ID NFAC4_HUMAN Reviewed; 902 AA. AC Q14934; B4DDG5; B4DY55; B5B2U7; B5B2U8; B5B2U9; B5B2V0; B5B2V1; B5B2V2; AC B5B2V3; B5B2V4; B5B2V5; B5B2V7; B5B2V8; B5B2V9; B5B2W0; B5B2W1; B5B2W2; AC B5B2W3; B5B2W4; B5B2W5; B5B2W6; B5B2W7; B5B2W8; B5B2W9; B5B2X0; Q7Z598; AC Q96H68; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 2. DT 27-MAR-2024, entry version 201. DE RecName: Full=Nuclear factor of activated T-cells, cytoplasmic 4; DE Short=NF-ATc4; DE Short=NFATc4; DE AltName: Full=T-cell transcription factor NFAT3 {ECO:0000303|PubMed:17875713, ECO:0000303|PubMed:7749981}; DE Short=NF-AT3 {ECO:0000303|PubMed:7749981}; GN Name=NFATC4; GN Synonyms=NFAT3 {ECO:0000303|PubMed:17213202, GN ECO:0000303|PubMed:17875713, ECO:0000303|PubMed:18668201, GN ECO:0000303|PubMed:7749981}; 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 1), FUNCTION, SUBUNIT, AND VARIANTS RP ALA-160 AND PRO-800. RC TISSUE=T-cell; RX PubMed=7749981; DOI=10.1016/1074-7613(95)90027-6; RA Hoey T., Sun Y.-L., Williamson K., Xu X.; RT "Isolation of two new members of the NF-AT gene family and functional RT characterization of the NF-AT proteins."; RL Immunity 2:461-472(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6; 7; 8; 9; 10; 11; 12; RP 13; 14; 15; 16; 17; 18; 19; 20; 21; 22; 23 AND 24), 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 12 AND 16). RC TISSUE=Adrenal gland, and Testis; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 61-902 (ISOFORMS 1/2/4/6), AND VARIANTS ALA-160 AND RP PRO-800. RC TISSUE=Ovary, and Rhabdomyosarcoma; 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 [5] 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 [6] RP FUNCTION, AND INTERACTION WITH CREBBP. RX PubMed=11514544; DOI=10.1074/jbc.m102961200; RA Yang T.T.C., Davis R.J., Chow C.-W.; RT "Requirement of two NFATc4 transactivation domains for CBP potentiation."; RL J. Biol. Chem. 276:39569-39576(2001). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-168 AND SER-170, AND RP MUTAGENESIS OF SER-168 AND SER-170. RX PubMed=11997522; DOI=10.1128/mcb.22.11.3892-3904.2002; RA Yang T.T.C., Xiong Q., Enslen H., Davis R.J., Chow C.-W.; RT "Phosphorylation of NFATc4 by p38 mitogen-activated protein kinases."; RL Mol. Cell. Biol. 22:3892-3904(2002). RN [8] RP SUBCELLULAR LOCATION, 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 [9] RP FUNCTION, INTERACTION WITH MAPK8 AND MAPK9, PHOSPHORYLATION AT SER-213 AND RP SER-217, AND MUTAGENESIS OF SER-213 AND SER-217. RX PubMed=17875713; DOI=10.1158/0008-5472.can-06-4788; RA Yao K., Cho Y.-Y., Bergen H.R. III, Madden B.J., Choi B.Y., Ma W.-Y., RA Bode A.M., Dong Z.; RT "Nuclear factor of activated T3 is a negative regulator of Ras-JNK1/2-AP-1 RT induced cell transformation."; RL Cancer Res. 67:8725-8735(2007). RN [10] RP FUNCTION, INTERACTION WITH RPS6KA3, PHOSPHORYLATION AT SER-289 AND SER-344, RP AND SUBCELLULAR LOCATION. RX PubMed=17213202; DOI=10.1074/jbc.m611322200; RA Cho Y.-Y., Yao K., Bode A.M., Bergen H.R. III, Madden B.J., Oh S.-M., RA Ermakova S., Kang B.S., Choi H.S., Shim J.-H., Dong Z.; RT "RSK2 mediates muscle cell differentiation through regulation of NFAT3."; RL J. Biol. Chem. 282:8380-8392(2007). RN [11] RP FUNCTION, INTERACTION WITH ESR1 AND ESR2, SUBCELLULAR LOCATION, AND RP ACTIVITY REGULATION. RX PubMed=18668201; DOI=10.1007/s00018-008-8273-1; RA Qin X., Wang X.-H., Yang Z.-H., Ding L.-H., Xu X.-J., Cheng L., Niu C., RA Sun H.-W., Zhang H., Ye Q.-N.; RT "Repression of NFAT3 transcriptional activity by estrogen receptors."; RL Cell. Mol. Life Sci. 65:2752-2762(2008). RN [12] RP UBIQUITINATION. RX PubMed=19026640; DOI=10.1016/j.febslet.2008.11.009; RA Fan Y., Xie P., Zhang T., Zhang H., Gu D., She M., Li H.; RT "Regulation of the stability and transcriptional activity of NFATc4 by RT ubiquitination."; RL FEBS Lett. 582:4008-4014(2008). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient RT phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [14] RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-168 AND SER-170, AND RP INTERACTION WITH MTOR AND MAPK7. RX PubMed=18347059; DOI=10.1128/mcb.01847-07; RA Yang T.T.C., Yu R.Y.L., Agadir A., Gao G.-J., Campos-Gonzalez R., RA Tournier C., Chow C.-W.; RT "Integration of protein kinases mTOR and extracellular signal-regulated RT kinase 5 in regulating nucleocytoplasmic localization of NFATc4."; RL Mol. Cell. Biol. 28:3489-3501(2008). RN [15] RP SUBCELLULAR LOCATION, INTERACTION WITH IRAK1, AND PHOSPHORYLATION AT RP 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 [16] RP INTERACTION WITH HOMER1; 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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [18] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-689, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [19] RP FUNCTION. 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 [20] RP STRUCTURE BY NMR OF 585-691. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the TIG domain from human nuclear factor of RT activated T-cells, cytoplasmic 4."; RL Submitted (FEB-2008) to the PDB data bank. 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 CC (PubMed:7749981, PubMed:11514544, PubMed:11997522, PubMed:17875713, CC PubMed:17213202, PubMed:18668201, PubMed:25663301). Involved in T-cell CC activation, stimulating the transcription of cytokine genes, including CC that of IL2 and IL4 (PubMed:7749981, PubMed:18668201, PubMed:18347059). CC Along with NFATC3, involved in embryonic heart development. Following CC JAK/STAT signaling activation and as part of a complex with NFATC3 and CC STAT3, binds to the alpha-beta E4 promoter region of CRYAB and CC activates transcription in cardiomyocytes (By similarity). Involved in CC mitochondrial energy metabolism required for cardiac morphogenesis and CC function (By similarity). Transactivates many genes involved in the CC cardiovascular system, including AGTR2, NPPB/BNP (in synergy with CC GATA4), NPPA/ANP/ANF and MYH7/beta-MHC (By similarity). Involved in the CC regulation of adult hippocampal neurogenesis. Involved in BDNF-driven CC pro-survival signaling in hippocampal adult-born neurons. Involved in CC the formation of long-term spatial memory and long-term potentiation CC (By similarity). In cochlear nucleus neurons, may play a role in CC deafferentation-induced apoptosis during the developmental critical CC period, when auditory neurons depend on afferent input for survival (By CC similarity). Binds to and activates the BACE1/Beta-secretase 1 CC promoter, hence may regulate the proteolytic processing of the amyloid CC precursor protein (APP) (PubMed:25663301). Plays a role in adipocyte CC differentiation (PubMed:11997522). May be involved in myoblast CC differentiation into myotubes (PubMed:17213202). Binds the consensus CC DNA sequence 5'-GGAAAAT-3' (Probable). In the presence of CREBBP, CC activates TNF transcription (PubMed:11514544). Binds to PPARG gene CC promoter and regulates its activity (PubMed:11997522). Binds to PPARG CC and REG3G gene promoters (By similarity). CC {ECO:0000250|UniProtKB:D3Z9H7, ECO:0000250|UniProtKB:Q8K120, CC ECO:0000269|PubMed:11514544, ECO:0000269|PubMed:11997522, CC ECO:0000269|PubMed:17213202, ECO:0000269|PubMed:17875713, CC ECO:0000269|PubMed:18347059, ECO:0000269|PubMed:18668201, CC ECO:0000269|PubMed:25663301, ECO:0000269|PubMed:7749981, ECO:0000305}. CC -!- ACTIVITY REGULATION: Transcriptional activity may be repressed by ESR1 CC and ESR2. {ECO:0000269|PubMed:18668201}. 