Details for: PHF2

Gene ID: 5253

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PHF2

Ensembl ID: ENSG00000197724

Description: PHD finger protein 2

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • ionocyte CL0005006
    CSI 5.73
    rCSI 6.14%
    PRS 91.34
  • melanocyte CL0000148
    CSI 5.4
    rCSI 4%
    PRS 86.24
  • astrocyte of the cerebral cortex CL0002605
    CSI 4.31
    rCSI 9.67%
    PRS 77.26
  • peripheral nervous system neuron CL2000032
    CSI 4.1
    rCSI 5.58%
    PRS 83.65
  • lung ciliated cell CL1000271
    CSI 4
    rCSI 4.63%
    PRS 84.39
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.78
    rCSI 4.51%
    PRS 76.88
  • CD4-positive, alpha-beta memory T cell CL0000897
    CSI 3.62
    rCSI 2.6%
    PRS 97.54
  • type B pancreatic cell CL0000169
    CSI 3.41
    rCSI 7.56%
    PRS 89.94
  • kidney connecting tubule epithelial cell CL1000768
    CSI 3.37
    rCSI 8.55%
    PRS 83.62
  • brush cell of tracheobronchial tree CL0002075
    CSI 3.2
    rCSI 9.5%
    PRS 95.36
  • pancreatic D cell CL0000173
    CSI 3.14
    rCSI 3.09%
    PRS 91.66
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 3.12
    rCSI 8.08%
    PRS 86.99
  • caudal ganglionic eminence derived cortical interneuron CL4023064
    CSI 3.06
    rCSI 5.41%
    PRS 76.29
  • pancreatic A cell CL0000171
    CSI 3.04
    rCSI 3.18%
    PRS 91.85
  • fibroblast of lung CL0002553
    CSI 2.98
    rCSI 2.77%
    PRS 91.18
  • cerebellar granule cell CL0001031
    CSI 2.94
    rCSI 4.33%
    PRS 84.71
  • interneuron CL0000099
    CSI 2.87
    rCSI 5.76%
    PRS 83.79
  • alveolar type 1 fibroblast cell CL4028004
    CSI 2.85
    rCSI 3.12%
    PRS 91.47
  • epithelial cell of lower respiratory tract CL0002632
    CSI 2.84
    rCSI 2.2%
    PRS 92.49
  • neural crest cell CL0011012
    CSI 2.79
    rCSI 2.2%
    PRS 82.88
  • pro-B cell CL0000826
    CSI 2.74
    rCSI 2.27%
    PRS 91.41
  • Kupffer cell CL0000091
    CSI 2.74
    rCSI 6.26%
    PRS 91.01
  • group 3 innate lymphoid cell CL0001071
    CSI 2.68
    rCSI 2.01%
    PRS 93.31
  • regular ventricular cardiac myocyte CL0002131
    CSI 2.63
    rCSI 16.41%
    PRS 83.76
  • retinal blood vessel endothelial cell CL0002585
    CSI 2.61
    rCSI 4.17%
    PRS 92.25
  • lamp5 GABAergic cortical interneuron CL4023011
    CSI 2.59
    rCSI 4.35%
    PRS 76.83
  • epithelial cell of lung CL0000082
    CSI 2.56
    rCSI 2.12%
    PRS 90.74
  • multi-ciliated epithelial cell CL0005012
    CSI 2.54
    rCSI 2.53%
    PRS 84.4
