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 |
273-275 (NLS) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
Autoinhibited structure
Activated structure
1 structures for P97305
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P97305-F1 | Predicted | AlphaFoldDB |
No variants for P97305
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P97305 | |||||
No associated diseases with P97305
6 regional properties for P97305
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 27 - 279 | IPR000719 |
| active_site | Serine/threonine-protein kinase, active site | 146 - 158 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 33 - 56 | IPR017441 |
| domain | PRKAA1, UBA-like autoinhibitory domain | 296 - 360 | IPR028797 |
| domain | AMPK, C-terminal adenylate sensor domain | 406 - 480 | IPR032270 |
| domain | 5'-AMP-activated protein kinase alpha 1 catalytic subunit, C-terminal | 404 - 557 | IPR039137 |
Functions
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| 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. |
8 GO annotations of molecular function
| Name | Definition |
|---|---|
| chromatin binding | Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase. |
| DNA binding | Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid). |
| DNA-binding transcription activator activity, RNA polymerase II-specific | A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II. |
| DNA-binding transcription factor activity | A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons. |
| 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. |
| sequence-specific DNA binding | Binding to DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA e.g. promotor binding or rDNA binding. |
| transcription cis-regulatory region binding | Binding to a specific sequence of DNA that is part of a regulatory region that controls transcription of that section of the DNA. The transcribed region might be described as a gene, cistron, or operon. |
29 GO annotations of biological process
| Name | Definition |
|---|---|
| blood vessel remodeling | The reorganization or renovation of existing blood vessels. |
| branching involved in blood vessel morphogenesis | The process of coordinated growth and sprouting of blood vessels giving rise to the organized vascular system. |
| 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+). |
| cardiac muscle hypertrophy in response to stress | The physiological enlargement or overgrowth of all or part of the heart muscle due to an increase in size (not length) of individual cardiac muscle fibers, without cell division, as a result of a disturbance in organismal or cellular homeostasis. |
| cellular respiration | The enzymatic release of energy from inorganic and organic compounds (especially carbohydrates and fats) which either requires oxygen (aerobic respiration) or does not (anaerobic respiration). |
| cellular response to calcium ion | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a calcium ion stimulus. |
| cellular response to lithium ion | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lithium (Li+) ion stimulus. |
| DN4 thymocyte differentiation | The process in which a relatively unspecialized cell acquires the specialized features of a DN4 thymocyte. A DN4 thymocyte is a CD4-,CD8- thymocyte that is also CD44-,CD25-. |
| heart development | The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood. |
| myotube cell development | The process aimed at the progression of a myotube cell over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell. Myotubes are multinucleated cells that are formed when proliferating myoblasts exit the cell cycle, differentiate and fuse. |
| myotube differentiation | The process in which a relatively unspecialized cell acquires specialized features of a myotube cell. Myotube differentiation starts with myoblast fusion and the appearance of specific cell markers (this is the cell development step). Then individual myotubes can fuse to form bigger myotubes and start to contract. Myotubes are multinucleated cells that are formed when proliferating myoblasts exit the cell cycle, differentiate and fuse. |
| positive regulation of apoptotic process | Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process. |
| positive regulation of artery morphogenesis | Any process that activates or increases the frequency, rate or extent of artery morphogenesis. |
| positive regulation of cardiac muscle hypertrophy | Any process that increases the rate, frequency or extent of the enlargement or overgrowth of all or part of the heart due to an increase in size (not length) of individual cardiac muscle fibers, without cell division. |
| positive regulation of DNA-templated transcription | Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription. |
