ID PHF2_MOUSE Reviewed; 1096 AA.
AC Q9WTU0; Q6A023; Q80WA8;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 15-AUG-2003, sequence version 2.
DT 27-MAR-2024, entry version 154.
DE RecName: Full=Lysine-specific demethylase PHF2;
DE EC=1.14.11.- {ECO:0000250|UniProtKB:O75151};
DE AltName: Full=GRC5;
DE AltName: Full=PHD finger protein 2;
GN Name=Phf2; Synonyms=Kiaa0662;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Limb;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 59-1096.
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-474; SER-651; SER-677;
RP TYR-724; SER-726; SER-729; SER-730; SER-734; SER-873; SER-876 AND SER-893,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP CATALYTIC ACTIVITY.
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 [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH RELA.
RX PubMed=22921934; DOI=10.1016/j.molcel.2012.07.020;
RA Stender J.D., Pascual G., Liu W., Kaikkonen M.U., Do K., Spann N.J.,
RA Boutros M., Perrimon N., Rosenfeld M.G., Glass C.K.;
RT "Control of proinflammatory gene programs by regulated trimethylation and
RT demethylation of histone H4K20.";
RL Mol. Cell 48:28-38(2012).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-716, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Lysine demethylase that demethylates both histones and non-
CC histone proteins (PubMed:22921934). Enzymatically inactive by itself,
CC and becomes active following phosphorylation by PKA: forms a complex
CC with ARID5B and mediates demethylation of methylated ARID5B.
CC Demethylation of ARID5B leads to target the PHF2-ARID5B complex to
CC target promoters, where PHF2 mediates demethylation of dimethylated
CC 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation
CC of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A
CC in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3
CC (H3K4me3) at rDNA promoters and promotes expression of rDNA (By
CC similarity). Involved in the activation of toll-like receptor 4 (TLR4)-
CC target inflammatory genes in macrophages by catalyzing the
CC demethylation of trimethylated histone H4 lysine 20 (H4K20me3) at the
CC gene promoters (PubMed:22921934). {ECO:0000250|UniProtKB:O75151,
CC ECO:0000269|PubMed:22921934}.
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:0000250|UniProtKB:O75151};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60193;
CC Evidence={ECO:0000250|UniProtKB:O75151};
CC -!- ACTIVITY REGULATION: Enzymatically inactive by itself, and become
CC active following phosphorylation by PKA. {ECO:0000250}.
CC -!- SUBUNIT: Component of the PHF2-ARID5B complex, at least composed of
CC PHF2 and ARID5B. Interacts with HNF4A and NR1H4 (By similarity).
CC Interacts with RELA (PubMed:22921934). {ECO:0000250|UniProtKB:O75151,
CC ECO:0000269|PubMed:22921934}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleolus
CC {ECO:0000250|UniProtKB:O75151}. Chromosome, centromere, kinetochore
CC {ECO:0000250|UniProtKB:O75151}.
CC -!- DOMAIN: The PHD-type zinc finger mediates the binding to H3K4me2 and
CC H3K4me3. {ECO:0000250}.
CC -!- PTM: Phosphorylated by PKA on specific serine residues, leading to the
CC formation of an active lysine demethylase complex. {ECO:0000250}.
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. {ECO:0000305}.
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DR EMBL; AF043726; AAD21792.1; -; mRNA.
DR EMBL; AC109249; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC051633; AAH51633.1; -; mRNA.
DR EMBL; AK172995; BAD32273.1; -; mRNA.
DR CCDS; CCDS26496.1; -.
DR RefSeq; NP_035208.2; NM_011078.3.
DR AlphaFoldDB; Q9WTU0; -.
DR SMR; Q9WTU0; -.
DR BioGRID; 202144; 6.
DR IntAct; Q9WTU0; 5.
DR STRING; 10090.ENSMUSP00000047308; -.
DR iPTMnet; Q9WTU0; -.
DR PhosphoSitePlus; Q9WTU0; -.
DR SwissPalm; Q9WTU0; -.
DR EPD; Q9WTU0; -.
DR jPOST; Q9WTU0; -.
DR MaxQB; Q9WTU0; -.
DR PaxDb; 10090-ENSMUSP00000047308; -.
DR PeptideAtlas; Q9WTU0; -.
DR ProteomicsDB; 287703; -.
DR Pumba; Q9WTU0; -.
DR Antibodypedia; 2009; 122 antibodies from 24 providers.
DR DNASU; 18676; -.
DR Ensembl; ENSMUST00000035540.9; ENSMUSP00000047308.8; ENSMUSG00000038025.9.
DR GeneID; 18676; -.
DR KEGG; mmu:18676; -.
DR UCSC; uc007qim.1; mouse.
DR AGR; MGI:1338034; -.
DR CTD; 5253; -.
DR MGI; MGI:1338034; Phf2.
DR VEuPathDB; HostDB:ENSMUSG00000038025; -.
DR eggNOG; KOG1633; Eukaryota.
DR GeneTree; ENSGT00940000158148; -.
DR HOGENOM; CLU_003540_2_0_1; -.
DR InParanoid; Q9WTU0; -.
DR OMA; KDIVHTQ; -.
DR OrthoDB; 2784357at2759; -.
DR PhylomeDB; Q9WTU0; -.
DR TreeFam; TF106480; -.
DR Reactome; R-MMU-3214842; HDMs demethylate histones.
DR BioGRID-ORCS; 18676; 0 hits in 83 CRISPR screens.
