RNA demethylase ALKBH5

Basic Information
Short Name	ALKBH5
UNP ID	Q6P6C2
Organism	Homo sapiens
Cys Site	Cys200
Family/Domain	2OG-Fe(II) oxygenase superfamily, Alkb family
Known Ligand	Ligand list
Function Type	Nucleic acid modification

Summary

Protein Function

ALKBH5 belongs to the conserved AlkB family of non-heme Fe(II)/alpha-KG-dependent dioxygenases that repair N-alkylated nucleobases by oxidative demethylation. It could catalyze the demethylation of m6A of ssRNA. N6-Methyladenosine (m6A) is the most prevalent and abundant internal methylated nucleoside in mammalian mRNA and is also found in the RNA of plants and viruses. Mapping of m6A in human and mouse RNA identified that m6A modification happens mainly within the consensus sequence (G/A)(G/A)m6AC(A/C/U) in a non-stoichiometric manner with only three to five m6A sites observed per mRNA molecule.m6A sites are enriched near stop codons and in the 3'-UTR of mRNA.

ALKBH5 is localized to the nucleus, has 2OG and iron-dependent activity and is upregulated under hypoxic conditions by the hypoxia-inducible factor (HIF) transcription factor pathway. ALKBH5 was observed to be highly expressed in the lung, followed by testis, pancreas, spleen and ovary. It was also reported that ALKBH5 localized to nuclear speckles and that decreased ALKBH5 levels affect mRNA export and processing, leading to altered spermatogenesis.

Cys Function & Property

The catalytic triad in Caspase-3 comprises Cys320, His277 and the backbone carbonyl oxygen atom of Arg219, which points towards the Nϵ atom of His277.

• Hydrophobic property:

• SASA:

Unkown

Protein Sequence

MAAASGYTDL REKLKSMTSR DNYKAGSREA AAAAAAAVAA AAAAAAAAEP
YPVSGAKRKY QEDSDPERSD YEEQQLQKEE EARKVKSGIR QMRLFSQDEC
AKIEARIDEV VSRAEKGLYN EHTVDRAPLR NKYFFGEGYT YGAQLQKRGP
GQERLYPPGD VDEIPEWVHQ LVIQKLVEHR VIPEGFVNSA VINDYQPGGC
IVSHVDPIHI FERPIVSVSF FSDSALCFGC KFQFKPIRVS EPVLSLPVRR
GSVTVLSGYA ADEITHCIRP QDIKERRAVI ILRKTRLDAP RLETKSLSSS
VLPPSYASDR LSGNNRDPAL KPKRSHRKAD PDAAHRPRIL EMDKEENRRS
VLLPTHRRRG SFSSENYWRK SYESSEDCSE AAGSPARKVK MRRH

Structural Information

• Known structure with covalent ligand:
  

4NJ4

• Protein structure:

Related Pathway

Unknown

Experimental Evidence

Crystallography

Reference

1. Aik W S, Scotti J S, Choi H, et al. Structure of human RNA N 6-methyladenine demethylase ALKBH5 provides insights into its mechanisms of nucleic acid recognition and demethylation[J]. Nucleic acids research, 2014, 42(7): 4741-4754. 24489119