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 (PubMed:7749981). Component of a promoter-binding CC complex composed of STAT3, NFATC3 and NFATC4; complex formation is CC enhanced by calcineurin (By similarity). Interacts with CREBBP; this CC interaction potentiates transcription activation (PubMed:11514544). CC Interacts with MAPK8/JNK1 and MAPK9/JNK2 (PubMed:17875713). Interacts CC with GATA4 (via the second Zn finger) (By similarity). Interacts (via CC N-terminus) with IRAK1 (via C-terminus) (PubMed:18691762). Interacts CC with RPS6KA3 (PubMed:17213202). Interacts with HOMER1, HOMER2 and CC HOMER3; this interaction competes with calcineurin/PPP3CA-binding and CC hence prevents NFATC4 dephosphorylation and activation CC (PubMed:18218901). Interacts with ESR1 and ESR2; this interaction CC decreases NFATC4 transcriptional activity (PubMed:18668201). Interacts CC with MTOR and MAPK7/ERK5 (PubMed:18347059). Interacts with TRIM17; this CC interaction prevents NFATC3 nuclear localization (By similarity). CC {ECO:0000250|UniProtKB:Q8K120, ECO:0000269|PubMed:11514544, CC ECO:0000269|PubMed:17213202, ECO:0000269|PubMed:17875713, CC ECO:0000269|PubMed:18218901, ECO:0000269|PubMed:18347059, CC ECO:0000269|PubMed:18668201, ECO:0000269|PubMed:18691762, CC ECO:0000269|PubMed:7749981}. CC -!- INTERACTION: CC Q14934; P0CG48: UBC; NbExp=3; IntAct=EBI-3905796, EBI-3390054; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11997522, CC ECO:0000269|PubMed:17213202, ECO:0000269|PubMed:18347059, CC ECO:0000269|PubMed:18668201}. Nucleus {ECO:0000269|PubMed:11997522, CC ECO:0000269|PubMed:12370307, ECO:0000269|PubMed:17213202, CC ECO:0000269|PubMed:18347059, ECO:0000269|PubMed:18668201, CC ECO:0000269|PubMed:18691762}. Note=When hyperphosphorylated, localizes CC in the cytosol. When intracellular Ca(2+) levels increase, CC dephosphorylation by calcineurin/PPP3CA leads to translocation into the CC nucleus (PubMed:11997522, PubMed:18347059). MAPK7/ERK5 and MTOR CC regulate NFATC4 nuclear export through phosphorylation at Ser-168 and CC Ser-170 (PubMed:18347059). {ECO:0000269|PubMed:11997522, CC ECO:0000269|PubMed:18347059}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=24; CC Name=1; Synonyms=ID-IXL; CC IsoId=Q14934-1; Sequence=Displayed; CC Name=2; Synonyms=IA-IXL; CC IsoId=Q14934-2; Sequence=VSP_036701; CC Name=3; Synonyms=IA-IXi; CC IsoId=Q14934-3; Sequence=VSP_036701, VSP_036705; CC Name=4; Synonyms=IC-IXL; CC IsoId=Q14934-4; Sequence=VSP_036702; CC Name=5; Synonyms=IC-IXi; CC IsoId=Q14934-5; Sequence=VSP_036702, VSP_036705; CC Name=6; Synonyms=IB-IXL; CC IsoId=Q14934-6; Sequence=VSP_036703; CC Name=7; Synonyms=IB-IXi; CC IsoId=Q14934-7; Sequence=VSP_036703, VSP_036705; CC Name=8; Synonyms=ID-IXi; CC IsoId=Q14934-8; Sequence=VSP_036705; CC Name=9; Synonyms=IE-IXL; CC IsoId=Q14934-9; Sequence=VSP_036700; CC Name=10; Synonyms=IE-IXi; CC IsoId=Q14934-10; Sequence=VSP_036700, VSP_036705; CC Name=11; Synonyms=IA-IXS; CC IsoId=Q14934-11; Sequence=VSP_036701, VSP_036704; CC Name=12; Synonyms=IEi-IXL; CC IsoId=Q14934-12; Sequence=VSP_036699; CC Name=13; Synonyms=IEi-IXi; CC IsoId=Q14934-13; Sequence=VSP_036699, VSP_036705; CC Name=14; Synonyms=IC-IXS; CC IsoId=Q14934-14; Sequence=VSP_036702, VSP_036704; CC Name=15; Synonyms=IB-IXS; CC IsoId=Q14934-15; Sequence=VSP_036703, VSP_036704; CC Name=16; Synonyms=ID-IXS; CC IsoId=Q14934-16; Sequence=VSP_036704; CC Name=17; Synonyms=IE-IXS; CC IsoId=Q14934-17; Sequence=VSP_036700, VSP_036704; CC Name=18; Synonyms=IEi-IXS; CC IsoId=Q14934-18; Sequence=VSP_036699, VSP_036704; CC Name=19; Synonyms=IV-IXL; CC IsoId=Q14934-19; Sequence=VSP_036698; CC Name=20; Synonyms=IV-IXi; CC IsoId=Q14934-20; Sequence=VSP_036698, VSP_036705; CC Name=21; Synonyms=IV-IXS; CC IsoId=Q14934-21; Sequence=VSP_036698, VSP_036704; CC Name=22; Synonyms=VI-IXL; CC IsoId=Q14934-22; Sequence=VSP_036697; CC Name=23; Synonyms=VI-IXi; CC IsoId=Q14934-23; Sequence=VSP_036697, VSP_036705; CC Name=24; Synonyms=VI-IXS; CC IsoId=Q14934-24; Sequence=VSP_036697, VSP_036704; CC -!