Overview
| Uniprot ID | Q6P6C2 |
|---|
| Protein Name | RNA demethylase ALKBH5 |
|---|
| Gene Name | ALKBH5 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 328 |
KPKRSHRKADPDAAH |
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)
Protein Sequence
10
MAAASGYTDL
20
REKLKSMTSR
30
DNYKAGSREA
40
AAAAAAAVAA
50
AAAAAAAAEP
60
YPVSGAKRKY
70
QEDSDPERSD
80
YEEQQLQKEE
90
EARKVKSGIR
100
QMRLFSQDEC
110
AKIEARIDEV
120
VSRAEKGLYN
130
EHTVDRAPLR
140
NKYFFGEGYT
150
YGAQLQKRGP
160
GQERLYPPGD
170
VDEIPEWVHQ
180
LVIQKLVEHR
190
VIPEGFVNSA
200
VINDYQPGGC
210
IVSHVDPIHI
220
FERPIVSVSF
230
FSDSALCFGC
240
KFQFKPIRVS
250
EPVLSLPVRR
260
GSVTVLSGYA
270
ADEITHCIRP
280
QDIKERRAVI
290
ILRKTRLDAP
300
RLETKSLSSS
310
VLPPSYASDR
320
LSGNNRDPAL
330
KPKRSHRKAD
340
PDAAHRPRIL
350
EMDKEENRRS
360
VLLPTHRRRG
370
SFSSENYWRK
380
SYESSEDCSE
390
AAGSPARKVK
MRRH
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0016607 |
nuclear speck |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Cellular Component |
GO:0042382 |
paraspeckles |
| Molecular Function |
GO:0016706 |
2-oxoglutarate-dependent dioxygenase activity |
| Molecular Function |
GO:0046872 |
metal ion binding |
| Molecular Function |
GO:0140693 |
molecular condensate scaffold activity |
| Molecular Function |
GO:1990931 |
mRNA N6-methyladenosine dioxygenase activity |
| Molecular Function |
GO:0035515 |
oxidative RNA demethylase activity |
| Molecular Function |
GO:0003723 |
RNA binding |
| Biological Process |
GO:0030154 |
cell differentiation |
| Biological Process |
GO:0140694 |
membraneless organelle assembly |
| Biological Process |
GO:0061157 |
mRNA destabilization |
| Biological Process |
GO:0006397 |
mRNA processing |
| Biological Process |
GO:0010793 |
regulation of mRNA export from nucleus |
| Biological Process |
GO:0050684 |
regulation of mRNA processing |
| Biological Process |
GO:0006417 |
regulation of translation |
| Biological Process |
GO:0001666 |
response to hypoxia |
| Biological Process |
GO:0007283 |
spermatogenesis |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.