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Literature summary for 1.14.11.65 extracted from
- The histone H3K9 demethylase KDM3A promotes anoikis by transcriptionally activating pro-apoptotic genes BNIP3 and BNIP3L (2016), eLife, 5, e16844 .
Application
| Application | Comment | Organism |
|---|---|---|
| medicine | KDM3A expression in human breast cancer cell lines and tumors is defective | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| expressed in Mus musculus | Homo sapiens |
| gene KDM3A, quantitative RT-PCR enzyme expression analysis, recombinant expression of wild-type KDM3A or catalytically inactive KDM3A mutant [KDM3A(H1120G/D1122N)] in MCF-10A cells | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| H1120G/D1122N | a catalytically-inactive KDM3A mutant | Homo sapiens |
| additional information | RNAi-mediated knockdown of KDM3A, Kdm3a knockdown 4T07 cells | Homo sapiens |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| extracellular matrix | - |
Homo sapiens | 31012 | - |
| nucleus | - |
Homo sapiens | 5634 | - |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 | Homo sapiens | - |
histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2 | - |
? |  |
| histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2 | Homo sapiens | - |
histone H3 L-lysine9 + succinate + formaldehyde + CO2 | - |
? | |
| additional information | Homo sapiens | KDM3A is a histone demethylase that specifically demethylates mono-methylated (me1) and di-methylated (me2) histone H3 lysine 9 (H3K9) | ? | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2 | Homo sapiens | overall reaction | [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2 | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2 | - |
? | |
| [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2 | Homo sapiens | - |
[histone H3]-L-lysine9 + succinate + formaldehyde + CO2 | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | - |
- |
- |
| Homo sapiens | Q9Y4C1 | - |
- |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| breast carcinoma cell | - |
Homo sapiens | - |
| breast epithelial cell | - |
Homo sapiens | - |
| BT-549 cell | - |
Homo sapiens | - |
| epithelial cell | - |
Homo sapiens | - |
| MCF-10A cell | - |
Homo sapiens | - |
| MCF-7 cell | - |
Homo sapiens | - |
| MDA-MB-231 cell | - |
Homo sapiens | - |
| SUM-149 cell | - |
Homo sapiens | - |
| SUM-149PT cell | - |
Homo sapiens | - |
| T-47D cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| histone H3 N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 | - |
Homo sapiens | histone H3 N6-methyl-L-lysine9 + succinate + formaldehyde + CO2 | - |
? | |
| histone H3 N6-methyl-L-lysine9 + 2-oxoglutarate + O2 | - |
Homo sapiens | histone H3 L-lysine9 + succinate + formaldehyde + CO2 | - |
? | |
| additional information | KDM3A is a histone demethylase that specifically demethylates mono-methylated (me1) and di-methylated (me2) histone H3 lysine 9 (H3K9) | Homo sapiens | ? | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine9 + 2 2-oxoglutarate + 2 O2 | overall reaction | Homo sapiens | [histone H3]-L-lysine9 + 2 succinate + 2 formaldehyde + 2 CO2 | - |
? | |
| [histone H3]-N6,N6-dimethyl-L-lysine9 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-N6-methyl-L-lysine9 + succinate + formaldehyde + CO2 | - |
? | |
| [histone H3]-N6-methyl-L-lysine9 + 2-oxoglutarate + O2 | - |
Homo sapiens | [histone H3]-L-lysine9 + succinate + formaldehyde + CO2 | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| H3K9 mono- and di-demethylase | - |
Homo sapiens |
| histone H3 lysine 9 mono- and di-demethylase | - |
Homo sapiens |
| histone H3K9 demethylase | - |
Homo sapiens |
| Kdm3a | - |
Homo sapiens |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Homo sapiens | in attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. Expression of either EGFR or MEK2DD decreases the levels of KDM3A in detached MCF10A cells | down |
| Homo sapiens | in attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. KDM3A protein levels are increased in attached MCF-10A cells treated with the EGFR inhibitor gefitinib. Detachment and loss of integrin and growth factor receptor signaling induces KDM3A expression | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | RNAi-mediated knockdown of KDM3A substantially reduces apoptosis following detachment and, conversely, ectopic expression of KDM3A induces cell death in attached cells. Knockdown of Kdm3a enhances metastatic potential in a mouse model of breast cancer metastasis. Defective KDM3A expression in human breast cancer cell lines and tumors. Kdm3a knockdown significantly increases the number of cells that survived in the mouse lung relative to the control NS shRNA | Homo sapiens |
| malfunction | switching off the enzyme in cancer cells increases their ability to move around the body | Homo sapiens |
| additional information | in attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression | Homo sapiens |
| physiological function | epithelial cells that lose attachment to the extracellular matrix (ECM), or attach to an inappropriate ECM, undergo a specialized form of apoptosis called anoikis. Anoikis has an important role in preventing oncogenesis, particularly metastasis, by eliminating cells that lack proper ECM cues. Histone H3K9 demethylase KDM3A promotes anoikis by transcriptionally activating pro-apoptotic genes BNIP3 and BNIP3L. KDM3A demethylates H3K9me1/2 to stimulate expression of one or more pro-apoptotic genes. KDM3A promotes anoikis through transcriptional activation of BNIP3 and BNIP3L, which encode pro-apoptotic proteins. Identification of KDM3A as an anoikis effector in breast cancer epithelial cells, overview | Homo sapiens |
| physiological function | in attached breast epithelial cells, KDM3A expression is maintained at low levels by integrin signaling. Following detachment, integrin signaling is decreased resulting in increased KDM3A expression. Knockdown of KDM3A substantially reduces apoptosis following detachment and, ectopic expression of KDM3A induces cell death in attached cells. KDM3A promotes anoikis through transcriptional activation of BNIP3 and BNIP3L, which encode pro-apoptotic proteins | Homo sapiens |
| physiological function | the enzyme prevents metastasis | Homo sapiens |
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