- TISSUE SPECIFICITY: Widely expressed, with high levels in placenta, CC lung, kidney, testis and ovary (PubMed:18675896). Weakly expressed in CC spleen and thymus (PubMed:18675896). In the hippocampus, expressed in CC the granular layer of the dentate gyrus, in the pyramidal neurons of CC CA3 region, and in the hippocampal fissure (PubMed:18675896). Expressed CC in the heart (at protein level) (PubMed:12370307). CC {ECO:0000269|PubMed:12370307, ECO:0000269|PubMed:18675896}. 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/JNK1 CC and MAPK9/JNK2, and on Ser-289 and Ser-344 by RPS6KA3 (PubMed:11997522, CC PubMed:17875713, PubMed:17213202, PubMed:18347059). Phosphorylated by CC GSK3B (PubMed:18347059). Phosphorylation by GSK3B markedly increases CC NFATC4 ubiquitination (By similarity). Phosphorylation at Ser-168 and CC Ser-170 is stimulated by UV irradiation (PubMed:18347059). CC Phosphorylation determines subcellular location: the CC hyperphosphorylated protein is cytosolic, while the dephosphorylated CC form is targeted to the nucleus. {ECO:0000250|UniProtKB:D3Z9H7, CC ECO:0000269|PubMed:11997522, ECO:0000269|PubMed:17213202, CC ECO:0000269|PubMed:17875713, ECO:0000269|PubMed:18347059}. 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:0000269|PubMed:19026640}. CC -!- MISCELLANEOUS: [Isoform 3]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 5]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 7]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 8]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 10]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 12]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 13]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 18]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 20]: Due to an intron retention. {ECO:0000305}. CC -!- MISCELLANEOUS: [Isoform 23]: Due to an intron retention. {ECO:0000305}. 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; L41066; AAA79175.1; -; mRNA. DR EMBL; EU887632; ACG55652.1; -; mRNA. DR EMBL; EU887633; ACG55653.1; -; mRNA. DR EMBL; EU887634; ACG55654.1; -; mRNA. DR EMBL; EU887635; ACG55655.1; -; mRNA. DR EMBL; EU887636; ACG55656.1; -; mRNA. DR EMBL; EU887637; ACG55657.1; -; mRNA. DR EMBL; EU887638; ACG55658.1; -; mRNA. DR EMBL; EU887639; ACG55659.1; -; mRNA. DR EMBL; EU887640; ACG55660.1; -; mRNA. DR EMBL; EU887641; ACG55661.1; -; mRNA. DR EMBL; EU887642; ACG55662.1; -; mRNA. DR EMBL; EU887643; ACG55663.1; -; mRNA. DR EMBL; EU887644; ACG55664.1; -; mRNA. DR EMBL; EU887645; ACG55665.1; -; mRNA. DR EMBL; EU887646; ACG55666.1; -; mRNA. DR EMBL; EU887647; ACG55667.1; -; mRNA. DR EMBL; EU887648; ACG55668.1; -; mRNA. DR EMBL; EU887649; ACG55669.1; -; mRNA. DR EMBL; EU887650; ACG55670.1; -; mRNA. DR EMBL; EU887651; ACG55671.1; -; mRNA. DR EMBL; EU887652; ACG55672.1; -; mRNA. DR EMBL; EU887653; ACG55673.1; -; mRNA. DR EMBL; EU887654; ACG55674.1; -; mRNA. DR EMBL; EU887655; ACG55675.1; -; mRNA. DR EMBL; AK293185; BAG56726.1; -; mRNA. DR EMBL; AK302271; BAG63617.1; -; mRNA. DR EMBL; BC008857; AAH08857.2; -; mRNA. DR EMBL; BC053855; AAH53855.1; -; mRNA. DR CCDS; CCDS45089.1; -. [Q14934-3] DR CCDS; CCDS55909.1; -. [Q14934-11] DR CCDS; CCDS55910.1; -. [Q14934-16] DR CCDS; CCDS55911.1; -. [Q14934-12] DR CCDS; CCDS73625.1; -. [Q14934-10] DR CCDS; CCDS86379.1; -. [Q14934-17] DR CCDS; CCDS86380.1; -. [Q14934-9] DR CCDS; CCDS9629.1; -. [Q14934-1] DR RefSeq; NP_001129494.1; NM_001136022.2. [Q14934-3] DR RefSeq; NP_001185894.1; NM_001198965.1. [Q14934-16] DR RefSeq; NP_001185895.1; NM_001198966.2. [Q14934-12] DR RefSeq; NP_001185896.1; NM_001198967.2. [Q14934-11] DR RefSeq; NP_001275731.1; NM_001288802.1. [Q14934-10] DR RefSeq; NP_001306972.1; NM_001320043.1. [Q14934-2] DR RefSeq; NP_004545.2; NM_004554.4. [Q14934-1] DR RefSeq; XP_011535099.1; XM_011536797.2. DR