SEPHS2: Selenophosphate Synthetase 2
Key enzyme in selenium metabolism and selenoprotein biosynthesis
Gene Information Card
| Symbol | SEPHS2 |
|---|---|
| Full Name | Selenophosphate Synthetase 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p11.2 |
| NCBI Gene ID | 22928 ncbi.nlm.nih.gov/gene/22928 |
| Ensembl ID | ENSG00000103657 |
| UniProt ID | Q99611 |
| OMIM ID | 606218 |
| HGNC ID | 19686 |
| Aliases | SPS2, SELD, SPSII |
Description
SEPHS2 encodes selenophosphate synthetase 2, an enzyme that catalyzes the synthesis of selenophosphate from selenide and ATP. Selenophosphate is the essential selenium donor for the co-translational incorporation of selenocysteine into selenoproteins. SEPHS2 is critical for antioxidant defense, thyroid hormone metabolism, and redox regulation. Mutations or dysregulation of SEPHS2 are linked to selenoprotein deficiency, cancer progression, and neurodegenerative disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Selenoprotein deficiency | Impaired selenocysteine incorporation due to reduced selenophosphate synthesis | PMID: 23431279 |
| Colorectal cancer | Overexpression of SEPHS2 promotes tumor growth by supporting selenoprotein synthesis and redox balance | PMID: 29712941 |
| Breast cancer | SEPHS2 upregulation correlates with poor prognosis and resistance to oxidative stress | PMID: 31570863 |
| Neurodegeneration (Alzheimer's disease) | Altered selenium metabolism and SEPHS2 expression affect neuronal antioxidant capacity | PMID: 25655837 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | High |
| Kidney | 9.8 | Medium |
| Testis | 8.2 | Medium |
| Brain | 6.1 | Low |
| Heart | 5.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.3 | Hepatocellular carcinoma cell line |
| MCF7 | 10.1 | Breast cancer cell line |
| HEK293 | 7.6 | Embryonic kidney cells |
| SH-SY5Y | 5.2 | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.94G>A (p.Gly32Arg) | Missense | <0.01% | Reduced enzymatic activity; associated with selenoprotein deficiency |
| c.347T>C (p.Leu116Pro) | Missense | <0.01% | Impaired selenophosphate synthesis; reported in familial cases |
| c.568A>G (p.Thr190Ala) | Missense | 0.02% | Decreased stability; potential modifier in cancer |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Gly32Arg, p.Leu116Pro) reduce or abolish selenophosphate synthetase activity, leading to deficient selenoprotein synthesis.
Gain of Function (GOF)
Not documented; no activating mutations reported.
Dominant Negative (DN)
Not documented; no dominant-negative variants described.
View complete mutation data：
Gene Ontology (GO)
| • selenide | • water dikinase activity |
| • ATP binding | • selenocysteine incorporation |
| • selenium compound metabolic process | • response to oxidative stress |
Pathways
• Selenocysteine biosynthesis
• Selenium metabolism
• Selenoprotein synthesis
Protein Summary
SEPHS2 is a 448-amino acid protein localized in the cytoplasm and nucleus. It functions as a homodimer, utilizing ATP to phosphorylate selenide to selenophosphate. The enzyme is essential for the biosynthesis of selenocysteine, the 21st amino acid, which is incorporated into selenoproteins such as glutathione peroxidases and thioredoxin reductases. SEPHS2 activity is regulated by selenium availability and redox status. Structural studies reveal a catalytic domain with a conserved ATP-binding site and a flexible loop critical for substrate binding.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SEPHS2 Knockout HEK293 Cell Line | EDJ-KQ2292 | Human | 22928 | Details Get a Quote |
| SEPHS2 Knockout HCT 116 Cell Line | EDJ-KQ22650 | Human | 22928 | Details Get a Quote |
| SEPHS2 Knockout HeLa Cell Line | EDJ-KQ22651 | Human | 22928 | Details Get a Quote |
| SEPHS2 Knockout A-549 Cell Line | EDJ-KQ64157 | Human | 22928 | Details Get a Quote |
