NFAC4_HUMAN
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 03-AUG-2022, entry version 192.
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, ECO:0000303|PubMed:17875713,
GN ECO:0000303|PubMed:18668201, 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. 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). 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; P46934: NEDD4; NbExp=2; IntAct=EBI-3905796, EBI-726944;
CC Q14934; P0CG48: UBC; NbExp=3; IntAct=EBI-3905796, EBI-3390054;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {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; 54.
DR IntAct; Q14934; 29.
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; Q14934; -.
DR PeptideAtlas; Q14934; -.
DR PRIDE; 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 Antibodypedia; 9248; 494 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 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; PTEGYNE; -.
DR OrthoDB; 95502at2759; -.
DR PhylomeDB; Q14934; -.
DR TreeFam; TF326480; -.
DR PathwayCommons; Q14934; -.
DR SignaLink; Q14934; -.
DR SIGNOR; Q14934; -.
DR BioGRID-ORCS; 4776; 11 hits in 1093 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 92 other tissues.
DR ExpressionAtlas; Q14934; baseline and differential.
DR Genevisible; Q14934; HS.
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: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:0035562; P:negative regulation of chromatin binding; IEA:Ensembl.
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:0032091; P:negative regulation of protein binding; IEA:Ensembl.
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; IEA:Ensembl.
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 Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 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.
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;
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 A-
FT 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 A-
FT 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
