| Post Translational Modifications | Phosphorylated at Ser-87 and Ser-325 in response to reactive oxygen species (ROS), promoting sumoylation and inactivation. Acetylated by KAT8 at Lys-235, promoting interaction with PSPC1, thereby facilitating recognition of N(6)-methyladenosine (m6A) mRNA by ALKBH5. Deacetylated at Lys-235 by HDAC7. Sumoylated at Lys-86 and Lys-321 by PIAS4 following phosphorylation at Ser-87 and Ser-325 in response to reactive oxygen species (ROS), inhibiting the RNA demethylase activity. Desumoylated by SENP1.relieving RNA demethylase inhibition, leading to N(6)-methyladenosine-containing mRNAs demethylation. Ubiquitinated at Lys-57 via 'Lys-48'-linked polyubiquitin chain, leading to its degradation by the proteasome. Deubiquitinated at Lys-57 by USP9X, promoting its stabilizazion. |
| Function | Dioxygenase that specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Demethylates RNA by oxidative demethylation, which requires molecular oxygen, alpha-ketoglutarate and iron. Demethylation of m6A mRNA affects mRNA processing, translation and export. Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro). Required for the late meiotic and haploid phases of spermatogenesis by mediating m6A demethylation in spermatocytes and round spermatids: m6A demethylation of target transcripts is required for correct splicing and the production of longer 3'-UTR mRNAs in male germ cells. Involved in paraspeckle assembly, a nuclear membraneless organelle, by undergoing liquid-liquid phase separation. Paraspeckle assembly is coupled with m6A demethylation of RNAs, such as NEAT1 non-coding RNA. Also acts as a negative regulator of T-cell development: inhibits gamma-delta T-cell proliferation via demethylation of JAG1 and NOTCH2 transcripts. Inhibits regulatory T-cell (Treg) recruitment by mediating demethylation and destabilization of CCL28 mRNAs. |
| Protein Name | Rna Demethylase Alkbh5Alkylated Dna Repair Protein Alkb Homolog 5Alpha-Ketoglutarate-Dependent Dioxygenase Alkb Homolog 5 |
| Database Links | Reactome: R-HSA-73943 |
| Cellular Localisation | Nucleus SpecklePromotes Formation And Localizes To ParaspecklesA Nuclear Membraneless Organelle |
| Alternative Protein Names | Rna Demethylase Alkbh5 proteinAlkylated Dna Repair Protein Alkb Homolog 5 proteinAlpha-Ketoglutarate-Dependent Dioxygenase Alkb Homolog 5 proteinALKBH5 proteinABH5 proteinOFOXD1 protein |
Information sourced from Uniprot.org
