NFAC2_HUMAN
ID NFAC2_HUMAN Reviewed; 925 AA.
AC Q13469; B5B2N8; B5B2N9; B5B2P0; B5B2P2; B5B2P3; Q13468; Q5TFW7; Q5TFW8;
AC Q9NPX6; Q9NQH3; Q9UJR2;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=Nuclear factor of activated T-cells, cytoplasmic 2;
DE Short=NF-ATc2;
DE Short=NFATc2;
DE AltName: Full=NFAT pre-existing subunit;
DE Short=NF-ATp;
DE AltName: Full=T-cell transcription factor NFAT1;
GN Name=NFATC2; Synonyms=NFAT1, NFATP;
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] (ISOFORMS 1 AND 3), ALTERNATIVE SPLICING, AND
RP TISSUE SPECIFICITY.
RX PubMed=8668213; DOI=10.1128/mcb.16.7.3955;
RA Luo C., Burgeon E., Carew J.A., McCaffrey P.G., Badalian T.M., Lane W.S.,
RA Hogan P.G., Rao A.;
RT "Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and
RT mediates transcription of several cytokine genes.";
RL Mol. Cell. Biol. 16:3955-3966(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4 AND 5), AND ALTERNATIVE
RP SPLICING.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-330, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [8]
RP FUNCTION, AND INTERACTION WITH FOXP3.
RX PubMed=15790681; DOI=10.1073/pnas.0501675102;
RA Bettelli E., Dastrange M., Oukka M.;
RT "Foxp3 interacts with nuclear factor of activated T cells and NF-kappa B to
RT repress cytokine gene expression and effector functions of T helper
RT cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:5138-5143(2005).
RN [9]
RP DOMAIN.
RX PubMed=17467953; DOI=10.1016/j.ygeno.2007.02.003;
RA Piskacek S., Gregor M., Nemethova M., Grabner M., Kovarik P., Piskacek M.;
RT "Nine-amino-acid transactivation domain: establishment and prediction
RT utilities.";
RL Genomics 89:756-768(2007).
RN [10]
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 [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-148; SER-330; SER-755;
RP SER-759 AND SER-859, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-757 AND SER-759, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP FUNCTION.
RX PubMed=21871017; DOI=10.1042/bj20110530;
RA Yiu G.K., Kaunisto A., Chin Y.R., Toker A.;
RT "NFAT promotes carcinoma invasive migration through glypican-6.";
RL Biochem. J. 440:157-166(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-107; SER-110; SER-326 AND
RP SER-856, AND IDENTIFICATION BY 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 [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23 AND SER-148, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP INTERACTION WITH PPP3CA.
RX PubMed=26248042; DOI=10.1371/journal.pone.0134569;
RA Guasch A., Aranguren-Ibanez A., Perez-Luque R., Aparicio D.,
RA Martinez-Hoyer S., Mulero M.C., Serrano-Candelas E., Perez-Riba M.,
RA Fita I.;
RT "Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl
RT Isomerization.";
RL PLoS ONE 10:E0134569-E0134569(2015).
RN [17]
RP UBIQUITINATION.
RX PubMed=26766444; DOI=10.1016/j.devcel.2015.12.015;
RA Scholz B., Korn C., Wojtarowicz J., Mogler C., Augustin I., Boutros M.,
RA Niehrs C., Augustin H.G.;
RT "Endothelial RSPO3 controls vascular stability and pruning through non-
RT canonical WNT/Ca(2+)/NFAT signaling.";
RL Dev. Cell 36:79-93(2016).
RN [18] {ECO:0007744|PDB:3QRF}
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 396-678 IN COMPLEX WITH DNA AND
RP FOXP3, AND INTERACTION WITH FOXP3.
RX PubMed=21458306; DOI=10.1016/j.immuni.2011.02.017;
RA Bandukwala H.S., Wu Y., Feuerer M., Chen Y., Barboza B., Ghosh S.,
RA Stroud J.C., Benoist C., Mathis D., Rao A., Chen L.;
RT "Structure of a domain-swapped FOXP3 dimer on DNA and its function in
RT regulatory T cells.";
RL Immunity 34:479-491(2011).
CC -!- FUNCTION: Plays a role in the inducible expression of cytokine genes in
CC T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha
CC or GM-CSF. Promotes invasive migration through the activation of GPC6
CC expression and WNT5A signaling pathway. {ECO:0000269|PubMed:15790681,
CC ECO:0000269|PubMed:21871017}.
