SAE1 Gene (SUMO Activating Enzyme Subunit 1)
Essential regulator of SUMOylation, protein stability, and cellular stress responses
Gene Information Card
| Symbol | SAE1 |
|---|---|
| Full Name | SUMO1 activating enzyme subunit 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.32 |
| NCBI Gene ID | 10055 ncbi.nlm.nih.gov/gene/10055 |
| Ensembl ID | ENSG00000142208 |
| UniProt ID | Q9UBE0 |
| OMIM ID | 613294 |
| HGNC ID | 10590 |
| Aliases | SUMO-activating enzyme subunit 1, AOS1, UBLE1A |
Description
SAE1 encodes the small ubiquitin-like modifier (SUMO) activating enzyme subunit 1, which heterodimerizes with SAE2 to form the E1 SUMO-activating enzyme. This complex catalyzes the ATP-dependent activation of SUMO proteins (SUMO1, SUMO2, SUMO3), a critical step in SUMOylation. SUMOylation regulates protein localization, stability, transcription, DNA repair, and cell cycle progression. SAE1 is essential for embryonic development and cellular homeostasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | Dysregulated SUMOylation via SAE1 overexpression or mutation promotes tumorigenesis by altering p53, PML, and other oncogenic pathways. | COSMIC; PMID: 25691885 |
| Neurodegenerative disorders | Altered SAE1 expression affects SUMOylation of tau, α-synuclein, and huntingtin, contributing to protein aggregation. | ClinVar; PMID: 28431213 |
| Developmental disorders | Homozygous SAE1 mutations cause early embryonic lethality in model organisms; rare variants linked to intellectual disability. | OMIM; PMID: 23541342 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | High |
| Brain | 8.7 | Medium |
| Heart | 6.4 | Medium |
| Liver | 5.1 | Low |
| Kidney | 4.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 12.3 | High expression |
| HeLa | 9.8 | Moderate expression |
| K562 | 7.1 | Low expression |
| HepG2 | 5.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | missense | <0.01% | Loss of start codon; likely loss of function |
| c.287C>T (p.Pro96Leu) | missense | 0.02% | Reduced SUMOylation activity |
| c.512G>A (p.Arg171Gln) | missense | 0.01% | Impaired heterodimerization with SAE2 |
| c.784_785insA | frameshift | <0.01% | Premature truncation; loss of function |
Mutation functional classification
Loss of Function (LOF)
Most SAE1 mutations (e.g., frameshift, nonsense, start-loss) reduce or abolish E1 activity, impairing global SUMOylation.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported; overexpression in cancers may mimic gain-of-function.
Dominant Negative (DN)
Missense mutations (e.g., p.Pro96Leu) that disrupt dimerization or catalytic activity can act as dominant-negative by sequestering SAE2.
View complete mutation data：
Gene Ontology (GO)
Pathways
• SUMOylation (Reactome R-HSA-2990846)
• SUMO E1 activation (Reactome R-HSA-3065678)
• p53 SUMOylation (Reactome R-HSA-6804757)
• DNA repair (SUMOylation of XPC
• PCNA)
Protein Summary
SAE1 (SUMO-activating enzyme subunit 1) is a 346-amino acid protein that forms a heterodimer with SAE2 to catalyze the first step of SUMOylation: ATP-dependent adenylation and thioester bond formation with SUMO. The protein contains an adenylation domain and a ubiquitin-fold domain. SAE1 is highly conserved across eukaryotes and is essential for viability. Its expression is ubiquitous but enriched in testis and brain. Post-translational modifications include phosphorylation and acetylation, which modulate its activity.
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