Recombinant Human ALKBH5 protein (DDDDK tag N-Terminus)

Specifications

Form

Liquid

Additional notes

Affinity purified.

General info

Function

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, PubMed : 40793791). 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).

Sequence similarities

Belongs to the alkB family.

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 (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).

Subcellular localisation

Nucleus speckle