PHF2_HUMAN
ID PHF2_HUMAN Reviewed; 1096 AA.
AC O75151; Q4VXG0; Q8N3K2; Q9Y6N4;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 4.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Lysine-specific demethylase PHF2;
DE EC=1.14.11.- {ECO:0000269|PubMed:21532585};
DE AltName: Full=GRC5;
DE AltName: Full=PHD finger protein 2;
GN Name=PHF2 {ECO:0000312|HGNC:HGNC:8920};
GN Synonyms=CENP-35 {ECO:0000303|PubMed:20813266}, KIAA0662;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10051327; DOI=10.1007/s003359900989;
RA Hasenpusch-Theil K., Chadwick B.P., Theil T., Heath S.K., Wilkinson D.G.,
RA Frischauf A.M.;
RT "PHF2, a novel PHD finger gene located on human chromosome 9q22.";
RL Mamm. Genome 10:294-298(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=9734811; DOI=10.1093/dnares/5.3.169;
RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H.,
RA Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. X. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 5:169-176(1998).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT "Construction of expression-ready cDNA clones for KIAA genes: manual
RT curation of 330 KIAA cDNA clones.";
RL DNA Res. 9:99-106(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-1096.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-539 AND SER-882, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-882, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [11]
RP SUBCELLULAR LOCATION.
RX PubMed=20813266; DOI=10.1016/j.cell.2010.07.047;
RA Ohta S., Bukowski-Wills J.C., Sanchez-Pulido L., Alves Fde L., Wood L.,
RA Chen Z.A., Platani M., Fischer L., Hudson D.F., Ponting C.P., Fukagawa T.,
RA Earnshaw W.C., Rappsilber J.;
RT "The protein composition of mitotic chromosomes determined using
RT multiclassifier combinatorial proteomics.";
RL Cell 142:810-821(2010).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474; THR-479; SER-705 AND
RP SER-882, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION BY PKA, PHOSPHORYLATION AT
RP SER-1056, INTERACTION WITH ARID5B; HNF4A AND NR1H4, IDENTIFICATION BY MASS
RP SPECTROMETRY, TISSUE SPECIFICITY, IDENTIFICATION IN THE PHF2-ARID5B
RP COMPLEX, AND MUTAGENESIS OF HIS-249; SER-757; SER-899; SER-954 AND
RP SER-1056.
RX PubMed=21532585; DOI=10.1038/ncb2228;
RA Baba A., Ohtake F., Okuno Y., Yokota K., Okada M., Imai Y., Ni M.,
RA Meyer C.A., Igarashi K., Kanno J., Brown M., Kato S.;
RT "PKA-dependent regulation of the histone lysine demethylase complex PHF2-
RT ARID5B.";
RL Nat. Cell Biol. 13:668-675(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-705, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-539; SER-655; SER-705 AND
RP SER-882, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474; SER-681; SER-882 AND
RP SER-899, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-711, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) OF 1-70 IN COMPLEX WITH ZINC, DOMAIN
RP PHD-TYPE ZINC-FINGER, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP TYR-7 AND TRP-29.
RX PubMed=20129925; DOI=10.1074/jbc.c109.097667;
RA Wen H., Li J., Song T., Lu M., Kan P.Y., Lee M.G., Sha B., Shi X.;
RT "Recognition of histone H3K4 trimethylation by the plant homeodomain of
RT PHF2 modulates histone demethylation.";
RL J. Biol. Chem. 285:9322-9326(2010).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 60-451 IN COMPLEX WITH IRON AND
RP N-OXALYLGLYCINE, FUNCTION, AND MUTAGENESIS OF TYR-321.
RX PubMed=21167174; DOI=10.1016/j.jmb.2010.12.013;
RA Horton J.R., Upadhyay A.K., Hashimoto H., Zhang X., Cheng X.;
RT "Structural basis for human PHF2 Jumonji domain interaction with metal
RT ions.";
RL J. Mol. Biol. 406:1-8(2011).
CC -!- FUNCTION: Lysine demethylase that demethylates both histones and non-
CC histone proteins (PubMed:20129925, PubMed:21167174, PubMed:21532585).
