ALKBH5
entrez
54890
canonical
uniprot
Q6P6C2
canonical
ensembl
ENSG00000091542
resolver
ensp
ENSP00000382091
resolver
genesymbol
ALKBH5
resolver
genesymbol_syn
ABH5
resolver
genesymbol_syn
OFOXD1
resolver
hgnc
HGNC:25996
resolver
uniprot
B4DVJ4
resolver
uniprot
D3DXC6
resolver
uniprot
Q9NXD6
resolver
uniprot_entry
ALKB5_HUMAN
resolver
uniprot_sec
B4DVJ4
resolver
uniprot_sec
D3DXC6
resolver
uniprot_sec
Q9NXD6
resolver
activity_regulation
ACTIVITY REGULATION: RNA demethylase activity is inhibited following sumoylation (PubMed:34048572, PubMed:37257451). Inhibition is relieved following desumoylation (PubMed:34048572, PubMed:37257451). {ECO:0000269|PubMed:34048572, ECO:0000269|PubMed:37257451}.
uniprot
proteins
amino_acid_sequence
MAAASGYTDLREKLKSMTSRDNYKAGSREAAAAAAAAVAAAAAAAAAAEPYPVSGAKRKYQEDSDPERSDYEEQQLQKEEEARKVKSGIRQMRLFSQDECAKIEARIDEVVSRAEKGLYNEHTVDRAPLRNKYFFGEGYTYGAQLQKRGPGQERLYPPGDVDEIPEWVHQLVIQKLVEHRVIPEGFVNSAVINDYQPGGCIVSHVDPIHIFERPIVSVSFFSDSALCFGCKFQFKPIRVSEPVLSLPVRRGSVTVLSGYAADEITHCIRPQDIKERRAVIILRKTRLDAPRLETKSLSSSVLPPSYASDRLSGNNRDPALKPKRSHRKADPDAAHRPRILEMDKEENRRSVLLPTHRRRGSFSSENYWRKSYESSEDCSEAAGSPARKVKMRRH
uniprot
proteins
ec_number
1.14.11.53
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:Q3TSG4, ECO:0000269|PubMed:21264265, ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:24489119, ECO:0000269|PubMed:24616105, ECO:0000269|PubMed:24778178, ECO:0000269|PubMed:34048572, ECO:0000269|PubMed:36944332, ECO:0000269|PubMed:37257451, ECO:0000269|PubMed:37369679, ECO:0000269|PubMed:37474102, ECO:0000269|PubMed:40793791}.
uniprot
proteins
mass_dalton
44256
uniprot
proteins
mutagenesis
MUTAGEN 57; /note="K->R: Abolished ubiquitination and degradation by the proteasome."; /evidence="ECO:0000269|PubMed:37454738"; MUTAGEN 64; /note="S->A: Does not affect sumoylation."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 69; /note="S->A: Does not affect sumoylation."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 86; /note="K->R: Decreased sumoylation. Abolished sumoylation, leading to increased mRNA demethylase activity; when associated with R-321."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 87; /note="S->A: Decreased phosphorylation and subsequent sumoylation."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 116; /note="K->R: Does not affect sumoylation."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 123; /note="T->A: Does not affect interaction with RBM3."; /evidence="ECO:0000269|PubMed:37257451"; MUTAGEN 128; /note="P->A: Does not affect interaction with RBM3."; /evidence="ECO:0000269|PubMed:37257451"; MUTAGEN 130; /note="R->A: Abolishes catalytic activity."; /evidence="ECO:0000269|PubMed:24616105, ECO:0000269|PubMed:24778178"; MUTAGEN 132; /note="K->A: No effect on catalytic activity with N(6)-methyladenosine in single-stranded DNA. Strongly reduced interaction with RBM33, leading to decreased RNA demethylase activity."; /evidence="ECO:0000269|PubMed:24616105, ECO:0000269|PubMed:37257451"; MUTAGEN 139; /note="Y->A: Abolishes catalytic activity."; /evidence="ECO:0000269|PubMed:24616105, ECO:0000269|PubMed:24778178"; MUTAGEN 141; /note="Y->A: Abolishes catalytic activity with N(6)-methyladenosine in single-stranded DNA."; /evidence="ECO:0000269|PubMed:24616105"; MUTAGEN 147; /note="K->R: Does not affect ubiquitination."; /evidence="ECO:0000269|PubMed:37454738"; MUTAGEN 151; /note="G->A: Does not affect interaction with RBM3."; /evidence="ECO:0000269|PubMed:37257451"; MUTAGEN 153; /note="E->A: No effect on catalytic activity. Strongly reduced interaction with RBM33, leading to decreased RNA demethylase activity."; /evidence="ECO:0000269|PubMed:24778178, ECO:0000269|PubMed:37257451"; MUTAGEN 195; /note="Y->A: Abolishes catalytic