  • intestinal tuft cell CL0019032
    CSI 2.52
    rCSI 3.85%
    PRS 91.81
  • choroid plexus epithelial cell CL0000706
    CSI 2.42
    rCSI 3.95%
    PRS 82.78
  • cerebral cortex endothelial cell CL1001602
    CSI 2.4
    rCSI 4.16%
    PRS 84.54
  • nasal mucosa goblet cell CL0002480
    CSI 2.38
    rCSI 2.76%
    PRS 90.38
  • respiratory suprabasal cell CL4033048
    CSI 2.29
    rCSI 2.94%
    PRS 91.67
  • lung neuroendocrine cell CL1000223
    CSI 2.29
    rCSI 3.38%
    PRS 91.69
  • chondrocyte CL0000138
    CSI 2.26
    rCSI 3.6%
    PRS 85.24
  • hepatic stellate cell CL0000632
    CSI 2.21
    rCSI 8.27%
    PRS 85.2
  • cardiac endothelial cell CL0010008
    CSI 2.19
    rCSI 8.83%
    PRS 90.6
  • retinal bipolar neuron CL0000748
    CSI 2.17
    rCSI 4.06%
    PRS 81.44
  • CD14-low, CD16-positive monocyte CL0002396
    CSI 2.02
    rCSI 1.56%
    PRS 92.94
  • ependymal cell CL0000065
    CSI 1.99
    rCSI 4.04%
    PRS 72.29
  • ciliated epithelial cell CL0000067
    CSI 1.99
    rCSI 1.75%
    PRS 81.29
  • lung secretory cell CL1000272
    CSI 1.95
    rCSI 4.84%
    PRS 90.44
  • kidney loop of Henle thin descending limb epithelial cell CL1001111
    CSI 1.9
    rCSI 2.7%
    PRS 87.63
  • cardiac muscle cell CL0000746
    CSI 1.77
    rCSI 2.54%
    PRS 82.18
  • pvalb GABAergic cortical interneuron CL4023018
    CSI 1.62
    rCSI 2.02%
    PRS 74.65
  • extravillous trophoblast CL0008036
    CSI 1.61
    rCSI 2%
    PRS 88.6
  • near-projecting glutamatergic cortical neuron CL4023012
    CSI 1.55
    rCSI 5.84%
    PRS 77.01
  • sst GABAergic cortical interneuron CL4023017
    CSI 1.54
    rCSI 1.98%
    PRS 77.93
  • neuroendocrine cell CL0000165
    CSI 1.45
    rCSI 5.62%
    PRS 93.08
  • enteroendocrine cell CL0000164
    CSI 1.4
    rCSI 1.91%
    PRS 88.54
  • neural progenitor cell CL0011020
    CSI 1.14
    rCSI 5.02%
    PRS 79.63
  • parietal epithelial cell CL1000452
    CSI 1.13
    rCSI 3.01%
    PRS 84.49
  • blood vessel smooth muscle cell CL0019018
    CSI 0.86
    rCSI 6.98%
    PRS 86.98
  • GABAergic neuron CL0000617
    CSI 0.86
    rCSI 2.87%
    PRS 76.55
  • L2/3-6 intratelencephalic projecting glutamatergic neuron CL4023040
    CSI 0.83
    rCSI 2.02%
    PRS 74.61
  • L6b glutamatergic cortical neuron CL4023038
    CSI 0.68
    rCSI 2.13%
    PRS 78.22
  • indirect pathway medium spiny neuron CL4023029
    CSI 0.29
    rCSI 6.9%
    PRS 74.63
  • direct pathway medium spiny neuron CL4023026
    CSI 0.27
    rCSI 6.47%
    PRS 74.45

