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Protein

Histone lysine demethylase PHF8

Gene

Phf8

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Has activity toward H4K20Me1 only 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 (By similarity).By similarity

Catalytic activityi

Protein N6,N(6)-dimethyl-L-lysine + 2-oxoglutarate + O2 = protein N(6)-methyl-L-lysine + succinate + formaldehyde + CO2.
Protein N(6)-methyl-L-lysine + 2-oxoglutarate + O2 = protein L-lysine + succinate + formaldehyde + CO2.

Cofactori

Fe2+By similarityNote: Binds 1 Fe2+ ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei244SubstrateBy similarity1
Metal bindingi247Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi249Iron; catalyticPROSITE-ProRule annotation1
Binding sitei264SubstrateBy similarity1
Metal bindingi319Iron; catalyticPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri5 – 56PHD-typePROSITE-ProRule annotationAdd BLAST52

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, Chromatin regulator, Dioxygenase, Oxidoreductase
Biological processCell cycle, Transcription, Transcription regulation
LigandIron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2299718. Condensation of Prophase Chromosomes.
R-MMU-3214842. HDMs demethylate histones.

Names & Taxonomyi

Protein namesi
Recommended name:
Histone lysine demethylase PHF8 (EC:1.14.11.27)
Alternative name(s):
PHD finger protein 8
Gene namesi
Name:Phf8
Synonyms:Kiaa1111
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:2444341. Phf8.

Subcellular locationi

  • Nucleus By similarity
  • Nucleusnucleolus By similarity

  • Note: Recruited to H3K4me3 sites on chromatin during interphase. Dissociates from chromatin when cells enter mitosis (By similarity).By similarity

GO - Cellular componenti

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3038497.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000592961 – 1023Histone lysine demethylase PHF8Add BLAST1023

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei33Phosphoserine; by CDK1By similarity1
Modified residuei84Phosphoserine; by CDK1By similarity1
Modified residuei615PhosphoserineCombined sources1
Modified residuei668PhosphotyrosineCombined sources1
Modified residuei669PhosphothreonineCombined sources1
Modified residuei670PhosphothreonineCombined sources1
Modified residuei686PhosphoserineBy similarity1
Modified residuei768PhosphoserineBy similarity1
Modified residuei790PhosphoserineCombined sources1
Modified residuei797PhosphoserineCombined sources1
Modified residuei817PhosphoserineBy similarity1
Modified residuei820PhosphoserineCombined sources1
Modified residuei843PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-33 and Ser-84 are required for dissociation from chromatin and accumulation of H4K20Me1 levels during prophase.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ80TJ7.
PaxDbiQ80TJ7.
PeptideAtlasiQ80TJ7.
PRIDEiQ80TJ7.

PTM databases

iPTMnetiQ80TJ7.
PhosphoSitePlusiQ80TJ7.
SwissPalmiQ80TJ7.

Expressioni

Gene expression databases

BgeeiENSMUSG00000023350.
CleanExiMM_PHF8.
ExpressionAtlasiQ80TJ7. baseline and differential.
GenevisibleiQ80TJ7. MM.

Interactioni

Subunit structurei

Interacts with POLR1B, UBTF, SETD1A, HCFC1, E2F1 and ZNF711.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000040765.

Structurei

Secondary structure

11023
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi16 – 18Combined sources3
Beta strandi20 – 23Combined sources4
Turni24 – 26Combined sources3
Beta strandi29 – 31Combined sources3
Helixi32 – 35Combined sources4
Helixi39 – 42Combined sources4
Beta strandi46 – 48Combined sources3
Turni51 – 56Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WEPNMR-A1-63[»]
ProteinModelPortaliQ80TJ7.
SMRiQ80TJ7.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ80TJ7.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini195 – 351JmjCPROSITE-ProRule annotationAdd BLAST157

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni65 – 79LinkerBy similarityAdd BLAST15

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi733 – 771Ser-richAdd BLAST39

