ID NFAC4_MOUSE Reviewed; 901 AA. AC Q8K120; B5B2X2; Q3TXW7; Q9EP91; DT 24-MAR-2009, integrated into UniProtKB/Swiss-Prot. DT 24-MAR-2009, sequence version 2. DT 27-MAR-2024, entry version 155. DE RecName: Full=Nuclear factor of activated T-cells, cytoplasmic 4 {ECO:0000250|UniProtKB:Q14934}; DE Short=NF-ATc4 {ECO:0000250|UniProtKB:Q14934}; DE Short=NFATc4 {ECO:0000303|PubMed:18354019}; DE AltName: Full=T-cell transcription factor NFAT3 {ECO:0000303|PubMed:18675896}; DE Short=NF-AT3 {ECO:0000303|PubMed:9568714}; GN Name=Nfatc4 {ECO:0000312|MGI:MGI:1920431}; GN Synonyms=Nfat3 {ECO:0000303|PubMed:18675896}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1). RC STRAIN=129/SvEv; RX PubMed=11344309; DOI=10.1073/pnas.101602398; RA Graef I.A., Gastier J.M., Francke U., Crabtree G.R.; RT "Evolutionary relationships among Rel domains indicate functional RT diversification by recombination."; RL Proc. Natl. Acad. Sci. U.S.A. 98:5740-5745(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND RP DEVELOPMENTAL STAGE. RC STRAIN=C57BL/6J; 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 MRNA] (ISOFORM 1). RC TISSUE=Rathke gland; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Mammary tumor; 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 FUNCTION, AND INTERACTION WITH GATA4. RX PubMed=9568714; DOI=10.1016/s0092-8674(00)81573-1; RA Molkentin J.D., Lu J.-R., Antos C.L., Markham B., Richardson J., RA Robbins J., Grant S.R., Olson E.N.; RT "A calcineurin-dependent transcriptional pathway for cardiac hypertrophy."; RL Cell 93:215-228(1998). RN [7] RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY. RX PubMed=12370307; DOI=10.1128/mcb.22.21.7603-7613.2002; RA Wilkins B.J., De Windt L.J., Bueno O.F., Braz J.C., Glascock B.J., RA Kimball T.F., Molkentin J.D.; RT "Targeted disruption of NFATc3, but not NFATc4, reveals an intrinsic defect RT in calcineurin-mediated cardiac hypertrophic growth."; RL Mol. Cell. Biol. 22:7603-7613(2002). RN [8] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=12750314; DOI=10.1161/01.res.0000077045.84609.9f; RA Bushdid P.B., Osinska H., Waclaw R.R., Molkentin J.D., Yutzey K.E.; RT "NFATc3 and NFATc4 are required for cardiac development and mitochondrial RT function."; RL Circ. Res. 92:1305-1313(2003). RN [9] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=17198697; DOI=10.1016/j.ydbio.2006.11.036; RA Yang X.Y., Yang T.T.C., Schubert W., Factor S.M., Chow C.-W.; RT "Dosage-dependent transcriptional regulation by the calcineurin/NFAT RT signaling in developing myocardium transition."; RL Dev. Biol. 303:825-837(2007). RN [10] RP TISSUE SPECIFICITY. RX PubMed=17579027; DOI=10.4049/jimmunol.179.1.103; RA Cante-Barrett K., Winslow M.M., Crabtree G.R.; RT "Selective role of NFATc3 in positive selection of thymocytes."; RL J. Immunol. 179:103-110(2007). RN [11] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=18354019; DOI=10.1523/jneurosci.5227-07.2008; RA Luoma J.I., Zirpel L.; RT "Deafferentation-induced activation of NFAT (nuclear factor of activated T- RT cells) in cochlear nucleus neurons during a developmental critical period: RT a role for NFATc4-dependent apoptosis in the CNS."; RL J. Neurosci. 28:3159-3169(2008). RN [12] RP PHOSPHORYLATION AT SER-168 AND SER-170. RX PubMed=18691762; DOI=10.1016/j.molimm.2008.06.023; RA Wang D., Fasciano S., Li L.; RT "The interleukin-1 receptor associated kinase 1 contributes to the RT regulation of NFAT."; RL Mol. Immunol. 