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. The
CC phosphorylated form specifically interacts with XPO1; which mediates
CC nuclear export. NFATC proteins bind to DNA as monomers. Interacts with
CC NFATC2IP (By similarity). Interacts with FOXP3 (PubMed:15790681).
CC Interacts with TBX21 ('Thr-303' phosphorylated form) (By similarity).
CC Interacts with KAT2A (By similarity). Interacts with HOMER2 and HOMER3;
CC this interaction competes with calcineurin/PPP3CA-binding and hence
CC prevents NFATC2 dephosphorylation and activation (PubMed:18218901).
CC Interacts with protein phosphatase PPP3CA/calcineurin A
CC (PubMed:26248042). {ECO:0000250|UniProtKB:Q60591,
CC ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:18218901,
CC ECO:0000269|PubMed:21458306, ECO:0000269|PubMed:26248042}.
CC -!- INTERACTION:
CC Q13469; P16220: CREB1; NbExp=2; IntAct=EBI-716258, EBI-711855;
CC Q13469; Q5S007: LRRK2; NbExp=3; IntAct=EBI-716258, EBI-5323863;
CC Q13469; Q08209-1: PPP3CA; NbExp=2; IntAct=EBI-716258, EBI-15637215;
CC Q13469; Q9UPT9: USP22; NbExp=2; IntAct=EBI-716258, EBI-723510;
CC Q13469; Q86Y07-1: VRK2; NbExp=3; IntAct=EBI-716258, EBI-1207633;
CC Q13469; Q86Y07-2: VRK2; NbExp=4; IntAct=EBI-716258, EBI-1207636;
CC Q13469-2; P05412: JUN; NbExp=6; IntAct=EBI-10087113, EBI-852823;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Cytoplasmic for the
CC phosphorylated form and nuclear after activation that is controlled by
CC calcineurin-mediated dephosphorylation. Rapid nuclear exit of NFATC is
CC thought to be one mechanism by which cells distinguish between
CC sustained and transient calcium signals. The subcellular localization
CC of NFATC plays a key role in the regulation of gene transcription.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=C, NFATc2_IB_IIL;
CC IsoId=Q13469-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=Q13469-2; Sequence=VSP_005595;
CC Name=3; Synonyms=NFATc2_IA_IIL;
CC IsoId=Q13469-3; Sequence=VSP_042757, VSP_005595;
CC Name=4;
CC IsoId=Q13469-4; Sequence=VSP_042757;
CC Name=5;
CC IsoId=Q13469-5; Sequence=VSP_055926, VSP_005595;
CC -!- TISSUE SPECIFICITY: Expressed in thymus, spleen, heart, testis, brain,
CC placenta, muscle and pancreas. Isoform 1 is highly expressed in the
CC small intestine, heart, testis, prostate, thymus, placenta and thyroid.
CC Isoform 3 is highly expressed in stomach, uterus, placenta, trachea and
CC thyroid. {ECO:0000269|PubMed:8668213}.
CC -!- INDUCTION: Inducibly expressed in T-lymphocytes upon activation of the
CC T-cell receptor (TCR) complex. Induced after co-addition of phorbol 12-
CC myristate 13-acetate (PMA) and ionomycin.
CC -!- DOMAIN: the 9aaTAD motif is a transactivation domain present in a large
CC number of yeast and animal transcription factors.
CC {ECO:0000269|PubMed:17467953}.
CC -!- DOMAIN: Rel Similarity Domain (RSD) allows DNA-binding and cooperative
CC interactions with AP1 factors. {ECO:0000250}.
CC -!- PTM: In resting cells, phosphorylated by NFATC-kinase on at least 18
CC sites in the 99-363 region. Upon cell stimulation, all these sites
CC except Ser-243 are dephosphorylated by calcineurin. Dephosphorylation
CC induces a conformational change that simultaneously exposes an NLS and
CC masks an NES, which results in nuclear localization. Simultaneously,
CC Ser-53 or Ser-56 is phosphorylated; which is required for full
CC transcriptional activity. {ECO:0000250|UniProtKB:Q60591}.
CC -!- PTM: Ubiquitinated in endothelial cells by RNF213 downstream of the
CC non-canonical Wnt signaling pathway, leading to its degradation by the
CC proteasome. {ECO:0000269|PubMed:26766444}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/NFATC2ID44004ch20q13.html";
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DR EMBL; U43341; AAC50886.1; -; mRNA.
DR EMBL; U43342; AAC50887.1; -; mRNA.
DR EMBL; EU887573; ACG55593.1; -; mRNA.
DR EMBL; EU887574; ACG55594.1; -; mRNA.
