Descriptions

NFAT1 plays a role in the inducible expression of cytokine genes in T-cells. NFAT transcription factors are highly phosphorylated proteins that are regulated by the calcium-dependent phosphatase calcineurin. NFAT1 is phosphorylated on fourteen conserved phosphoserine residues in its regulatory domain (100-400), thirteen of which are dephosphorylated upon stimulation. Dephosphorylation of all thirteen residues is required to mask a nuclear export signal (NES), causes full exposure of a nuclear localization signal (NLS), and promotes transcriptional activity. Mutations in the serine-rich region (SRR-1, specifically 170-183) enhances the localization of NFAT1 to the nucleus, while the full-length NFAT1 does not move into the nucleus. This represents that the SRR-1 region inhibits the translocation of NFAT1 to the nucleus. In addition, SRR-1 region also regulates the active conformation of NFAT1.

Autoinhibitory domains (AIDs)

Target domain

257-259 (NLS)

Relief mechanism

PTM

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for O77638

Entry ID Method Resolution Chain Position Source
AF-O77638-F1 Predicted AlphaFoldDB

No variants for O77638

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for O77638

No associated diseases with O77638

3 regional properties for O77638

Type Name Position InterPro Accession
domain IPT domain 585 - 684 IPR002909
domain Rel homology domain, DNA-binding domain 400 - 582 IPR011539
domain Rel homology dimerisation domain 588 - 686 IPR032397

Functions

Description
EC Number
Subcellular Localization
  • Cytoplasm
  • Nucleus
  • Cytoplasmic for the phosphorylated form and nuclear after activation that is controlled by calcineurin-mediated dephosphorylation
  • Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals
  • Translocation to the nucleus is increased in the presence of calcium in pre-osteoblasts (By similarity)
  • The subcellular localization of NFATC plays a key role in the regulation of gene transcription
  • Nuclear translocation OF NFATC1 is enhanced in the presence of TNFSF11
  • Nuclear translocation is decreased in the presence of FBN1 which can bind and sequester TNFSF11
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
transcription regulator complex A protein complex that is capable of associating with DNA by direct binding, or via other DNA-binding proteins or complexes, and regulating transcription.

2 GO annotations of molecular function

Name Definition
DNA-binding transcription factor activity, RNA polymerase II-specific A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II.
RNA polymerase II cis-regulatory region sequence-specific DNA binding Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II.

2 GO annotations of biological process

Name Definition
calcineurin-NFAT signaling cascade Any intracellular signal transduction in which the signal is passed on within the cell by activation of a member of the NFAT protein family as a consequence of NFAT dephosphorylation by Ca(2+)-activated calcineurin. The cascade begins with calcium-dependent activation of the phosphatase calcineurin. Calcineurin dephosphorylates multiple phosphoserine residues on NFAT, resulting in the translocation of NFAT to the nucleus. The cascade ends with regulation of transcription by NFAT. The calcineurin-NFAT cascade lies downstream of many cell surface receptors, including G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) that signal to mobilize calcium ions (Ca2+).
regulation of transcription by RNA polymerase II Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.

3 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P98201 NFATC1 Nuclear factor of activated T-cells, cytoplasmic 1 Bos taurus (Bovine) SS
O95644 NFATC1 Nuclear factor of activated T-cells, cytoplasmic 1 Homo sapiens (Human) SS
O88942 Nfatc1 Nuclear factor of activated T-cells, cytoplasmic 1 Mus musculus (Mouse) EV
10 20 30 40 50 60
MTGLEEDQEF DFDFLFEFNQ SDEGAAAAGA TAERYSYATT GISSALPLPT APPTLPAPCH
70 80 90 100 110 120
DQQASAAGIS AVGSAGHPAG YAGAVDGGPS GYFLPSGGVR PNGAPALESP RIEITSYLGL
130 140 150 160 170 180
HHNNGQFFHD VAVEDVLPNP RRSPSTATLS LPNLEAYRDP SCLSPASSLS SRSCNSEASS
190 200 210 220 230 240
YESSFSYPYA SPQTSPWQSP CVSPKTTDPE EGFPRGLGAC SLLGSPRHSP STSPRTSVTE
250 260 270 280 290 300
ESWLGARTSR PSSPCNKRKY GLNGRQLFCS PHASPTPSPH SSPRVSVTDD TWLGNTTQYT
310 320 330 340 350 360
SSAIVAAINA LSTDSSLDLG DGVPVKARKT ALDHSPSLAL KVEPAAEDLG ATPPTSDFPP
370 380 390 400 410 420
EEFPPFQHIR KGAFCDQYLS VPQHPYPWAR PRSPTPYASP SLPALDWQLP SHSGPYELRI
430 440 450 460 470 480
EVQPKSHHRA HYETEGSRGA VKASAGGHPS VQLHGYVESE PLTLQLFIGT ADDRLLRPHA
490 500 510 520 530 540
FYQVHRITGK TVSTTSHEAV LSNTKVLEIP LLPENNMRAI IDCAGILKLR NSDIELRKGE
550 560 570 580 590 600
TDIGRKNTRV RLVFRVHIPQ PNGRTLSLQV ASNPIECSQR SAQELPLVEK QSAASCPVLG
610 620 630 640 650 660
GKRMVLTGHN FLQDSKVVFV EKAPDGHHIW EMEAKTDGDL CKPNSLVVEI PPFRNQRITS
670 680 690 700 710 720
PVQVNFYVCN GKRKRSQYQH FTYLPANAPV IKTEPSDDYE PALTCGPVSQ GLNPLTKPCY
730 740 750 760 770 780
GPPLALPPDP SSCLVAGFPP CPQRSAVMSP PPSASPKLHD LSCAPYSKGM AGPGHLGLQR
790 800 810 820
PAGGVLGGQE APRPGGPHPG APQLHPLNLS QSIVTRLTEP QP