NFAC1_HUMAN
ID NFAC1_HUMAN Reviewed; 943 AA.
AC O95644; B5B2M4; B5B2M5; B5B2M6; B5B2M7; B5B2M8; B5B2M9; B5B2N1; Q12865;
AC Q15793; Q2M1S3;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 3.
DT 03-AUG-2022, entry version 221.
DE RecName: Full=Nuclear factor of activated T-cells, cytoplasmic 1;
DE Short=NF-ATc1;
DE Short=NFATc1;
DE AltName: Full=NFAT transcription complex cytosolic component;
DE Short=NF-ATc;
DE Short=NFATc;
GN Name=NFATC1; Synonyms=NFAT2, NFATC;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A-ALPHA).
RC TISSUE=Peripheral blood lymphocyte, and T-cell;
RX PubMed=8202141; DOI=10.1038/369497a0;
RA Northrop J.P., Ho S.N., Chen L., Thomas D.J., Timmerman L.A., Nolan G.P.,
RA Admon A., Crabtree G.R.;
RT "NF-AT components define a family of transcription factors targeted in T-
RT cell activation.";
RL Nature 369:497-502(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B-BETA).
RC TISSUE=B-cell;
RX PubMed=8702849; DOI=10.1074/jbc.271.34.20914;
RA Park J., Takeuchi A., Sharma S.;
RT "Characterization of a new isoform of the NFAT (nuclear factor of activated
RT T cells) gene family member NFATc.";
RL J. Biol. Chem. 271:20914-20921(1996).
RN [3]
RP ERRATUM OF PUBMED:8702849.
RA Park J., Takeuchi A., Sharma S.;
RL J. Biol. Chem. 271:33705-33705(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A-ALPHA; B-ALPHA AND C-BETA).
RC TISSUE=B-cell lymphoma;
RX PubMed=10072078; DOI=10.1016/s1074-7613(00)80026-6;
RA Chuvpilo S., Zimmer M., Kerstan A., Gloeckner J., Avots A., Escher C.,
RA Fischer C., Inashkina I., Jankevics E., Berberich-Siebelt F., Schmitt E.,
RA Serfling E.;
RT "Alternative polyadenylation events contribute to the induction of NF-ATc
RT in effector T cells.";
RL Immunity 10:261-269(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS C-ALPHA; IA-DELTAIX AND IB-DELTAIX),
RP ALTERNATIVE SPLICING, AND TISSUE SPECIFICITY.
RX PubMed=18675896; DOI=10.1016/j.ygeno.2008.06.011;
RA Vihma H., Pruunsild P., Timmusk T.;
RT "Alternative splicing and expression of human and mouse NFAT genes.";
RL Genomics 92:279-291(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A-ALPHA).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP IDENTIFICATION OF ISOFORM A-ALPHA'.
RX PubMed=9111316; DOI=10.1128/mcb.17.5.2475;
RA Lyakh L., Ghosh P., Rice N.R.;
RT "Expression of NFAT-family proteins in normal human T cells.";
RL Mol. Cell. Biol. 17:2475-2484(1997).
RN [10]
RP PHOSPHORYLATION BY GSK3B.
RX PubMed=9072970; DOI=10.1126/science.275.5308.1930;
RA Beals C.R., Sheridan C.M., Turck C.W., Gardner P., Crabtree G.R.;
RT "Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3.";
RL Science 275:1930-1934(1997).
RN [11]
RP REVIEW.
RX PubMed=10089876; DOI=10.1016/s0092-8674(00)80571-1;
RA Crabtree G.R.;
RT "Generic signals and specific outcomes: signaling through Ca2+,
RT calcineurin, and NF-AT.";
RL Cell 96:611-614(1999).
RN [12]
RP ALTERNATIVE SPLICING, CHARACTERIZATION, AND FUNCTION.
RX PubMed=10358178;
RA Chuvpilo S., Avots A., Berberich-Siebelt F., Gloeckner J., Fischer C.,
RA Kerstan A., Escher C., Inashkina I., Hlubek F., Jankevics E., Brabletz T.,
RA Serfling E.;
RT "Multiple NF-ATc isoforms with individual transcriptional properties are
RT synthesized in T lymphocytes.";
RL J. Immunol. 162:7294-7301(1999).
RN [13]
RP MUTAGENESIS OF SER-169; SER-172 AND SER-187.
