UniProt Accession

 PHF8_HUMAN; Q9UPP1; B7Z911; Q5H9U5; Q5JPR9; Q5JPS0; Q5JPS2; Q5JPS3; Q5VUJ4; Q7Z6D4; Q9HAH2 

Genbank Protein ID

 AB029034; CR933612; AK021696; AK304272; AL589872; AL732374; Z98051; Z98051; AL732374; AL732374; Z98051; AL732374; AL589872; Z98051; AL732374; Z98051; Z98051; AL732374; Z98051; AL589872; AL732374; AL732374; AL732374; BC053861 

Genbank Nucleotide ID

 BAA83063.1; CAI45929.1; BAB13877.1; BAH14147.1; CAH70724.1; CAH70724.1; CAH70724.1; CAQ08299.1; CAQ08299.1; CAI41578.2; CAI41578.2; CAI41576.1; CAI41576.1; CAI41576.1; CAI41577.1; CAI41577.1; CAI42861.1; CAI42861.1; CAI42860.1; CAI42860.1; CAI42860.1; CAI41582.1; CAI41581.1; AAH53861.1 

Protein Name

 Histone lysine demethylase PHF8 

Protein Synonyms/Alias

 PHD finger protein 8 

Gene Name

 PHF8 

Gene Synonyms/Alias

 KIAA1111; ZNF422 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
36	RTLQGRAKMASVPVY	ubiquitination	[1]
100	HGPSIMKKRRGSSKG	ubiquitination	[1]
117	THKGKPVKTGSPTFV	ubiquitination	[1]
166	VPILVLKKDGLGMTL	ubiquitination	[1]
191	EHYVGSDKEIDVIDV	ubiquitination	[1]
207	RQADCKMKLGDFVKY	ubiquitination	[1]
213	MKLGDFVKYYYSGKR	ubiquitination	[1]
219	VKYYYSGKREKVLNV	ubiquitination	[1]
446	AFRAWTRKEALPDHE	ubiquitination	[1]
467	VRTVQLIKDLAREIR	ubiquitination	[1]
486	IFQQNVGKTSNIFGL	ubiquitination	[1, 2]
523	SRLSLPSKNGSKKKG	ubiquitination	[1]
528	PSKNGSKKKGLKPKE	ubiquitination	[1]
665	DERLGKEKATLIIRP	ubiquitination	[1]
732	GGILDLLKASRQVGG	ubiquitination	[1, 2]
915	GLAAAAAKLAQQELQ	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 

Functional Description

 Histone lysine demethylase with selectivity for the di- and monomethyl states that plays a key role cell cycle progression, rDNA transcription and brain development. Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2), dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks. Involved in cell cycle progression by being required to control G1-S transition. Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes. Required for brain development, probably by regulating expression of neuron-specific genes. Only has activity toward H4K20Me1 when nucleosome is used as a substrate and when not histone octamer is used as substrate. May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo. Specifically binds trimethylated 'Lys-4' of histone H3 (H3K4me3), affecting histone demethylase specificity: has weak activity toward H3K9Me2 in absence of H3K4me3, while it has high activity toward H3K9me2 when binding H3K4me3. 

Sequence Annotation

 DOMAIN 231 387 JmjC.
 ZN_FING 41 92 PHD-type.
 REGION 101 115 Linker.
 METAL 283 283 Iron; catalytic.
 METAL 285 285 Iron; catalytic.
 METAL 355 355 Iron; catalytic.
 BINDING 280 280 Substrate.
 BINDING 300 300 Substrate.
 MOD_RES 69 69 Phosphoserine; by CDK1.
 MOD_RES 120 120 Phosphoserine; by CDK1.
 MOD_RES 651 651 Phosphoserine.
 MOD_RES 705 705 Phosphothreonine.
 MOD_RES 706 706 Phosphothreonine.
 MOD_RES 804 804 Phosphoserine.
 MOD_RES 854 854 Phosphoserine.
 MOD_RES 857 857 Phosphoserine.
 MOD_RES 880 880 Phosphoserine.  

Keyword

 3D-structure; Activator; Alternative splicing; Cell cycle; Chromatin regulator; Complete proteome; Dioxygenase; Disease mutation; Iron; Mental retardation; Metal-binding; Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; Transcription; Transcription regulation; Zinc; Zinc-finger. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1060 AA 

Protein Sequence

Gene Ontology

 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0071558; F:histone demethylase activity (H3-K27 specific); IDA:UniProtKB.
 GO:0051864; F:histone demethylase activity (H3-K36 specific); IDA:UniProtKB.
 GO:0032454; F:histone demethylase activity (H3-K9 specific); IDA:UniProtKB.
 GO:0035575; F:histone demethylase activity (H4-K20 specific); IDA:UniProtKB.
 GO:0005506; F:iron ion binding; IDA:UniProtKB.
 GO:0035064; F:methylated histone residue binding; IDA:UniProtKB.
 GO:0016702; F:oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen; IEA:UniProtKB-KW.
 GO:0008270; F:zinc ion binding; IDA:UniProtKB.
 GO:0007420; P:brain development; ISS:UniProtKB.
 GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB.
 GO:0061188; P:negative regulation of chromatin silencing at rDNA; IDA:UniProtKB.
 GO:0045943; P:positive regulation of transcription from RNA polymerase I promoter; IDA:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 

Interpro

 IPR003347; JmjC_dom.
 IPR019786; Zinc_finger_PHD-type_CS.
 IPR011011; Znf_FYVE_PHD.
 IPR001965; Znf_PHD.
 IPR019787; Znf_PHD-finger.
 IPR013083; Znf_RING/FYVE/PHD. 

Pfam

 PF02373; JmjC
 PF00628; PHD 

SMART

 SM00558; JmjC
 SM00249; PHD 

PROSITE

 PS51184; JMJC
 PS01359; ZF_PHD_1
 PS50016; ZF_PHD_2 

PRINTS