Difference between revisions of "RNA demethylase ALKBH5"
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===Protein Function === | ===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. <br/> | |
| − | + | 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. <br/> | |
===Cys Function & Property=== | ===Cys Function & Property=== | ||
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* Hydrophobic property: | * Hydrophobic property: | ||
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* SASA: | * SASA: | ||
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==Protein Sequence== | ==Protein Sequence== | ||
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*Protein structure: | *Protein structure: | ||
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==Related Pathway== | ==Related Pathway== | ||
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==Reference== | ==Reference== | ||
# 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. [https://www.ncbi.nlm.nih.gov/pubmed/?term=24489119 24489119]<br/> | # 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. [https://www.ncbi.nlm.nih.gov/pubmed/?term=24489119 24489119]<br/> | ||
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[[Category:2OG-Fe(II) oxygenase superfamily]] | [[Category:2OG-Fe(II) oxygenase superfamily]] | ||
[[Category:Alkb family]] | [[Category:Alkb family]] | ||
Latest revision as of 20:09, 26 May 2020
| 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:
- Protein structure:
Related Pathway
- Unknown
Experimental Evidence
- Crystallography
Reference
- 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
