Details for: TFAP2C

Gene ID: 7022

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: TFAP2C

Ensembl ID: ENSG00000087510

Description: transcription factor AP-2 gamma

Cell Significance Landscape

Associated with

Significant Cells

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

  • ionocyte CL0005006
    CSI 11.59
    rCSI 12.43%
    PRS 98.7
  • progenitor cell CL0011026
    CSI 7.29
    rCSI 15.51%
    PRS 96.16
  • squamous epithelial cell CL0000076
    CSI 6.09
    rCSI 14.44%
    PRS 95.83
  • forebrain radial glial cell CL0013000
    CSI 5.77
    rCSI 18.51%
    PRS 98.34
  • GABAergic amacrine cell CL4030027
    CSI 5.67
    rCSI 19.42%
    PRS 92.89
  • respiratory suprabasal cell CL4033048
    CSI 5.39
    rCSI 6.91%
    PRS 98.85
  • fallopian tube secretory epithelial cell CL4030006
    CSI 5.21
    rCSI 5.01%
    PRS 97.94
  • keratinocyte CL0000312
    CSI 4.63
    rCSI 3.88%
    PRS 97.77
  • radial glial cell CL0000681
    CSI 4.02
    rCSI 5.58%
    PRS 98.4
  • epithelial cell of lung CL0000082
    CSI 3.68
    rCSI 3.05%
    PRS 99.09
  • myoepithelial cell CL0000185
    CSI 3.59
    rCSI 9.08%
    PRS 98.99
  • epithelial cell of lower respiratory tract CL0002632
    CSI 3.52
    rCSI 2.73%
    PRS 99.18
  • basal-myoepithelial cell of mammary gland CL0002324
    CSI 3.18
    rCSI 6.02%
    PRS 99.32
  • glioblast CL0000030
    CSI 3.12
    rCSI 4.97%
    PRS 95.91
  • epithelial cell CL0000066
    CSI 3.07
    rCSI 4.72%
    PRS 93.39
  • respiratory basal cell CL0002633
    CSI 3.01
    rCSI 3.12%
    PRS 98.72
  • conjunctival epithelial cell CL1000432
    CSI 2.85
    rCSI 4.35%
    PRS 97.74
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 2.72
    rCSI 3.14%
    PRS 96.04
  • acinar cell CL0000622
    CSI 2.66
    rCSI 3.9%
    PRS 99.19
  • luminal epithelial cell of mammary gland CL0002326
    CSI 2.49
    rCSI 4.53%
    PRS 98.98
  • extravillous trophoblast CL0008036
    CSI 2.49
    rCSI 3.08%
    PRS 97.8
  • basal cell of prostate epithelium CL0002341
    CSI 2.42
    rCSI 6.99%
    PRS 98.72
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 2.23
    rCSI 2.86%
    PRS 97.58
  • syncytiotrophoblast cell CL0000525
    CSI 2.2
    rCSI 6.35%
    PRS 97.32
  • basal cell CL0000646
    CSI 2.2
    rCSI 2.94%
    PRS 97.54
  • placental villous trophoblast CL2000060
    CSI 2.13
    rCSI 3.29%
    PRS 97.71
  • mammary gland epithelial cell CL0002327
    CSI 1.46
    rCSI 5.11%
    PRS 99.08
  • hair follicular keratinocyte CL2000092
    CSI 0.42
    rCSI 7.25%
    PRS 97.97

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)

Loading network (please wait)...

