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Protein

Lysine-specific demethylase PHF2

Gene

PHF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Lysine demethylase that demethylates both histones and non-histone proteins. Enzymatically inactive by itself, and becomes active following phosphorylation by PKA: forms a complex with ARID5B and mediates demethylation of methylated ARID5B. Demethylation of ARID5B leads to target the PHF2-ARID5B complex to target promoters, where PHF2 mediates demethylation of dimethylated 'Lys-9' of histone H3 (H3K9me2), followed by transcription activation of target genes. The PHF2-ARID5B complex acts as a coactivator of HNF4A in liver. PHF2 is recruited to trimethylated 'Lys-4' of histone H3 (H3K4me3) at rDNA promoters and promotes expression of rDNA.3 Publications

Caution

In contrast to the related histone demethylases JHDM1D and PHF8, the conserved active His in position 321 is replaced by a Tyr. However, the presence of a Tyr residue neither affects binding to the catalytic iron nor abolishes demethylase activity (PubMed:21167174).1 Publication

Activity regulationi

Enzymatically inactive by itself, and become active following phosphorylation by PKA.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei193Alpha-ketoglutarate1
Binding sitei246Alpha-ketoglutarate1
Metal bindingi249Iron; catalyticPROSITE-ProRule annotation1 Publication1
Metal bindingi251Iron; catalyticPROSITE-ProRule annotation1 Publication1
Binding sitei259Alpha-ketoglutarate1
Binding sitei266Alpha-ketoglutarate1
Metal bindingi321Iron; catalyticPROSITE-ProRule annotation1 Publication1
Binding sitei321Alpha-ketoglutarate1
Binding sitei323Alpha-ketoglutarate1

Regions

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

GO - Molecular functioni

GO - Biological processi

  • liver development Source: UniProtKB
  • negative regulation of chromatin silencing at rDNA Source: UniProtKB
  • protein demethylation Source: UniProtKB

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-3214842 HDMs demethylate histones

Names & Taxonomyi

Protein namesi
Recommended name:
Lysine-specific demethylase PHF2 (EC:1.14.11.-)
Alternative name(s):
GRC5
PHD finger protein 2
Gene namesi
Name:PHF2Imported
Synonyms:CENP-351 Publication, KIAA0662
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000197724.10
HGNCiHGNC:8920 PHF2
MIMi604351 gene
neXtProtiNX_O75151

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Centromere, Chromosome, Kinetochore, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi7Y → A: Abolishes binding to H3K4me2 and H3K4me3. 1 Publication1
Mutagenesisi29W → A: Abolishes binding to H3K4me2 and H3K4me3. 1 Publication1
Mutagenesisi249H → A: Abolishes demethylase activity. 1 Publication1
Mutagenesisi321Y → H: Does not alter iron-binding nor activates histone demethylase activity. 1 Publication1
Mutagenesisi757S → A: Abolishes phosphorylation by PKA and activation of demethylase activity; when associated with A-899; A-954 and A-1056. 1 Publication1
Mutagenesisi899S → A: Abolishes phosphorylation by PKA and activation of demethylase activity; when associated with A-757; A-954 and A-1056. 1 Publication1
Mutagenesisi954S → A: Abolishes phosphorylation by PKA and activation of demethylase activity; when associated with A-757; A-899 and A-1056. 1 Publication1
Mutagenesisi1056S → A: Abolishes phosphorylation by PKA and activation of demethylase activity; when associated with A-757; A-899 and A-954. 1 Publication1

Organism-specific databases

DisGeNETi5253
OpenTargetsiENSG00000197724
PharmGKBiPA33260

Polymorphism and mutation databases

BioMutaiPHF2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000592901 – 1096Lysine-specific demethylase PHF2Add BLAST1096