CC Enzymatically inactive by itself, and becomes active following
CC phosphorylation by PKA: forms a complex with ARID5B and mediates
CC demethylation of methylated ARID5B (PubMed:21532585). Demethylation of
CC ARID5B leads to target the PHF2-ARID5B complex to target promoters,
CC where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3
CC (H3K9me2), followed by transcription activation of target genes
CC (PubMed:21532585). The PHF2-ARID5B complex acts as a coactivator of
CC HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone
CC H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA
CC (PubMed:21532585). Involved in the activation of toll-like receptor 4
CC (TLR4)-target inflammatory genes in macrophages by catalyzing the
CC demethylation of trimethylated histone H4 lysine 20 (H4K20me3) at the
CC gene promoters (By similarity). {ECO:0000250|UniProtKB:Q9WTU0,
CC ECO:0000269|PubMed:20129925, ECO:0000269|PubMed:21167174,
CC ECO:0000269|PubMed:21532585}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxoglutarate + N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] +
CC O2 = CO2 + formaldehyde + N(6)-methyl-L-lysyl(9)-[histone H3] +
CC succinate; Xref=Rhea:RHEA:60192, Rhea:RHEA-COMP:15541, Rhea:RHEA-
CC COMP:15542, ChEBI:CHEBI:15379, ChEBI:CHEBI:16526, ChEBI:CHEBI:16810,
CC ChEBI:CHEBI:16842, ChEBI:CHEBI:30031, ChEBI:CHEBI:61929,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000269|PubMed:21532585};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60193;
CC Evidence={ECO:0000269|PubMed:21532585};
CC -!- ACTIVITY REGULATION: Enzymatically inactive by itself, and become
CC active following phosphorylation by PKA.
CC -!- SUBUNIT: Component of the PHF2-ARID5B complex, at least composed of
CC PHF2 and ARID5B (PubMed:21532585). Interacts with HNF4A and NR1H4
CC (PubMed:21532585). Interacts with RELA (By similarity).
CC {ECO:0000250|UniProtKB:Q9WTU0, ECO:0000269|PubMed:21532585}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:20129925}.
CC Chromosome, centromere, kinetochore {ECO:0000269|PubMed:20813266}.
CC -!- TISSUE SPECIFICITY: Widely expressed, including in liver (at protein
CC level). {ECO:0000269|PubMed:21532585}.
CC -!- DOMAIN: The PHD-type zinc finger mediates the binding to H3K4me2 and
CC H3K4me3. {ECO:0000269|PubMed:20129925}.
CC -!- PTM: Phosphorylated by PKA on specific serine residues, leading to the
CC formation of an active lysine demethylase complex.
CC {ECO:0000269|PubMed:21532585}.
CC -!- SIMILARITY: Belongs to the JHDM1 histone demethylase family. JHDM1D
CC subfamily. {ECO:0000305}.
CC -!- CAUTION: In contrast to the related histone demethylases JHDM1D and
CC PHF8, the conserved active His in position 321 is replaced by a Tyr.
CC However, the presence of a Tyr residue neither affects binding to the
CC catalytic iron nor abolishes demethylase activity (PubMed:21167174).
CC {ECO:0000305|PubMed:21167174}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA31637.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF043725; AAD21791.1; -; mRNA.
DR EMBL; AB014562; BAA31637.2; ALT_INIT; mRNA.
DR EMBL; AL353629; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359181; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471089; EAW62867.1; -; Genomic_DNA.
DR EMBL; AL834263; CAD38938.1; -; mRNA.
DR CCDS; CCDS35069.1; -.
DR PIR; T00369; T00369.
DR RefSeq; NP_005383.3; NM_005392.3.
DR PDB; 3KQI; X-ray; 1.78 A; A=1-70.
DR PDB; 3PTR; X-ray; 1.95 A; B=60-451.
DR PDB; 3PU3; X-ray; 1.95 A; A/B=60-451.
DR PDB; 3PU8; X-ray; 1.94 A; A/B=60-451.
DR PDB; 3PUA; X-ray; 1.89 A; A=60-451.
DR PDB; 3PUS; X-ray; 2.08 A; A/B=60-451.
DR PDB; 7M10; X-ray; 1.15 A; A=1-70.
DR PDBsum; 3KQI; -.
DR PDBsum; 3PTR; -.
DR PDBsum; 3PU3; -.
DR PDBsum; 3PU8; -.
DR PDBsum; 3PUA; -.
DR PDBsum; 3PUS; -.
DR PDBsum; 7M10; -.
DR AlphaFoldDB; O75151; -.
DR SMR; O75151; -.
DR BioGRID; 111272; 46.
DR IntAct; O75151; 8.
DR MINT; O75151; -.
DR STRING; 9606.ENSP00000352185; -.
DR BindingDB; O75151; -.
