NFAC4_MOUSE
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 03-AUG-2022, entry version 146.
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 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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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). 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:22586092, ECO:0000269|PubMed:9568714,
CC 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). 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:25215946, ECO:0000269|PubMed:9568714,
CC ECO:0000305|PubMed:9568714}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18354019,
CC ECO:0000269|PubMed:22586092}. Nucleus {ECO:0000269|PubMed:18354019,
CC ECO:0000269|PubMed:22586092, 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). {ECO:0000269|PubMed:12370307,
CC ECO:0000269|PubMed:18354019, ECO:0000269|PubMed:18675896,
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. {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}.
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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 jPOST; Q8K120; -.
DR MaxQB; Q8K120; -.
DR PaxDb; Q8K120; -.
DR PeptideAtlas; Q8K120; -.
DR PRIDE; Q8K120; -.
DR ProteomicsDB; 252958; -. [Q8K120-1]
DR ProteomicsDB; 252959; -. [Q8K120-2]
DR Antibodypedia; 9248; 494 antibodies from 38 providers.
DR DNASU; 73181; -.
DR Ensembl; ENSMUST00000024179; ENSMUSP00000024179; ENSMUSG00000023411. [Q8K120-1]
DR Ensembl; ENSMUST00000172271; ENSMUSP00000132763; ENSMUSG00000023411. [Q8K120-2]
DR GeneID; 73181; -.
DR KEGG; mmu:73181; -.
DR UCSC; uc007uax.2; mouse. [Q8K120-1]
DR UCSC; uc011zlq.1; mouse. [Q8K120-2]
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; PTEGYNE; -.
DR OrthoDB; 95502at2759; -.
DR PhylomeDB; Q8K120; -.
DR TreeFam; TF326480; -.
DR BioGRID-ORCS; 73181; 2 hits in 74 CRISPR screens.
DR PRO; PR:Q8K120; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8K120; protein.
DR Bgee; ENSMUSG00000023411; Expressed in gastrula and 191 other tissues.
DR ExpressionAtlas; Q8K120; baseline and differential.
DR Genevisible; Q8K120; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
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: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:0035562; P:negative regulation of chromatin binding; IDA:MGI.
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:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP: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:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
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 Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 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.
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 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