RX PubMed=10652349; DOI=10.1074/jbc.275.5.3543;
RA Porter C.M., Havens M.A., Clipstone N.A.;
RT "Identification of amino acid residues and protein kinases involved in the
RT regulation of NFATc subcellular localization.";
RL J. Biol. Chem. 275:3543-3551(2000).
RN [14]
RP PHOSPHORYLATION AT SER-245; SER-269 AND SER-294.
RX PubMed=12351631; DOI=10.1074/jbc.m207029200;
RA Sheridan C.M., Heist E.K., Beals C.R., Crabtree G.R., Gardner P.;
RT "Protein kinase A negatively modulates the nuclear accumulation of NF-ATc1
RT by priming for subsequent phosphorylation by glycogen synthase kinase-3.";
RL J. Biol. Chem. 277:48664-48676(2002).
RN [15]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RX PubMed=16511445; DOI=10.1038/nature04631;
RA Gwack Y., Sharma S., Nardone J., Tanasa B., Iuga A., Srikanth S.,
RA Okamura H., Bolton D., Feske S., Hogan P.G., Rao A.;
RT "A genome-wide Drosophila RNAi screen identifies DYRK-family kinases as
RT regulators of NFAT.";
RL Nature 441:646-650(2006).
RN [16]
RP INTERACTION WITH HOMER2 AND HOMER3.
RX PubMed=18218901; DOI=10.1126/science.1151227;
RA Huang G.N., Huso D.L., Bouyain S., Tu J., McCorkell K.A., May M.J., Zhu Y.,
RA Lutz M., Collins S., Dehoff M., Kang S., Whartenby K., Powell J., Leahy D.,
RA Worley P.F.;
RT "NFAT binding and regulation of T cell activation by the cytoplasmic
RT scaffolding Homer proteins.";
RL Science 319:476-481(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP STRUCTURE BY NMR OF 416-591.
RX PubMed=8990122; DOI=10.1038/385172a0;
RA Wolfe S.A., Zhou P., Dotsch V., Chen L., You A., Ho S.N., Crabtree G.R.,
RA Wagner G., Verdine G.L.;
RT "Unusual Rel-like architecture in the DNA-binding domain of the
RT transcription factor NFATc.";
RL Nature 385:172-176(1997).
RN [19]
RP STRUCTURE BY NMR OF 416-591 IN COMPLEX WITH DNA.
RX PubMed=9506523; DOI=10.1016/s0092-8674(00)81136-8;
RA Zhou P., Sun L.J., Dotsch V., Wagner G., Verdine G.L.;
RT "Solution structure of the core NFATC1/DNA complex.";
RL Cell 92:687-696(1998).
RN [20]
RP VARIANT [LARGE SCALE ANALYSIS] THR-315.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Plays a role in the inducible expression of cytokine genes in
CC T-cells, especially in the induction of the IL-2 or IL-4 gene
CC transcription. Also controls gene expression in embryonic cardiac
CC cells. Could regulate not only the activation and proliferation but
CC also the differentiation and programmed death of T-lymphocytes as well
CC as lymphoid and non-lymphoid cells (PubMed:10358178). Required for
CC osteoclastogenesis and regulates many genes important for osteoclast
CC differentiation and function (By similarity).
CC {ECO:0000250|UniProtKB:O88942, ECO:0000269|PubMed:10358178}.
CC -!- SUBUNIT: Member of the multicomponent NFATC transcription complex that
CC consists of at least two components, a pre-existing cytoplasmic
CC component NFATC2 and an inducible nuclear component NFATC1. Other
CC members such as NFATC4, NFATC3 or members of the activating protein-1
CC family, MAF, GATA4 and Cbp/p300 can also bind the complex. NFATC
CC proteins bind to DNA as monomers (PubMed:9506523). Interacts with
CC HOMER2 and HOMER3; this interaction may compete with
CC calcineurin/PPP3CA-binding and hence prevent NFATC1 dephosphorylation
CC and activation (PubMed:18218901). Interacts with TLE6/GRG6 (By
CC similarity). {ECO:0000250|UniProtKB:O88942,
CC ECO:0000269|PubMed:18218901, ECO:0000269|PubMed:9506523}.