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 [TFAP2C](/details-gene/7022), also known as Transcription Factor AP-2 Gamma, is a protein-coding gene located on chromosome 20q13.31. As a member of the activator protein 2 (AP-2) family of transcription factors, it plays a critical role in regulating gene expression during embryonic development and in the maintenance of specific cell lineages. Functionally, [TFAP2C](/details-gene/7022) binds to specific DNA sequences to either activate or repress transcription, influencing a wide array of cellular processes including proliferation, signaling, and differentiation. Its expression profile indicates a highly specialized role, with significant expression observed in diverse cell types such as [ionocyte](/details-cell/CL0005006), various progenitor and epithelial cells, and neural glial cells. The gene's activity is further modulated by post-translational modifications like sumoylation, which fine-tunes its regulatory function ([Link](https://pubmed.ncbi.nlm.nih.gov/12072434/)). Clinically, it is associated with developmental processes and has potential implications in disease, as noted by its OMIM association ([601602](https://omim.org/entry/601602)). ## Cellular Roles and Expression Landscape The expression pattern of [TFAP2C](/details-gene/7022) highlights its importance in epithelial biology, development, and specialized cellular functions. **Overall**, the gene shows the highest significance in [ionocyte](/details-cell/CL0005006), a cell type responsible for ion transport, suggesting it is a key regulator of their identity and function. Beyond this highly specialized cell, [TFAP2C](/details-gene/7022) demonstrates a broad role in establishing and maintaining epithelial and developmental lineages. It is a significant marker in [progenitor cell](/details-cell/CL0011026) populations and various epithelial cell types, including [squamous epithelial cell](/details-cell/CL0000076), [keratinocyte](/details-cell/CL0000312), [epithelial cell of lung](/details-cell/CL0000082), and [fallopian tube secretory epithelial cell](/details-cell/CL4030006). This widespread expression across different epithelial tissues suggests a fundamental role in epithelial cell differentiation and homeostasis. Furthermore, [TFAP2C](/details-gene/7022) appears to be important in the nervous system, specifically within glial and progenitor populations. Its high significance in [forebrain radial glial cell](/details-cell/CL0013000), [radial glial cell](/details-cell/CL0000681), and [glioblast](/details-cell/CL0000030) indicates a potential role in neurogenesis and glial cell biology. The notable absence of high significance in mature immune cells or muscle lineages suggests its function is primarily concentrated within developmental, epithelial, and neuro-glial contexts. ## Pathways and Molecular Function [TFAP2C](/details-gene/7022) functions as a sequence-specific DNA-binding transcription factor ([GO:0003700](https://www.ebi.ac.uk/QuickGO/term/GO:0003700)), capable of both activating and repressing gene expression via RNA polymerase II ([GO:0001228](https://www.ebi.ac.uk/QuickGO/term/GO:0001228), [GO:0001227](https://www.ebi.ac.uk/QuickGO/term/GO:0001227)). Its activity is central to the [Transcriptional regulation by the ap-2 (tfap2) family of transcription factors](https://reactome.org/content/detail/R-HSA-8864260). This broad regulatory capacity underpins its involvement in a variety of fundamental biological processes. Consistent with its expression in progenitor and developmental cell types, [TFAP2C](/details-gene/7022) is heavily implicated in [Developmental biology](https://reactome.org/content/detail/R-HSA-1266738), including critical early events like [Gastrulation](https://reactome.org/content/detail/R-HSA-9758941) and the [Specification of primordial germ cells](https://reactome.org/content/detail/R-HSA-9827857). Its function extends to the regulation of cell growth, as it is involved in pathways that control cell population proliferation ([GO:0042127](https://www.ebi.ac.uk/QuickGO/term/GO:0042127)) and the transcription of growth factors and their receptors ([R-HSA-8866910](https://reactome.org/content/detail/R-HSA-8866910)). The regulatory activity of [TFAP2C](/details-gene/7022) is itself subject to control. It is a target of [Sumoylation](https://reactome.org/content/detail/R-HSA-2990846), a post-translational modification that can alter protein function and stability ([Link](https://pubmed.ncbi.nlm.nih.gov/12072434/)). This suggests a mechanism for fine-tuning its transcriptional output in response to cellular signals, which is critical for precise developmental timing and tissue homeostasis. ## Research Directions The specific expression patterns and annotated functions of [TFAP2C](/details-gene/7022) suggest several avenues for future investigation. **Proposed Hypotheses:** 1. **[TFAP2C](/details-gene/7022) is a master regulator of epithelial barrier function.** Given its high significance in diverse epithelial cells like [keratinocyte](/details-cell/CL0000312) and [squamous epithelial cell](/details-cell/CL0000076), and its role in regulating cell proliferation, it may be indispensable for establishing and maintaining the integrity of tissues such as the skin and respiratory tract. 2. **Dysregulation of [TFAP2C](/details-gene/7022) sumoylation contributes to developmental abnormalities.** The established role of sumoylation in modulating its activity ([Link](https://pubmed.ncbi.nlm.nih.gov/12072434/)) combined with its importance in gastrulation and gonad development suggests that mutations affecting its sumoylation sites or the sumoylation machinery could underlie specific congenital disorders. 3. **[TFAP2C](/details-gene/7022) acts as a context-dependent oncogene in specific epithelial and glial cancers.** Its role in promoting proliferation and its high expression in [glioblast](/details-cell/CL0000030) suggests that its aberrant reactivation or overexpression could drive tumorigenesis in these tissues. **Experimental Approach:** To test the hypothesis that [TFAP2C](/details-gene/7022) is a master regulator of epithelial barrier function (Hypothesis 1), a conditional knockout mouse model could be generated using a Cre-Lox system to specifically delete *Tfap2c* in epidermal keratinocytes (e.g., using a KRT14-Cre driver). The resulting phenotype would be assessed for defects in skin development, wound healing, and barrier integrity via transepidermal water loss measurements. Histological analysis and single-cell RNA sequencing of the mutant epidermis would reveal changes in cellular composition, differentiation trajectories, and the downstream gene networks controlled by [TFAP2C](/details-gene/7022). **Therapeutic Potential:** As a transcription factor, [TFAP2C](/details-gene/7022) represents a challenging direct therapeutic target. However, its potential role as an oncogenic driver in certain contexts, such as glioblastoma, makes it a candidate for indirect therapeutic strategies. Inhibition would be the most likely approach. This could involve developing small molecules that disrupt its interaction with critical co-activators like p300/CBP or CITED family members ([Link](https://pubmed.ncbi.nlm.nih.gov/12586840/)) or that target the enzymatic machinery responsible for its oncogenic post-translational modifications. Such an approach could selectively dampen its pro-proliferative activity in cancer cells while potentially sparing other tissues.