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei474PhosphoserineCombined sources1
Modified residuei479PhosphothreonineCombined sources1
Modified residuei539PhosphoserineCombined sources1
Modified residuei655PhosphoserineCombined sources1
Modified residuei681PhosphoserineCombined sources1
Modified residuei705PhosphoserineCombined sources1
Cross-linki711Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei720N6-acetyllysineBy similarity1
Modified residuei728PhosphotyrosineBy similarity1
Modified residuei730PhosphoserineBy similarity1
Modified residuei733PhosphoserineBy similarity1
Modified residuei734PhosphoserineBy similarity1
Modified residuei738PhosphoserineBy similarity1
Modified residuei879PhosphoserineBy similarity1
Modified residuei882PhosphoserineCombined sources1
Modified residuei899PhosphoserineCombined sources1
Modified residuei1056Phosphoserine; by PKA1 Publication1

Post-translational modificationi

Phosphorylated by PKA on specific serine residues, leading to the formation of an active lysine demethylase complex.1 Publication

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO75151
MaxQBiO75151
PaxDbiO75151
PeptideAtlasiO75151
PRIDEiO75151
ProteomicsDBi49817

PTM databases

iPTMnetiO75151
PhosphoSitePlusiO75151

Expressioni

Tissue specificityi

Widely expressed, including in liver (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000197724 Expressed in 216 organ(s), highest expression level in forebrain
CleanExiHS_PHF2
ExpressionAtlasiO75151 baseline and differential
GenevisibleiO75151 HS

Organism-specific databases

HPAiHPA010831

Interactioni

Subunit structurei

Component of the PHF2-ARID5B complex, at least composed of PHF2 and ARID5B. Interacts with HNF4A and NR1H4.3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111272, 8 interactors
IntActiO75151, 1 interactor
STRINGi9606.ENSP00000352185

Structurei

Secondary structure

11096
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO75151
SMRiO75151
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75151

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini197 – 353JmjCPROSITE-ProRule annotationAdd BLAST157

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi472 – 518Pro-richAdd BLAST47
Compositional biasi487 – 648Lys-richAdd BLAST162
Compositional biasi960 – 1020Ser/Thr-richAdd BLAST61

Domaini

The PHD-type zinc finger mediates the binding to H3K4me2 and H3K4me3.1 Publication

Sequence similaritiesi

Zinc finger

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

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG1633 Eukaryota
ENOG410Y2FD LUCA
GeneTreeiENSGT00550000074396
HOGENOMiHOG000231232
HOVERGENiHBG045631
InParanoidiO75151
KOiK19414
OMAiDSCLQTT
OrthoDBiEOG091G09DB
PhylomeDBiO75151
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