activity."; /evidence="ECO:0000269|PubMed:24616105"; MUTAGEN 204; /note="H->A: Abolishes catalytic activity."; /evidence="ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:24616105"; MUTAGEN 206; /note="D->A: Does not affect interaction with RBM3."; /evidence="ECO:0000269|PubMed:37257451"; MUTAGEN 209..210; /note="HI->AA: Abolishes catalytic activity."; /evidence="ECO:0000269|PubMed:24616105"; MUTAGEN 232..234; /note="FQF->DDE: Impaired catalytic activity."; /evidence="ECO:0000269|PubMed:24616105"; MUTAGEN 235; /note="K->Q: Mimics acetylation; promoting RNA demethylase activity."; /evidence="ECO:0000269|PubMed:37369679"; MUTAGEN 235; /note="K->R: Abolished acetylation by KAT8; inhibiting RNA demethylase activity."; /evidence="ECO:0000269|PubMed:37369679"; MUTAGEN 265; /note="T->A: Strongly reduced interaction with RBM33, leading to decreased RNA demethylase activity."; /evidence="ECO:0000269|PubMed:37257451"; MUTAGEN 266; /note="H->A: Impaired catalytic activity."; /evidence="ECO:0000269|PubMed:23177736"; MUTAGEN 267; /note="C->A: Does not affect interaction with RBM3."; /evidence="ECO:0000269|PubMed:37257451"; MUTAGEN 277; /note="R->A: Abolishes catalytic activity; when associated with A-283."; /evidence="ECO:0000269|PubMed:24616105"; MUTAGEN 283; /note="R->A: Abolishes catalytic activity; when associated with A-277."; /evidence="ECO:0000269|PubMed:24616105"; MUTAGEN 284; /note="K->R: Does not affect sumoylation."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 295; /note="K->R: Does not affect ubiquitination."; /evidence="ECO:0000269|PubMed:37454738"; MUTAGEN 321; /note="K->R: Decreased sumoylation. Abolished sumoylation, leading to increased mRNA demethylase activity; when associated with R-86."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 325; /note="S->A: Strongly decreased phosphorylation and subsequent sumoylation."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 361; /note="S->A: Does not affect sumoylation."; /evidence="ECO:0000269|PubMed:34048572"; MUTAGEN 390; /note="K->R: Does not affect sumoylation."; /evidence="ECO:0000269|PubMed:34048572
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Ser-87 and Ser-325 in response to reactive oxygen species (ROS), promoting sumoylation and inactivation. {ECO:0000269|PubMed:34048572}.; PTM: 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). {ECO:0000269|PubMed:37369679}.; PTM: 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). {ECO:0000269|PubMed:34048572, ECO:0000269|PubMed:37257451}.; PTM: 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). {ECO:0000269|PubMed:37454738}.
uniprot
proteins
protein_family
AlkB family
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16625196
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17979886
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
21264265
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
22761421
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23177736
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24489119
uniprot
proteins
pubmed
24616105
uniprot
proteins
pubmed
24778178
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
34048572
uniprot
proteins
pubmed
35333330
uniprot
proteins
pubmed
36944332
uniprot
proteins
pubmed
37257451
uniprot
proteins
pubmed
37369679
uniprot
proteins
pubmed
37454738
uniprot
proteins
pubmed
37474102
uniprot
proteins
pubmed
40793791
uniprot
proteins
sequence_length
394
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus speckle {ECO:0000269|PubMed:21264265, ECO:0000269|PubMed:23177736, ECO:0000269|PubMed:37474102}. Nucleus, nucleoplasm {ECO:0000269|PubMed:40793791}. Note=Promotes formation and localizes to paraspeckles, a nuclear membraneless organelle. {ECO:0000269|PubMed:37474102}.
uniprot
proteins