DR ChiTaRS; Phf1; mouse.
DR PRO; PR:Q9WTU0; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9WTU0; Protein.
DR Bgee; ENSMUSG00000038025; Expressed in ascending aorta and 250 other cell types or tissues.
DR Genevisible; Q9WTU0; MM.
DR GO; GO:0000776; C:kinetochore; ISS:UniProtKB.
DR GO; GO:0005730; C:nucleolus; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0032452; F:histone demethylase activity; IBA:GO_Central.
DR GO; GO:0032454; F:histone H3K9 demethylase activity; ISS:UniProtKB.
DR GO; GO:0035575; F:histone H4K20 demethylase activity; IMP:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; ISS:UniProtKB.
DR GO; GO:0035064; F:methylated histone binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0003712; F:transcription coregulator activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0061188; P:negative regulation of rDNA heterochromatin formation; ISS:UniProtKB.
DR GO; GO:0006482; P:protein demethylation; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0045815; P:transcription initiation-coupled chromatin remodeling; IMP:UniProtKB.
DR CDD; cd15554; PHD_PHF2_like; 1.
DR Gene3D; 1.20.58.1360; -; 1.
DR Gene3D; 2.60.120.650; Cupin; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 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 PANTHER; PTHR23123:SF14; LYSINE-SPECIFIC DEMETHYLASE PHF2; 1.
DR PANTHER; PTHR23123; PHD/F-BOX CONTAINING PROTEIN; 1.
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; SSF51197; Clavaminate synthase-like; 1.
DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 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 Acetylation; Activator; Centromere; Chromatin regulator; Chromosome;
KW Dioxygenase; Iron; Isopeptide bond; Kinetochore; Metal-binding; Nucleus;
KW 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_0000059291"
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 448..630
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 719..755
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 811..841
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 871..1080
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 461..475
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 515..533
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 548..562
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 578..625
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 721..749
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 879..896
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 953..1041
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1053..1067
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 /evidence="ECO:0000250"
FT BINDING 246
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
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 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 259
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT BINDING 266
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
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 BINDING 323
FT /ligand="2-oxoglutarate"
FT /ligand_id="ChEBI:CHEBI:16810"
FT /evidence="ECO:0000250"
FT MOD_RES 474
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 479
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75151"
FT MOD_RES 536
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75151"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 677
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 701
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75151"
FT MOD_RES 716
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT MOD_RES 724
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 726
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 729
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 730
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 734
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 873
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 876
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 893
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1057
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O75151"
FT CROSSLNK 707
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:O75151"
FT CONFLICT 938
FT /note="Q -> L (in Ref. 1; AAD21792)"
FT /evidence="ECO:0000305"
FT CONFLICT 955
FT /note="P -> S (in Ref. 4; BAD32273)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1096 AA; 120814 MW; 778B822C007D8860 CRC64;
MATVPVYCVC RLPYDVTRFM IECDACKDWF HGSCVGVEEE EAPDIDIYHC PNCEKTHGKS
TLKKKRTWHK HGPGPTPDVK PVQNGSQLFI KELRSRTFPS AEDVVSRVPG SQLTVGYMEE
HGFTEPILVP KKDGLGLAVP APTFYVSDVE NYVGPERSVD VTDVTKQKDC KMKLKEFVDY
YYSTNRKRVL NVTNLEFSDT RMSSFVEPPD IVKKLSWVEN YWPDDALLAK PKVTKYCLIC
VKDSYTDFHI DSGGASAWYH VLKGEKIFYL IRPASANISL YERWRSASNH SEMFFADQVD
RCYKCTVKQG QTLFIPSGWI YATLTPVDCL AFAGHFLHSL SVEMQMRAYE VERRLKLGSL
TQFPNFETAC WYMGKHLLEA FKGSHKSGKQ LPPHLVQGAK ILNGAFRSWT KKQALAEHED
ELPEHFRPSQ LIKDLAKEIR LSENASKTVR PEVNAAASSD EVCDGDREKE EPPSPVETTP
PRSLLEKVSK KKTSKTVKMP KPSKIPKPPK SPKPPKTLKL KDGSKKKGKK CKESASPTIP
NLDLLEAHTK EALTKMEPPK KGKTPKSVLS VPNKDTVHTQ NDMERLEIRE QTKSKSEAKW
KYKNSKPDSL LKMEEEQRLE KSPLAGNKDK FSFSFSNRKL LGSKALRPPS SPGVFGALQS
FKEDKAKPVR DEYEYVSDDG ELKIDEFPIR RKKSAPKRDL SFLLDKKEAL LMPTSKPKLD
SAVYKSDDSS DEGSLHIDTD TKPGRNAKVK KESGSSAAGI LDLLQASEEV GALEYNPNSQ
PPASPSTQEA IQGMLSMANL QASDSCLQTT WGTGQAKGGS LAAHGARKIG GGNKGTGKRL
LKRTAKNSVD LEDYEEQDHL DACFKDSDYV YPSLESDEDN PVFKSRSKKR KGSDDAPYSP
TARVGPSVPR QDRPVREGTR VASIETGLAA AAAKLSQQEE QKNRKKKNTK RKPAPNTASP
SISTSASAST GTTSASTTPA STTPASTTPA STTPASTSTA SSQASQEGSS PEPPPESHSS
SLADHEYTAA GTFSGSQAGR ASQPMAPGVF LTQRRPSASS PNNTAAKGKR TKKGMATAKQ
RLGKILKIHR NGKLLL
//