| positive regulation of nitric oxide biosynthetic process | Any process that activates or increases the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of nitric oxide. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| positive thymic T cell selection | The process of sparing immature T cells in the thymus which react with self-MHC protein complexes with low affinity levels from apoptotic death. |
| protein import into nucleus | The directed movement of a protein from the cytoplasm to the nucleus. |
| regulation of DNA-templated transcription | Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription. |
| regulation of store-operated calcium entry | Any process that modulates the frequency, rate or extent of store-operated calcium entry. |
| regulation of transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| response to hypoxia | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level. |
| skeletal muscle fiber development | The process whose specific outcome is the progression of the skeletal muscle fiber over time, from its formation to the mature structure. Muscle fibers are formed by the maturation of myotubes. They can be classed as slow, intermediate/fast or fast. |
| T cell differentiation | The process in which a precursor cell type acquires characteristics of a more mature T-cell. A T cell is a type of lymphocyte whose definin characteristic is the expression of a T cell receptor complex. |
| thymus development | The process whose specific outcome is the progression of the thymus over time, from its formation to the mature structure. The thymus is a symmetric bi-lobed organ involved primarily in the differentiation of immature to mature T cells, with unique vascular, nervous, epithelial, and lymphoid cell components. |
| transcription by RNA polymerase II | The synthesis of RNA from a DNA template by RNA polymerase II (RNAP II), originating at an RNA polymerase II promoter. Includes transcription of messenger RNA (mRNA) and certain small nuclear RNAs (snRNAs). |
| vascular associated smooth muscle cell development | The process aimed at the progression of a vascular smooth muscle cell over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell. A vascular smooth muscle cell is a non-striated, elongated, spindle-shaped cell found lining the blood vessels. |
| vascular associated smooth muscle cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of a vascular smooth muscle cell. |
3 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q8K120 | Nfatc4 | Nuclear factor of activated T-cells, cytoplasmic 4 | Mus musculus (Mouse) | PR |
| Q60591 | Nfatc2 | Nuclear factor of activated T-cells, cytoplasmic 2 | Mus musculus (Mouse) | PR |
| O88942 | Nfatc1 | Nuclear factor of activated T-cells, cytoplasmic 1 | Mus musculus (Mouse) | EV |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MTTANCGAHD | ELDFKLVFGE | DGAPAPPPPG | SRPADLEPDD | CASIYIFNVD | PPPSTLTTPL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| CLPHHGLPSH | SSVLSPSFQL | QSHKNYEGTC | EIPESKYSPL | GGPKPFECPS | IQFTSISPNC |
| 130 | 140 | 150 | 160 | 170 | 180 |
| QQELDAHEDD | LQINDPEREF | LERPSRDHLY | LPLEPSYRES | SLSPSPASSI | SSRSWFSDAS |
| 190 | 200 | 210 | 220 | 230 | 240 |
| SCESLSHIYD | DVDSELNEAA | ARFTLGSPLT | SPGGSPGGCP | GEESWHQQYG | SGHSLSPRQS |
| 250 | 260 | 270 | 280 | 290 | 300 |
| PCHSPRSSIT | DENWLSPRPA | SGPSSRPTSP | CGKRRHSSAE | VCYAGSLSPH | HSPVPSPGHS |
| 310 | 320 | 330 | 340 | 350 | 360 |
| PRGSVTEDTW | LTAPVHTGSG | LSPAPFPFQY | CVETDIPLKT | RKTSEDQAAI | LPGKLEICSD |
| 370 | 380 | 390 | 400 | 410 | 420 |
| DQGNLSPSRE | TSVDDGLGSQ | YPLKKDSSGD | QFLSVPSPFT | WSKPKPGHTP | IFRTSSLPPL |
| 430 | 440 | 450 | 460 | 470 | 480 |
| DWPLPTHFGQ | CELKIEVQPK | THHRAHYETE | GSRGAVKAST | GGHPVVKLLG | YSEKPINLQM |
| 490 | 500 | 510 | 520 | 530 | 540 |
| FIGTADDRYL | RPHAFYQVHR | ITGKTVATAS | QEIIIASTKV | LEIPLLPENN | MSASIDCAGI |
| 550 | 560 | 570 | 580 | 590 | 600 |
| LKLRNSDIEL | RKGETDIGRK | NTRVRLVFRV | HIPQPSGKVL | SLQIASIPVE | CSQRSAQELP |
| 610 | 620 | 630 | 640 | 650 | 660 |
| HIEKYSINSC | SVNGGHEMIV | TGSNFLPESK | IIFLEKGQDG | GPHWEVEGKI | IREKCQGAHI |
| 670 | 680 | 690 | 700 | 710 | 720 |
| VLEVPPYHNP | AVTSAVQVHF | YLCNGKRKKS | QSQRFTYTPV | LMKQEQREDT | DLPSVPSLPV |
| 730 | 740 | 750 | 760 | 770 | 780 |
| PHSAQAQRPS | SETGHPHDRA | MSAPGGLLCQ | VQPAYTSMVA | STHLPQLQCR | DEGAGKEQHI |
| 790 | 800 | 810 | 820 | 830 | 840 |
| ATSSVMHQPF | QVTPTSPIGS | SYQSIQTSMY | NGPTCLPVNP | ASSQEFDPVL | FQQDAALSSL |
| 850 | 860 | 870 | 880 | 890 | 900 |
| VNLGCQPLSP | IPFHSSNSDA | TGHLLAHSPH | SVQTPPHLQS | MGYHCSNAGQ | TALSSPVADQ |
| 910 | 920 | 930 | 940 | 950 | 960 |
| ITGQPSSHLQ | PITYCPSHPG | SATAASPAAS | HPLASSPISG | PSSPQLQPMP | YQSPSSGTAS |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| SPSPTTRMHS | GQHSTQAQST | GQGGLSVPSS | LVCHSLCDPA | SFPPGGATVS | IKPEPEDQEP |
| 1030 | 1040 | 1050 | 1060 | 1070 | |
| NFATIGLQDI | TLDDVNEIIG | RDMSQISVSQ | ATEVMRDTPL | PGPASPDLMT | SHSAH |