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

O75151-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MATVPVYCVC RLPYDVTRFM IECDACKDWF HGSCVGVEEE EAPDIDIYHC
60 70 80 90 100
PNCEKTHGKS TLKKKRTWHK HGPGQAPDVK PVQNGSQLFI KELRSRTFPS
110 120 130 140 150
AEDVVARVPG SQLTLGYMEE HGFTEPILVP KKDGLGLAVP APTFYVSDVE
160 170 180 190 200
NYVGPERSVD VTDVTKQKDC KMKLKEFVDY YYSTNRKRVL NVTNLEFSDT
210 220 230 240 250
RMSSFVEPPD IVKKLSWVEN YWPDDALLAK PKVTKYCLIC VKDSYTDFHI
260 270 280 290 300
DSGGASAWYH VLKGEKTFYL IRPASANISL YERWRSASNH SEMFFADQVD
310 320 330 340 350
KCYKCIVKQG QTLFIPSGWI YATLTPVDCL AFAGHFLHSL SVEMQMRAYE
360 370 380 390 400
VERRLKLGSL TQFPNFETAC WYMGKHLLEA FKGSHKSGKQ LPPHLVQGAK
410 420 430 440 450
ILNGAFRSWT KKQALAEHED ELPEHFKPSQ LIKDLAKEIR LSENASKAVR
460 470 480 490 500
PEVNTVASSD EVCDGDREKE EPPSPIEATP PQSLLEKVSK KKTPKTVKMP
510 520 530 540 550
KPSKIPKPPK PPKPPRPPKT LKLKDGGKKK GKKSRESASP TIPNLDLLEA
560 570 580 590 600
HTKEALTKME PPKKGKATKS VLSVPNKDVV HMQNDVERLE IREQTKSKSE
610 620 630 640 650
AKWKYKNSKP DSLLKMEEEQ KLEKSPLAGN KDNKFSFSFS NKKLLGSKAL
660 670 680 690 700
RPPTSPGVFG ALQNFKEDKP KPVRDEYEYV SDDGELKIDE FPIRRKKNAP
710 720 730 740 750
KRDLSFLLDK KAVLPTPVTK PKLDSAAYKS DDSSDEGSLH IDTDTKPGRN
760 770 780 790 800
ARVKKESGSS AAGILDLLQA SEEVGALEYN PSSQPPASPS TQEAIQGMLS
810 820 830 840 850
MANLQASDSC LQTTWGAGQA KGSSLAAHGA RKNGGGSGKS AGKRLLKRAA
860 870 880 890 900
KNSVDLDDYE EEQDHLDACF KDSDYVYPSL ESDEDNPIFK SRSKKRKGSD
910 920 930 940 950
DAPYSPTARV GPSVPRQDRP VREGTRVASI ETGLAAAAAK LSQQEEQKSK
960 970 980 990 1000
KKKSAKRKLT PNTTSPSTST SISAGTTSTS TTPASTTPAS TTPASTSTAS
1010 1020 1030 1040 1050
SQASQEGSSP EPPPESHSSS LADHEYTAAG TFTGAQAGRT SQPMAPGVFL
1060 1070 1080 1090
TQRRPSASSP NNNTAAKGKR TKKGMATAKQ RLGKILKIHR NGKLLL
Length:1,096
Mass (Da):120,775
Last modified:November 25, 2008 - v4
Checksum:iDD088363DB76674D
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7ET14E7ET14_HUMAN
Lysine-specific demethylase PHF2
PHF2
309Annotation score:
A0A087WW48A0A087WW48_HUMAN
Lysine-specific demethylase PHF2
PHF2
328Annotation score:

Sequence cautioni

The sequence BAA31637 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19 – 41FMIEC…VEEEE → PRAARPPARPGPTRAAQRRG RAT in BAA31637 (PubMed:9734811).CuratedAdd BLAST23
Sequence conflicti75 – 76QA → PT in AAD21791 (PubMed:10051327).Curated2
Sequence conflicti100S → R in BAA31637 (PubMed:9734811).Curated1
Sequence conflicti106A → S in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti115L → V in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti621K → R in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti633Missing in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti642K → R in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti654T → S in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti664N → S in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti670P → A in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti698N → S in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti712 – 719AVLPTPVT → EALLMPTS in AAD21791 (PubMed:10051327).Curated8
Sequence conflicti727A → V in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti752R → K in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti782S → N in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti817A → T in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti823S → G in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti833N → I in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti837 – 841SGKSA → NKGT in AAD21791 (PubMed:10051327).Curated5
Sequence conflicti849A → T in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti857D → E in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti862Missing in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti888I → V in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti949 – 950SK → NR in AAD21791 (PubMed:10051327).Curated2
Sequence conflicti954 – 955SA → NT in AAD21791 (PubMed:10051327).Curated2
Sequence conflicti959 – 960LT → PA in AAD21791 (PubMed:10051327).Curated2
Sequence conflicti964T → A in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti968T → I in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti972I → ASASTGTT in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti975G → S in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti978 – 979ST → PA in AAD21791 (PubMed:10051327).Curated2
Sequence conflicti996T → TTPAST in BAA31637 (PubMed:9734811).Curated1
Sequence conflicti996T → TTPAST in CAD38938 (PubMed:17974005).Curated1
Sequence conflicti1033 – 1035TGA → SGS in AAD21791 (PubMed:10051327).Curated3
Sequence conflicti1040T → A in AAD21791 (PubMed:10051327).Curated1
Sequence conflicti1063Missing in AAD21791 (PubMed:10051327).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04755356T → P. Corresponds to variant dbSNP:rs34279404Ensembl.1
Natural variantiVAR_0515981058S → L. Corresponds to variant dbSNP:rs35236745Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043725 mRNA Translation: AAD21791.1
AB014562 mRNA Translation: BAA31637.2 Different initiation.
AL353629 Genomic DNA No translation available.
AL359181 Genomic DNA No translation available.
CH471089 Genomic DNA Translation: EAW62867.1
AL834263 mRNA Translation: CAD38938.1
CCDSiCCDS35069.1
PIRiT00369
RefSeqiNP_005383.3, NM_005392.3
UniGeneiHs.211441