DR ChEMBL; CHEMBL4295672; -.
DR GlyGen; O75151; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75151; -.
DR PhosphoSitePlus; O75151; -.
DR SwissPalm; O75151; -.
DR BioMuta; PHF2; -.
DR EPD; O75151; -.
DR jPOST; O75151; -.
DR MassIVE; O75151; -.
DR MaxQB; O75151; -.
DR PaxDb; O75151; -.
DR PeptideAtlas; O75151; -.
DR PRIDE; O75151; -.
DR ProteomicsDB; 49817; -.
DR Antibodypedia; 2009; 99 antibodies from 23 providers.
DR DNASU; 5253; -.
DR Ensembl; ENST00000359246.9; ENSP00000352185.4; ENSG00000197724.11.
DR GeneID; 5253; -.
DR KEGG; hsa:5253; -.
DR MANE-Select; ENST00000359246.9; ENSP00000352185.4; NM_005392.4; NP_005383.3.
DR UCSC; uc004aub.4; human.
DR CTD; 5253; -.
DR DisGeNET; 5253; -.
DR GeneCards; PHF2; -.
DR HGNC; HGNC:8920; PHF2.
DR HPA; ENSG00000197724; Low tissue specificity.
DR MIM; 604351; gene.
DR neXtProt; NX_O75151; -.
DR OpenTargets; ENSG00000197724; -.
DR PharmGKB; PA33260; -.
DR VEuPathDB; HostDB:ENSG00000197724; -.
DR eggNOG; KOG1633; Eukaryota.
DR GeneTree; ENSGT00940000158148; -.
DR HOGENOM; CLU_003540_2_0_1; -.
DR InParanoid; O75151; -.
DR OMA; AKKTKFQ; -.
DR OrthoDB; 1384737at2759; -.
DR PhylomeDB; O75151; -.
DR TreeFam; TF106480; -.
DR BioCyc; MetaCyc:G66-32922-MON; -.
DR PathwayCommons; O75151; -.
DR Reactome; R-HSA-3214842; HDMs demethylate histones.
DR SignaLink; O75151; -.
DR SIGNOR; O75151; -.
DR BioGRID-ORCS; 5253; 25 hits in 1089 CRISPR screens.
DR ChiTaRS; PHF2; human.
DR EvolutionaryTrace; O75151; -.
DR GenomeRNAi; 5253; -.
DR Pharos; O75151; Tbio.
DR PRO; PR:O75151; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; O75151; protein.
DR Bgee; ENSG00000197724; Expressed in ganglionic eminence and 183 other tissues.
DR ExpressionAtlas; O75151; baseline and differential.
DR Genevisible; O75151; HS.
DR GO; GO:0000776; C:kinetochore; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; TAS:ProtInc.
DR GO; GO:0032454; F:histone H3-methyl-lysine-9 demethylase activity; IDA:UniProtKB.
DR GO; GO:0035575; F:histone H4-methyl-lysine-20 demethylase activity; ISS:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; IDA:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; ISS:UniProtKB.
DR GO; GO:0033169; P:histone H3-K9 demethylation; IEA:Ensembl.
DR GO; GO:0035574; P:histone H4-K20 demethylation; ISS:UniProtKB.
DR GO; GO:0001889; P:liver development; TAS:UniProtKB.
DR GO; GO:0061188; P:negative regulation of ribosomal DNA heterochromatin assembly; IMP:UniProtKB.
DR GO; GO:0006482; P:protein demethylation; IDA:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 3.30.40.10; -; 1.
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 InterPro; IPR013083; Znf_RING/FYVE/PHD.
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 3D-structure; Acetylation; Activator; Centromere; Chromatin regulator;
KW Chromosome; Dioxygenase; Iron; Isopeptide bond; Kinetochore; Metal-binding;
KW Nucleus; Oxidoreductase; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..1096
FT /note="Lysine-specific demethylase PHF2"
FT /id="PRO_0000059290"
FT DOMAIN 197..353
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 447..634
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 646..674
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 719..799
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 817..846
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 877..1078
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 501..516
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 518..536
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 551..565
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 581..628
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 725..753
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..799
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 885..902
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 959..1026
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1052..1068
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 193
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT BINDING 246
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT BINDING 249
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538,
FT ECO:0000269|PubMed:21167174"
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 ECO:0000269|PubMed:21167174"
FT BINDING 259
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT BINDING 266
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT BINDING 321
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT BINDING 321
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00538,
FT ECO:0000269|PubMed:21167174"
FT BINDING 323
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT MOD_RES 474
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 539
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 655
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 681
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 705
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 720
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTU0"
FT MOD_RES 728
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTU0"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTU0"
FT MOD_RES 733
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTU0"
FT MOD_RES 734
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTU0"
FT MOD_RES 738
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTU0"
FT MOD_RES 879
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WTU0"
FT MOD_RES 882
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 899
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 1056
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:21532585"
FT CROSSLNK 711
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 56
FT /note="T -> P (in dbSNP:rs34279404)"
FT /id="VAR_047553"
FT VARIANT 1058
FT /note="S -> L (in dbSNP:rs35236745)"
FT /id="VAR_051598"
FT MUTAGEN 7
FT /note="Y->A: Abolishes binding to H3K4me2 and H3K4me3."