Domaini

The PHD-type zinc finger mediates the binding to H3K4me3. Binding to H3K4me3 promotes its access to H3K9me2 (By similarity).By similarity
The linker region is a critical determinant of demethylase specificity. It enables the active site of JmjC to reach the target H3K9me2 when the PHD-type zinc finger binds to H3K4me3 (By similarity).By similarity

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri5 – 56PHD-typePROSITE-ProRule annotationAdd BLAST52

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1633. Eukaryota.
ENOG410XQXU. LUCA.
GeneTreeiENSGT00550000074396.
HOVERGENiHBG045631.
InParanoidiQ80TJ7.
KOiK11445.
K19415.
OMAiLGTCFKD.
OrthoDBiEOG090B01WN.
PhylomeDBiQ80TJ7.
TreeFamiTF106480.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in 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.
PfamiView protein in Pfam
PF02373. JmjC. 1 hit.
PF00628. PHD. 1 hit.
SMARTiView protein in SMART
SM00558. JmjC. 1 hit.
SM00249. PHD. 1 hit.
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiView protein in PROSITE
PS51184. JMJC. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q80TJ7-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASVPVYCLC RLPYDVTRFM IECDMCQDWF HGSCVGVEEE KAADIDLYHC
60 70 80 90 100
PNCEVLHGPS IMKKRRGSSK GHDNHKGKPL KTGSSMFIRE LRGRTFDSSD
110 120 130 140 150
EVILKPTGSQ LTVEFLEENS FSVPILVLKK DGLGMTLPSP SFTVRDVEHY
160 170 180 190 200
VGSDKEIDVI DVARQADCKM KLGDFVKYYY SGKREKVLNV ISLEFSDTRL
210 220 230 240 250
SNLVETPRIV RKLSWVENLW PEECVFERPN VQKYCLMSVR DSYTDFHIDF
260 270 280 290 300
GGTSVWYHVL KGEKIFYLIR PTNANLTLFE CWSSSSNQNE MFFGDQVEKC
310 320 330 340 350
YKCSVKQGQT LFIPTGWIHA VLTPVDCLAF GGNFLHSLNI EMQLKAYEIE
360 370 380 390 400
KRLSTADLFK FPNFETICWY VGKHILDIFR GLRENRRHPA SYLVHGGKAL
410 420 430 440 450
NLAFRAWTKK EALPDHEDEI PETVRTVQLI KDLAREIRLV EDIFQQNVGK
460 470 480 490 500
TSNIFGLQRI FPAGSIPLTK PAHSTSVSMS KLSLPSKNGS KKKGLKPKDI
510 520 530 540 550
FKKAERKGKQ SSALGPAGQL SYNLMDPYSH QALKTGPSQK AKFNMSGTSL
560 570 580 590 600
NDSDDDSADM DLDGSENPLA LLMANGSTKR MKSVSKSRRA KIAKKVDSAR
610 620 630 640 650
LVAEQVMGDE FDLDSDDELQ IDERLGKEKA NLLIRSKFPR KLPRAKPCSD
660 670 680 690 700
PNRIREPGEV EFDIEEDYTT DEDMVEGVES KLGNGSGAGG ILDLLKASRQ
710 720 730 740 750
VGGPDYAALT EAPASPSTQE AIQGMLCMAN LQSSSSSPAT SSLQAWWTGG
760 770 780 790 800
QERSSGSSSS GLGTVSSSPA SQRTPGKRPI KRPAYWKNES EEEENASLDE
810 820 830 840 850
QDSLGACFKD AEYIYPSLES DDDDPALKSR PKKKKNSDDA PWSPKARVTP
860 870 880 890 900
TLPKQDRPVR EGTRVASIET GLAAAAAKLA QQELQKAQKK KYIKKKPLLK
910 920 930 940 950
EVEQPRPQDS NPIMTMPAPT VATTPQPDTS SSPQPPPEPK QEALSGSLAD
960 970 980 990 1000
HEYTARPNAF GMAQANRSTT PMAPGVFLTQ RRPSVGSQSS QAGQGKRPKK
1010 1020
GLATAKQRLG RILKIHRNGK LLL
Length:1,023
Mass (Da):113,553
Last modified:August 16, 2005 - v2
Checksum:i7B9351944C000487
GO
Isoform 2 (identifier: Q80TJ7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     442-542: Missing.
     883-896: ELQKAQKKKYIKKK → VRVDTQLVALLLMT
     897-1023: Missing.