CC -!- INTERACTION:
CC O95644; P18846: ATF1; NbExp=3; IntAct=EBI-6907210, EBI-852794;
CC O95644; P15336: ATF2; NbExp=2; IntAct=EBI-6907210, EBI-1170906;
CC O95644; P18847: ATF3; NbExp=2; IntAct=EBI-6907210, EBI-712767;
CC O95644; P16220: CREB1; NbExp=3; IntAct=EBI-6907210, EBI-711855;
CC O95644; P31276: HOXC13; NbExp=2; IntAct=EBI-6907210, EBI-2293590;
CC O95644; P05412: JUN; NbExp=5; IntAct=EBI-6907210, EBI-852823;
CC O95644; O15294: OGT; NbExp=2; IntAct=EBI-6907210, EBI-539828;
CC O95644; Q08209-1: PPP3CA; NbExp=4; IntAct=EBI-6907210, EBI-15637215;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16511445}. Nucleus
CC {ECO:0000269|PubMed:16511445}. Note=Cytoplasmic for the phosphorylated
CC form and nuclear after activation that is controlled by calcineurin-
CC mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to
CC be one mechanism by which cells distinguish between sustained and
CC transient calcium signals. The subcellular localization of NFATC plays
CC a key role in the regulation of gene transcription (PubMed:16511445).
CC Nuclear translocation of NFATC1 is enhanced in the presence of TNFSF11.
CC Nuclear translocation is decreased in the presence of FBN1 which can
CC bind and sequester TNFSF11 (By similarity).
CC {ECO:0000250|UniProtKB:O88942, ECO:0000269|PubMed:16511445}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=10;
CC Comment=Isoform C-alpha and isoform C-beta are the strongest
CC activator of gene transcription, followed by isoform A-alpha and
CC isoform A-beta, whereas isoform B-alpha and isoform B-beta are the
CC weakest. Isoform B-alpha, isoform B-beta, isoform C-alpha and isoform
CC C-beta, both present in T-cells, can modulate their transcriptional
CC activity.;
CC Name=C-alpha;
CC IsoId=O95644-1; Sequence=Displayed;
CC Name=A-alpha; Synonyms=IA-VIII;
CC IsoId=O95644-2; Sequence=VSP_005591, VSP_005592;
CC Name=A-beta; Synonyms=IB-VIII;
CC IsoId=O95644-3; Sequence=VSP_005590, VSP_005591, VSP_005592;
CC Name=B-alpha; Synonyms=IA-IXS;
CC IsoId=O95644-4; Sequence=VSP_005593;
CC Name=B-beta; Synonyms=IB-IXS;
CC IsoId=O95644-5; Sequence=VSP_005590, VSP_005593;
CC Name=C-beta; Synonyms=IB-IXL;
CC IsoId=O95644-6; Sequence=VSP_005590;
CC Name=A-alpha';
CC IsoId=O95644-8; Sequence=VSP_018978, VSP_005591, VSP_005592;
CC Name=IA-deltaIX;
CC IsoId=O95644-10; Sequence=VSP_047820;
CC Name=IB-deltaIX;
CC IsoId=O95644-11; Sequence=VSP_005590, VSP_047820;
CC Name=10;
CC IsoId=O95644-17; Sequence=VSP_053806, VSP_005593;
CC -!- TISSUE SPECIFICITY: Expressed in thymus, peripheral leukocytes as T-
CC cells and spleen. Isoforms A are preferentially expressed in effector
CC T-cells (thymus and peripheral leukocytes) whereas isoforms B and
CC isoforms C are preferentially expressed in naive T-cells (spleen).
CC Isoforms B are expressed in naive T-cells after first antigen exposure
CC and isoforms A are expressed in effector T-cells after second antigen
CC exposure. Isoforms IA are widely expressed but not detected in liver
CC nor pancreas, neural expression is strongest in corpus callosum.
CC Isoforms IB are expressed mostly in muscle, cerebellum, placenta and
CC thymus, neural expression in fetal and adult brain, strongest in corpus
CC callosum. {ECO:0000269|PubMed:18675896}.
CC -!- INDUCTION: Only isoforms A are inducibly expressed in T lymphocytes
CC upon activation of the T-cell receptor (TCR) complex. Induced after co-
CC addition of phorbol 12-myristate 13-acetate (PMA) and ionomycin. Also
CC induced after co-addition of 12-O-tetradecanoylphorbol-13-acetate (TPA)
CC and ionomycin. Weakly induced with PMA, ionomycin and cyclosporin A.