FT /evidence="ECO:0000269|PubMed:20129925"
FT MUTAGEN 29
FT /note="W->A: Abolishes binding to H3K4me2 and H3K4me3."
FT /evidence="ECO:0000269|PubMed:20129925"
FT MUTAGEN 249
FT /note="H->A: Abolishes demethylase activity."
FT /evidence="ECO:0000269|PubMed:21532585"
FT MUTAGEN 321
FT /note="Y->H: Does not alter iron-binding nor activates
FT histone demethylase activity."
FT /evidence="ECO:0000269|PubMed:21167174"
FT MUTAGEN 757
FT /note="S->A: Abolishes phosphorylation by PKA and
FT activation of demethylase activity; when associated with A-
FT 899; A-954 and A-1056."
FT /evidence="ECO:0000269|PubMed:21532585"
FT MUTAGEN 899
FT /note="S->A: Abolishes phosphorylation by PKA and
FT activation of demethylase activity; when associated with A-
FT 757; A-954 and A-1056."
FT /evidence="ECO:0000269|PubMed:21532585"
FT MUTAGEN 954
FT /note="S->A: Abolishes phosphorylation by PKA and
FT activation of demethylase activity; when associated with A-
FT 757; A-899 and A-1056."
FT /evidence="ECO:0000269|PubMed:21532585"
FT MUTAGEN 1056
FT /note="S->A: Abolishes phosphorylation by PKA and
FT activation of demethylase activity; when associated with A-
FT 757; A-899 and A-954."
FT /evidence="ECO:0000269|PubMed:21532585"
FT CONFLICT 19..41
FT /note="FMIECDACKDWFHGSCVGVEEEE -> PRAARPPARPGPTRAAQRRGRAT
FT (in Ref. 2; BAA31637)"
FT /evidence="ECO:0000305"
FT CONFLICT 75..76
FT /note="QA -> PT (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 100
FT /note="S -> R (in Ref. 2; BAA31637)"
FT /evidence="ECO:0000305"
FT CONFLICT 106
FT /note="A -> S (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 115
FT /note="L -> V (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 621
FT /note="K -> R (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 633
FT /note="Missing (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 642
FT /note="K -> R (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 654
FT /note="T -> S (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 664
FT /note="N -> S (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 670
FT /note="P -> A (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 698
FT /note="N -> S (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 712..719
FT /note="AVLPTPVT -> EALLMPTS (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 727
FT /note="A -> V (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 752
FT /note="R -> K (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 782
FT /note="S -> N (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 817
FT /note="A -> T (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 823
FT /note="S -> G (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 833
FT /note="N -> I (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 837..841
FT /note="SGKSA -> NKGT (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 849
FT /note="A -> T (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 857
FT /note="D -> E (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 862
FT /note="Missing (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 888
FT /note="I -> V (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 949..950
FT /note="SK -> NR (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 954..955
FT /note="SA -> NT (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 959..960
FT /note="LT -> PA (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 964
FT /note="T -> A (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 968
FT /note="T -> I (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 972
FT /note="I -> ASASTGTT (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 975
FT /note="G -> S (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 978..979
FT /note="ST -> PA (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 996
FT /note="T -> TTPAST (in Ref. 2; BAA31637 and 6; CAD38938)"
