Overview
| Uniprot ID | Q9UPP1 |
| Protein Name | Histone lysine demethylase PHF8 |
| Gene Name | PHF8 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 891 |
RVTPTLPKQDRPVRE |
| 915 |
GLAAAAAKLAQQELQ |
| 923 |
LAQQELQKAQKKKYI |
Function
Histone lysine demethylase with selectivity for mono- and dimethylated residues. It plays an essential role in cell cycle progression and rDNA transcription (PubMed:19843542, PubMed:20531378, PubMed:20548336, PubMed:20622854). Demethylates mono- and dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2) and monomethylated histone H4 'Lys-20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1, H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks (PubMed:20101266, PubMed:20208542, PubMed:20346720, PubMed:20622853, PubMed:20622854). Displays a very low intrinsic activity toward dimethylated H3 'Lys-27' (H3K27Me2) (PubMed:20346720). May also have weak activity toward dimethylated H3 'Lys-36' (H3K36Me2), however, the relevance of this result remains unsure in vivo (PubMed:19843542, PubMed:20023638, PubMed:20346720). Involved in cell cycle progression by being required to control G1-S transition (PubMed:20622854). Acts as a coactivator of rDNA transcription, by activating polymerase I (pol I) mediated transcription of rRNA genes (PubMed:20531378). 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 (PubMed:20023638, PubMed:20346720, PubMed:20421419). Positively modulates transcription of histone demethylase KDM5C, acting synergistically with transcription factor ARX; synergy may be related to enrichment of histone H3K4me3 in regulatory elements (PubMed:31691806). Required for brain development, probably by regulating expression of neuron-specific genes (By similarity)
Protein Sequence
10
MNRSRAIVQR
20
GRVLPPPAPL
30
DTTNLAGRRT
40
LQGRAKMASV
50
PVYCLCRLPY
60
DVTRFMIECD
70
MCQDWFHGSC
80
VGVEEEKAAD
90
IDLYHCPNCE
100
VLHGPSIMKK
110
RRGSSKGHDT
120
HKGKPVKTGS
130
PTFVRELRSR
140
TFDSSDEVIL
150
KPTGNQLTVE
160
FLEENSFSVP
170
ILVLKKDGLG
180
MTLPSPSFTV
190
RDVEHYVGSD
200
KEIDVIDVTR
210
QADCKMKLGD
220
FVKYYYSGKR
230
EKVLNVISLE
240
FSDTRLSNLV
250
ETPKIVRKLS
260
WVENLWPEEC
270
VFERPNVQKY
280
CLMSVRDSYT
290
DFHIDFGGTS
300
VWYHVLKGEK
310
IFYLIRPTNA
320
NLTLFECWSS
330
SSNQNEMFFG
340
DQVDKCYKCS
350
VKQGQTLFIP
360
TGWIHAVLTP
370
VDCLAFGGNF
380
LHSLNIEMQL
390
KAYEIEKRLS
400
TADLFRFPNF
410
ETICWYVGKH
420
ILDIFRGLRE
430
NRRHPASYLV
440
HGGKALNLAF
450
RAWTRKEALP
460
DHEDEIPETV
470
RTVQLIKDLA
480
REIRLVEDIF
490
QQNVGKTSNI
500
FGLQRIFPAG
510
SIPLTRPAHS
520
TSVSMSRLSL
530
PSKNGSKKKG
540
LKPKELFKKA
550
ERKGKESSAL
560
GPAGQLSYNL
570
MDTYSHQALK
580
TGSFQKAKFN
590
ITGACLNDSD
600
DDSPDLDLDG
610
NESPLALLMS
620
NGSTKRVKSL
630
SKSRRTKIAK
640
KVDKARLMAE
650
QVMEDEFDLD
660
SDDELQIDER
670
LGKEKATLII
680
RPKFPRKLPR
690
AKPCSDPNRV
700
REPGEVEFDI
710
EEDYTTDEDM
720
VEGVEGKLGN
730
GSGAGGILDL
740
LKASRQVGGP
750
DYAALTEAPA
760
SPSTQEAIQG
770
MLCMANLQSS
780
SSSPATSSLQ
790
AWWTGGQDRS
800
SGSSSSGLGT
810
VSNSPASQRT
820
PGKRPIKRPA
830
YWRTESEEEE
840
ENASLDEQDS
850
LGACFKDAEY
860
IYPSLESDDD
870
DPALKSRPKK
880
KKNSDDAPWS
890
PKARVTPTLP
900
KQDRPVREGT
910
RVASIETGLA
920
AAAAKLAQQE
930
LQKAQKKKYI
940
KKKPLLKEVE
950
QPRPQDSNLS
960
LTVPAPTVAA
970
TPQLVTSSSP
980
LPPPEPKQEA
990
LSGSLADHEY
1000
TARPNAFGMA
1010
QANRSTTPMA
1020
PGVFLTQRRP
1030
SVGSQSNQAG
1040
QGKRPKKGLA
1050
TAKQRLGRIL
1060
KIHRNGKLLL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005730 |
nucleolus |
| Biological Process |
GO:0006338 |
chromatin remodeling |
| Biological Process |
GO:0006351 |
DNA-templated transcription |
| Biological Process |
GO:0000082 |
G1/S transition of mitotic cell cycle |
| Biological Process |
GO:0061188 |
negative regulation of rDNA heterochromatin formation |
| Biological Process |
GO:0045893 |
positive regulation of DNA-templated transcription |
| Biological Process |
GO:0045943 |
positive regulation of transcription by RNA polymerase I |
| Biological Process |
GO:0045944 |
positive regulation of transcription by RNA polymerase II |
| Biological Process |
GO:0006357 |
regulation of transcription by RNA polymerase II |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0003682 |
chromatin binding |
| Molecular Function |
GO:0032452 |
histone demethylase activity |
| Molecular Function |
GO:0071558 |
histone H3K27me2/H3K27me3 demethylase activity |
| Molecular Function |
GO:0051864 |
histone H3K36 demethylase activity |
| Molecular Function |
GO:0140002 |
histone H3K4me3 reader activity |
| Molecular Function |
GO:0032454 |
histone H3K9 demethylase activity |
| Molecular Function |
GO:0140683 |
histone H3K9me/H3K9me2 demethylase activity |
| Molecular Function |
GO:0035575 |
histone H4K20 demethylase activity |
| Molecular Function |
GO:0005506 |
iron ion binding |
| Molecular Function |
GO:0003712 |
transcription coregulator activity |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0007420 |
brain development |
Reference
[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.