DR EMBL; EU887575; ACG55595.1; -; mRNA.
DR EMBL; EU887576; ACG55596.1; -; mRNA.
DR EMBL; EU887577; ACG55597.1; -; mRNA.
DR EMBL; EU887578; ACG55598.1; -; mRNA.
DR EMBL; AL132866; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL035682; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL035684; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75602.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75603.1; -; Genomic_DNA.
DR EMBL; BC136418; AAI36419.1; -; mRNA.
DR EMBL; BC144074; AAI44075.1; -; mRNA.
DR CCDS; CCDS13437.1; -. [Q13469-1]
DR CCDS; CCDS33488.1; -. [Q13469-2]
DR CCDS; CCDS46614.1; -. [Q13469-3]
DR CCDS; CCDS68156.1; -. [Q13469-5]
DR CCDS; CCDS68157.1; -. [Q13469-4]
DR PIR; G02326; G02326.
DR RefSeq; NP_001129493.1; NM_001136021.2. [Q13469-3]
DR RefSeq; NP_001245221.1; NM_001258292.1. [Q13469-4]
DR RefSeq; NP_001245223.1; NM_001258294.1. [Q13469-5]
DR RefSeq; NP_001245225.1; NM_001258296.1. [Q13469-5]
DR RefSeq; NP_036472.2; NM_012340.4. [Q13469-2]
DR RefSeq; NP_775114.1; NM_173091.3. [Q13469-1]
DR PDB; 1A02; X-ray; 2.70 A; N=392-678.
DR PDB; 1OWR; X-ray; 3.00 A; M/N/P/Q=396-678.
DR PDB; 1P7H; X-ray; 2.60 A; L/M/N/O=393-678.
DR PDB; 1PZU; X-ray; 3.10 A; B/D/H/I/L/M=396-678.
DR PDB; 1S9K; X-ray; 3.10 A; C=399-678.
DR PDB; 2AS5; X-ray; 2.70 A; M/N=392-678.
DR PDB; 2O93; X-ray; 3.05 A; L/M/O=396-678.
DR PDB; 3QRF; X-ray; 2.80 A; M/N=396-678.
DR PDBsum; 1A02; -.
DR PDBsum; 1OWR; -.
DR PDBsum; 1P7H; -.
DR PDBsum; 1PZU; -.
DR PDBsum; 1S9K; -.
DR PDBsum; 2AS5; -.
DR PDBsum; 2O93; -.
DR PDBsum; 3QRF; -.
DR AlphaFoldDB; Q13469; -.
DR SMR; Q13469; -.
DR BioGRID; 110846; 191.
DR ComplexPortal; CPX-480; AP-1 transcription factor complex FOS-JUN-NFATC2.
DR CORUM; Q13469; -.
DR DIP; DIP-27630N; -.
DR ELM; Q13469; -.
DR IntAct; Q13469; 17.
DR MINT; Q13469; -.
DR STRING; 9606.ENSP00000379330; -.
DR GlyGen; Q13469; 7 sites, 2 O-linked glycans (7 sites).
DR iPTMnet; Q13469; -.
DR PhosphoSitePlus; Q13469; -.
DR BioMuta; NFATC2; -.
DR DMDM; 68846905; -.
DR EPD; Q13469; -.
DR jPOST; Q13469; -.
DR MassIVE; Q13469; -.
DR MaxQB; Q13469; -.
DR PaxDb; Q13469; -.
DR PeptideAtlas; Q13469; -.
DR PRIDE; Q13469; -.
DR ProteomicsDB; 59464; -. [Q13469-1]
DR ProteomicsDB; 59465; -. [Q13469-2]
DR ProteomicsDB; 59466; -. [Q13469-3]
DR Antibodypedia; 1758; 544 antibodies from 46 providers.
DR DNASU; 4773; -.
DR Ensembl; ENST00000371564.8; ENSP00000360619.3; ENSG00000101096.20. [Q13469-2]
DR Ensembl; ENST00000396009.7; ENSP00000379330.3; ENSG00000101096.20. [Q13469-1]
DR Ensembl; ENST00000414705.5; ENSP00000396471.1; ENSG00000101096.20. [Q13469-3]
DR Ensembl; ENST00000609507.1; ENSP00000477342.1; ENSG00000101096.20. [Q13469-5]
DR Ensembl; ENST00000609943.5; ENSP00000477370.1; ENSG00000101096.20. [Q13469-4]
DR Ensembl; ENST00000610033.5; ENSP00000477142.1; ENSG00000101096.20. [Q13469-5]
DR GeneID; 4773; -.
