ALKBH5

The C-terminal disordered region undergoes liquid-liquid phase separation (LLPS) for the formation of paraspeckle membraneless compartment.

Dioxygenase that specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (PubMed:23177736, PubMed:24489119, PubMed:24616105, PubMed:24778178, PubMed:34048572, PubMed:36944332, PubMed:37257451, PubMed:37369679). Demethylates RNA by oxidative demethylation, which requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:21264265, PubMed:23177736, PubMed:24489119, PubMed:24616105, PubMed:24778178). Demethylation of m6A mRNA affects mRNA processing, translation and export (PubMed:23177736, PubMed:34048572, PubMed:36944332, PubMed:37257451). Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (PubMed:24616105). 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 (By similarity). Involved in paraspeckle assembly, a nuclear membraneless organelle, by undergoing liquid-liquid phase separation (PubMed:37369679, PubMed:37474102). Paraspeckle assembly is coupled with m6A demethylation of RNAs, such as NEAT1 non-coding RNA (PubMed:37474102). Also acts as a negative regulator of T-cell development: inhibits gamma-delta T-cell proliferation via demethylation of JAG1 and NOTCH2 transcripts (By similarity). Inhibits regulatory T-cell (Treg) recruitment by mediating demethylation and destabilization of CCL28 mRNAs (By similarity).

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 (PubMed:37369679). Deacetylated at Lys-235 by HDAC7 (PubMed:37369679).

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 (PubMed:34048572, PubMed:37257451). Desumoylated by SENP1; relieving RNA demethylase inhibition, leading to N(6)-methyladenosine-containing mRNAs demethylation (PubMed:34048572, PubMed:37257451).

Ubiquitinated at Lys-57 via 'Lys-48'-linked polyubiquitin chain, leading to its degradation by the proteasome (PubMed:37454738). Deubiquitinated at Lys-57 by USP9X, promoting its stabilizazion (PubMed:37454738).

Belongs to the alkB family.

Widely expressed, with highest expression in lung, followed by testis, pancreas, spleen and ovary.

• Nucleus speckle
• Promotes formation and localizes to paraspeckles, a nuclear membraneless organelle.

ABH5, OFOXD1, ALKBH5, RNA demethylase ALKBH5, Alkylated DNA repair protein alkB homolog 5, Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5

• entrezGene:54890
• swissprot:Q6P6C2

Proteins

Epigenetics

44256Da