45:3902-3908(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Kidney, and Lung; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [14] RP FUNCTION, IDENTIFICATION IN A COMPLEX WITH NFATC3 AND STAT3, TISSUE RP SPECIFICITY, AND INDUCTION BY CALCINEURIN. RX PubMed=19538478; DOI=10.1111/j.1582-4934.2009.00804.x; RA Manukyan I., Galatioto J., Mascareno E., Bhaduri S., Siddiqui M.A.; RT "Cross-talk between calcineurin/NFAT and Jak/STAT signalling induces RT cardioprotective alphaB-crystallin gene expression in response to RT hypertrophic stimuli."; RL J. Cell. Mol. Med. 14:1707-1716(2010). RN [15] RP TISSUE SPECIFICITY. RX PubMed=21435446; DOI=10.1016/j.ajpath.2010.12.054; RA Reddy R.N., Pena J.A., Roberts B.R., Williams S.R., Price S.R., Gooch J.L.; RT "Rescue of calcineurin Aalpha(-/-) mice reveals a novel role for the alpha RT isoform in the salivary gland."; RL Am. J. Pathol. 178:1605-1613(2011). RN [16] RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, RP DISRUPTION PHENOTYPE, AND INDUCTION BY BDNF. RX PubMed=22586092; DOI=10.1073/pnas.1202068109; RA Quadrato G., Benevento M., Alber S., Jacob C., Floriddia E.M., Nguyen T., RA Elnaggar M.Y., Pedroarena C.M., Molkentin J.D., Di Giovanni S.; RT "Nuclear factor of activated T cells (NFATc4) is required for BDNF- RT dependent survival of adult-born neurons and spatial memory formation in RT the hippocampus."; RL Proc. Natl. Acad. Sci. U.S.A. 109:E1499-E1508(2012). RN [17] RP SUBCELLULAR LOCATION. RX PubMed=24970700; DOI=10.1159/000362647; RA Ranjan R., Deng J., Chung S., Lee Y.G., Park G.Y., Xiao L., Joo M., RA Christman J.W., Karpurapu M.; RT "The transcription factor nuclear factor of activated T cells c3 modulates RT the function of macrophages in sepsis."; RL J. Innate Immun. 6:754-764(2014). RN [18] RP TISSUE SPECIFICITY. RX PubMed=25663301; DOI=10.1007/s11064-015-1533-1; RA Mei Z., Yan P., Tan X., Zheng S., Situ B.; RT "Transcriptional regulation of BACE1 by NFAT3 leads to enhanced RT amyloidogenic processing."; RL Neurochem. Res. 40:829-836(2015). RN [19] RP INTERACTION WITH TRIM17, AND SUBCELLULAR LOCATION. RX PubMed=25215946; DOI=10.1038/cdd.2014.141; RA Mojsa B., Mora S., Bossowski J.P., Lassot I., Desagher S.; RT "Control of neuronal apoptosis by reciprocal regulation of NFATc3 and RT Trim17."; RL Cell Death Differ. 22:274-286(2015). CC -!- FUNCTION: Ca(2+)-regulated transcription factor that is involved in CC several processes, including the development and function of the CC immune, cardiovascular, musculoskeletal, and nervous systems. Involved CC in T-cell activation, stimulating the transcription of cytokine genes, CC including that of IL2 and IL4 (PubMed:17198697). Following JAK/STAT CC signaling activation and as part of a complex with NFATC3 and STAT3, CC binds to the alpha-beta E4 promoter region of CRYAB and activates CC transcription in cardiomyocytes (PubMed:19538478). Along with NFATC3, CC involved in embryonic heart development (PubMed:12750314, CC PubMed:17198697). Involved in mitochondrial energy metabolism required CC for cardiac morphogenesis and function (PubMed:12750314). CC Transactivates many genes involved in heart physiology. Along with CC GATA4, binds to and activates NPPB/BNP promoter (PubMed:9568714). CC Activates NPPA/ANP/ANF and MYH7/beta-MHC transcription (By similarity). CC Binds to and transactivates AGTR2 gene promoter (PubMed:17198697). CC Involved in the regulation of adult hippocampal neurogenesis. Involved CC in BDNF-driven pro-survival signaling in hippocampal adult-born CC neurons. Involved in the formation of long-term spatial memory and CC long-term potentiation (PubMed:22586092). In cochlear nucleus neurons, CC may play a role in deafferentation-induced apoptosis during a CC developmental critical period when auditory neurons depend on afferent CC input for survival (PubMed:18354019). Binds to and activates the CC BACE1/Beta-secretase 1 promoter, hence may regulate the proteolytic CC processing of the amyloid precursor protein (APP). Plays a role in CC adipocyte differentiation. May be involved in myoblast differentiation CC into myotubes (By similarity). Binds the consensus DNA sequence 5'- CC GGAAAAT-3' (Probable). In the presence of CREBBP, activates TNF CC transcription. Binds to PPARG gene promoter and regulates its activity CC (By similarity). Binds to PPARG and REG3G gene promoters CC (PubMed:17198697). {ECO:0000250|UniProtKB:D3Z9H7, CC ECO:0000250|UniProtKB:Q14934, ECO:0000269|PubMed:12750314, CC ECO:0000269|PubMed:17198697, ECO:0000269|PubMed:18354019, CC ECO:0000269|PubMed:19538478, ECO:0000269|PubMed:22586092, CC ECO:0000269|PubMed:9568714, ECO:0000305|PubMed:9568714}. 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 NFAT CC proteins, such as NFATC3, or members of the activating protein-1 (AP-1) CC family and MAF can also bind the complex. NFAT proteins can bind DNA as CC monomers or dimers (Probable). Component of a promoter-binding complex CC composed of STAT3, NFATC3 and NFATC4; complex formation is enhanced by CC calcineurin (PubMed:19538478). Interacts with CREBBP; this interaction CC potentiates transcription activation (By similarity). Interacts with CC MAPK8/JNK1 and MAPK9/JNK2 (By similarity). Interacts with GATA4 (via CC the second Zn finger) (PubMed:9568714). Interacts (via N-terminus) with CC IRAK1 (via C-terminus) (By similarity). Interacts with RPS6KA3 (By CC similarity). Interacts with HOMER1, HOMER2 and HOMER3; this interaction CC competes with calcineurin/PPP3CA-binding and hence prevents NFATC4 CC dephosphorylation and activation (By similarity). Interacts with ESR1 CC and ESR2; this interaction decreases NFATC4 transcriptional activity CC (By similarity). Interacts with MTOR and MAPK7/ERK5 (By similarity). CC Interacts with TRIM17; this interaction prevents NFATC3 nuclear CC localization (PubMed:25215946). {ECO:0000250|UniProtKB:Q14934, CC ECO:0000269|PubMed:19538478, ECO:0000269|PubMed:25215946, CC ECO:0000269|PubMed:9568714, ECO:0000305|PubMed:9568714}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18354019, CC ECO:0000269|PubMed:22586092, ECO:0000269|PubMed:24970700}. Nucleus CC {ECO:0000269|PubMed:18354019, ECO:0000269|PubMed:22586092, CC ECO:0000269|PubMed:24970700, ECO:0000269|PubMed:25215946}. Note=When CC hyperphosphorylated, localizes in the cytosol. When intracellular CC Ca(2+) levels increase, dephosphorylation by calcineurin/PPP3CA leads CC to translocation into the nucleus (By similarity). MAPK7/ERK5 and MTOR CC regulate NFATC4 nuclear export through phosphorylation at Ser-168 and CC Ser-170 (By similarity). {ECO:0000250|UniProtKB:Q14934}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1 {ECO:0000269|PubMed:11344309, ECO:0000269|PubMed:15489334, CC ECO:0000269|PubMed:16141072, ECO:0000269|PubMed:18675896}; CC Synonyms=I-IXL {ECO:0000269|PubMed:18675896}; CC IsoId=Q8K120-1; Sequence=Displayed; CC Name=2 {ECO:0000269|PubMed:18675896}; Synonyms=I-IXi CC {ECO:0000269|PubMed:18675896}; CC IsoId=Q8K120-2; Sequence=VSP_053054, VSP_053055; CC -!