Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q8K120 (NFAC4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nuclear factor of activated T-cells, cytoplasmic 4

Short name=NF-ATc4
Short name=NFATc4
Alternative name(s):
T-cell transcription factor NFAT3
Short name=NF-AT3
Gene names
Name:Nfatc4
Synonyms:Nfat3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length901 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2 and IL-4. Transcriptionally repressed by estrogen receptors; this inhibition is further enhanced by estrogen. Increases the transcriptional activity of PPARG and has a direct role in adipocyte differentiation. May play an important role in myotube differentiation By similarity. May play a critical role in cardiac development and hypertrophy. May play a role in deafferentation-induced apoptosis of sensory neurons. Ref.6 Ref.7 Ref.8 UniProtKB Q14934

Subunit structure

Member of the multicomponent NFATC transcription complex that consists of at least two components, a pre-existing cytoplasmic component NFATC2 and an inducible nuclear component NFATC1. Other members such as NFATC4, NFATC3 or members of the activating protein-1 family, MAF, GATA4 and Cbp/p300 can also bind the complex. NFATC proteins bind to DNA as monomers. Interacts with CREBBP, GATA4, IRAK1, MAPK8, MAPK9 and RPS6KA3. Ref.6 UniProtKB Q14934

Subcellular location

Cytoplasm. Nucleus. Note: Cytoplasmic for the phosphorylated form and nuclear after activation that is controlled by calcineurin-mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals. The subcellular localization of NFATC plays a key role in the regulation of gene transcription.

Tissue specificity

Expressed in all tissues analyzed including brain, lung, heart, testis and muscle. Ref.2

Domain

Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors By similarity. UniProtKB O95644

Post-translational modification

Phosphorylated by NFATC-kinases; dephosphorylated by calcineurin. Phosphorylated on Ser-168 and Ser-170 by MTOR, IRAK1, MAPK7 and MAPK14, on Ser-213 and Ser-217 by MAPK8 and MAPK9, and on Ser-289 and Ser-344 by RPS6KA3. Phosphorylated by GSK3B. Ref.9 UniProtKB Q14934

Ubiquitinated, leading to its degradation by the proteasome and reduced transcriptional activity. Ubiquitination and reduction in transcriptional activity can be further facilitated through GSK3B-dependent phosphorylation. Polyubiquitin linkage is mainly through 'Lys-48' By similarity. UniProtKB Q14934

Sequence similarities

Contains 1 IPT/TIG domain.

Contains 1 RHD (Rel-like) domain.

Ontologies

Keywords
   Biological processDifferentiation
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular respiration

Inferred from direct assay PubMed 12750314. Source: MGI

cellular response to UV

Inferred from genetic interaction PubMed 17242187. Source: MGI

cellular response to lithium ion

Inferred from direct assay PubMed 20530871. Source: MGI

heart development

Inferred from genetic interaction PubMed 12750314PubMed 17229811. Source: MGI

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from mutant phenotype PubMed 17242187. Source: MGI

muscle cell development

Inferred from genetic interaction PubMed 11439183. Source: MGI

patterning of blood vessels

Inferred from genetic interaction PubMed 11439183. Source: MGI

positive regulation of apoptotic process

Inferred from mutant phenotype Ref.8. Source: MGI

positive regulation of apoptotic signaling pathway

Inferred from mutant phenotype PubMed 20530871. Source: MGI

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 16803872PubMed 17430895PubMed 20385772. Source: MGI

positive regulation of tumor necrosis factor production

Inferred from mutant phenotype PubMed 17242187. Source: MGI

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12796475. Source: MGI

smooth muscle cell differentiation

Inferred from genetic interaction PubMed 11439183. Source: MGI

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 17242187. Source: GOC

   Cellular_componentcytosol

Inferred from direct assay PubMed 16803872PubMed 17242187Ref.8. Source: MGI

intermediate filament cytoskeleton

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 11439183PubMed 16803872PubMed 17242187Ref.8. Source: MGI

transcription factor complex

Inferred from direct assay PubMed 20385772. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 12796475PubMed 17242187. Source: MGI

protein binding

Inferred from physical interaction PubMed 20385772. Source: MGI

sequence-specific DNA binding RNA polymerase II transcription factor activity

Inferred from direct assay PubMed 17242187. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12796475. Source: MGI

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 Ref.1 Ref.2 Ref.3 Ref.4 Ref.5 (identifier: Q8K120-1)

Also known as: I-IXL;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 Ref.2 (identifier: Q8K120-2)

Also known as: I-IXi;

The sequence of this isoform differs from the canonical sequence as follows:
     880-894: VSEIIGRDLSGFPAR → GGCGTGGCECK
     895-901: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 901901Nuclear factor of activated T-cells, cytoplasmic 4
PRO_0000367433

Regions

Repeat213 – 22917SP 1
Repeat277 – 29317SP 2; approximate
Domain401 – 582182RHD
Domain586 – 68398IPT/TIG
DNA binding430 – 4378 By similarity UniProtKB Q14934
Region114 – 1196Calcineurin-binding By similarity UniProtKB Q14934
Region213 – 293812 approximate SP repeats
Motif268 – 2703Nuclear localization signal
Motif672 – 6743Nuclear localization signal
Compositional bias23 – 327305Pro-rich
Compositional bias692 – 836145Pro-rich

Amino acid modifications

Modified residue1681Phosphoserine; by MAPK7 and MAPK14 Ref.9
Modified residue1701Phosphoserine; by MAPK7 and MAPK14 Ref.9
Modified residue2131Phosphoserine; by MAPK8 and MAPK9 By similarity UniProtKB Q14934
Modified residue2171Phosphoserine; by MAPK8 and MAPK9 By similarity UniProtKB Q14934
Modified residue2891Phosphoserine; by RPS6KA3 By similarity UniProtKB Q14934
Modified residue3341Phosphoserine; by RPS6KA3 By similarity UniProtKB Q14934
Modified residue3441Phosphoserine By similarity