RefSeq; XP_011535101.1; XM_011536799.2. DR PDB; 2YRP; NMR; -; A=585-691. DR PDBsum; 2YRP; -. DR AlphaFoldDB; Q14934; -. DR BMRB; Q14934; -. DR SMR; Q14934; -. DR BioGRID; 110849; 57. DR IntAct; Q14934; 27. DR MINT; Q14934; -. DR STRING; 9606.ENSP00000388910; -. DR GlyGen; Q14934; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q14934; -. DR PhosphoSitePlus; Q14934; -. DR BioMuta; NFATC4; -. DR DMDM; 215274090; -. DR CPTAC; CPTAC-1749; -. DR EPD; Q14934; -. DR jPOST; Q14934; -. DR MassIVE; Q14934; -. DR MaxQB; Q14934; -. DR PaxDb; 9606-ENSP00000388910; -. DR PeptideAtlas; Q14934; -. DR ProteomicsDB; 60223; -. [Q14934-1] DR ProteomicsDB; 60224; -. [Q14934-10] DR ProteomicsDB; 60225; -. [Q14934-11] DR ProteomicsDB; 60226; -. [Q14934-12] DR ProteomicsDB; 60227; -. [Q14934-13] DR ProteomicsDB; 60228; -. [Q14934-14] DR ProteomicsDB; 60229; -. [Q14934-15] DR ProteomicsDB; 60230; -. [Q14934-16] DR ProteomicsDB; 60231; -. [Q14934-17] DR ProteomicsDB; 60232; -. [Q14934-18] DR ProteomicsDB; 60233; -. [Q14934-19] DR ProteomicsDB; 60234; -. [Q14934-2] DR ProteomicsDB; 60235; -. [Q14934-20] DR ProteomicsDB; 60236; -. [Q14934-21] DR ProteomicsDB; 60237; -. [Q14934-22] DR ProteomicsDB; 60238; -. [Q14934-23] DR ProteomicsDB; 60239; -. [Q14934-24] DR ProteomicsDB; 60240; -. [Q14934-3] DR ProteomicsDB; 60241; -. [Q14934-4] DR ProteomicsDB; 60242; -. [Q14934-5] DR ProteomicsDB; 60243; -. [Q14934-6] DR ProteomicsDB; 60244; -. [Q14934-7] DR ProteomicsDB; 60245; -. [Q14934-8] DR ProteomicsDB; 60246; -. [Q14934-9] DR Pumba; Q14934; -. DR Antibodypedia; 9248; 555 antibodies from 38 providers. DR DNASU; 4776; -. DR Ensembl; ENST00000250373.9; ENSP00000250373.4; ENSG00000100968.14. [Q14934-1] DR Ensembl; ENST00000413692.6; ENSP00000388910.2; ENSG00000100968.14. [Q14934-3] DR Ensembl; ENST00000422617.7; ENSP00000396788.3; ENSG00000100968.14. [Q14934-10] DR Ensembl; ENST00000424781.6; ENSP00000388668.2; ENSG00000100968.14. [Q14934-7] DR Ensembl; ENST00000539237.6; ENSP00000439350.2; ENSG00000100968.14. [Q14934-5] DR Ensembl; ENST00000553469.5; ENSP00000451502.1; ENSG00000100968.14. [Q14934-14] DR Ensembl; ENST00000553708.5; ENSP00000450590.1; ENSG00000100968.14. [Q14934-8] DR Ensembl; ENST00000553879.5; ENSP00000452349.1; ENSG00000100968.14. [Q14934-12] DR Ensembl; ENST00000554050.5; ENSP00000451151.1; ENSG00000100968.14. [Q14934-16] DR Ensembl; ENST00000554344.5; ENSP00000450469.1; ENSG00000100968.14. [Q14934-12] DR Ensembl; ENST00000554473.5; ENSP00000450810.1; ENSG00000100968.14. [Q14934-21] DR Ensembl; ENST00000554591.5; ENSP00000452039.1; ENSG00000100968.14. [Q14934-11] DR Ensembl; ENST00000554661.5; ENSP00000450733.1; ENSG00000100968.14. [Q14934-18] DR Ensembl; ENST00000554966.5; ENSP00000450644.1; ENSG00000100968.14. [Q14934-15] DR Ensembl; ENST00000555167.1; ENSP00000451395.1; ENSG00000100968.14. [Q14934-20] DR Ensembl; ENST00000555393.5; ENSP00000451801.1; ENSG00000100968.14. [Q14934-23] DR Ensembl; ENST00000555453.5; ENSP00000450686.1; ENSG00000100968.14. [Q14934-9] DR Ensembl; ENST00000555590.5; ENSP00000451224.1; ENSG00000100968.14. [Q14934-6] DR Ensembl; ENST00000555802.1; ENSP00000451590.1; ENSG00000100968.14. [Q14934-22] DR Ensembl; ENST00000556169.5; ENSP00000451454.1; ENSG00000100968.14. [Q14934-17] DR Ensembl; ENST00000556279.5; ENSP00000452270.1; ENSG00000100968.14. [Q14934-4] DR Ensembl; ENST00000556759.5; ENSP00000451183.1; ENSG00000100968.14. [Q14934-19] DR Ensembl; ENST00000557451.5; ENSP00000451284.1; ENSG00000100968.14. [Q14934-13] DR Ensembl; ENST00000557767.5; ENSP00000451496.1; ENSG00000100968.14. [Q14934-24] DR Ensembl; ENST00000642182.1; ENSP00000495011.1; ENSG00000285485.2. [Q14934-18] DR Ensembl; ENST00000642302.2; ENSP00000494405.1; ENSG00000285485.2. [Q14934-1] DR Ensembl; ENST00000642423.1; ENSP00000495052.1; ENSG00000285485.2. [Q14934-14] DR