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PHF2](/details-gene/5253), or PHD Finger Protein 2, is a protein-coding gene located on chromosome 9q22.31. It functions as a lysine-specific histone demethylase, playing a crucial role in epigenetic regulation. Its primary molecular functions include histone demethylase activity, specifically targeting H3K9 and H4K20, which links it to fundamental biological processes such as [chromatin remodeling](/details-go/GO:0006338) and the [positive regulation of DNA-templated transcription](/details-go/GO:0045893). Expression data indicates that [PHF2](/details-gene/5253) is a significant gene in a diverse array of specialized cell types, including [ionocytes](/details-cell/CL0005006), [melanocytes](/details-cell/CL0000148), and various neuronal and epithelial cells, suggesting it is a key regulator for maintaining distinct cellular identities and functions. ## Cellular Roles and Expression Landscape The expression profile of [PHF2](/details-gene/5253) reveals its importance across a wide spectrum of differentiated cell types, pointing to a role as a fundamental epigenetic modulator rather than a simple lineage marker. **Overall**, the gene shows the highest significance in cells with specialized secretory or barrier functions, such as [ionocytes](/details-cell/CL0005006) (CSI: 5.73) and [lung ciliated cells](/details-cell/CL1000271) (CSI: 4.00). Its prominence extends to cells of the neural lineage, with high significance scores in [melanocytes](/details-cell/CL0000148) (CSI: 5.40), [astrocytes of the cerebral cortex](/details-cell/CL0002605) (CSI: 4.31), and multiple types of [interneurons](/details-cell/CL4023016). This pattern suggests a role in establishing and maintaining the specific transcriptional programs that define these neural and glial cell fates. Furthermore, [PHF2](/details-gene/5253) is significantly expressed in various endocrine and epithelial cells, including [type B pancreatic cells](/details-cell/CL0000169) and [kidney connecting tubule epithelial cells](/details-cell/CL1000768). Its presence in [CD4-positive, alpha-beta memory T cells](/details-cell/CL0000897) also indicates a potential role in the epigenetic memory of the adaptive immune system. The broad but distinct expression landscape implies that [PHF2](/details-gene/5253) is a critical transcriptional coactivator required for the function of many terminally differentiated cells. ## Pathways and Molecular Function Functionally, [PHF2](/details-gene/5253) is primarily annotated as a chromatin-modifying enzyme. Its molecular activities are centered on its role as a [histone demethylase](/details-go/GO:0032452), with specificity for both [histone H3K9](/details-go/GO:0032454) and [histone H4K20](/details-go/GO:0035575). As demethylation of these marks is generally associated with transcriptional activation, this function is consistent with its annotated roles as a [transcription coactivator](/details-go/GO:0003713) and a positive regulator of transcription. These activities are integral to the Reactome pathways of [Chromatin modifying enzymes](/details-pathway/R-HSA-3247509) and [HDMs demethylate histones](/details-pathway/R-HSA-3214842). Cellular component annotations place the protein within the [nucleus](/details-go/GO:0005634), [nucleoplasm](/details-go/GO:0005654), and [nucleolus](/details-go/GO:0005730), which is consistent with its function in regulating gene expression and chromatin structure. Research has also indicated that the activity of the PHF2-ARID5B demethylase complex can be regulated by PKA-dependent phosphorylation, suggesting a mechanism by which extracellular signals can modulate its epigenetic function ([Link](https://doi.org/10.1038/ncb2228)). ## Research Directions The diverse expression pattern of [PHF2](/details-gene/5253) in highly specialized cells, combined with its function as a transcriptional coactivator, opens several avenues for future investigation, particularly in the context of disease. Its role in epigenetic regulation makes it a compelling candidate for study in developmental disorders and cancers where chromatin states are frequently dysregulated. Based on the available data, several testable hypotheses can be proposed: 1. Given its high significance in [melanocytes](/details-cell/CL0000148), [PHF2](/details-gene/5253) may function as a lineage-specific coactivator for key melanocyte transcription factors like MITF. Its dysregulation or mutation could contribute to melanoma by altering the epigenetic landscape and promoting oncogenic transcriptional programs. 2. The high expression of [PHF2](/details-gene/5253) across multiple secretory cell types (e.g., [pancreatic B cells](/details-cell/CL0000169), [ionocytes](/details-cell/CL0005006)) suggests it is required to maintain an open chromatin state at loci encoding essential transport proteins and hormones. In diseases like cystic fibrosis or diabetes, reduced [PHF2](/details-gene/5253) activity could lead to diminished expression of critical genes like *CFTR* or *INS*. A key experiment to test the first hypothesis would be to investigate the role of [PHF2](/details-gene/5253) in melanoma. This could be achieved by using CRISPR-Cas9 to knock out [PHF2](/details-gene/5253) in a panel of melanoma cell lines. Subsequent analysis using RNA-seq would identify global transcriptional changes, while ChIP-seq for H3K9me2/3 would determine if target gene promoters exhibit altered histone methylation. These experiments would clarify whether [PHF2](/details-gene/5253) is a critical dependency for maintaining the malignant phenotype in melanoma. As a therapeutic target, [PHF2](/details-gene/5253) presents both opportunities and challenges. As an enzyme, it is potentially druggable with small molecule inhibitors. In the context of cancers like melanoma where it may act as a coactivator for oncogenic programs, inhibition would be the therapeutic strategy. However, its significant role in a wide range of healthy, differentiated cell types raises concerns about potential on-target toxicity. A successful therapeutic approach would likely require highly specific inhibitors or be used in combination therapies targeted to cancer cells.