DR KEGG; hsa:4773; -.
DR MANE-Select; ENST00000371564.8; ENSP00000360619.3; NM_012340.5; NP_036472.2. [Q13469-2]
DR UCSC; uc002xwc.4; human. [Q13469-1]
DR CTD; 4773; -.
DR DisGeNET; 4773; -.
DR GeneCards; NFATC2; -.
DR HGNC; HGNC:7776; NFATC2.
DR HPA; ENSG00000101096; Tissue enhanced (choroid).
DR MIM; 600490; gene.
DR neXtProt; NX_Q13469; -.
DR OpenTargets; ENSG00000101096; -.
DR PharmGKB; PA31583; -.
DR VEuPathDB; HostDB:ENSG00000101096; -.
DR eggNOG; ENOG502QTJI; Eukaryota.
DR GeneTree; ENSGT00940000156230; -.
DR HOGENOM; CLU_010185_1_1_1; -.
DR InParanoid; Q13469; -.
DR OMA; PAYSEHT; -.
DR OrthoDB; 277998at2759; -.
DR PhylomeDB; Q13469; -.
DR TreeFam; TF326480; -.
DR PathwayCommons; Q13469; -.
DR Reactome; R-HSA-2025928; Calcineurin activates NFAT.
DR Reactome; R-HSA-2871809; FCERI mediated Ca+2 mobilization.
DR Reactome; R-HSA-5607763; CLEC7A (Dectin-1) induces NFAT activation.
DR Reactome; R-HSA-8877330; RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs).
DR SignaLink; Q13469; -.
DR SIGNOR; Q13469; -.
DR BioGRID-ORCS; 4773; 18 hits in 1103 CRISPR screens.
DR ChiTaRS; NFATC2; human.
DR EvolutionaryTrace; Q13469; -.
DR GeneWiki; NFATC2; -.
DR GenomeRNAi; 4773; -.
DR Pharos; Q13469; Tbio.
DR PRO; PR:Q13469; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q13469; protein.
DR Bgee; ENSG00000101096; Expressed in vena cava and 175 other tissues.
DR Genevisible; Q13469; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:1990904; C:ribonucleoprotein complex; IEA:Ensembl.
DR GO; GO:0035976; C:transcription factor AP-1 complex; IPI:ComplexPortal.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; TAS:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0014904; P:myotube cell development; IEA:Ensembl.
DR GO; GO:1905064; P:negative regulation of vascular associated smooth muscle cell differentiation; IDA:BHF-UCL.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:1901741; P:positive regulation of myoblast fusion; IEA:Ensembl.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; TAS:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR DisProt; DP01344; -.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 1.
DR IDEAL; IID00470; -.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR008366; NFAT.
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 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 splicing; Cytoplasm; DNA-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..925
FT /note="Nuclear factor of activated T-cells, cytoplasmic 2"
FT /id="PRO_0000205178"
FT REPEAT 184..200
FT /note="1"
FT REPEAT 213..229
FT /note="2"
FT REPEAT 272..286
FT /note="3; approximate"
FT DOMAIN 392..574
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT DNA_BIND 421..428
FT REGION 1..95
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 111..116
FT /note="Calcineurin-binding"
FT /evidence="ECO:0000269|PubMed:26248042"
FT REGION 119..199
FT /note="Trans-activation domain A (TAD-A)"
FT REGION 161..175
FT /note="Required for cytoplasmic retention of the
FT phosphorylated form"
FT /evidence="ECO:0000250"
FT REGION 184..286
FT /note="3 X approximate SP repeats"
FT REGION 195..297
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 839..894
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 26..34
FT /note="9aaTAD"
FT MOTIF 251..253
FT /note="Nuclear localization signal"
FT MOTIF 664..666
FT /note="Nuclear localization signal"
FT MOTIF 904..913
FT /note="Nuclear export signal"
FT COMPBIAS 209..224
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 847..878
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 148
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 168
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 175
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 177
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 180
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 213
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 217
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 221
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 236
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 274
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 280
