NFATC2

Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene.^[5]

NFATC2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A02, 1OWR, 1P7H, 1PZU, 2AS5, 2O93, 3QRF
Identifiers
Aliases	NFATC2, NFAT1, NFATP, nuclear factor of activated T-cells 2, nuclear factor of activated T cells 2
External IDs	OMIM: 600490; MGI: 102463; HomoloGene: 7861; GeneCards: NFATC2; OMA:NFATC2 - orthologs
Gene location (Human) Chr. Chromosome 20 (human)[1] Band 20q13.2 Start 51,386,957 bp[1] End 51,562,831 bp[1]
Gene location (Mouse) Chr. Chromosome 2 (mouse)[2] Band 2 H3|2 88.91 cM Start 168,318,330 bp[2] End 168,443,577 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in vena cava synovial joint synovial membrane nipple buccal mucosa cell pylorus tendon of biceps brachii cartilage tissue saphenous vein skin of arm Top expressed in lumbar subsegment of spinal cord motor neuron substantia nigra ankle condyle facial motor nucleus stroma of bone marrow soleus muscle mesenteric lymph nodes Epithelium of choroid plexus More reference expression data BioGPS n/a
Gene ontology Molecular function DNA binding sequence-specific DNA binding DNA-binding transcription factor activity DNA-binding transcription activator activity, RNA polymerase II-specific transcription factor binding chromatin binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription repressor activity, RNA polymerase II-specific protein binding transcription cis-regulatory region binding phosphatase binding DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component cytoplasm transcription regulator complex nucleoplasm nucleus cytosol ribonucleoprotein complex Biological process B cell receptor signaling pathway regulation of transcription, DNA-templated cytokine production calcineurin-NFAT signaling cascade negative regulation of transcription by RNA polymerase II transcription by RNA polymerase II myotube cell development transcription, DNA-templated cellular response to DNA damage stimulus positive regulation of transcription, DNA-templated Fc-epsilon receptor signaling pathway positive regulation of myoblast fusion positive regulation of gene expression positive regulation of B cell proliferation cell migration positive regulation of transcription by RNA polymerase II regulation of regulatory T cell differentiation negative regulation of vascular associated smooth muscle cell differentiation Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 4773 18019 Ensembl ENSG00000101096 ENSMUSG00000027544 UniProt Q13469 Q60591 RefSeq (mRNA) NM_001136021 NM_001258292 NM_001258294 NM_001258295 NM_001258296 NM_001258297 NM_012340 NM_173091 NM_001037177 NM_001037178 NM_001136073 NM_001291168 NM_001291169 NM_001291170 NM_001291171 NM_001291172 NM_001291173 NM_001291174 NM_001291175 NM_001291176 NM_001291177 NM_001291178 NM_001291179 NM_010899 RefSeq (protein) NP_001129493 NP_001245221 NP_001245223 NP_001245224 NP_001245225 NP_001245226 NP_036472 NP_775114 NP_001032254 NP_001032255 NP_001129545 NP_001278097 NP_001278098 NP_001278099 NP_001278100 NP_001278101 NP_001278102 NP_001278103 NP_001278104 NP_001278105 NP_001278106 NP_001278107 NP_001278108 NP_035029 Location (UCSC) Chr 20: 51.39 – 51.56 Mb Chr 2: 168.32 – 168.44 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[6]

Clinical significance

Translocation forming an in frame fusions product between EWSR1 gene and the NFATc2 gene has been described in bone tumor with a Ewing sarcoma-like clinical appearance. The translocation breakpoint led to the loss of the controlling elements of the NFATc2 protein and the fusion of the N terminal region of the EWSR1 gene conferred constant activation of the protein.^[7]

Interactions

NFATC2 has been shown to interact with MEF2D,^[8] EP300,^[9] IRF4^[10] and Protein kinase Mζ.^[11] Prostaglandin F2alpha stimulates a NFCT2 pathway stimulating growth of skeletal muscle cells.^[12]

References

1. GRCh38: Ensembl release 89: ENSG00000101096 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000027544 – 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: NFATC2 nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2".
7. Szuhai K, Ijszenga M, de Jong D, Karseladze A, Tanke HJ, Hogendoorn PC (Apr 2009). "The NFATc2 gene is involved in a novel cloned translocation in a Ewing sarcoma variant that couples its function in immunology to oncology". Clinical Cancer Research. 15 (7): 2259–68. doi:10.1158/1078-0432.CCR-08-2184. PMID 19318479.
8. Youn HD, Chatila TA, Liu JO (Aug 2000). "Integration of calcineurin and MEF2 signals by the coactivator p300 during T-cell apoptosis". The EMBO Journal. 19 (16): 4323–31. doi:10.1093/emboj/19.16.4323. PMC 302027. PMID 10944115.
9. García-Rodríguez C, Rao A (Jun 1998). "Nuclear factor of activated T cells (NFAT)-dependent transactivation regulated by the coactivators p300/CREB-binding protein (CBP)". The Journal of Experimental Medicine. 187 (12): 2031–6. doi:10.1084/jem.187.12.2031. PMC 2212364. PMID 9625762.
10. Rengarajan J, Mowen KA, McBride KD, Smith ED, Singh H, Glimcher LH (Apr 2002). "Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression". The Journal of Experimental Medicine. 195 (8): 1003–12. doi:10.1084/jem.20011128. PMC 2193700. PMID 11956291.
11. San-Antonio B, Iñiguez MA, Fresno M (Jul 2002). "Protein kinase Czeta phosphorylates nuclear factor of activated T cells and regulates its transactivating activity". The Journal of Biological Chemistry. 277 (30): 27073–80. doi:10.1074/jbc.M106983200. PMID 12021260.
12. Horsley V, Pavlath GK (2003). "Prostaglandin F2(alpha) stimulates growth of skeletal muscle cells via an NFATC2-dependent pathway". J Cell Biol. 161 (1): 111–8. doi:10.1083/jcb.200208085. PMC 2172881. PMID 12695501.

