PHF8_DANRE
ID PHF8_DANRE Reviewed; 1032 AA.
AC P0CH95;
DT 05-OCT-2010, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Histone lysine demethylase PHF8;
DE EC=1.14.11.27 {ECO:0000250|UniProtKB:Q9UPP1};
DE EC=1.14.11.65 {ECO:0000250|UniProtKB:Q9UPP1};
DE AltName: Full=PHD finger protein 8;
DE Short=zPHF8;
DE AltName: Full=[histone H3]-dimethyl-L-lysine(36) demethylase PHF8 {ECO:0000305};
DE AltName: Full=[histone H3]-dimethyl-L-lysine(9) demethylase PHF8 {ECO:0000305};
GN Name=phf8;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP HIS-323.
RX PubMed=20622853; DOI=10.1038/nature09261;
RA Qi H.H., Sarkissian M., Hu G.Q., Wang Z., Bhattacharjee A., Gordon D.B.,
RA Gonzales M., Lan F., Ongusaha P.P., Huarte M., Yaghi N.K., Lim H.,
RA Garcia B.A., Brizuela L., Zhao K., Roberts T.M., Shi Y.;
RT "Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and
RT craniofacial development.";
RL Nature 466:503-507(2010).
CC -!- FUNCTION: Histone lysine demethylase with selectivity for the di- and
CC monomethyl states that plays a key role cell cycle progression, rDNA
CC transcription and brain development. Demethylates mono- and
CC dimethylated histone H3 'Lys-9' residue (H3K9Me1 and H3K9Me2),
CC dimethylated H3 'Lys-27' (H3K27Me2) and monomethylated histone H4 'Lys-
CC 20' residue (H4K20Me1). Acts as a transcription activator as H3K9Me1,
CC H3K9Me2, H3K27Me2 and H4K20Me1 are epigenetic repressive marks.
CC Involved in cell cycle progression by being required to control G1-S
CC transition. Acts as a coactivator of rDNA transcription, by activating
CC polymerase I (pol I) mediated transcription of rRNA genes. Has activity
CC toward H4K20Me1 only when nucleosome is used as a substrate and when
CC not histone octamer is used as substrate (By similarity). Required for
CC brain development, probably by regulating expression of neuron-specific
CC genes. {ECO:0000250, ECO:0000269|PubMed:20622853}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3]
CC + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(36)-[histone H3] + 2
CC succinate; Xref=Rhea:RHEA:42032, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC COMP:9787, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:61976; EC=1.14.11.27;
CC Evidence={ECO:0000250|UniProtKB:Q9UPP1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3]
CC + 2 O2 = 2 CO2 + 2 formaldehyde + L-lysyl(9)-[histone H3] + 2
CC succinate; Xref=Rhea:RHEA:60188, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC COMP:15546, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:29969, ChEBI:CHEBI:30031,
CC ChEBI:CHEBI:61976; EC=1.14.11.65;
CC Evidence={ECO:0000250|UniProtKB:Q9UPP1};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033; Evidence={ECO:0000250};
CC Note=Binds 1 Fe(2+) ion per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Nucleus, nucleolus
CC {ECO:0000250}. Note=Recruited to H3K4me3 sites on chromatin during
CC interphase. Dissociates from chromatin when cells enter mitosis (By
CC similarity). {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: First detected at 14 hours post-fertilization
CC (hpf) in the head and tail regions. Found mostly in the head region.
CC Also detectable in the jaw of the embryo at 3 dpf.
CC -!- DOMAIN: The PHD-type zinc finger mediates the binding to H3K4me3.
CC Binding to H3K4me3 promotes its access to H3K9me2 (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: The linker region is a critical determinant of demethylase
CC specificity. It enables the active site of JmjC to reach the target
CC H3K9me2 when the PHD-type zinc finger binds to H3K4me3 (By similarity).
