Protein: RNA demethylase ALKBH5 (EC 1.14.11.53) (Alkylated DNA repair protein alkB homolog 5) (Alpha-ketoglutarate-dependent dioxygenase alkB homolog 5) (Q6P6C2)
Organism: Homo sapiens (Human)
Function: Dioxygenase that demethylates RNA by oxidative demethylation: specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes. Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro). Requires molecular oxygen, alpha-ketoglutarate and iron. Demethylation of m6A mRNA affects mRNA processing and export. 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).
Subcellular location: Nucleus speckle {ECO:0000269|PubMed:21264265, ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:37474102}. Note=Promotes formation and localizes to paraspeckles, a nuclear membraneless organelle. {ECO:0000269|PubMed:37474102}.
Sequence: MAAASGYTDLREKLKSMTSRDNYKAGSREAAAAAAAAVAAAAAAAAAAEPYPVSGAKRKYQEDSDPERSDYEEQQLQKEEEARKVKSGIRQMRLFSQDECAKIEARIDEVVSRAEKGLYNEHTVDRAPLRNKYFFGEGYTYGAQLQKRGPGQERLYPPGDVDEIPEWVHQLVIQKLVEHRVIPEGFVNSAVINDYQPGGCIVSHVDPIHIFERPIVSVSFFSDSALCFGCKFQFKPIRVSEPVLSLPVRRGSVTVLSGYAADEITHCIRPQDIKERRAVIILRKTRLDAPRLETKSLSSSVLPPSYASDRLSGNNRDPALKPKRSHRKADPDAAHRPRILEMDKEENRRSVLLPTHRRRGSFSSENYWRKSYESSEDCSEAAGSPARKVKMRRH
InterPro domains: - IPR037151: Alpha-ketoglutarate-dependent dioxygenase AlkB-like superfamily (homologous_superfamily) [64-292]
- IPR027450: Alpha-ketoglutarate-dependent dioxygenase AlkB-like (domain) [114-274]
- IPR032860: RNA demethylase ALKBH5 (family) [161-394]
Interaction partners: - Alpha-ketoglutarate-dependent dioxygenase FTO-)-demethylase FTO)
- Probable ATP-dependent RNA helicase DDX46
- Nucleic acid dioxygenase ALKBH1
- YTH domain-containing family protein 1
- N
- Pre-mRNA-splicing regulator WTAP
- N
- 3'-5' RNA helicase YTHDC2
- YTH domain-containing protein 1
- YTH domain-containing family protein 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0032451 (demethylase activity), GO:1901363 (heterocyclic compound binding), GO:0140640 (catalytic activity, acting on a nucleic acid), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0016491 (oxidoreductase activity), GO:0003676 (nucleic acid binding), GO:0140098 (catalytic activity, acting on RNA), GO:0051213 (dioxygenase activity), GO:0016705 (oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen), GO:0000166 (nucleotide binding), GO:0016706 (2-oxoglutarate-dependent dioxygenase activity), GO:0003723 (RNA binding), GO:0140101 (catalytic activity, acting on a tRNA)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0065007 (biological regulation), GO:0050789 (regulation of biological process), GO:0022414 (reproductive process), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0019953 (sexual reproduction), GO:0065008 (regulation of biological quality), GO:0044237 (cellular metabolic process), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0050794 (regulation of cellular process), GO:0044238 (primary metabolic process), GO:0071704 (organic substance metabolic process), GO:0032504 (multicellular organism reproduction), GO:0003006 (developmental process involved in reproduction), GO:0048609 (multicellular organismal reproductive process), GO:0070988 (demethylation), GO:0009894 (regulation of catabolic process), GO:0007276 (gamete generation), GO:1901360 (organic cyclic compound metabolic process), GO:0043487 (regulation of RNA stability), GO:0006139 (nucleobase-containing compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0043170 (macromolecule metabolic process), GO:0007283 (spermatogenesis), GO:0043412 (macromolecule modification), GO:0090304 (nucleic acid metabolic process), GO:0043488 (regulation of mRNA stability), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0031329 (regulation of cellular catabolic process), GO:0048232 (male gamete generation), GO:0010468 (regulation of gene expression), GO:0009451 (RNA modification), GO:0016070 (RNA metabolic process), GO:0061013 (regulation of mRNA catabolic process), GO:1903311 (regulation of mRNA metabolic process), GO:0010608 (post-transcriptional regulation of gene expression)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005654 (nucleoplasm), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0043229 (intracellular organelle), GO:0016607 (nuclear speck), GO:0043233 (organelle lumen), GO:0043227 (membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0043231 (intracellular membrane-bounded organelle), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)