Further reading

• Rao A, Luo C, Hogan PG (1997). "Transcription factors of the NFAT family: regulation and function". Annual Review of Immunology. 15: 707–747. 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): 611–614. doi:10.1016/S0092-8674(00)80571-1. PMID 10089876. S2CID 8817053.
• Horsley V, Pavlath GK (Mar 2002). "NFAT: ubiquitous regulator of cell differentiation and adaptation". The Journal of Cell Biology. 156 (5): 771–774. doi:10.1083/jcb.200111073. PMC 2173310. PMID 11877454.
• Aramburu J, Azzoni L, Rao A, Perussia B (Sep 1995). "Activation and expression of the nuclear factors of activated T cells, NFATp and NFATc, in human natural killer cells: regulation upon CD16 ligand binding". The Journal of Experimental Medicine. 182 (3): 801–810. doi:10.1084/jem.182.3.801. PMC 2192167. PMID 7650486.
• Auffray C, Behar G, Bois F, Bouchier C, Da Silva C, Devignes MD, Duprat S, Houlgatte R, Jumeau MN, Lamy B (Feb 1995). "[IMAGE: molecular integration of the analysis of the human genome and its expression]". Comptes Rendus de l'Académie des Sciences, Série III. 318 (2): 263–72. PMID 7757816.
• Li X, Ho SN, Luna J, Giacalone J, Thomas DJ, Timmerman LA, Crabtree GR, Francke U (1995). "Cloning and chromosomal localization of the human and murine genes for the T-cell transcription factors NFATc and NFATp". Cytogenetics and Cell Genetics. 68 (3–4): 185–191. doi:10.1159/000133910. PMID 7842733.
• Ho S, Timmerman L, Northrop J, Crabtree GR (1994). "Cloning and Characterization of NF-ATc and NF-ATp: The Cytoplasmic Components of NF-AT". Mechanisms of Lymphocyte Activation and Immune Regulation V. Advances in Experimental Medicine and Biology. Vol. 365. pp. 167–73. doi:10.1007/978-1-4899-0987-9_17. ISBN 978-1-4899-0989-3. PMID 7887301.
• 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): 2646–2652. doi:10.1002/eji.1830241112. PMID 7957556. S2CID 30435577.
• 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): 467–474. doi:10.1006/bbrc.1994.2689. PMID 7999066.
• Jain J, McCaffrey PG, Miner Z, Kerppola TK, Lambert JN, Verdine GL, Curran T, Rao A (Sep 1993). "The T-cell transcription factor NFATp is a substrate for calcineurin and interacts with Fos and Jun". Nature. 365 (6444): 352–355. Bibcode:1993Natur.365..352J. doi:10.1038/365352a0. PMID 8397339. S2CID 4283223.
• Luo C, Burgeon E, Carew JA, McCaffrey PG, Badalian TM, Lane WS, Hogan PG, Rao A (Jul 1996). "Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes". Molecular and Cellular Biology. 16 (7): 3955–66. doi:10.1128/mcb.16.7.3955. PMC 231392. PMID 8668213.
• 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): 2181–2188. doi:10.1002/eji.1830260933. PMID 8814265. S2CID 23430217.
• Copeland KF, McKay PJ, Rosenthal KL (Jan 1996). "Suppression of the human immunodeficiency virus long terminal repeat by CD8+ T cells is dependent on the NFAT-1 element". AIDS Research and Human Retroviruses. 12 (2): 143–148. doi:10.1089/aid.1996.12.143. PMID 8834464.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Hodge MR, Chun HJ, Rengarajan J, Alt A, Lieberson R, Glimcher LH (Dec 1996). "NF-AT-Driven interleukin-4 transcription potentiated by NIP45". Science. 274 (5294): 1903–1905. Bibcode:1996Sci...274.1903H. doi:10.1126/science.274.5294.1903. PMID 8943202. S2CID 29436825.
• Lyakh L, Ghosh P, Rice NR (May 1997). "Expression of NFAT-family proteins in normal human T cells". Molecular and Cellular Biology. 17 (5): 2475–84. doi:10.1128/mcb.17.5.2475. PMC 232096. PMID 9111316.
• Amasaki Y, Masuda ES, Imamura R, Arai K, Arai N (Mar 1998). "Distinct NFAT family proteins are involved in the nuclear NFAT-DNA binding complexes from human thymocyte subsets". Journal of Immunology. 160 (5): 2324–33. doi:10.4049/jimmunol.160.5.2324. PMID 9498773. S2CID 19932048.
• Chen L, Glover JN, Hogan PG, Rao A, Harrison SC (Mar 1998). "Structure of the DNA-binding domains from NFAT, Fos and Jun bound specifically to DNA". Nature. 392 (6671): 42–48. Bibcode:1998Natur.392...42C. doi:10.1038/32100. PMID 9510247. S2CID 4305535.

External links

• NFATC2+protein,+human at the U.S. 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.