NFAT

NFAT (Nuclear Factor of Activated T-Cells) proteins are transcription factors that are integral for the development and function of the immune system. Five NFAT isoforms have been identified to date, NFATC1-C4 and NFAT5.

Products
Background
Literature
Gene Data

Inhibitors

Cat No Product Name / Activity
3930 NFAT Inhibitor
Inhibitor of calcineurin-mediated NFAT activation
5710 NFAT inhibitor, Cell Permeable
Cell permeable NFAT inhibitor

Other

Cat No Product Name / Activity
4210 Ascomycin
Calcineurin phosphatase inhibitor; analog of FK 506 (Cat. No. 3631)
1891 Calcineurin Autoinhibitory Peptide
Selective calcineurin inhibitor
1101 Cyclosporin A
Calcineurin inhibitor
3631 FK 506
Potent calcineurin inhibitor; immunosuppressant
2162 INCA-6
Inhibitor of calcineurin-NFAT association

The NFAT (Nuclear Factor of Activated T-Cells) family of transcription factors consists of five members; NFATC1 (NFAT2, NFATc), NFATC2 (NFAT1, NFATp), NFATC3 (NFAT4), NFATC4 (NFAT3) and NFAT5. The transcriptional activity of the NFATC1-C4 isoforms is mediated by the calcium/calmodulin-dependent phosphatase calcineurin. In contrast NFAT5 is calcineurin-independent, being activated by osmotic stress. From here on in NFAT will be used to refer to the NFATC1-C4 isoforms.

Under basal conditions, NFAT is phosphorylated and confined to the cytoplasm. Following an increase in intracellular calcium [Ca2+]i, NFAT is dephosphorylated by calcineurin, exposing its nuclear localization signal (NLS), and resulting in nuclear translocation and entry. As long as [Ca2+]i levels are elevated NFAT remains in the nucleus. A decrease in [Ca2+]i below the threshold results in rephosphorylation of NFAT, masking the NLS and exposing the nuclear export signal (NES), leading to the export of NFAT back into the cytoplasm. In the nucleus NFAT induces the expression of a number of genes including IL-2, IL-3, IL-4, IL-10, TNF-α, IFNγ and COX-2. However NFAT itself has weak DNA binding affinity, therefore it binds to cofactors including AP-1, GATA and MEF to induce transcription.

Several kinases phosphorylate NFAT to regulate its activity. PKA primes NFAT for phosphorylation by 14.3.3 proteins, which maintains its localization in the cytosol. GSK3, PKA, CK1, DYRK1/2 and JNK promote NFAT nuclear export, whereas MEKK1 and CK1 can suppress nuclear export. NFAT is also regulated by sumoylation and proteasome degradation.

The role of NFAT in the immune system is well established, through its induction of cytokine gene expression, and development and activation of T-cells. NFAT is important for the adaptive and innate immune responses, also regulating the activation of macrophages, mast cells and dendritic cells. NFAT is also vital during embryonic development, being important for skeletal, cardiac and nervous system development. Dysregulation of NFAT expression has been implicated in the pathology of inflammatory diseases, such as inflammatory bowel disease, and autoimmune diseases, such as rheumatoid arthritis and lupus. There is also evidence that NFATC1 could be involved in the progression and metastasis of certain cancers, whereas NFATC2 has been shown to induce cell cycle arrest and apoptosis.

Literature for NFAT

Immunology

Immunology Product Listing

A collection of over 190 products for immunology research, the guide includes research tools for the study of:

  • Chemokine and Cytokine Signaling
  • Chemotaxis
  • Complement System
  • Immune Cell Signaling
  • Inflammation

NFAT Gene Data

Gene Species Gene Symbol Gene Accession No. Protein Accession No.
NFATC1 Human NFATC1 NM_172390 O95644
Mouse Nfatc1 NM_016791 O88942
Rat Nfatc1 NM_001244933 NP_001231862
NFATC2 Human NFATC2 NM_012340 Q13469
Mouse Nfatc2 NM_010899 Q60591
Rat Nfatc2 NM_001107805 NP_001101275
NFATC3 Human NFATC3 NM_004555 Q12968
Mouse Nfatc3 NM_010901 P97305
Rat Nfatc3 NM_001108447 NP_001101917
NFATC4 Human NFATC4 NM_004554 Q14934
Mouse Nfatc4 NM_023699 Q8K120
Rat Nfatc4 NM_001107264 NP_001100734
NFAT5 Human NFAT5 NM_138714 O94916
Mouse Nfat5 NM_133957 Q9WV30
Rat Nfat5 NM_001107425 NP_001100895