Ensembl; ENST00000642571.1; ENSP00000493808.1; ENSG00000285485.2. [Q14934-4] DR Ensembl; ENST00000642650.1; ENSP00000495758.1; ENSG00000285485.2. [Q14934-13] DR Ensembl; ENST00000643468.1; ENSP00000494577.1; ENSG00000285485.2. [Q14934-12] DR Ensembl; ENST00000643679.1; ENSP00000493557.1; ENSG00000285485.2. [Q14934-8] DR Ensembl; ENST00000643941.1; ENSP00000493733.1; ENSG00000285485.2. [Q14934-9] DR Ensembl; ENST00000644025.1; ENSP00000494705.1; ENSG00000285485.2. [Q14934-16] DR Ensembl; ENST00000644166.1; ENSP00000496192.1; ENSG00000285485.2. [Q14934-7] DR Ensembl; ENST00000644182.1; ENSP00000495766.1; ENSG00000285485.2. [Q14934-12] DR Ensembl; ENST00000644376.1; ENSP00000493885.1; ENSG00000285485.2. [Q14934-3] DR Ensembl; ENST00000644583.1; ENSP00000496733.1; ENSG00000285485.2. [Q14934-23] DR Ensembl; ENST00000644758.1; ENSP00000495684.1; ENSG00000285485.2. [Q14934-6] DR Ensembl; ENST00000645116.1; ENSP00000493851.1; ENSG00000285485.2. [Q14934-5] DR Ensembl; ENST00000645397.1; ENSP00000493943.1; ENSG00000285485.2. [Q14934-19] DR Ensembl; ENST00000645587.1; ENSP00000495213.1; ENSG00000285485.2. [Q14934-21] DR Ensembl; ENST00000645795.1; ENSP00000495926.1; ENSG00000285485.2. [Q14934-20] DR Ensembl; ENST00000646023.1; ENSP00000494993.1; ENSG00000285485.2. [Q14934-10] DR Ensembl; ENST00000646364.1; ENSP00000496579.1; ENSG00000285485.2. [Q14934-15] DR Ensembl; ENST00000646650.1; ENSP00000496777.1; ENSG00000285485.2. [Q14934-11] DR Ensembl; ENST00000646652.1; ENSP00000496108.1; ENSG00000285485.2. [Q14934-24] DR Ensembl; ENST00000647017.1; ENSP00000496558.1; ENSG00000285485.2. [Q14934-22] DR Ensembl; ENST00000647345.1; ENSP00000493614.1; ENSG00000285485.2. [Q14934-17] DR GeneID; 4776; -. DR KEGG; hsa:4776; -. DR MANE-Select; ENST00000250373.9; ENSP00000250373.4; NM_004554.5; NP_004545.2. DR UCSC; uc001wpc.5; human. [Q14934-1] DR AGR; HGNC:7778; -. DR CTD; 4776; -. DR DisGeNET; 4776; -. DR GeneCards; NFATC4; -. DR HGNC; HGNC:7778; NFATC4. DR HPA; ENSG00000100968; Low tissue specificity. DR MIM; 602699; gene. DR neXtProt; NX_Q14934; -. DR OpenTargets; ENSG00000100968; -. DR PharmGKB; PA31584; -. DR VEuPathDB; HostDB:ENSG00000100968; -. DR eggNOG; ENOG502RIHQ; Eukaryota. DR GeneTree; ENSGT00940000160923; -. DR HOGENOM; CLU_010185_2_0_1; -. DR InParanoid; Q14934; -. DR OMA; NMTAIDC; -. DR OrthoDB; 5405363at2759; -. DR PhylomeDB; Q14934; -. DR TreeFam; TF326480; -. DR PathwayCommons; Q14934; -. DR SignaLink; Q14934; -. DR SIGNOR; Q14934; -. DR BioGRID-ORCS; 4776; 13 hits in 1173 CRISPR screens. DR ChiTaRS; NFATC4; human. DR EvolutionaryTrace; Q14934; -. DR GeneWiki; NFATC4; -. DR GenomeRNAi; 4776; -. DR Pharos; Q14934; Tbio. DR PRO; PR:Q14934; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; Q14934; Protein. DR Bgee; ENSG00000100968; Expressed in endocervix and 94 other cell types or tissues. DR ExpressionAtlas; Q14934; baseline and differential. DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016607; C:nuclear speck; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central. 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; IGI:BHF-UCL. DR GO; GO:0042975; F:peroxisome proliferator activated receptor binding; IEA:Ensembl. 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:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB. DR GO; GO:0031547; P:brain-derived neurotrophic factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl. DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IBA:GO_Central. DR GO; GO:0045333; P:cellular respiration; IEA:Ensembl. DR GO; GO:0071285; P:cellular response to lithium ion; IEA:Ensembl. DR GO; GO:0034644; P:cellular response to UV; IEA:Ensembl. DR GO; GO:0048813; P:dendrite morphogenesis; IEA:Ensembl. DR GO; GO:0007507; P:heart development; IEA:Ensembl. DR GO; GO:0006954; P:inflammatory response; TAS:ProtInc. DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl. DR GO; GO:0007616; P:long-term memory; ISS:UniProtKB. DR GO; GO:0060291; P:long-term synaptic potentiation; ISS:UniProtKB. DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; IEA:Ensembl. DR GO; GO:1902894; P:negative regulation of miRNA transcription; IGI:BHF-UCL. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB. DR GO; GO:2000297; P:negative regulation of synapse maturation; IEA:Ensembl. DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl. DR GO; GO:2001235; P:positive regulation of apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IEA:Ensembl. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central. DR GO; GO:0060074; P:synapse maturation; IEA:Ensembl. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0097084; P:vascular associated smooth muscle cell development; IEA:Ensembl. 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 IDEAL; IID00474; -. 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; Q14934; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Cytoplasm; KW Developmental protein; Differentiation; DNA-binding; Isopeptide bond; KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Transcription; KW Transcription regulation; Ubl conjugation. FT CHAIN 1..902 FT /note="Nuclear factor of activated T-cells, cytoplasmic 4" FT /id="PRO_0000205182" FT REPEAT 213..229 FT /note="SP 1" FT REPEAT 277..293 FT /note="SP 2; approximate" FT DOMAIN 401..582 FT /note="RHD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265" FT DOMAIN 586..683 FT /note="IPT/TIG" FT DNA_BIND 430..437 FT REGION 16..180 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 114..119 FT /note="Calcineurin-binding" FT REGION 208..369 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 213..293 FT /note="2 approximate SP repeats" FT REGION 791..870 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 268..270 FT /note="Nuclear localization signal" FT MOTIF 672..674 FT /note="Nuclear localization signal" FT COMPBIAS 55..83 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 217..231 FT /note="Pro 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 294..309 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 806..824 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 168 FT /note="Phosphoserine; by MAPK7 and MAPK14" FT /evidence="ECO:0000269|PubMed:11997522, FT ECO:0000269|PubMed:18347059" FT MOD_RES 170 FT /note="Phosphoserine; by MAPK7 and MAPK14" FT /evidence="ECO:0000269|PubMed:11997522, FT ECO:0000269|PubMed:18347059" FT MOD_RES 213 FT /note="Phosphoserine; by MAPK8 and MAPK9" FT /evidence="ECO:0000269|PubMed:17875713" FT MOD_RES 217 FT /note="Phosphoserine; by MAPK8 and MAPK9" FT /evidence="ECO:0000269|PubMed:17875713" FT MOD_RES 289 FT /note="Phosphoserine; by RPS6KA3" FT /evidence="ECO:0000269|PubMed:17213202" FT MOD_RES 344 FT /note="Phosphoserine; by RPS6KA3" FT /evidence="ECO:0000269|PubMed:17213202" FT CROSSLNK 689 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 1..712 FT /note="Missing (in isoform 22, isoform 23 and isoform 24)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_036697" FT VAR_SEQ 1..465 FT /note="Missing (in isoform 19, isoform 20 and isoform 21)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_036698" FT VAR_SEQ 1..70 FT /note="Missing (in isoform 12, isoform 13 and isoform 18)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:18675896" FT /id="VSP_036699" FT VAR_SEQ 1..32 FT /note="MGAASCEDEELEFKLVFGEEKEAPPLGAGGLG -> MPASISSIFPGPTLLL FT SCGS (in isoform 9, isoform 10 and isoform 17)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_036700" FT VAR_SEQ 1 FT /note="M -> MITTLPSLLPASLASISHRVTNLPSNSLSHNPGLSKPDFPGNSSPGL FT PSSSSPGRDLGAPAGSM (in isoform 2, isoform 3 and isoform 11)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_036701" FT