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Nuclear factor of activated T-cells (NFAT) is a general name applied to 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.
The NFAT transcription factor family consists of five members NFATc1, NFATc2, NFATc3, and NFATc4.[1] NFATc1 through NFATc4 are regulated by calcium signaling. Calcium signaling is critical to NFAT activation because calmodulin (CaM), a well known calcium sensor protein, activates the serine/threonine phosphatase calcineurin (CN). Activated CN rapidly dephosphorylates the serine rich region (SRR) and SP-repeats in the amino termini of NFAT proteins resulting in a conformational change that exposes a nuclear localization signal resulting in NFAT nuclear import. Nuclear import of NFAT proteins is opposed by maintenance kinases in the cytoplasm and export kinases in the nucleus. Export kinases, such as PKA and GSK-3ί, must be inactivated for NFAT nuclear retention. NFAT proteins have weak DNA binding capacity. Therefore, to effectively bind DNA NFAT proteins must cooperate with other nuclear resident transcription factors generically referred to as NFATn.[2] This important feature of NFAT transcription factors enables integration and coincidence detection of calcium signals with other signaling pathways such as ras-MAPK or PKC. Additionally, this signaling integration is involved in tissue specific gene expression during development.
References
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Transcription factors and intracellular receptors |
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(1) Basic domains |
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Activating transcription factor ( AATF, 1, 2, 3, 4, 5, 6, 7) AP-1 ( c-Fos, FOSB, FOSL1, FOSL2, c-Jun, JUNB, JUND) BACH ( 1, 2) BATF BLZF1 C/EBP ( a, ί, ?, d, e, ?) CREB ( 1, 3, L1) CREM DBP DDIT3 GABPA HLF MAF ( B, F, G, K) NFE ( 2, L1, L2) NRL NRF1 XBP1
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(1.2) Basic helix-loop-helix ( bHLH)
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ATOH1 AhR AHRR ARNT ASCL1 BHLHB2 BMAL ( ARNTL, ARNTL2) CLOCK EPAS1 HAND ( 1, 2) HES ( 5, 6) HEY ( 1, 2, L) HES1 HIF ( 1A, 3A) ID ( 1, 2, 3, 4) LYL1 MXD4 MYCL1 MYCN Myogenic regulatory factors ( MyoD, Myogenin, MYF5, MYF6) Neurogenins NeuroD ( 1, 2) NPAS ( 1, 2, 3) OLIG ( 1, 2) Scleraxis TAL1 Twist USF1
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(1.4) NF-1
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(1.5) RF-X
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(1.6) Basic helix-span-helix (bHSH)
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(2) Zinc finger DNA-binding domains |
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subfamily 1 ( Thyroid hormone ( a, ί), CAR, FXR, LXR ( a, ί), PPAR ( a, ί/d, ?), PXR, RAR ( a, ί, ?), ROR ( a, ί, ?), Rev-ErbA ( a, ί), VDR)
subfamily 2 ( COUP-TF ( I, II), Ear-2, HNF4 ( a, ?), PNR, RXR ( a, ί, ?), Testicular receptor ( 2, 4), TLX)
subfamily 3 ( Steroid hormone ( Androgen, Estrogen ( a, ί), Glucocorticoid, Mineralocorticoid, Progesterone), Estrogen related ( a, ί, ?))
subfamily 4 NUR ( NGFIB, NOR1, NURR1) subfamily 5 ( LRH-1, SF1) subfamily 6 ( GCNF) subfamily 0 ( DAX1, SHP)
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(2.2) Other Cys4
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(2.3) Cys2His2
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General transcription factors ( TFIIA, TFIIB, TFIID, TFIIE, TFIIF ( 1, 2), TFIIH ( 1, 2, 4, 2I, 3A, 3C1, 3C2))
ATBF1 BCL ( 6, 11A, 11B) CTCF E4F1 EGR ( 2, 3) ERV3 GFI1 GLI-Krόppel family ( 1, 2, 3, S2, YY1) HIC ( 1, 2) HIVEP ( 1, 2, 3) IKZF ( 1, 2, 3) ILF ( 2, 3) KLF ( 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 17 ) MTF1 MYT1 OSR1 SP ( 1, 2, 4, 7) Zbtb7 ( 7A, 7B) ZBTB ( 16, 17, 20, 32, 33, 40) zinc finger ( 3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 649, 655)
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(2.4) Cys6
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(2.5) Alternating composition
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(3) Helix-turn-helix domains |
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ARX CDX ( 1, 2) CRX CUTL1 DLX ( 3, 4, 5) EMX2 EN ( 1, 2) FHL ( 1, 2, 3) HESX1 HHEX HLX Homeobox ( A1, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) HOPX MEIS ( 1, 2) MEOX2 MNX1 MSX ( 1, 2) NANOG NKX ( 2-1, 2-2, 2-3, 2-5, 3-1, 3-2) PBX ( 1, 2, 3) PHF ( 1, 3, 6, 8, 10, 16, 17, 20, 21A) PITX ( 1, 2, 3) POU domain ( PIT-1, BRN-3: A, B, C, Octamer transcription factor: 1, 2, 3/4, 6, 7, 11) OTX ( 1, 2) PDX1
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(3.2) Paired box
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E2F ( 1, 2, 3, 4, 5) FOX proteins ( C1, C2, E1, G1, H1, K2, L2, M1, N3, O1A, O3A, O4, P1, P2, P3)
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(3.5) Tryptophan clusters
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ELF ( 4, 5) EGF ELK ( 1, 3, 4) ERF ERG ETS ( 1, 2, SPIB) ETV ( 1, 4, 5, 6) FLI1 Interferon regulatory factors ( 1, 2, 3, 4, 5, 6, 7, 8) MYB MYBL2
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(3.6) TEA domain
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transcriptional enhancer factor 1, 2
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(4) ί-Scaffold factors with minor groove contacts |
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(4.1) Rel homology region
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(4.3) p53
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HMGB ( 1, 2, 3) HNF ( 1A, 1B) LEF1 SOX ( 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 18, 21) SRY SSRP1 TOX ( 1, 2, 3, 4)
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(4.10) Cold-shock domain
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(4.11) Runt
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(0) Other transcription factors |
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(0.2) HMGI(Y)
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(0.6) Miscellaneous
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ARID ( 1A, 1B, 2, 3A, 3B, 4A) CAP IFI ( 16, 35) MLL ( 2, 3, T1) MNDA NFI ( A, B, C, X) NFY ( A, B, C) Rho/ Sigma R-SMAD
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