Details for: TFAP2B

Gene ID: 7021

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: TFAP2B

Ensembl ID: ENSG00000008196

Description: transcription factor AP-2 beta

Cell Significance Landscape

Associated with

Significant Cells

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

  • melanocyte CL0000148
    CSI 12.35
    rCSI 9.15%
    PRS 98.91
  • retina horizontal cell CL0000745
    CSI 10.76
    rCSI 16.41%
    PRS 98.77
  • amacrine cell CL0000561
    CSI 9.49
    rCSI 27.49%
    PRS 97.64
  • GABAergic amacrine cell CL4030027
    CSI 9.08
    rCSI 31.08%
    PRS 96.26
  • interneuron CL0000099
    CSI 8.38
    rCSI 16.82%
    PRS 98.45
  • neural crest cell CL0011012
    CSI 8.19
    rCSI 6.47%
    PRS 99.1
  • neuroblast (sensu Nematoda and Protostomia) CL0000338
    CSI 7.76
    rCSI 8.97%
    PRS 98.18
  • neuroblast (sensu Vertebrata) CL0000031
    CSI 7.18
    rCSI 9.22%
    PRS 98.7
  • glycinergic amacrine cell CL4030028
    CSI 5.27
    rCSI 13.73%
    PRS 97.29
  • H1 horizontal cell CL0004217
    CSI 4.88
    rCSI 19.34%
    PRS 97.54
  • H2 horizontal cell CL0004218
    CSI 4.68
    rCSI 23.27%
    PRS 97.85
  • basal cell CL0000646
    CSI 4.38
    rCSI 5.86%
    PRS 99.12
  • luminal epithelial cell of mammary gland CL0002326
    CSI 4.07
    rCSI 7.4%
    PRS 99.54
  • kidney loop of Henle thin ascending limb epithelial cell CL1001107
    CSI 3.06
    rCSI 7.9%
    PRS 99.19
  • renal principal cell CL0005009
    CSI 2.69
    rCSI 7%
    PRS 99.43
  • starburst amacrine cell CL0004232
    CSI 1.89
    rCSI 15.87%
    PRS 95.14
  • kidney loop of Henle thick ascending limb epithelial cell CL1001106
    CSI 1.73
    rCSI 14.94%
    PRS 98.34
  • central nervous system neuron CL2000029
    CSI 1.5
    rCSI 11.04%
    PRS 97.95
  • kidney distal convoluted tubule epithelial cell CL1000849
    CSI 0.8
    rCSI 8.46%
    PRS 98.46
  • hair follicular keratinocyte CL2000092
    CSI 0.58
    rCSI 10.04%
    PRS 99.17

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.

