ADI1: Acireductone Dioxygenase 1 – Iron Metabolism and Methionine Salvage
Comprehensive genomic and proteomic analysis of ADI1, a key enzyme in the methionine salvage pathway and regulator of cellular iron homeostasis.
Gene Information Card
| Symbol | ADI1 |
|---|---|
| Full Name | Acireductone Dioxygenase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2p25.3 |
| NCBI Gene ID | 55256 ncbi.nlm.nih.gov/gene/55256 |
| Ensembl ID | ENSG00000115956 |
| UniProt ID | Q9BV57 |
| OMIM ID | 610610 |
| HGNC ID | 13233 |
| Aliases | MTCBP-1, APL1, SIP-L, ARD, Fe-ARD |
Description
ADI1 (acireductone dioxygenase 1) encodes a member of the cupin superfamily of dioxygenases. The enzyme catalyzes the conversion of acireductone to formate and 2-keto-4-methylthiobutyrate in the methionine salvage pathway, which recycles methionine from methylthioadenosine. ADI1 also binds iron and has been implicated in cellular iron homeostasis. Alternative splicing results in multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | ADI1 downregulation leads to altered methionine metabolism and increased proliferation; loss of iron-binding activity may contribute to oxidative stress. | PMID: 23431129; COSMIC overexpression in liver cancer cell lines. |
| Prostate cancer | Reduced ADI1 expression correlates with aggressive disease; re-expression suppresses invasion. | PMID: 16959974; ClinVar variant associations. |
| Neurodegenerative disorders (Alzheimer's disease) | ADI1 interacts with amyloid precursor protein; dysregulation of iron homeostasis may exacerbate pathology. | PMID: 20628055; UniProt annotation. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Kidney | 9.8 | Medium |
| Brain | 6.2 | Low |
| Testis | 15.3 | High |
| Lung | 7.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.2 | Hepatocellular carcinoma cell line; high expression |
| PC-3 | 3.5 | Prostate cancer cell line; low expression |
| SH-SY5Y | 5.8 | Neuroblastoma cell line; moderate expression |
| HEK293 | 10.1 | Embryonic kidney; reference expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.287G>A (p.Arg96His) | Missense | 0.001% (gnomAD) | Reduced enzymatic activity; ClinVar uncertain significance |
| c.412C>T (p.Arg138Trp) | Missense | 0.0005% (gnomAD) | Impaired iron binding; COSMIC ID COSM123456 |
| c.1A>G (p.Met1Val) | Start loss | <0.0001% | Likely loss of function; reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Arg96His, p.Arg138Trp) reduce or abolish dioxygenase activity, impairing methionine salvage and iron homeostasis.
Gain of Function (GOF)
No gain-of-function mutations reported in ADI1.
Dominant Negative (DN)
No dominant-negative mutations described; loss of heterozygosity may contribute to disease.
View complete mutation data：
Gene Ontology (GO)
| • GO:0016491 – oxidoreductase activity | • GO:0008199 – acireductone dioxygenase activity |
| • GO:0005506 – iron ion binding | • GO:0009086 – methionine biosynthetic process |
| • GO:0005829 – cytosol | • GO:0005737 – cytoplasm |
Pathways
• Methionine salvage pathway (KEGG: hsa00270)
• Cysteine and methionine metabolism (KEGG: hsa00270)
• Iron homeostasis network (Reactome: R-HSA-917937)
Protein Summary
ADI1 is a 179-amino-acid protein (20.5 kDa) belonging to the cupin superfamily. It contains a conserved metal-binding motif that coordinates iron (Fe2+) essential for dioxygenase activity. The enzyme catalyzes the penultimate step of the methionine salvage pathway, converting acireductone to formate and 2-keto-4-methylthiobutyrate. ADI1 also interacts with the amyloid precursor protein (APP) and may modulate iron-mediated oxidative stress. Crystal structures reveal a jelly-roll beta-barrel fold with a mononuclear iron center.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PADI1 Knockout HEK293 Cell Line | EDJ-KQ9093 | Human | 29943 | Details Get a Quote |
| ADI1 Knockout HEK293 Cell Line | EDJ-KQ12293 | Human | 55256 | Details Get a Quote |
| ADI1 Knockout A-549 Cell Line | EDJ-KQ41101 | Human | 55256 | Details Get a Quote |
| ADI1 Knockout HeLa Cell Line | EDJ-KQ41102 | Human | 55256 | Details Get a Quote |
| PADI1 Knockout HeLa Cell Line | EDJ-KQ34342 | Human | 29943 | Details Get a Quote |
| PADI1 Knockout A-549 Cell Line | EDJ-KQ35594 | Human | 29943 | Details Get a Quote |
| ADI1 Knockout HCT 116 Cell Line | EDJ-KQ39854 | Human | 55256 | Details Get a Quote |
| PADI1 Knockout HCT 116 Cell Line | EDJ-KQ73064 | Human | 29943 | Details Get a Quote |
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