- TISSUE SPECIFICITY: Widely expressed (PubMed:18675896). In the brain, CC expressed in neurons (PubMed:18675896, PubMed:25663301). Expressed in CC the hippocampus (at protein level) (PubMed:25663301). In the CC hippocampus, expressed in both the CA1-CA3 pyramidal cells and the CC dentate gyrus granular cells (PubMed:22586092). Expressed in a subset CC of hippocampal cells representing adult-born neurons (at protein level) CC (PubMed:22586092). Expressed in the submandibular gland (at protein CC level) (PubMed:21435446). In the olfactory system, expressed at low CC levels in the glomerular and granular layers and in the mitral cell CC layer (PubMed:18675896). In the cerebellum, expressed at moderate CC levels in granular neurons (PubMed:18675896). Expressed at moderate CC levels in the choroid plexus and ependymal cells (PubMed:18675896). CC Expressed in neurons of the cochlear nucleus (at protein level) CC (PubMed:18354019). Expressed at low levels in the heart (at protein CC level) (PubMed:12370307). Expressed in ventricular cardiomyocytes (at CC protein level) (PubMed:19538478). Expressed in the lung CC (PubMed:17579027). {ECO:0000269|PubMed:12370307, CC ECO:0000269|PubMed:17579027, ECO:0000269|PubMed:18354019, CC ECO:0000269|PubMed:18675896, ECO:0000269|PubMed:19538478, CC ECO:0000269|PubMed:21435446, ECO:0000269|PubMed:22586092, CC ECO:0000269|PubMed:25663301}. CC -!- DEVELOPMENTAL STAGE: Expressed at high levels in the embryonic brain at CC 13.5 dpc (PubMed:18675896, PubMed:22586092). Expression decreases CC thereafter, reaching the lowest levels at postnatal day 14 and CC remaining unchanged in adulthood (PubMed:18675896). Expressed in the CC developing heart at 13.5 and 16.5 dpc, during the transition from CC spongy to compact myocardium (PubMed:17198697). CC {ECO:0000269|PubMed:17198697, ECO:0000269|PubMed:18675896, CC ECO:0000269|PubMed:22586092}. CC -!- INDUCTION: Up-regulated by BDNF (PubMed:22586092). Induced by CC calcineurin in ventricular tissue (PubMed:19538478). CC {ECO:0000269|PubMed:19538478, ECO:0000269|PubMed:22586092}. CC -!- DOMAIN: Rel similarity domain (RSD) or Rel homology domain (RHD) allows CC DNA-binding and cooperative interactions with AP-1 factors. CC {ECO:0000250|UniProtKB:O95644}. CC -!- PTM: Phosphorylated by NFATC-kinases; dephosphorylated by CC calcineurin/PPP3CA. Phosphorylated on Ser-168 and Ser-170 by MTOR, CC IRAK1, MAPK7/ERK5 and MAPK14/p38, on Ser-213 and Ser-217 by MAPK8 and CC MAPK9, and on Ser-289 and Ser-344 by RPS6KA3 (PubMed:18691762). CC Phosphorylated by GSK3B (By similarity). Phosphorylation by GSK3B CC markedly increases NFATC4 ubiquitination (By similarity). CC Phosphorylation by MAPK8/JNK1, MAPK9/JNK2 and RPS6KA3 may stimulate CC NFATC4 transcriptional activity. Phosphorylation at Ser-168 and Ser-170 CC is stimulated by UV irradiation (By similarity). CC {ECO:0000250|UniProtKB:D3Z9H7, ECO:0000250|UniProtKB:Q14934, CC ECO:0000269|PubMed:18691762}. CC -!