FT /evidence="ECO:0000305"
FT CONFLICT 1033..1035
FT /note="TGA -> SGS (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 1040
FT /note="T -> A (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT CONFLICT 1063
FT /note="Missing (in Ref. 1; AAD21791)"
FT /evidence="ECO:0000305"
FT TURN 8..11
FT /evidence="ECO:0007829|PDB:7M10"
FT STRAND 20..22
FT /evidence="ECO:0007829|PDB:7M10"
FT TURN 24..26
FT /evidence="ECO:0007829|PDB:7M10"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:7M10"
FT HELIX 32..35
FT /evidence="ECO:0007829|PDB:7M10"
FT HELIX 39..44
FT /evidence="ECO:0007829|PDB:7M10"
FT STRAND 45..47
FT /evidence="ECO:0007829|PDB:7M10"
FT HELIX 51..57
FT /evidence="ECO:0007829|PDB:7M10"
FT HELIX 87..95
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 115..121
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 127..131
FT /evidence="ECO:0007829|PDB:3PUA"
FT TURN 133..136
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 146..153
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 158..163
FT /evidence="ECO:0007829|PDB:3PUA"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 169..173
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 174..181
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 190..196
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 201..205
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 210..215
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 217..221
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 236..240
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 245..249
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 252..254
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 256..271
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 275..286
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 290..292
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 295..298
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 303..308
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 320..336
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 339..341
FT /evidence="ECO:0007829|PDB:3PU8"
FT HELIX 342..355
FT /evidence="ECO:0007829|PDB:3PUA"
FT STRAND 359..361
FT /evidence="ECO:0007829|PDB:3PU3"
FT HELIX 366..387
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 393..409
FT /evidence="ECO:0007829|PDB:3PUA"
FT TURN 412..414
FT /evidence="ECO:0007829|PDB:3PU8"
FT HELIX 415..418
FT /evidence="ECO:0007829|PDB:3PU8"
FT HELIX 419..421
FT /evidence="ECO:0007829|PDB:3PUA"
FT HELIX 428..443
FT /evidence="ECO:0007829|PDB:3PUA"
SQ SEQUENCE 1096 AA; 120775 MW; DD088363DB76674D CRC64;
MATVPVYCVC RLPYDVTRFM IECDACKDWF HGSCVGVEEE EAPDIDIYHC PNCEKTHGKS
TLKKKRTWHK HGPGQAPDVK PVQNGSQLFI KELRSRTFPS AEDVVARVPG SQLTLGYMEE
HGFTEPILVP KKDGLGLAVP APTFYVSDVE NYVGPERSVD VTDVTKQKDC KMKLKEFVDY
YYSTNRKRVL NVTNLEFSDT RMSSFVEPPD IVKKLSWVEN YWPDDALLAK PKVTKYCLIC
VKDSYTDFHI DSGGASAWYH VLKGEKTFYL IRPASANISL YERWRSASNH SEMFFADQVD
KCYKCIVKQG QTLFIPSGWI YATLTPVDCL AFAGHFLHSL SVEMQMRAYE VERRLKLGSL
TQFPNFETAC WYMGKHLLEA FKGSHKSGKQ LPPHLVQGAK ILNGAFRSWT KKQALAEHED
ELPEHFKPSQ LIKDLAKEIR LSENASKAVR PEVNTVASSD EVCDGDREKE EPPSPIEATP
PQSLLEKVSK KKTPKTVKMP KPSKIPKPPK PPKPPRPPKT LKLKDGGKKK GKKSRESASP
TIPNLDLLEA HTKEALTKME PPKKGKATKS VLSVPNKDVV HMQNDVERLE IREQTKSKSE
AKWKYKNSKP DSLLKMEEEQ KLEKSPLAGN KDNKFSFSFS NKKLLGSKAL RPPTSPGVFG
ALQNFKEDKP KPVRDEYEYV SDDGELKIDE FPIRRKKNAP KRDLSFLLDK KAVLPTPVTK
PKLDSAAYKS DDSSDEGSLH IDTDTKPGRN ARVKKESGSS AAGILDLLQA SEEVGALEYN
PSSQPPASPS TQEAIQGMLS MANLQASDSC LQTTWGAGQA KGSSLAAHGA RKNGGGSGKS
AGKRLLKRAA KNSVDLDDYE EEQDHLDACF KDSDYVYPSL ESDEDNPIFK SRSKKRKGSD
DAPYSPTARV GPSVPRQDRP VREGTRVASI ETGLAAAAAK LSQQEEQKSK KKKSAKRKLT
PNTTSPSTST SISAGTTSTS TTPASTTPAS TTPASTSTAS SQASQEGSSP EPPPESHSSS
LADHEYTAAG TFTGAQAGRT SQPMAPGVFL TQRRPSASSP NNNTAAKGKR TKKGMATAKQ
RLGKILKIHR NGKLLL
