NFATC4

Nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2YRP​
Identifiers
Symbols	NFATC4 ; NF-AT3; NF-ATC4; NFAT3
External IDs	OMIM: 602699 MGI: 1920431 HomoloGene: 3349 GeneCards: NFATC4 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcription coactivator activity • protein binding • transcription factor binding • peroxisome proliferator activated receptor binding Cellular component • nucleus • transcription factor complex • cytoplasm • cytosol • intermediate filament cytoskeleton Biological process • negative regulation of transcription from RNA polymerase II promoter • patterning of blood vessels • transcription from RNA polymerase II promoter • inflammatory response • heart development • intrinsic apoptotic signaling pathway in response to DNA damage • positive regulation of tumor necrosis factor production • calcineurin-NFAT signaling cascade • cellular response to UV • negative regulation of chromatin binding • cellular respiration • positive regulation of transcription from RNA polymerase II promoter • regulation of synaptic plasticity • negative regulation of dendrite morphogenesis • smooth muscle cell differentiation • muscle cell development • cellular response to lithium ion • negative regulation of synapse maturation • positive regulation of apoptotic signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4776	73181
Ensembl	ENSG00000100968	ENSMUSG00000023411
UniProt	Q14934	Q8K120
RefSeq (mRNA)	NM_001136022	NM_001168346
RefSeq (protein)	NP_001129494	NP_001161818
Location (UCSC)	Chr 14: 24.37 – 24.38 Mb	Chr 14: 55.82 – 55.83 Mb
PubMed search

Nuclear factor of activated T-cells, cytoplasmic 4 is a protein that in humans is encoded by the NFATC4 gene.^[1][2]

Function

The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family of nuclear factors of activated T cells also participate in the formation of this complex. The product of this gene plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of the IL-2 and IL-4.^[2]

NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed NFAT3 (NFATc4) is an inhibitor of cell motility by blocking the expression of LCN2.^[3]

Interactions

NFATC4 has been shown to interact with CREB-binding protein.^[4]

See also

• NFAT

References

1. Hoey T, Sun YL, Williamson K, Xu X (May 1995). "Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins". Immunity 2 (5): 461–72. doi:10.1016/1074-7613(95)90027-6. PMID 7749981.
2. "Entrez Gene: NFATC4 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 4".
3. Fougère M, Gaudineau B, Barbier J, Guaddachi F, Feugeas JP, Auboeuf D, Jauliac S (Apr 2010). "NFAT3 transcription factor inhibits breast cancer cell motility by targeting the Lipocalin 2 gene". Oncogene 29 (15): 2292–301. doi:10.1038/onc.2009.499. PMID 20101218.
4. Yang T, Davis RJ, Chow CW (Oct 2001). "Requirement of two NFATc4 transactivation domains for CBP potentiation". The Journal of Biological Chemistry 276 (43): 39569–76. doi:10.1074/jbc.M102961200. PMID 11514544.

Further reading

• Rao A, Luo C, Hogan PG (1997). "Transcription factors of the NFAT family: regulation and function". Annual Review of Immunology 15: 707–47. doi:10.1146/annurev.immunol.15.1.707. PMID 9143705.
• Crabtree GR (Mar 1999). "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT". Cell 96 (5): 611–4. doi:10.1016/S0092-8674(00)80571-1. PMID 10089876.
• Horsley V, Pavlath GK (Mar 2002). "NFAT: ubiquitous regulator of cell differentiation and adaptation". The Journal of Cell Biology 156 (5): 771–4. doi:10.1083/jcb.200111073. PMC 2173310. PMID 11877454.
• Jabado N, Le Deist F, Fisher A, Hivroz C (Nov 1994). "Interaction of HIV gp120 and anti-CD4 antibodies with the CD4 molecule on human CD4+ T cells inhibits the binding activity of NF-AT, NF-kappa B and AP-1, three nuclear factors regulating interleukin-2 gene enhancer activity". European Journal of Immunology 24 (11): 2646–52. doi:10.1002/eji.1830241112. PMID 7957556.
• Vacca A, Farina M, Maroder M, Alesse E, Screpanti I, Frati L, Gulino A (Nov 1994). "Human immunodeficiency virus type-1 tat enhances interleukin-2 promoter activity through synergism with phorbol ester and calcium-mediated activation of the NF-AT cis-regulatory motif". Biochemical and Biophysical Research Communications 205 (1): 467–74. doi:10.1006/bbrc.1994.2689. PMID 7999066.
• Di Somma MM, Majolini MB, Burastero SE, Telford JL, Baldari CT (Sep 1996). "Cyclosporin A sensitivity of the HIV-1 long terminal repeat identifies distinct p56lck-dependent pathways activated by CD4 triggering". European Journal of Immunology 26 (9): 2181–8. doi:10.1002/eji.1830260933. PMID 8814265.
• Molkentin JD, Lu JR, Antos CL, Markham B, Richardson J, Robbins J, Grant SR, Olson EN (Apr 1998). "A calcineurin-dependent transcriptional pathway for cardiac hypertrophy". Cell 93 (2): 215–28. doi:10.1016/S0092-8674(00)81573-1. PMID 9568714.
• Aramburu J, Garcia-Cózar F, Raghavan A, Okamura H, Rao A, Hogan PG (Apr 1998). "Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFAT". Molecular Cell 1 (5): 627–37. doi:10.1016/S1097-2765(00)80063-5. PMID 9660947.
• Chow CW, Davis RJ (Jan 2000). "Integration of calcium and cyclic AMP signaling pathways by 14-3-3". Molecular and Cellular Biology 20 (2): 702–12. doi:10.1128/MCB.20.2.702-712.2000. PMC 85175. PMID 10611249.
• Graef IA, Chen F, Chen L, Kuo A, Crabtree GR (Jun 2001). "Signals transduced by Ca(2+)/calcineurin and NFATc3/c4 pattern the developing vasculature". Cell 105 (7): 863–75. doi:10.1016/S0092-8674(01)00396-8. PMID 11439183.
• Yang T, Davis RJ, Chow CW (Oct 2001). "Requirement of two NFATc4 transactivation domains for CBP potentiation". The Journal of Biological Chemistry 276 (43): 39569–76. doi:10.1074/jbc.M102961200. PMID 11514544.
• Yang TT, Xiong Q, Enslen H, Davis RJ, Chow CW (Jun 2002). "Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases". Molecular and Cellular Biology 22 (11): 3892–904. doi:10.1128/MCB.22.11.3892-3904.2002. PMC 133816. PMID 11997522.
• Bennasser Y, Badou A, Tkaczuk J, Bahraoui E (Nov 2002). "Signaling pathways triggered by HIV-1 Tat in human monocytes to induce TNF-alpha". Virology 303 (1): 174–80. doi:10.1006/viro.2002.1676. PMID 12482669.
• Graef IA, Wang F, Charron F, Chen L, Neilson J, Tessier-Lavigne M, Crabtree GR (May 2003). "Neurotrophins and netrins require calcineurin/NFAT signaling to stimulate outgrowth of embryonic axons". Cell 113 (5): 657–70. doi:10.1016/S0092-8674(03)00390-8. PMID 12787506.
• Lahti AL, Manninen A, Saksela K (May 2003). "Regulation of T cell activation by HIV-1 accessory proteins: Vpr acts via distinct mechanisms to cooperate with Nef in NFAT-directed gene expression and to promote transactivation by CREB". Virology 310 (1): 190–6. doi:10.1016/S0042-6822(03)00164-8. PMID 12788643.

External links

• NFATC4 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.