Note: No experimental confirmation available.
Show »
Length:795
Mass (Da):88,919
Checksum:iE14CF1810F1D3492
GO
Isoform 3 (identifier: Q80TJ7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     442-464: DIFQQNVGKTSNIFGLQRIFPAG → VRSMGEGKAFGKGWRLKWQVRTL
     465-1023: Missing.

Note: No experimental confirmation available.
Show »
Length:464
Mass (Da):53,421
Checksum:iA0A47C4A877F9291
GO

Sequence cautioni

The sequence CAM17163 differs from that shown. Reason: Erroneous gene model prediction.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014966442 – 542Missing in isoform 2. 1 PublicationAdd BLAST101
Alternative sequenceiVSP_014967442 – 464DIFQQ…IFPAG → VRSMGEGKAFGKGWRLKWQV RTL in isoform 3. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_014968465 – 1023Missing in isoform 3. 1 PublicationAdd BLAST559
Alternative sequenceiVSP_014969883 – 896ELQKA…YIKKK → VRVDTQLVALLLMT in isoform 2. 1 PublicationAdd BLAST14
Alternative sequenceiVSP_014970897 – 1023Missing in isoform 2. 1 PublicationAdd BLAST127

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK036609 mRNA. Translation: BAC29505.1.
AK040943 mRNA. Translation: BAC30755.2.
AK040969 mRNA. Translation: BAC30763.1.
AL662922 Genomic DNA. Translation: CAM17161.1.
AL840642, AL662922 Genomic DNA. Translation: CAM15464.1.
AL662922, AL840642 Genomic DNA. Translation: CAM17159.1.
AL662922 Genomic DNA. Translation: CAM17163.1. Sequence problems.
AK122447 mRNA. Translation: BAC65729.1.
AF528164 Genomic DNA. Translation: AAO17385.1. Sequence problems.
CCDSiCCDS30470.1. [Q80TJ7-2]
CCDS53223.1. [Q80TJ7-1]
RefSeqiNP_001009544.1. NM_001009544.2.
NP_001106825.1. NM_001113354.1. [Q80TJ7-1]
NP_796175.1. NM_177201.5. [Q80TJ7-2]
XP_006528938.1. XM_006528875.3. [Q80TJ7-1]
XP_006528940.1. XM_006528877.3. [Q80TJ7-1]
XP_006528943.1. XM_006528880.3. [Q80TJ7-1]
UniGeneiMm.17156.
Mm.84774.

Genome annotation databases

EnsembliENSMUST00000046950; ENSMUSP00000040765; ENSMUSG00000041229. [Q80TJ7-1]
ENSMUST00000046962; ENSMUSP00000041312; ENSMUSG00000041229. [Q80TJ7-2]
ENSMUST00000112662; ENSMUSP00000108281; ENSMUSG00000041229. [Q80TJ7-2]
ENSMUST00000112666; ENSMUSP00000108285; ENSMUSG00000041229. [Q80TJ7-3]
ENSMUST00000168501; ENSMUSP00000127653; ENSMUSG00000041229. [Q80TJ7-1]
GeneIDi320595.
74042.
KEGGimmu:320595.
mmu:74042.
UCSCiuc009upd.1. mouse. [Q80TJ7-3]
uc012hqt.1. mouse. [Q80TJ7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK036609 mRNA. Translation: BAC29505.1.
AK040943 mRNA. Translation: BAC30755.2.
AK040969 mRNA. Translation: BAC30763.1.
AL662922 Genomic DNA. Translation: CAM17161.1.
AL840642, AL662922 Genomic DNA. Translation: CAM15464.1.
AL662922, AL840642 Genomic DNA. Translation: CAM17159.1.
AL662922 Genomic DNA. Translation: CAM17163.1. Sequence problems.
AK122447 mRNA. Translation: BAC65729.1.
AF528164 Genomic DNA. Translation: AAO17385.1. Sequence problems.
CCDSiCCDS30470.1. [Q80TJ7-2]
CCDS53223.1. [Q80TJ7-1]
RefSeqiNP_001009544.1. NM_001009544.2.
NP_001106825.1. NM_001113354.1. [Q80TJ7-1]
NP_796175.1. NM_177201.5. [Q80TJ7-2]
XP_006528938.1. XM_006528875.3. [Q80TJ7-1]
XP_006528940.1. XM_006528877.3. [Q80TJ7-1]
XP_006528943.1. XM_006528880.3. [Q80TJ7-1]
UniGeneiMm.17156.
Mm.84774.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WEPNMR-A1-63[»]
ProteinModelPortaliQ80TJ7.
SMRiQ80TJ7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000040765.

