association studies link SUMO4 polymorphisms with increased risk of rheumatoid arthritis in certain populations. | OMIM 608833; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 4.2 | Medium |
| Lymph Node | 3.8 | Medium |
| Spleen | 3.5 | Medium |
| Pancreas | 2.1 | Low |
| Liver | 1.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 5.1 | Moderate expression |
| Jurkat T cells | 6.3 | High expression |
| HeLa | 2.8 | Low expression |
| HepG2 | 1.9 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.163A>G (p.Met55Val) | Missense | Common (allele frequency ~0.3 in East Asians) | Alters SUMO4 function; associated with type 1 diabetes |
| c.1A>G (p.Met1Val) | Missense | Rare | Potential impact on translation initiation |
Mutation functional classification
Loss of Function (LOF)
The M55V variant is considered a hypomorphic allele with reduced ability to SUMOylate targets, leading to impaired negative regulation of NF-κB.
Gain of Function (GOF)
No gain-of-function mutations have been reported for SUMO4.
Dominant Negative (DN)
The M55V variant may act in a dominant-negative manner by competing with wild-type SUMO4 for target binding but failing to modify them properly.
View complete mutation data：
Gene Ontology (GO)
| • protein SUMOylation (GO:0016925) | • nucleus (GO:0005634) |
| • cytosol (GO:0005829) | • identical protein binding (GO:0042802) |
| • protein binding (GO:0005515) |
Pathways
• SUMOylation pathway (Reactome: R-HSA-2990846)
• NF-κB signaling (KEGG: hsa04064)
Protein Summary
SUMO4 is a 95-amino acid protein that belongs to the SUMO family. It shares high sequence similarity with SUMO2/3 but contains a unique proline-rich N-terminal region. SUMO4 is processed by SENP proteases to expose a C-terminal diglycine motif required for conjugation to lysine residues on target proteins. Unlike other SUMOs, SUMO4 is not stress-inducible and is primarily expressed in immune cells. The M55V variant reduces its SUMOylation efficiency and has been linked to autoimmune diseases.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SUMO4 Knockout HEK293 Cell Line | EDJ-KQ15566 | Human | 387082 | Details Get a Quote |
| SUMO4 Knockout HeLa Cell Line | EDJ-KQ59967 | Human | 387082 | Details Get a Quote |
| SUMO4 Knockout A-549 Cell Line | EDJ-KQ68429 | Human | 387082 | Details Get a Quote |
| SUMO4 Knockout HCT 116 Cell Line | EDJ-KQ76807 | Human | 387082 | Details Get a Quote |