Genular Protein ID: 923696306

Symbol: PHF2_HUMAN

Name: Lysine-specific demethylase PHF2

UniProtKB Accession Codes:

O75151 Q4VXG0 Q8N3K2 Q9Y6N4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioCyc 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChEBI 16 ChEMBL 1 ChiTaRS 1 ComplexPortal 1 DNASU 1 DisGeNET 1 DrugCentral 1 EMBL 6 Ensembl 1 EvolutionaryTrace 1 ExpressionAtlas 1 GO 16 Gene3D 3 GeneCards 1 GeneTree 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 8 KEGG 1 MANE-Select 1 MIM 1 MINT 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PDB 9 PDBsum 9 PIR 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 1 RefSeq 1 Rhea 4 SIGNOR 1 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissPalm 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10051327

Title: PHF2, a novel PHD finger gene located on human chromosome 9q22.

PubMed ID: 10051327

DOI: 10.1007/s003359900989

PubMed ID: 9734811

Title: Prediction of the coding sequences of unidentified human genes. X. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.

PubMed ID: 9734811

DOI: 10.1093/dnares/5.3.169

PubMed ID: 12168954

Title: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones.

PubMed ID: 12168954

DOI: 10.1093/dnares/9.3.99

PubMed ID: 15164053

Title: DNA sequence and analysis of human chromosome 9.

PubMed ID: 15164053

DOI: 10.1038/nature02465

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 17081983

Title: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.

PubMed ID: 17081983

DOI: 10.1016/j.cell.2006.09.026

PubMed ID: 18669648

Title: A quantitative atlas of mitotic phosphorylation.

PubMed ID: 18669648

DOI: 10.1073/pnas.0805139105

PubMed ID: 19413330

Title: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.

PubMed ID: 19413330

DOI: 10.1021/ac9004309

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 20813266

Title: The protein composition of mitotic chromosomes determined using multiclassifier combinatorial proteomics.

PubMed ID: 20813266

DOI: 10.1016/j.cell.2010.07.047

PubMed ID: 20068231

Title: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.

PubMed ID: 20068231

DOI: 10.1126/scisignal.2000475

PubMed ID: 21532585

Title: PKA-dependent regulation of the histone lysine demethylase complex PHF2-ARID5B.

PubMed ID: 21532585

DOI: 10.1038/ncb2228

PubMed ID: 21406692

Title: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.

PubMed ID: 21406692

DOI: 10.1126/scisignal.2001570

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 24275569

Title: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.

PubMed ID: 24275569

DOI: 10.1016/j.jprot.2013.11.014

PubMed ID: 28112733

Title: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.

PubMed ID: 28112733

DOI: 10.1038/nsmb.3366

PubMed ID: 20129925

Title: Recognition of histone H3K4 trimethylation by the plant homeodomain of PHF2 modulates histone demethylation.

PubMed ID: 20129925

DOI: 10.1074/jbc.c109.097667

PubMed ID: 21167174

Title: Structural basis for human PHF2 Jumonji domain interaction with metal ions.

PubMed ID: 21167174

DOI: 10.1016/j.jmb.2010.12.013

Sequence Information:

  • Length: 1096
  • Mass: 120775
  • Checksum: DD088363DB76674D
  • Sequence:
    • 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