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in
CC defects in brain and craniofacial development. Embryos show delays in
CC brain development at 24 hpf and apoptosis in the developing brain and
CC the neural tube at 30 hpf. {ECO:0000269|PubMed:20622853}.
CC -!- SIMILARITY: Belongs to the JHDM1 histone demethylase family. JHDM1D
CC subfamily. {ECO:0000305}.
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DR EMBL; CR352210; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001189376.1; NM_001202447.1.
DR RefSeq; XP_005162322.1; XM_005162265.3.
DR AlphaFoldDB; P0CH95; -.
DR SMR; P0CH95; -.
DR STRING; 7955.ENSDARP00000007140; -.
DR PaxDb; P0CH95; -.
DR PRIDE; P0CH95; -.
DR Ensembl; ENSDART00000026314; ENSDARP00000007140; ENSDARG00000006584.
DR Ensembl; ENSDART00000183639; ENSDARP00000148598; ENSDARG00000006584.
DR GeneID; 566534; -.
DR KEGG; dre:566534; -.
DR CTD; 23133; -.
DR ZFIN; ZDB-GENE-060419-1; phf8.
DR eggNOG; KOG1633; Eukaryota.
DR GeneTree; ENSGT00940000157847; -.
DR HOGENOM; CLU_003540_2_0_1; -.
DR InParanoid; P0CH95; -.
DR OMA; DIFHQNI; -.
DR OrthoDB; 1384737at2759; -.
DR PhylomeDB; P0CH95; -.
DR TreeFam; TF106480; -.
DR BRENDA; 1.14.11.65; 928.
DR Reactome; R-DRE-2299718; Condensation of Prophase Chromosomes.
DR Reactome; R-DRE-3214842; HDMs demethylate histones.
DR PRO; PR:P0CH95; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 23.
DR Bgee; ENSDARG00000006584; Expressed in testis and 29 other tissues.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0032452; F:histone demethylase activity; IBA:GO_Central.
DR GO; GO:0140680; F:histone H3-di/monomethyl-lysine-36 demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0140683; F:histone H3-di/monomethyl-lysine-9 demethylase activity; IEA:UniProtKB-EC.
DR GO; GO:0051864; F:histone H3-methyl-lysine-36 demethylase activity; ISS:UniProtKB.
DR GO; GO:0032454; F:histone H3-methyl-lysine-9 demethylase activity; ISS:UniProtKB.
DR GO; GO:0071558; F:histone H3-tri/di-methyl-lysine-27 demethylase activity; ISS:UniProtKB.
DR GO; GO:0035575; F:histone H4-methyl-lysine-20 demethylase activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IMP:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0048703; P:embryonic viscerocranium morphogenesis; IMP:ZFIN.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISS:UniProtKB.
DR GO; GO:0071557; P:histone H3-K27 demethylation; ISS:UniProtKB.
DR GO; GO:0070544; P:histone H3-K36 demethylation; ISS:UniProtKB.
DR GO; GO:0033169; P:histone H3-K9 demethylation; ISS:UniProtKB.
DR GO; GO:0035574; P:histone H4-K20 demethylation; ISS:UniProtKB.
DR GO; GO:0061188; P:negative regulation of ribosomal DNA heterochromatin assembly; ISS:UniProtKB.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0060319; P:primitive erythrocyte differentiation; IMP:ZFIN.
DR GO; GO:0006482; P:protein demethylation; IBA:GO_Central.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IGI:ZFIN.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR InterPro; IPR041070; JHD.
DR InterPro; IPR003347; JmjC_dom.
DR InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR InterPro; IPR001965; Znf_PHD.
DR InterPro; IPR019787; Znf_PHD-finger.
DR Pfam; PF17811; JHD; 1.
DR Pfam; PF02373; JmjC; 1.
DR Pfam; PF00628; PHD; 1.
DR SMART; SM00558; JmjC; 1.
DR SMART; SM00249; PHD; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51184; JMJC; 1.