CC -!- DOMAIN: Rel Similarity Domain (RSD) allows DNA-binding and cooperative
CC interactions with AP1 factors.
CC -!- DOMAIN: The N-terminal transactivation domain (TAD-A) binds to and is
CC activated by Cbp/p300. The dephosphorylated form contains two unmasked
CC nuclear localization signals (NLS), which allow translocation of the
CC protein to the nucleus.
CC -!- DOMAIN: Isoforms C have a C-terminal part with an additional trans-
CC activation domain, TAD-B, which acts as a transcriptional activator.
CC Isoforms B have a shorter C-terminal part without complete TAD-B which
CC acts as a transcriptional repressor.
CC -!- PTM: Phosphorylated by NFATC-kinase and GSK3B; phosphorylation induces
CC NFATC1 nuclear exit and dephosphorylation by calcineurin promotes
CC nuclear import. Phosphorylation by PKA and DYRK2 negatively modulates
CC nuclear accumulation, and promotes subsequent phosphorylation by GSK3B
CC or casein kinase 1. {ECO:0000269|PubMed:12351631,
CC ECO:0000269|PubMed:16511445, ECO:0000269|PubMed:9072970}.
CC -!- MISCELLANEOUS: [Isoform A-alpha']: Produced by alternative initiation
CC at Met-37 of isoform A-alpha. {ECO:0000305}.
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DR EMBL; U08015; AAA19601.1; -; mRNA.
DR EMBL; U59736; AAC50869.1; -; mRNA.
DR EMBL; U80917; AAD00450.1; -; mRNA.
DR EMBL; U80918; AAD00451.1; -; mRNA.
DR EMBL; U80919; AAD00452.1; -; mRNA.
DR EMBL; EU887559; ACG55579.1; -; mRNA.
DR EMBL; EU887560; ACG55580.1; -; mRNA.
DR EMBL; EU887561; ACG55581.1; -; mRNA.
DR EMBL; EU887562; ACG55582.1; -; mRNA.
DR EMBL; EU887563; ACG55583.1; -; mRNA.
DR EMBL; EU887564; ACG55584.1; -; mRNA.
DR EMBL; EU887565; ACG55585.1; -; mRNA.
DR EMBL; EU887566; ACG55586.1; -; mRNA.
DR EMBL; AC018445; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC023090; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471117; EAW66621.1; -; Genomic_DNA.
DR EMBL; CH471117; EAW66622.1; -; Genomic_DNA.
DR EMBL; BC104753; AAI04754.1; -; mRNA.
DR EMBL; BC112243; AAI12244.1; -; mRNA.
DR CCDS; CCDS12015.1; -. [O95644-4]
DR CCDS; CCDS12016.1; -. [O95644-17]
DR CCDS; CCDS32850.1; -. [O95644-6]
DR CCDS; CCDS59326.1; -. [O95644-2]
DR CCDS; CCDS59327.1; -. [O95644-5]
DR CCDS; CCDS62467.1; -. [O95644-1]
DR CCDS; CCDS62468.1; -. [O95644-10]
DR CCDS; CCDS62469.1; -. [O95644-11]
DR CCDS; CCDS62470.1; -. [O95644-3]
DR PIR; S45262; S45262.
DR RefSeq; NP_001265598.1; NM_001278669.1. [O95644-1]
DR RefSeq; NP_001265599.1; NM_001278670.1. [O95644-10]
DR RefSeq; NP_001265601.1; NM_001278672.1. [O95644-11]
DR RefSeq; NP_001265602.1; NM_001278673.1.
DR RefSeq; NP_001265604.1; NM_001278675.1. [O95644-3]
DR RefSeq; NP_006153.2; NM_006162.4. [O95644-4]
DR RefSeq; NP_765975.1; NM_172387.2. [O95644-6]
DR RefSeq; NP_765976.1; NM_172388.2. [O95644-17]
DR RefSeq; NP_765977.1; NM_172389.2. [O95644-5]
DR RefSeq; NP_765978.1; NM_172390.2. [O95644-2]
DR PDB; 1A66; NMR; -; A=414-591.
DR PDB; 1NFA; NMR; -; A=416-591.
DR PDB; 5SVE; X-ray; 2.60 A; C=384-400.
DR PDBsum; 1A66; -.
DR PDBsum; 1NFA; -.