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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 Transcription factor AP-2 beta ([TFAP2B](/details-gene/7021)) is a protein-coding gene that functions as a sequence-specific DNA-binding transcription factor. It plays a critical role in the development of a wide range of tissues, particularly those derived from the neural crest. **Overall**, expression data reveals its highest significance in `[melanocyte](/details-cell/CL0000148)`s and various retinal neurons, including `[retina horizontal cell](/details-cell/CL0000745)`s and `[amacrine cell](/details-cell/CL0000561)`s, underscoring its importance in the nervous system and skin pigmentation. Clinically, mutations in [TFAP2B](/details-gene/7021) are associated with developmental disorders such as Char syndrome ([169100](https://omim.org/entry/169100)) and patent ductus arteriosus ([601601](https://omim.org/entry/601601)), consistent with its fundamental role in embryogenesis. ## Cellular Roles and Expression Landscape The expression profile of [TFAP2B](/details-gene/7021) points to a central function in the development and maintenance of neural and neuroectodermal cell lineages. The gene's highest significance scores are observed in cells of the neural crest lineage, including `[melanocyte](/details-cell/CL0000148)` (CSI: 12.35) and `[neural crest cell](/details-cell/CL0011012)`s (CSI: 8.19), as well as in developing neurons like `[neuroblast (sensu Vertebrata)](/details-cell/CL0000031)` (CSI: 7.18). A particularly strong expression signature is found within the retina, where [TFAP2B](/details-gene/7021) shows high significance in inhibitory interneurons such as `[retina horizontal cell](/details-cell/CL0000745)`s (CSI: 10.76) and `[amacrine cell](/details-cell/CL0000561)`s (CSI: 9.49), including specific subtypes like `[GABAergic amacrine cell](/details-cell/CL4030027)`s and `[glycinergic amacrine cell](/details-cell/CL4030028)`s. This suggests a crucial role in shaping the circuitry and function of the inner retina. Beyond the nervous system, [TFAP2B](/details-gene/7021) is also significantly expressed in several epithelial cell types. This includes `[basal cell](/details-cell/CL0000646)`s (CSI: 4.38), `[luminal epithelial cell of mammary gland](/details-cell/CL0002326)`s (CSI: 4.07), and specialized cells of the kidney, such as `[kidney loop of Henle thin ascending limb epithelial cell](/details-cell/CL1001107)` (CSI: 3.06). This pattern is consistent with its known involvement in renal development ([Link](https://doi.org/10.1101/gad.11.15.1938)). ## Pathways and Molecular Function As a member of the AP-2 family of transcription factors, the primary molecular function of [TFAP2B](/details-gene/7021) involves `[Sequence-specific dna binding](/details-go/GO:0043565)` and `[Dna-binding transcription activator activity, rna polymerase ii-specific](/details-go/GO:0001228)`. It can form both homodimers ([GO:0042803](https://www.ebi.ac.uk/QuickGO/term/GO:0042803)) and heterodimers ([GO:0046982](https://www.ebi.ac.uk/QuickGO/term/GO:0046982)) with other proteins to regulate gene expression. Its activity is further modulated by post-translational modifications, including sumoylation, as it is known to interact with the SUMO-conjugating enzyme UBC9 ([Link](https://doi.org/10.1074/jbc.m202780200)). The biological processes regulated by [TFAP2B](/details-gene/7021) are predominantly related to `[Developmental biology](/details-reactome/R-HSA-1266738)`. Its high expression in neural cells is consistent with its role in `[Nervous system development](/details-go/GO:0007399)`, `[Retina layer formation](/details-go/GO:0010842)`, and the `[Specification of the neural plate border](/details-reactome/R-HSA-9834899)`. Similarly, its function in renal epithelial cells is supported by annotations for `[Kidney development](/details-go/GO:0001822)` and `[Collecting duct development](/details-go/GO:0072044)`. The clinical manifestations associated with [TFAP2B](/details-gene/7021) mutations are directly linked to these developmental pathways. For instance, its role in Char syndrome and patent ductus arteriosus ([Link](https://doi.org/10.1038/75578)) corresponds to its involvement in processes like `[Aorta morphogenesis](/details-go/GO:0035909)` and `[Ductus arteriosus closure](/details-go/GO:0097070)`. The gene's activity is situated within the broader context of the `[Transcriptional regulation by the ap-2 (tfap2) family of transcription factors](/details-reactome/R-HSA-8864260)` pathway. ## Research Directions The specific and high-level expression of [TFAP2B](/details-gene/7021) in distinct cell populations, coupled with its known role in developmental disorders, presents several avenues for future research. **Proposed Hypotheses:** 1. Given its prominent expression in `[retina horizontal cell](/details-cell/CL0000745)`s and `[amacrine cell](/details-cell/CL0000561)`s, [TFAP2B](/details-gene/7021) may function as a terminal selector gene essential for specifying the identity and maintaining the function of these inhibitory interneurons. Its loss would be predicted to disrupt retinal circuit formation and visual processing. 2. Based on its position as the top marker in `[melanocyte](/details-cell/CL0000148)`s, [TFAP2B](/details-gene/7021) likely acts as a master regulator of melanocyte differentiation and melanogenesis. It may directly control the expression of key pigmentation enzymes and could be dysregulated during the progression of melanoma. **Experimental Approach:** To test the hypothesis regarding its role in retinal interneuron identity, a conditional knockout of *Tfap2b* could be generated in mice using a retina-specific Cre driver line. The resulting phenotype could be analyzed using a combination of single-cell RNA sequencing (scRNA-seq) to identify changes in cell populations and gene expression profiles, immunohistochemistry to visualize retinal lamination and cell morphology, and electroretinography (ERG) to assess functional deficits in the retinal neural network. **Therapeutic Potential:** The primary clinical relevance of [TFAP2B](/details-gene/7021) is linked to haploinsufficiency causing developmental syndromes ([Link](https://doi.org/10.1073/pnas.0409852102)). This suggests that therapeutic strategies for these conditions would likely focus on restoring or augmenting its function, rather than inhibition. However, its high expression in `[melanocyte](/details-cell/CL0000148)`s suggests it could be a relevant factor in melanoma. If its activity is found to drive proliferation in a cancerous context, it could represent a potential target for inhibition. Conversely, if its loss contributes to malignancy, it could be explored as a tumor suppressor, making gene augmentation a possible strategy.

