NFATC1

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NFATC1
Protein NFATC1 PDB 1a66.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NFATC1 , NF-ATC, NFAT2, NFATc, NF-ATc1.2, nuclear factor of activated T-cells 1, nuclear factor of activated T cells 1
External IDs OMIM: 600489 MGI: 102469 HomoloGene: 32336 GeneCards: NFATC1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)
RefSeq (protein)

n/a

Location (UCSC) Chr 18: 79.4 – 79.53 Mb Chr 18: 80.65 – 80.76 Mb
PubMed search [3] [4]
Wikidata
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Nuclear factor of activated T-cells, cytoplasmic 1 is a protein that in humans is encoded by the NFATC1 gene. [5]

Function

The product of this gene is a component of the nuclear factor 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. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as ciclosporin. Five transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes. [6]

Interactions

NFATC1 has been shown to interact with PIM1. [7]

See also

Related Research Articles

<span class="mw-page-title-main">Calcineurin</span> Class of enzymes

Calcineurin (CaN) is a calcium and calmodulin dependent serine/threonine protein phosphatase. It activates the T cells of the immune system and can be blocked by drugs. Calcineurin activates nuclear factor of activated T cell cytoplasmic (NFATc), a transcription factor, by dephosphorylating it. The activated NFATc is then translocated into the nucleus, where it upregulates the expression of interleukin 2 (IL-2), which, in turn, stimulates the growth and differentiation of the T cell response. Calcineurin is the target of a class of drugs called calcineurin inhibitors, which include ciclosporin, voclosporin, pimecrolimus and tacrolimus.

Nuclear factor of activated T-cells (NFAT) is a family of transcription factors shown to be important in immune response. One or more members of the NFAT family is expressed in most cells of the immune system. NFAT is also involved in the development of cardiac, skeletal muscle, and nervous systems. NFAT was first discovered as an activator for the transcription of IL-2 in T cells but has since been found to play an important role in regulating many more body systems. NFAT transcription factors are involved in many normal body processes as well as in development of several diseases, such as inflammatory bowel diseases and several types of cancer. NFAT is also being investigated as a drug target for several different disorders.

<span class="mw-page-title-main">NFKB1</span> Protein-coding gene in the species Homo sapiens

Nuclear factor NF-kappa-B p105 subunit is a protein that in humans is encoded by the NFKB1 gene.

<span class="mw-page-title-main">IκBα</span> Protein-coding gene in the species Homo sapiens

IκBα is one member of a family of cellular proteins that function to inhibit the NF-κB transcription factor. IκBα inhibits NF-κB by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. In addition, IκBα blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-κB's proper functioning.

<span class="mw-page-title-main">RELA</span> Protein-coding gene in the species Homo sapiens

Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the RELA gene.

<span class="mw-page-title-main">NFKB2</span> Protein-coding gene in the species Homo sapiens

Nuclear factor NF-kappa-B p100 subunit is a protein that in humans is encoded by the NFKB2 gene.

<span class="mw-page-title-main">CEBPB</span> Protein-coding gene in the species Homo sapiens

CCAAT/enhancer-binding protein beta is a protein that in humans is encoded by the CEBPB gene.

<span class="mw-page-title-main">NFATC2</span> Protein-coding gene in the species Homo sapiens

Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene.

<span class="mw-page-title-main">NRF1</span> Protein-coding gene in the species Homo sapiens

Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor -like 1" which has an official symbol of NFE2L1.

<span class="mw-page-title-main">ILF3</span> Protein-coding gene in the species Homo sapiens

Interleukin enhancer-binding factor 3 is a protein that in humans is encoded by the ILF3 gene.

<span class="mw-page-title-main">TAF6</span> Protein-coding gene in the species Homo sapiens

Transcription initiation factor TFIID subunit 6 is a protein that in humans is encoded by the TAF6 gene.

<span class="mw-page-title-main">PRKCQ</span> Protein-coding gene in the species Homo sapiens

Protein kinase C theta (PKC-θ) is an enzyme that in humans is encoded by the PRKCQ gene. PKC-θ, a member of serine/threonine kinases, is mainly expressed in hematopoietic cells with high levels in platelets and T lymphocytes, where plays a role in signal transduction. Different subpopulations of T cells vary in their requirements of PKC-θ, therefore PKC-θ is considered as a potential target for inhibitors in the context of immunotherapy.

<span class="mw-page-title-main">SMARCB1</span> Protein-coding gene in the species Homo sapiens

SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 is a protein that in humans is encoded by the SMARCB1 gene.

<span class="mw-page-title-main">NFAT5</span> Mammalian protein found in Homo sapiens

Nuclear factor of activated T-cells 5, also known as NFAT5 and sometimes TonEBP, is a human gene that encodes a transcription factor that regulates the expression of genes involved in the osmotic stress.

<span class="mw-page-title-main">NFATC3</span> Protein-coding gene in the species Homo sapiens

Nuclear factor of activated T-cells, cytoplasmic 3 is a protein that in humans is encoded by the NFATC3 gene.

<span class="mw-page-title-main">NFATC4</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">NFIX</span> Protein-coding gene in the species Homo sapiens

Nuclear factor 1 X-type is a protein that in humans is encoded by the NFIX gene. NFI-X3, a splice variant of NFIX, regulates Glial fibrillary acidic protein and YKL-40 in astrocytes.

<span class="mw-page-title-main">NFKBIE</span> Protein-coding gene in the species Homo sapiens

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, epsilon, also known as NFKBIE, is a protein which in humans is encoded by the NFKBIE gene.

<span class="mw-page-title-main">NFKBIZ</span> Protein-coding gene in the species Homo sapiens

NF-kappa-B inhibitor zeta (IκBζ) is a protein that in humans is encoded by the NFKBIZ gene. This gene is a member of the ankyrin-repeat family and is induced by lipopolysaccharide (LPS). The C-terminal portion of the encoded product which contains the ankyrin repeats, shares high sequence similarity with the I kappa B family of proteins. The latter are known to play a role in inflammatory responses to LPS by their interaction with NF-B proteins through ankyrin-repeat domains. Studies in mouse indicate that this gene product is one of the nuclear I kappa B proteins and an activator of IL-6 production. Two transcript variants encoding different isoforms have been found for this gene.

Gerald R. Crabtree is the David Korn Professor at Stanford University and an Investigator in the Howard Hughes Medical Institute. He is known for defining the Ca2+-calcineurin-NFAT signaling pathway, pioneering the development of synthetic ligands for regulation of biologic processes and discovering chromatin regulatory mechanisms involved in cancer and brain development. He is a founder of Ariad Pharmaceuticals, Amplyx Pharmaceuticals, and Foghorn Therapeutics.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000131196 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000033016 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Northrop JP, Ho SN, Chen L, Thomas DJ, Timmerman LA, Nolan GP, Admon A, Crabtree GR (Jun 1994). "NF-AT components define a family of transcription factors targeted in T-cell activation". Nature. 369 (6480): 497–502. Bibcode:1994Natur.369..497N. doi:10.1038/369497a0. PMID   8202141. S2CID   9920546.
  6. "Entrez Gene: NFATC1 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1".
  7. Rainio EM, Sandholm J, Koskinen PJ (Feb 2002). "Cutting edge: Transcriptional activity of NFATc1 is enhanced by the Pim-1 kinase". Journal of Immunology. 168 (4): 1524–7. doi: 10.4049/jimmunol.168.4.1524 . PMID   11823475.

Further reading

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