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15144186,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 363
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60591"
FT MOD_RES 755
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 757
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 759
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 856
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 859
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VAR_SEQ 1..219
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:18675896"
FT /id="VSP_055926"
FT VAR_SEQ 1..43
FT /note="MNAPERQPQPDGGDAPGHEPGGSPQDELDFSILFDYEYLNPNE -> MQREA
FT AFRLGHCHPLRIMGSVDQ (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:18675896,
FT ECO:0000303|PubMed:8668213"
FT /id="VSP_042757"
FT VAR_SEQ 908..925
FT /note="VNEIIRKEFSGPPARNQT -> ELIDTHLSWIQNIL (in isoform 2,
FT isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:18675896, ECO:0000303|PubMed:8668213"
FT /id="VSP_005595"
FT VARIANT 446
FT /note="H -> R (in dbSNP:rs12479626)"
FT /id="VAR_051783"
FT CONFLICT 65
FT /note="L -> M (in Ref. 1; AAC50886/AAC50887)"
FT /evidence="ECO:0000305"
FT STRAND 397..399
FT /evidence="ECO:0007829|PDB:1OWR"
FT STRAND 402..405
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 408..414
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 436..439
FT /evidence="ECO:0007829|PDB:2AS5"
FT STRAND 442..445
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 450..452
FT /evidence="ECO:0007829|PDB:2AS5"
FT STRAND 454..461
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 464..466
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 474..478
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:3QRF"
FT STRAND 490..492
FT /evidence="ECO:0007829|PDB:1A02"
FT STRAND 494..496
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 498..503
FT /evidence="ECO:0007829|PDB:1P7H"
FT HELIX 505..507
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 510..512
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 515..520
FT /evidence="ECO:0007829|PDB:1P7H"
FT HELIX 523..526
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 529..531
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 541..552
FT /evidence="ECO:0007829|PDB:1P7H"
FT TURN 553..555
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 556..563
FT /evidence="ECO:0007829|PDB:1P7H"
FT HELIX 571..576
FT /evidence="ECO:0007829|PDB:1A02"
FT STRAND 579..584
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 586..589
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 595..602
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 608..614
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 616..618
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 620..626
FT /evidence="ECO:0007829|PDB:1P7H"
FT TURN 630..632
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 637..641
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 646..648
FT /evidence="ECO:0007829|PDB:3QRF"
FT STRAND 654..662
FT /evidence="ECO:0007829|PDB:1P7H"
FT TURN 663..665
FT /evidence="ECO:0007829|PDB:1P7H"
FT STRAND 671..676
FT /evidence="ECO:0007829|PDB:1P7H"
SQ SEQUENCE 925 AA; 100146 MW; 8DAE86855CCB58D3 CRC64;
MNAPERQPQP DGGDAPGHEP GGSPQDELDF SILFDYEYLN PNEEEPNAHK VASPPSGPAY
PDDVLDYGLK PYSPLASLSG EPPGRFGEPD RVGPQKFLSA AKPAGASGLS PRIEITPSHE
LIQAVGPLRM RDAGLLVEQP PLAGVAASPR FTLPVPGFEG YREPLCLSPA SSGSSASFIS
DTFSPYTSPC VSPNNGGPDD LCPQFQNIPA HYSPRTSPIM SPRTSLAEDS CLGRHSPVPR
PASRSSSPGA KRRHSCAEAL VALPPGASPQ RSRSPSPQPS SHVAPQDHGS PAGYPPVAGS
AVIMDALNSL ATDSPCGIPP KMWKTSPDPS PVSAAPSKAG LPRHIYPAVE FLGPCEQGER
RNSAPESILL VPPTWPKPLV PAIPICSIPV TASLPPLEWP LSSQSGSYEL RIEVQPKPHH
RAHYETEGSR GAVKAPTGGH PVVQLHGYME NKPLGLQIFI GTADERILKP HAFYQVHRIT
GKTVTTTSYE KIVGNTKVLE IPLEPKNNMR ATIDCAGILK LRNADIELRK GETDIGRKNT
RVRLVFRVHI PESSGRIVSL QTASNPIECS QRSAHELPMV ERQDTDSCLV YGGQQMILTG
QNFTSESKVV FTEKTTDGQQ IWEMEATVDK DKSQPNMLFV EIPEYRNKHI RTPVKVNFYV
INGKRKRSQP QHFTYHPVPA IKTEPTDEYD PTLICSPTHG GLGSQPYYPQ HPMVAESPSC
LVATMAPCQQ FRTGLSSPDA RYQQQNPAAV LYQRSKSLSP SLLGYQQPAL MAAPLSLADA
HRSVLVHAGS QGQSSALLHP SPTNQQASPV IHYSPTNQQL RCGSHQEFQH IMYCENFAPG
TTRPGPPPVS QGQRLSPGSY PTVIQQQNAT SQRAAKNGPP VSDQKEVLPA GVTIKQEQNL
DQTYLDDVNE IIRKEFSGPP ARNQT