DR PROSITE; PS01359; ZF_PHD_1; 1.
DR PROSITE; PS50016; ZF_PHD_2; 1.
PE 1: Evidence at protein level;
KW Activator; Cell cycle; Chromatin regulator; Dioxygenase; Iron;
KW Metal-binding; Nucleus; Oxidoreductase; Reference proteome; Transcription;
KW Transcription regulation; Zinc; Zinc-finger.
FT CHAIN 1..1032
FT /note="Histone lysine demethylase PHF8"
FT /id="PRO_0000399817"
FT DOMAIN 199..355
FT /note="JmjC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT ZN_FING 5..56
FT /note="PHD-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146"
FT REGION 65..83
FT /note="Linker"
FT /evidence="ECO:0000250"
FT REGION 455..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 577..660
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 697..857
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 875..923
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 943..1015
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 455..483
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 587..602
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 642..657
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 713..740
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 756..773
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 781..800
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 809..835
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 971..993
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 248
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 251
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 253
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT BINDING 268
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 323
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538"
FT MUTAGEN 323
FT /note="H->Y: Unable to rescue a phf8 morpholino mutant."
FT /evidence="ECO:0000269|PubMed:20622853"
SQ SEQUENCE 1032 AA; 114222 MW; FD86E98931F75D94 CRC64;
MASVPVYCLC RLPYDVTRFM IECDVCQDWF HGSCVGVEED KAAEIDLYHC PNCQVTHGPS
VMRKRRGAVK HADVGLGRDS GRPVKTGSAQ FVRELRCRTF PSADEVLLKP TGAQLTVEFL
EERSFSVPVL VLRKDGLGMN LPPSSFSVTD VEHYIGTEKE IDVIDVSRQA DLKMKLGEFV
EYYNSPNRDR VLNVISLEFS DTRLSNLVET PKIVRKLSWV ENLWPEESIF ERPNVQKYCL
MGVKDSYTDF HIDFGGTSVW YHVLRGEKIF YLIRPTAANL SLFERWSSSS NQNELFFGDQ
VDMCYKCSVK QGNTLFIPTG WIHAVLTPVD CLAFGGNFLH SLNIDMQLRA YEIEKRLSTA
DLFKFPNFET VCWYVGKHLL DTFRGLRENR RHPATYLVHG AKALNNAFRG WTRKESLGEH
EQEIPDTIKT QQLVKDLAKE IRLVEDIFQQ NIGRSGTPFG GSQGLPSPHP KAQLNTPLTF
SQHLSKKRGP KPKEAFGGGG VGPPGAKKKS QKGKEIKTEA GELDLLEIHT KHTLKKFQPG
CKVKKSKLEL PDDCLDDFEE KINKSKLKLV LTNGKLQGKK GRAGSANGAG SSLQQFQPHM
ATLSDFDSED ELQIDETPPP RRRPSLPSKK KLAGLPRKLP RAKPCSDPHR IREPGEVDFD
IEEDYTTDEE MLTMQGVKGG AGGILDLLKA SKQVAGLDSA LSEEAPASPS TRDAIQGMLS
MANPPSSSSS SSSSSPLSIS GGGEMMGLMK EKGGREGWMS GVKKSERKAV FQRPGKRPIK
RPARHLSDDE SLDEQETLGT CFKDSDYVYP SLESDEEDHV SKSKMKRKRN WDDTPWSPKA
RVTPTLPKQE RPVREGARVA SVETGLAAAA AKLAQQEQQK TITKRKYTKK KTPQEKVHST
VAQLQHQPDS APVSPPLPSE PPVDCIVEER RVEVYSASLL DHEYTAGPGP FSPGGPRGSG
AMAPGVFLTS RRPSLSPQNS SSYSPSAPSP GGLVTPTSAG ACQGKRPKKG LATAKQRLGK
ILKIHRNGKL LL