Genome annotation databases

EnsembliENST00000359246; ENSP00000352185; ENSG00000197724
GeneIDi5253
KEGGihsa:5253
UCSCiuc004aub.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF043725 mRNA Translation: AAD21791.1
AB014562 mRNA Translation: BAA31637.2 Different initiation.
AL353629 Genomic DNA No translation available.
AL359181 Genomic DNA No translation available.
CH471089 Genomic DNA Translation: EAW62867.1
AL834263 mRNA Translation: CAD38938.1
CCDSiCCDS35069.1
PIRiT00369
RefSeqiNP_005383.3, NM_005392.3
UniGeneiHs.211441

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3KQIX-ray1.78A1-70[»]
3PTRX-ray1.95B60-451[»]
3PU3X-ray1.95A/B60-451[»]
3PU8X-ray1.94A/B60-451[»]
3PUAX-ray1.89A60-451[»]
3PUSX-ray2.08A/B60-451[»]
ProteinModelPortaliO75151
SMRiO75151
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111272, 8 interactors
IntActiO75151, 1 interactor
STRINGi9606.ENSP00000352185

PTM databases

iPTMnetiO75151
PhosphoSitePlusiO75151

Polymorphism and mutation databases

BioMutaiPHF2

Proteomic databases

EPDiO75151
MaxQBiO75151
PaxDbiO75151
PeptideAtlasiO75151
PRIDEiO75151
ProteomicsDBi49817

Protocols and materials databases

DNASUi5253
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359246; ENSP00000352185; ENSG00000197724
GeneIDi5253
KEGGihsa:5253
UCSCiuc004aub.4 human

Organism-specific databases

CTDi5253
DisGeNETi5253
EuPathDBiHostDB:ENSG00000197724.10
GeneCardsiPHF2
H-InvDBiHIX0008184
HGNCiHGNC:8920 PHF2
HPAiHPA010831
MIMi604351 gene
neXtProtiNX_O75151
OpenTargetsiENSG00000197724
PharmGKBiPA33260
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1633 Eukaryota
ENOG410Y2FD LUCA
GeneTreeiENSGT00550000074396
HOGENOMiHOG000231232
HOVERGENiHBG045631
InParanoidiO75151
KOiK19414
OMAiDSCLQTT
OrthoDBiEOG091G09DB
PhylomeDBiO75151
TreeFamiTF106480

Enzyme and pathway databases

ReactomeiR-HSA-3214842 HDMs demethylate histones

Miscellaneous databases

ChiTaRSiPHF2 human
EvolutionaryTraceiO75151
GenomeRNAii5253
PROiPR:O75151
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197724 Expressed in 216 organ(s), highest expression level in forebrain
CleanExiHS_PHF2
ExpressionAtlasiO75151 baseline and differential
GenevisibleiO75151 HS

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 nameiPHF2_HUMAN
AccessioniPrimary (citable) accession number: O75151
Secondary accession number(s): Q4VXG0, Q8N3K2, Q9Y6N4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: November 25, 2008
Last modified: November 7, 2018
This is version 144 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
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