- PTM: Ubiquitinated, leading to degradation by the proteasome. CC Ubiquitination may be stimulated by GSK3B-dependent phosphorylation. CC Polyubiquitin linkage mainly occurs through 'Lys-48'. CC {ECO:0000250|UniProtKB:Q14934}. CC -!- DISRUPTION PHENOTYPE: No visible phenotype (PubMed:12370307). However, CC adult mutant animals show selective impairment in the formation of CC spatial long-term memory and long-term potentiation. They exhibit a CC reduced number of hippocampal adult-born neurons compared to wild-type CC littermates (PubMed:22586092). Simultaneous knockout of NFATC3 and CC NFATC4 results in embryonic death soon after 10.5 dpc. Embryos appear CC normal at 9.5 dpc. At 10.5 dpc, they exhibit defects in cardiac CC development, including dilated thin translucent hearts, pericardial CC effusion and anemia. Despite a mild generalized developmental delay, CC the heads, tails, and limb buds are well developed. By 11.5 dpc, mutant CC embryos are either necrotic or resorbed (PubMed:12750314). CC {ECO:0000269|PubMed:12370307, ECO:0000269|PubMed:12750314, CC ECO:0000269|PubMed:22586092}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF283284; AAF98174.1; -; mRNA. DR EMBL; AF309389; AAG39446.1; -; Genomic_DNA. DR EMBL; AF309388; AAG39446.1; JOINED; Genomic_DNA. DR EMBL; EU887656; ACG55676.1; -; mRNA. DR EMBL; EU887657; ACG55677.1; -; mRNA. DR EMBL; AK159078; BAE34797.1; -; mRNA. DR EMBL; CH466535; EDL36234.1; -; Genomic_DNA. DR EMBL; BC028928; AAH28928.1; -; mRNA. DR CCDS; CCDS27132.1; -. [Q8K120-1] DR CCDS; CCDS49500.1; -. [Q8K120-2] DR RefSeq; NP_001161818.1; NM_001168346.1. [Q8K120-2] DR RefSeq; NP_076188.3; NM_023699.3. [Q8K120-1] DR AlphaFoldDB; Q8K120; -. DR SMR; Q8K120; -. DR BioGRID; 215821; 2. DR STRING; 10090.ENSMUSP00000024179; -. DR iPTMnet; Q8K120; -. DR PhosphoSitePlus; Q8K120; -. DR SwissPalm; Q8K120; -. DR jPOST; Q8K120; -. DR MaxQB; Q8K120; -. DR PaxDb; 10090-ENSMUSP00000024179; -. DR PeptideAtlas; Q8K120; -. DR ProteomicsDB; 252958; -. [Q8K120-1] DR ProteomicsDB; 252959; -. [Q8K120-2] DR Pumba; Q8K120; -. DR Antibodypedia; 9248; 555 antibodies from 38 providers. DR DNASU; 73181; -. DR Ensembl; ENSMUST00000024179.6; ENSMUSP00000024179.6; ENSMUSG00000023411.13. [Q8K120-1] DR Ensembl; ENSMUST00000172271.9; ENSMUSP00000132763.2; ENSMUSG00000023411.13. [Q8K120-2] DR GeneID; 73181; -. DR KEGG; mmu:73181; -. DR UCSC; uc007uax.2; mouse. [Q8K120-1] DR UCSC; uc011zlq.1; mouse. [Q8K120-2] DR AGR; MGI:1920431; -. DR CTD; 4776; -. DR MGI; MGI:1920431; Nfatc4. DR VEuPathDB; HostDB:ENSMUSG00000023411; -. DR eggNOG; ENOG502RIHQ; Eukaryota. DR GeneTree; ENSGT00940000160923; -. DR HOGENOM; CLU_010185_2_0_1; -. DR InParanoid; Q8K120; -. DR OMA; NMTAIDC; -. DR OrthoDB; 5405363at2759; -. DR PhylomeDB; Q8K120; -. DR TreeFam; TF326480; -. DR BioGRID-ORCS; 73181; 2 hits in 79 CRISPR screens. DR PRO; PR:Q8K120; -. DR Proteomes; UP000000589; Chromosome 14. DR RNAct; Q8K120; Protein. DR Bgee; ENSMUSG00000023411; Expressed in gastrula and 193 other cell types or tissues. DR ExpressionAtlas; Q8K120; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0016607; C:nuclear speck; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI. DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:MGI. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB. DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; ISO:MGI. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI. DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB. DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IGI:MGI. DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IGI:MGI. DR GO; GO:0045333; P:cellular respiration; IDA:MGI. DR GO; GO:1904637; P:cellular response to ionomycin; ISO:MGI. DR GO; GO:0071285; P:cellular response to lithium ion; IDA:MGI. DR GO; GO:0034644; P:cellular response to UV; IGI:MGI. DR GO; GO:0048813; P:dendrite morphogenesis; IMP:MGI. DR GO; GO:0007507; P:heart development; IGI:MGI. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI. DR GO; GO:0007616; P:long-term memory; IMP:UniProtKB. DR GO; GO:0060291; P:long-term synaptic potentiation; IMP:UniProtKB. DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; IMP:MGI. DR GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:MGI. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB. DR GO; GO:0032091; P:negative regulation of protein binding; IDA:ParkinsonsUK-UCL. DR GO; GO:2000297; P:negative regulation of synapse maturation; IMP:MGI. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB. DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:ParkinsonsUK-UCL. DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IMP:MGI. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:MGI. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:MGI. DR GO; GO:0048167; P:regulation of synaptic plasticity; ISO:MGI. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0060074; P:synapse maturation; IMP:MGI. DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0097084; P:vascular associated smooth muscle cell development; IGI:MGI. DR GO; GO:0035886; P:vascular associated smooth muscle cell differentiation; IGI:MGI. DR CDD; cd01178; IPT_NFAT; 1. DR CDD; cd07881; RHD-n_NFAT; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 1. DR Gene3D; 2.60.40.340; Rel homology domain (RHD), DNA-binding domain; 1. 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_sf. DR InterPro; IPR032397; RHD_dimer. DR InterPro; IPR011539; RHD_DNA_bind_dom. DR InterPro; IPR037059; RHD_DNA_bind_dom_sf. DR PANTHER; PTHR12533; NFAT; 1. DR PANTHER; PTHR12533:SF11; NUCLEAR FACTOR OF ACTIVATED T-CELLS, CYTOPLASMIC 4; 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; SSF81296; E set domains; 1. DR SUPFAM; SSF49417; p53-like transcription factors; 1. DR PROSITE; PS50254; REL_2; 1. DR Genevisible; Q8K120; MM. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Cytoplasm; Developmental protein; KW Differentiation; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; Transcription; Transcription regulation; KW Ubl conjugation. FT CHAIN 1..901 FT /note="Nuclear factor of activated T-cells, cytoplasmic 4" FT /id="PRO_0000367433" FT REPEAT 213..229 FT /note="SP 1" FT /evidence="ECO:0000255" FT REPEAT 277..293 FT /note="SP 2; approximate" FT /evidence="ECO:0000255" FT DOMAIN 401..582 FT /note="RHD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265" FT DOMAIN 586..683 FT /note="IPT/TIG" FT /evidence="ECO:0000255" FT DNA_BIND 430..437 FT /evidence="ECO:0000250|UniProtKB:Q14934" FT REGION 15..179 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 114..119 FT /note="Calcineurin-binding" FT /evidence="ECO:0000250|UniProtKB:Q14934" FT REGION 203..362 