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Overview

Uniprot IDD3ZKD3
Protein NameRNA demethylase ALKBH5
Gene NameAlkbh5
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
324 RDPALKPKRSHRKAD

Function

Dioxygenase that specifically demethylates N(6)-methyladenosine (m6A) RNA, the most prevalent internal modification of messenger RNA (mRNA) in higher eukaryotes (By similarity). Demethylates RNA by oxidative demethylation, which requires molecular oxygen, alpha-ketoglutarate and iron (By similarity). Demethylation of m6A mRNA affects mRNA processing, translation and export (By similarity). Can also demethylate N(6)-methyladenosine in single-stranded DNA (in vitro) (By similarity). 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 (By similarity). Paraspeckle assembly is coupled with m6A demethylation of RNAs, such as NEAT1 non-coding RNA (By similarity). 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 YPVSGTTKRK 70 YQEDSDPERS 80 DYEEHQLQKE 90 EEARKVKSGI 100 RQIRLFSQDE 110 CSKIEARIDE 120 VVSRAEKGLY 130 NEHTVDRAPL 140 RNKYFFGEGY 150 TYGAQLQKRG 160 PGQERLYPPG 170 DVDEIPEWVH 180 QLVIQKLVEH 190 RVIPEGFVNS 200 AVINDYQPGG 210 CIVSHVDPIH 220 IFERPIVSVS 230 FFSDSALCFG 240 CKFQFKPIRV 250 SEPVLSLPVR 260 RGSVTVLSGY 270 AADEITHCIR 280 PQDIKERRAV 290 IILRKTRLDA 300 PRLETKSLSS 310 STLPPSYASD 320 RLSGNTRDPA 330 LKPKRSHRKA 340 DPDAAHRPRI 350 LEMDKEENRR 360 SVLLPTHRRR 370 GSFSSENYWR 380 KSYESSEDCP 390 EAASSPTRKV KMRRH

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016607 nuclear speck
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
Biological Process GO:0030154 cell differentiation
Biological Process GO:0046630 gamma-delta T cell proliferation
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:0043488 regulation of mRNA stability
Biological Process GO:0006417 regulation of translation
Biological Process GO:0001666 response to hypoxia
Biological Process GO:0007283 spermatogenesis

Reference

[1] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.