DR PDBsum; 5SVE; -.
DR AlphaFoldDB; O95644; -.
DR SMR; O95644; -.
DR BioGRID; 110845; 152.
DR DIP; DIP-44311N; -.
DR IntAct; O95644; 58.
DR MINT; O95644; -.
DR STRING; 9606.ENSP00000389377; -.
DR BindingDB; O95644; -.
DR ChEMBL; CHEMBL3876; -.
DR DrugBank; DB00852; Pseudoephedrine.
DR GlyGen; O95644; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O95644; -.
DR PhosphoSitePlus; O95644; -.
DR BioMuta; NFATC1; -.
DR CPTAC; CPTAC-983; -.
DR EPD; O95644; -.
DR jPOST; O95644; -.
DR MassIVE; O95644; -.
DR MaxQB; O95644; -.
DR PaxDb; O95644; -.
DR PeptideAtlas; O95644; -.
DR PRIDE; O95644; -.
DR ProteomicsDB; 50973; -. [O95644-1]
DR ProteomicsDB; 50974; -. [O95644-2]
DR ProteomicsDB; 50975; -. [O95644-3]
DR ProteomicsDB; 50976; -. [O95644-4]
DR ProteomicsDB; 50977; -. [O95644-5]
DR ProteomicsDB; 50978; -. [O95644-6]
DR ProteomicsDB; 50979; -. [O95644-8]
DR ProteomicsDB; 5935; -.
DR Antibodypedia; 3860; 614 antibodies from 41 providers.
DR DNASU; 4772; -.
DR Ensembl; ENST00000253506.9; ENSP00000253506.5; ENSG00000131196.18. [O95644-4]
DR Ensembl; ENST00000318065.9; ENSP00000316553.5; ENSG00000131196.18. [O95644-5]
DR Ensembl; ENST00000329101.8; ENSP00000327850.3; ENSG00000131196.18. [O95644-6]
DR Ensembl; ENST00000397790.6; ENSP00000380892.2; ENSG00000131196.18. [O95644-17]
DR Ensembl; ENST00000427363.7; ENSP00000389377.2; ENSG00000131196.18. [O95644-1]
DR Ensembl; ENST00000542384.5; ENSP00000442435.1; ENSG00000131196.18. [O95644-10]
DR Ensembl; ENST00000586434.1; ENSP00000466489.1; ENSG00000131196.18. [O95644-11]
DR Ensembl; ENST00000591814.5; ENSP00000466194.1; ENSG00000131196.18. [O95644-2]
DR Ensembl; ENST00000592223.5; ENSP00000467181.1; ENSG00000131196.18. [O95644-3]
DR GeneID; 4772; -.
DR KEGG; hsa:4772; -.
DR MANE-Select; ENST00000427363.7; ENSP00000389377.2; NM_001278669.2; NP_001265598.1.
DR UCSC; uc002lnc.3; human. [O95644-1]
DR CTD; 4772; -.
DR DisGeNET; 4772; -.
DR GeneCards; NFATC1; -.
DR HGNC; HGNC:7775; NFATC1.
DR HPA; ENSG00000131196; Low tissue specificity.
DR MIM; 600489; gene.
DR neXtProt; NX_O95644; -.
DR OpenTargets; ENSG00000131196; -.
DR PharmGKB; PA31582; -.
DR VEuPathDB; HostDB:ENSG00000131196; -.
DR eggNOG; ENOG502QTX8; Eukaryota.
DR GeneTree; ENSGT00940000157616; -.
DR HOGENOM; CLU_010185_1_0_1; -.
DR InParanoid; O95644; -.
DR OMA; RGLGACN; -.
DR OrthoDB; 277998at2759; -.
DR PhylomeDB; O95644; -.
DR TreeFam; TF326480; -.
DR PathwayCommons; O95644; -.
DR Reactome; R-HSA-2025928; Calcineurin activates NFAT.
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-HSA-4086398; Ca2+ pathway.
DR Reactome; R-HSA-5607763; CLEC7A (Dectin-1) induces NFAT activation.
DR SignaLink; O95644; -.
DR SIGNOR; O95644; -.
DR BioGRID-ORCS; 4772; 14 hits in 1102 CRISPR screens.
DR ChiTaRS; NFATC1; human.
DR EvolutionaryTrace; O95644; -.