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 213..293 FT /note="2 approximate SP repeats" FT /evidence="ECO:0000255" FT REGION 695..721 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 827..869 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 268..270 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT MOTIF 672..674 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 57..83 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 117..137 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 269..285 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 293..309 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 326..340 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 168 FT /note="Phosphoserine; by MAPK7 and MAPK14" FT /evidence="ECO:0000269|PubMed:18691762" FT MOD_RES 170 FT /note="Phosphoserine; by MAPK7 and MAPK14" FT /evidence="ECO:0000269|PubMed:18691762" FT MOD_RES 213 FT /note="Phosphoserine; by MAPK8 and MAPK9" FT /evidence="ECO:0000250|UniProtKB:Q14934" FT MOD_RES 217 FT /note="Phosphoserine; by MAPK8 and MAPK9" FT /evidence="ECO:0000250|UniProtKB:Q14934" FT MOD_RES 289 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 334 FT /note="Phosphoserine; by RPS6KA3" FT /evidence="ECO:0000250|UniProtKB:Q14934" FT MOD_RES 344 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q14934" FT CROSSLNK 689 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0000250|UniProtKB:Q14934" FT VAR_SEQ 880..894 FT /note="VSEIIGRDLSGFPAR -> GGCGTGGCECK (in isoform 2)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_053054" FT VAR_SEQ 895..901 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_053055" FT CONFLICT 135 FT /note="S -> P (in Ref. 5; AAH28928)" FT /evidence="ECO:0000305" FT CONFLICT 379..380 FT /note="AV -> TM (in Ref. 1; AAG39446/AAF98174)" FT /evidence="ECO:0000305" FT CONFLICT 394..395 FT /note="HS -> QT (in Ref. 1; AAG39446/AAF98174)" FT /evidence="ECO:0000305" FT CONFLICT 562 FT /note="G -> S (in Ref. 5; AAH28928)" FT /evidence="ECO:0000305" FT CONFLICT 589..590 FT /note="ET -> GD (in Ref. 1; AAG39446/AAF98174)" FT /evidence="ECO:0000305" FT CONFLICT 662 FT /note="V -> I (in Ref. 1; AAG39446/AAF98174)" FT /evidence="ECO:0000305" FT CONFLICT 730 FT /note="P -> L (in Ref. 1; AAG39446/AAF98174)" FT /evidence="ECO:0000305" SQ SEQUENCE 901 AA; 95782 MW; 5977695F888F6538 CRC64; MGAASCEDEE LEFKLVFGEE KEPPPLGPGG PGEELDSEDT PPCCRLALGE PLPYGAAPIG IPRPPPPRPG MHSPPPRPAP SPGTWESQPA RSVRLGGPGG NAGGAGGGRV LECPSIRITS ISPTPDPPTS LEDTSETWGD GSPRDYPPPE GFGGYREAGG QGGGAFFSPS PGSSSLSSWS FFSDASDEAA LYAACDEVES ELNEAASRFG LSSPLPSPRA SPRPWTPEDP WSLYGPSSGG RAPEDSWLLL SAPGPVPASP RPASPCGKRR YSSSGTPSSA SPALSRRGSL GEEGPEPPPP PPLPLVRDPS SPGPFDYVGA PPTESIPQKT RRTSSEQAVA LPRSEEPPSC NGKLPSGTED SVAAPGALRK EVAGMDYLAV PSPLAWSKAR IGGHSPIFRT SALPPLDWPL PSQYEQLELR IEVQPRAHHR AHYETEGSRG AVKAAPGGHP VVKLLGYSEK PLTLQMFIGT ADERSLRPHA FYQVHRITGK MVATASYEAV VSGTKVLEMT LLPENNMAAN IDCAGILKLR NSDIELRKGE TDIGRKNTRV RLVFRVHVPQ GGGKVVSVQA ASVPIECSQR SAQELPQVET YSPSACSVRG GEELVLTGSN FLPDSKVVFI ERGPDGKLQW EEEAAVNRLQ SSEVTLTLTI PEYSNKRVSR PVQVYFYVSN GRRKRSPTQS FKFLPVVFKE EPLPDSSLRG FPSTSGPPFG PDVDFSPPRP PYPSYPHEDP AYETPYLSEG FGYSTPALYP QTGPPPSYRS GLRMFPETGG TTGCARLPSV SFLPRPFPGD QYGGQGSSFA LGLPFSPPAP FRPPLPSSPP LEDPFHPQSA IHPLPPEGYN EVGPGYTPGE GASEQEKARG GYSSGFRDSV PIQGITLEEV SEIIGRDLSG FPARPGEEPP A //