Genular Protein ID: 3155884621

Symbol: AP2B_HUMAN

Name: Transcription factor AP-2-beta

UniProtKB Accession Codes:

Q92481 Q5JYX6 Q9NQ63 Q9NU99 Q9UJI7 Q9Y214 Q9Y3K3

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 6 Ensembl 1 ExpressionAtlas 1 GO 46 GeneCards 1 GeneReviews 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 5 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 2 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PRINTS 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 Reactome 5 RefSeq 2 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: 9271117

Title: Enhanced apoptotic cell death of renal epithelial cells in mice lacking transcription factor AP-2beta.

PubMed ID: 9271117

DOI: 10.1101/gad.11.15.1938

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

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: 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: 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: 15684060

Title: Syndromic patent ductus arteriosus: evidence for haploinsufficient TFAP2B mutations and identification of a linked sleep disorder.

PubMed ID: 15684060

DOI: 10.1073/pnas.0409852102

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: 18752453

Title: Novel TFAP2B mutation in nonsyndromic patent ductus arteriosus.

PubMed ID: 18752453

DOI: 10.1089/gte.2008.0015

PubMed ID: 21643846

Title: Familial nonsyndromic patent ductus arteriosus caused by mutations in TFAP2B.

PubMed ID: 21643846

DOI: 10.1007/s00246-011-0024-7

PubMed ID: 10802654

Title: Mutations in TFAP2B cause Char syndrome, a familial form of patent ductus arteriosus.

PubMed ID: 10802654

DOI: 10.1038/75578

PubMed ID: 11505339

Title: Novel TFAP2B mutations that cause Char syndrome provide a genotype-phenotype correlation.

PubMed ID: 11505339

DOI: 10.1086/323410

Sequence Information:

  • Length: 460
  • Mass: 50474
  • Checksum: A6420EA0C265DDA2
  • Sequence:
    • MHSPPRDQAA IMLWKLVENV KYEDIYEDRH DGVPSHSSRL SQLGSVSQGP YSSAPPLSHT 
PSSDFQPPYF PPPYQPLPYH QSQDPYSHVN DPYSLNPLHQ PQQHPWGQRQ RQEVGSEAGS 
LLPQPRAALP QLSGLDPRRD YHSVRRPDVL LHSAHHGLDA GMGDSLSLHG LGHPGMEDVQ 
SVEDANNSGM NLLDQSVIKK VPVPPKSVTS LMMNKDGFLG GMSVNTGEVF CSVPGRLSLL 
SSTSKYKVTV GEVQRRLSPP ECLNASLLGG VLRRAKSKNG GRSLRERLEK IGLNLPAGRR 
KAANVTLLTS LVEGEAVHLA RDFGYICETE FPAKAVSEYL NRQHTDPSDL HSRKNMLLAT 
KQLCKEFTDL LAQDRTPIGN SRPSPILEPG IQSCLTHFSL ITHGFGAPAI CAALTALQNY 
LTEALKGMDK MFLNNTTTNR HTSGEGPGSK TGDKEEKHRK