DR GeneWiki; NFATC1; -.
DR GenomeRNAi; 4772; -.
DR Pharos; O95644; Tchem.
DR PRO; PR:O95644; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O95644; protein.
DR Bgee; ENSG00000131196; Expressed in oocyte and 169 other tissues.
DR ExpressionAtlas; O95644; baseline and differential.
DR Genevisible; O95644; HS.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:BHF-UCL.
DR GO; GO:0005528; F:FK506 binding; TAS:ProtInc.
DR GO; GO:0048273; F:mitogen-activated protein kinase p38 binding; ISS:BHF-UCL.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISS:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0001223; F:transcription coactivator binding; IEA:Ensembl.
DR GO; GO:0003180; P:aortic valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI.
DR GO; GO:1905064; P:negative regulation of vascular associated smooth muscle cell differentiation; IDA:BHF-UCL.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; ISS:ParkinsonsUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISS:BHF-UCL.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR DisProt; DP01724; -.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 1.
DR IDEAL; IID00435; -.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR008366; NFAT.
DR InterPro; IPR015647; NFAT1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR032397; RHD_dimer.
DR InterPro; IPR011539; RHD_DNA_bind_dom.
DR InterPro; IPR037059; RHD_DNA_bind_dom_sf.
DR PANTHER; PTHR12533; PTHR12533; 1.
DR PANTHER; PTHR12533:SF5; PTHR12533:SF5; 1.
DR Pfam; PF16179; RHD_dimer; 1.
DR Pfam; PF00554; RHD_DNA_bind; 1.
DR PRINTS; PR01789; NUCFACTORATC.
DR SMART; SM00429; IPT; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS50254; REL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative initiation; Alternative splicing;
KW Cytoplasm; DNA-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..943
FT /note="Nuclear factor of activated T-cells, cytoplasmic 1"
FT /id="PRO_0000030329"
FT REPEAT 203..219
FT /note="1"
FT REPEAT 233..249
FT /note="2"
FT REPEAT 282..298
FT /note="3"
FT DOMAIN 410..592
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT DNA_BIND 439..446
FT REGION 22..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..123
FT /note="Calcineurin-binding"
FT REGION 126..218
FT /note="Trans-activation domain A (TAD-A)"
FT REGION 200..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 203..298
FT /note="3 X SP repeats"
FT REGION 703..943
FT /note="Trans-activation domain B (TAD-B)"
FT REGION 787..912
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 265..267
FT /note="Nuclear localization signal"
FT MOTIF 310..321
FT /note="Nuclear export signal"
FT MOTIF 682..684
FT /note="Nuclear localization signal"
FT MOTIF 924..933
FT /note="Nuclear export signal"
FT COMPBIAS 233..254
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 810..825
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 842..873
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 233
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88942"
FT MOD_RES 245
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:12351631"
FT MOD_RES 269
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:12351631"
FT MOD_RES 294
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:12351631"
FT VAR_SEQ 1..472
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000305"
FT /id="VSP_053806"
FT VAR_SEQ 1..42
FT /note="MPSTSFPVPSKFPLGPAAAVFGRGETLGPAPRAGGTMKSAEE -> MTGLED
FT QEFDFEFLFEFNQRDEGAAAAAP (in isoform A-beta, isoform B-beta,
FT isoform C-beta and isoform IB-deltaIX)"
FT /evidence="ECO:0000303|PubMed:10072078,
FT ECO:0000303|PubMed:18675896, ECO:0000303|PubMed:8702849"
FT /id="VSP_005590"
FT VAR_SEQ 1..36
FT /note="Missing (in isoform A-alpha')"
FT /evidence="ECO:0000305"
FT /id="VSP_018978"
FT VAR_SEQ 698..927
FT /note="Missing (in isoform IA-deltaIX and isoform IB-
FT deltaIX)"
FT /evidence="ECO:0000303|PubMed:18675896"
FT /id="VSP_047820"
FT VAR_SEQ 698..716
FT /note="VPIIKTEPTDDYEPAPTCG -> GNAIFLTVSREHERVGCFF (in
FT isoform A-alpha, isoform A-alpha' and isoform A-beta)"
FT /evidence="ECO:0000303|PubMed:10072078,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8202141"
FT /id="VSP_005591"
FT VAR_SEQ 717..943
FT /note="Missing (in isoform A-alpha, isoform A-alpha' and
FT isoform A-beta)"
FT /evidence="ECO:0000303|PubMed:10072078,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:8202141"
FT /id="VSP_005592"
FT VAR_SEQ 826..943
FT /note="Missing (in isoform B-alpha, isoform B-beta and
FT isoform 10)"
FT /evidence="ECO:0000303|PubMed:10072078,
FT ECO:0000303|PubMed:8702849"
FT /id="VSP_005593"
FT VARIANT 68
FT /note="P -> T (in dbSNP:rs1051978)"
FT /id="VAR_057145"
FT VARIANT 315
FT /note="A -> T (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs779866756)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036529"
FT VARIANT 751
FT /note="C -> G (in dbSNP:rs754093)"
FT /id="VAR_057146"
FT MUTAGEN 169
FT /note="S->A: No effect on subcellular localization."