Genular Protein ID: 2840926360

Symbol: AP2C_HUMAN

Name: Transcription factor AP-2 gamma

UniProtKB Accession Codes:

Q92754 B4DWK3 O00685 O00730 Q86V30 Q8IVB6 Q9P1X2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CORUM 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 ELM 1 EMBL 8 Ensembl 1 ExpressionAtlas 1 GO 19 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRINTS 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 Pumba 1 RNAct 1 Reactome 8 RefSeq 1 SIGNOR 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 8661133

Title: Chromosomal mapping of the human and mouse homologues of two new members of the AP-2 family of transcription factors.

PubMed ID: 8661133

DOI: 10.1006/geno.1996.0351

PubMed ID: 9113991

Title: Identification of ERF-1 as a member of the AP2 transcription factor family.

PubMed ID: 9113991

DOI: 10.1073/pnas.94.9.4342

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 11780052

Title: The DNA sequence and comparative analysis of human chromosome 20.

PubMed ID: 11780052

DOI: 10.1038/414865a

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 11694877

Title: Cardiac malformations, adrenal agenesis, neural crest defects and exencephaly in mice lacking Cited2, a new Tfap2 co-activator.

PubMed ID: 11694877

DOI: 10.1038/ng768

PubMed ID: 11744733

Title: Human CREB-binding protein/p300-interacting transactivator with ED-rich tail (CITED) 4, a new member of the CITED family, functions as a co-activator for transcription factor AP-2.

PubMed ID: 11744733

DOI: 10.1074/jbc.m110850200

PubMed ID: 12072434

Title: Transcription factor AP-2 interacts with the SUMO-conjugating enzyme UBC9 and is sumolated in vivo.

PubMed ID: 12072434

DOI: 10.1074/jbc.m202780200

PubMed ID: 12586840

Title: Physical and functional interactions among AP-2 transcription factors, p300/CREB-binding protein, and CITED2.

PubMed ID: 12586840

DOI: 10.1074/jbc.m208144200

PubMed ID: 15548692

Title: Physical and functional interactions between the Wwox tumor suppressor protein and the AP-2gamma transcription factor.

PubMed ID: 15548692

DOI: 10.1158/0008-5472.can-04-2055

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: 19115315

Title: The interaction of KCTD1 with transcription factor AP-2alpha inhibits its transactivation.

PubMed ID: 19115315

DOI: 10.1002/jcb.22002

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: 24413532

Title: Differential regulation of estrogen receptor alpha expression in breast cancer cells by metastasis-associated protein 1.

PubMed ID: 24413532

DOI: 10.1158/0008-5472.can-13-2020

Sequence Information:

  • Length: 450
  • Mass: 49177
  • Checksum: 2D4F5FBC269A34A8
  • Sequence:
    • MLWKITDNVK YEEDCEDRHD GSSNGNPRVP HLSSAGQHLY SPAPPLSHTG VAEYQPPPYF 
PPPYQQLAYS QSADPYSHLG EAYAAAINPL HQPAPTGSQQ QAWPGRQSQE GAGLPSHHGR 
PAGLLPHLSG LEAGAVSARR DAYRRSDLLL PHAHALDAAG LAENLGLHDM PHQMDEVQNV 
DDQHLLLHDQ TVIRKGPISM TKNPLNLPCQ KELVGAVMNP TEVFCSVPGR LSLLSSTSKY 
KVTVAEVQRR LSPPECLNAS LLGGVLRRAK SKNGGRSLRE KLDKIGLNLP AGRRKAAHVT 
LLTSLVEGEA VHLARDFAYV CEAEFPSKPV AEYLTRPHLG GRNEMAARKN MLLAAQQLCK 
EFTELLSQDR TPHGTSRLAP VLETNIQNCL SHFSLITHGF GSQAICAAVS ALQNYIKEAL 
IVIDKSYMNP GDQSPADSNK TLEKMEKHRK