VAR_SEQ 1 FT /note="M -> MADGGADSAAQRLPEGPGRVAPGRDLGAPAGSM (in isoform FT 4, isoform 5 and isoform 14)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_036702" FT VAR_SEQ 1 FT /note="M -> MLSGRDLGAPAGSM (in isoform 6, isoform 7 and FT isoform 15)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_036703" FT VAR_SEQ 773..880 FT /note="Missing (in isoform 11, isoform 14, isoform 15, FT isoform 16, isoform 17, isoform 18, isoform 21 and isoform FT 24)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:18675896" FT /id="VSP_036704" FT VAR_SEQ 881..902 FT /note="VSEIIGRDLSGFPAPPGEEPPA -> GGCGTGGCECECVQEIALHVC (in FT isoform 3, isoform 5, isoform 7, isoform 8, isoform 10, FT isoform 13, isoform 20 and isoform 23)" FT /evidence="ECO:0000303|PubMed:18675896" FT /id="VSP_036705" FT VARIANT 160 FT /note="G -> A (in dbSNP:rs2229309)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7749981" FT /id="VAR_046985" FT VARIANT 246 FT /note="S -> N (in dbSNP:rs2228231)" FT /id="VAR_046986" FT VARIANT 800 FT /note="S -> P (in dbSNP:rs7149586)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:7749981" FT /id="VAR_046987" FT MUTAGEN 168 FT /note="S->A: Promotes nuclear localization and increases FT transcriptional activity; when associated with A-170." FT /evidence="ECO:0000269|PubMed:11997522" FT MUTAGEN 170 FT /note="S->A: Promotes nuclear localization and increases FT transcriptional activity; when associated with A-168." FT /evidence="ECO:0000269|PubMed:11997522" FT MUTAGEN 213 FT /note="S->A: Marked decrease in phosphorylation by MAPK8 or FT MAPK9. Complete loss of phosphorylation by MAPK8 or MAPK9, FT but no effect on MAPK8/9-binding; when associated with FT A-217. Decreased transcriptional activity; when associated FT with A-217." FT /evidence="ECO:0000269|PubMed:17875713" FT MUTAGEN 217 FT /note="S->A: Marked decrease in phosphorylation by MAPK8 or FT MAPK9. Complete loss of phosphorylation by MAPK8 or MAPK9, FT but no effect on MAPK8/9-binding; when associated with FT A-213. Decreased transcriptional activity; when associated FT with A-213." FT /evidence="ECO:0000269|PubMed:17875713" FT CONFLICT 359 FT /note="E -> K (in Ref. 3; BAG56726)" FT /evidence="ECO:0000305" FT CONFLICT 646 FT /note="L -> P (in Ref. 3; BAG63617)" FT /evidence="ECO:0000305" FT STRAND 587..594 FT /evidence="ECO:0007829|PDB:2YRP" FT STRAND 602..610 FT /evidence="ECO:0007829|PDB:2YRP" FT STRAND 616..620 FT /evidence="ECO:0007829|PDB:2YRP" FT TURN 638..640 FT /evidence="ECO:0007829|PDB:2YRP" FT STRAND 645..649 FT /evidence="ECO:0007829|PDB:2YRP" FT STRAND 662..669 FT /evidence="ECO:0007829|PDB:2YRP" FT STRAND 671..673 FT /evidence="ECO:0007829|PDB:2YRP" FT STRAND 679..684 FT /evidence="ECO:0007829|PDB:2YRP" FT STRAND 687..689 FT /evidence="ECO:0007829|PDB:2YRP" SQ SEQUENCE 902 AA; 95449 MW; AE94C5D1325D24D7 CRC64; MGAASCEDEE LEFKLVFGEE KEAPPLGAGG LGEELDSEDA PPCCRLALGE PPPYGAAPIG IPRPPPPRPG MHSPPPRPAP SPGTWESQPA RSVRLGGPGG GAGGAGGGRV LECPSIRITS ISPTPEPPAA LEDNPDAWGD GSPRDYPPPE GFGGYREAGG QGGGAFFSPS PGSSSLSSWS FFSDASDEAA LYAACDEVES ELNEAASRFG LGSPLPSPRA SPRPWTPEDP WSLYGPSPGG RGPEDSWLLL SAPGPTPASP RPASPCGKRR YSSSGTPSSA SPALSRRGSL GEEGSEPPPP PPLPLARDPG SPGPFDYVGA PPAESIPQKT RRTSSEQAVA LPRSEEPASC NGKLPLGAEE SVAPPGGSRK EVAGMDYLAV PSPLAWSKAR IGGHSPIFRT SALPPLDWPL PSQYEQLELR IEVQPRAHHR AHYETEGSRG AVKAAPGGHP VVKLLGYSEK PLTLQMFIGT ADERNLRPHA FYQVHRITGK MVATASYEAV VSGTKVLEMT LLPENNMAAN IDCAGILKLR NSDIELRKGE TDIGRKNTRV RLVFRVHVPQ GGGKVVSVQA ASVPIECSQR SAQELPQVEA YSPSACSVRG GEELVLTGSN FLPDSKVVFI ERGPDGKLQW EEEATVNRLQ SNEVTLTLTV PEYSNKRVSR PVQVYFYVSN GRRKRSPTQS FRFLPVICKE EPLPDSSLRG FPSASATPFG TDMDFSPPRP PYPSYPHEDP ACETPYLSEG FGYGMPPLYP QTGPPPSYRP GLRMFPETRG TTGCAQPPAV SFLPRPFPSD PYGGRGSSFS LGLPFSPPAP FRPPPLPASP PLEGPFPSQS DVHPLPAEGY NKVGPGYGPG EGAPEQEKSR GGYSSGFRDS VPIQGITLEE VSEIIGRDLS GFPAPPGEEP PA //