PHD finger protein 2; lysine-specific demethylase PHF2; GRC5 (PHF2, KIAA0662)

Function

• Lys demethylase
• demethylates both histones & non-histone proteins
• enzymatically inactive by itself
  • becomes active following phosphorylation by PKA
  • phosphorylated by PKA on specific Ser, leading to formation of an active lysine demethylase complex
• forms a complex with ARID5B & mediates demethylation of methylated ARID5B
• demethylation of ARID5B targets the PHF2-ARID5B complex to target promoters
• PHF2 mediates demethylation of dimethylated Lys-9 of histone H3 (H3K9me2), followed by transcription activation of target genes
• PHF2 is recruited to trimethylated Lys-4 of histone H3 (H3K4me3) at rDNA promoters & promotes expression of rDNA
• component of the PHF2-ARID5B complex
• interacts with HNF4A & NR1H4

Structure

• the PHD-type Zn+2 finger mediates the binding to H3K4me2 & H3K4me3
• belongs to the JHDM1 histone demethylase family
• JHDM1D subfamily
• contains 1 JmjC domain
• contains 1 PHD-type Zn+2 finger

Compartment

nucleus, nucleolus

Expression

• widely expressed, including in liver (at protein level)

Notes

• in contrast to the related histone demethylases JHDM1D & PHF8, the conserved active His in position 321 is replaced by a Tyr
• the presence of Tyr neither affects binding to the catalytic iron nor abolishes demethylase activity

More general terms

• PHD finger protein
• nuclear protein
• demethylase

Component of

• PHF2-ARID5B complex

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=5253
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:5253
• OMIM: https://mirror.omim.org/entry/604351
• UniProt: http://www.uniprot.org/uniprot/O75151.html