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) Note: - 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

General

demethylase nuclear protein PHD finger protein

Properties

SIZE: entity length = 1096 aa MW = 121 kD COMPARTMENT: cell nucleus MOTIF: Zn finger PHD-type NAME: Zn finger PHD-type SITE: 5-56 EFFECTOR-BOUND: Zn+2 binding site SITE: 193-193 FOR-BINDING-OF: alpha-ketoglutarate JmjC {197-353} MOTIF: binding site SITE: 246-246 FOR-BINDING-OF: alpha-ketoglutarate Iron [Fe]-binding site SITE: 249-249 Iron [Fe]-binding site SITE: 251-251 binding site SITE: 259-259 FOR-BINDING-OF: alpha-ketoglutarate binding site SITE: 266-266 FOR-BINDING-OF: alpha-ketoglutarate Iron [Fe]-binding site SITE: 321-321 binding site SITE: 321-321 FOR-BINDING-OF: alpha-ketoglutarate binding site SITE: 323-323 FOR-BINDING-OF: alpha-ketoglutarate Ser phosphorylation site {S458} Ser phosphorylation site {S459} proline-rich region SITE: 472-518 MOTIF: proline residue (SEVERAL) lysine-rich region {487-648} MOTIF: lysine residue (SEVERAL) Ser phosphorylation site {S539} Ser phosphorylation site {S681} Ser phosphorylation site {S738} Ser phosphorylation site {S882} Ser phosphorylation site {S899} threonine-rich region {960-1020} MOTIF: threonine residue (SEVERAL) Ser phosphorylation site {S1056}

Database Correlations

OMIM 604351 UniProt O75151 PFAM correlations Entrez Gene 5253 Kegg hsa:5253

References

UniProt :accession O75151