Chemistry databases

ChEMBLiCHEMBL3038497.

PTM databases

iPTMnetiQ80TJ7.
PhosphoSitePlusiQ80TJ7.
SwissPalmiQ80TJ7.

Proteomic databases

EPDiQ80TJ7.
PaxDbiQ80TJ7.
PeptideAtlasiQ80TJ7.
PRIDEiQ80TJ7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000046950; ENSMUSP00000040765; ENSMUSG00000041229. [Q80TJ7-1]
ENSMUST00000046962; ENSMUSP00000041312; ENSMUSG00000041229. [Q80TJ7-2]
ENSMUST00000112662; ENSMUSP00000108281; ENSMUSG00000041229. [Q80TJ7-2]
ENSMUST00000112666; ENSMUSP00000108285; ENSMUSG00000041229. [Q80TJ7-3]
ENSMUST00000168501; ENSMUSP00000127653; ENSMUSG00000041229. [Q80TJ7-1]
GeneIDi320595.
74042.
KEGGimmu:320595.
mmu:74042.
UCSCiuc009upd.1. mouse. [Q80TJ7-3]
uc012hqt.1. mouse. [Q80TJ7-1]

Organism-specific databases

CTDi23133.
MGIiMGI:2444341. Phf8.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1633. Eukaryota.
ENOG410XQXU. LUCA.
GeneTreeiENSGT00550000074396.
HOVERGENiHBG045631.
InParanoidiQ80TJ7.
KOiK11445.
K19415.
OMAiLGTCFKD.
OrthoDBiEOG090B01WN.
PhylomeDBiQ80TJ7.
TreeFamiTF106480.

Enzyme and pathway databases

ReactomeiR-MMU-2299718. Condensation of Prophase Chromosomes.
R-MMU-3214842. HDMs demethylate histones.

Miscellaneous databases

ChiTaRSiPhf8. mouse.
EvolutionaryTraceiQ80TJ7.
PROiQ80TJ7.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000023350.
CleanExiMM_PHF8.
ExpressionAtlasiQ80TJ7. baseline and differential.
GenevisibleiQ80TJ7. MM.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiView protein in 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.
PfamiView protein in Pfam
PF02373. JmjC. 1 hit.
PF00628. PHD. 1 hit.
SMARTiView protein in SMART
SM00558. JmjC. 1 hit.
SM00249. PHD. 1 hit.
SUPFAMiSSF57903. SSF57903. 1 hit.
PROSITEiView protein in PROSITE
PS51184. JMJC. 1 hit.
PS01359. ZF_PHD_1. 1 hit.
PS50016. ZF_PHD_2. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiPHF8_MOUSE
AccessioniPrimary (citable) accession number: Q80TJ7
Secondary accession number(s): A2ABU8
, A2ABV0, A2ABV2, Q8BLX8, Q8BLY0, Q8BZ61, Q8CG26
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 19, 2004
Last sequence update: August 16, 2005
Last modified: February 15, 2017
This is version 117 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.