FT MUTAGEN 172
FT /note="S->A: Partial nuclear translocation."
FT /evidence="ECO:0000269|PubMed:10652349"
FT MUTAGEN 187
FT /note="S->A: No effect on subcellular localization."
FT /evidence="ECO:0000269|PubMed:10652349"
FT CONFLICT 232
FT /note="G -> S (in Ref. 2; AAC50869)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="R -> Q (in Ref. 1; AAA19601)"
FT /evidence="ECO:0000305"
FT STRAND 426..432
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 443..445
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 454..456
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 460..465
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 468..470
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 472..480
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 483..485
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 509..511
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 514..521
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 523..525
FT /evidence="ECO:0007829|PDB:1A66"
FT HELIX 541..545
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 551..553
FT /evidence="ECO:0007829|PDB:1NFA"
FT STRAND 559..570
FT /evidence="ECO:0007829|PDB:1A66"
FT TURN 571..573
FT /evidence="ECO:0007829|PDB:1A66"
FT STRAND 574..586
FT /evidence="ECO:0007829|PDB:1A66"
SQ SEQUENCE 943 AA; 101243 MW; E72FAB10ECEB2D66 CRC64;
MPSTSFPVPS KFPLGPAAAV FGRGETLGPA PRAGGTMKSA EEEHYGYASS NVSPALPLPT
AHSTLPAPCH NLQTSTPGII PPADHPSGYG AALDGGPAGY FLSSGHTRPD GAPALESPRI
EITSCLGLYH NNNQFFHDVE VEDVLPSSKR SPSTATLSLP SLEAYRDPSC LSPASSLSSR
SCNSEASSYE SNYSYPYASP QTSPWQSPCV SPKTTDPEEG FPRGLGACTL LGSPRHSPST
SPRASVTEES WLGARSSRPA SPCNKRKYSL NGRQPPYSPH HSPTPSPHGS PRVSVTDDSW
LGNTTQYTSS AIVAAINALT TDSSLDLGDG VPVKSRKTTL EQPPSVALKV EPVGEDLGSP
PPPADFAPED YSSFQHIRKG GFCDQYLAVP QHPYQWAKPK PLSPTSYMSP TLPALDWQLP
SHSGPYELRI EVQPKSHHRA HYETEGSRGA VKASAGGHPI VQLHGYLENE PLMLQLFIGT
ADDRLLRPHA FYQVHRITGK TVSTTSHEAI LSNTKVLEIP LLPENSMRAV IDCAGILKLR
NSDIELRKGE TDIGRKNTRV RLVFRVHVPQ PSGRTLSLQV ASNPIECSQR SAQELPLVEK
QSTDSYPVVG GKKMVLSGHN FLQDSKVIFV EKAPDGHHVW EMEAKTDRDL CKPNSLVVEI
PPFRNQRITS PVHVSFYVCN GKRKRSQYQR FTYLPANVPI IKTEPTDDYE PAPTCGPVSQ
GLSPLPRPYY SQQLAMPPDP SSCLVAGFPP CPQRSTLMPA APGVSPKLHD LSPAAYTKGV
ASPGHCHLGL PQPAGEAPAV QDVPRPVATH PGSPGQPPPA LLPQQVSAPP SSSCPPGLEH
SLCPSSPSPP LPPATQEPTC LQPCSPACPP ATGRPQHLPS TVRRDESPTA GPRLLPEVHE
DGSPNLAPIP VTVKREPEEL DQLYLDDVNE IIRNDLSSTS THS