Natural variations

Alternative sequence880 – 89415VSEII…GFPAR → GGCGTGGCECK in isoform 2. Ref.2
VSP_053054
Alternative sequence895 – 9017Missing in isoform 2. Ref.2
VSP_053055

Experimental info

Sequence conflict1351S → P in AAH28928. Ref.5
Sequence conflict379 – 3802AV → TM in AAG39446. Ref.1
Sequence conflict379 – 3802AV → TM in AAF98174. Ref.1
Sequence conflict394 – 3952HS → QT in AAG39446. Ref.1
Sequence conflict394 – 3952HS → QT in AAF98174. Ref.1
Sequence conflict5621G → S in AAH28928. Ref.5
Sequence conflict589 – 5902ET → GD in AAG39446. Ref.1
Sequence conflict589 – 5902ET → GD in AAF98174. Ref.1
Sequence conflict6621V → I in AAG39446. Ref.1
Sequence conflict6621V → I in AAF98174. Ref.1
Sequence conflict7301P → L in AAG39446. Ref.1
Sequence conflict7301P → L in AAF98174. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (I-IXL) [UniParc].

Last modified March 24, 2009. Version 2.
Checksum: 5977695F888F6538

FASTA90195,782
        10         20         30         40         50         60 
MGAASCEDEE LEFKLVFGEE KEPPPLGPGG PGEELDSEDT PPCCRLALGE PLPYGAAPIG 

        70         80         90        100        110        120 
IPRPPPPRPG MHSPPPRPAP SPGTWESQPA RSVRLGGPGG NAGGAGGGRV LECPSIRITS 

       130        140        150        160        170        180 
ISPTPDPPTS LEDTSETWGD GSPRDYPPPE GFGGYREAGG QGGGAFFSPS PGSSSLSSWS 

       190        200        210        220        230        240 
FFSDASDEAA LYAACDEVES ELNEAASRFG LSSPLPSPRA SPRPWTPEDP WSLYGPSSGG 

       250        260        270        280        290        300 
RAPEDSWLLL SAPGPVPASP RPASPCGKRR YSSSGTPSSA SPALSRRGSL GEEGPEPPPP 

       310        320        330        340        350        360 
PPLPLVRDPS SPGPFDYVGA PPTESIPQKT RRTSSEQAVA LPRSEEPPSC NGKLPSGTED 

       370        380        390        400        410        420 
SVAAPGALRK EVAGMDYLAV PSPLAWSKAR IGGHSPIFRT SALPPLDWPL PSQYEQLELR 

       430        440        450        460        470        480 
IEVQPRAHHR AHYETEGSRG AVKAAPGGHP VVKLLGYSEK PLTLQMFIGT ADERSLRPHA 

       490        500        510        520        530        540 
FYQVHRITGK MVATASYEAV VSGTKVLEMT LLPENNMAAN IDCAGILKLR NSDIELRKGE 

       550        560        570        580        590        600 
TDIGRKNTRV RLVFRVHVPQ GGGKVVSVQA ASVPIECSQR SAQELPQVET YSPSACSVRG 

       610        620        630        640        650        660 
GEELVLTGSN FLPDSKVVFI ERGPDGKLQW EEEAAVNRLQ SSEVTLTLTI PEYSNKRVSR 

       670        680        690        700        710        720 
PVQVYFYVSN GRRKRSPTQS FKFLPVVFKE EPLPDSSLRG FPSTSGPPFG PDVDFSPPRP 

       730        740        750        760        770        780 
PYPSYPHEDP AYETPYLSEG FGYSTPALYP QTGPPPSYRS GLRMFPETGG TTGCARLPSV 

       790        800        810        820        830        840 
SFLPRPFPGD QYGGQGSSFA LGLPFSPPAP FRPPLPSSPP LEDPFHPQSA IHPLPPEGYN 

       850        860        870        880        890        900 
EVGPGYTPGE GASEQEKARG GYSSGFRDSV PIQGITLEEV SEIIGRDLSG FPARPGEEPP 


A 

« Hide

Isoform 2 (I-IXi) [UniParc].

Checksum: 1083BBF9972F0742
Show »

FASTA89094,459

References

« Hide 'large scale' references
[1]"Evolutionary relationships among Rel domains indicate functional diversification by recombination."
Graef I.A., Gastier J.M., Francke U., Crabtree G.R.
Proc. Natl. Acad. Sci. U.S.A. 98:5740-5745(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
Strain: 129/SvEv.
[2]"Alternative splicing and expression of human and mouse NFAT genes."
Vihma H., Pruunsild P., Timmusk T.
Genomics 92:279-291(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Strain: C57BL/6.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Rathke gland.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Mammary tumor.
[6]"A calcineurin-dependent transcriptional pathway for cardiac hypertrophy."
Molkentin J.D., Lu J.-R., Antos C.L., Markham B., Richardson J., Robbins J., Grant S.R., Olson E.N.
Cell 93:215-228(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GATA4.
[7]"Dosage-dependent transcriptional regulation by the calcineurin/NFAT signaling in developing myocardium transition."
Yang X.Y., Yang T.T.C., Schubert W., Factor S.M., Chow C.-W.
Dev. Biol. 303:825-837(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Deafferentation-induced activation of NFAT (nuclear factor of activated T-cells) in cochlear nucleus neurons during a developmental critical period: a role for NFATc4-dependent apoptosis in the CNS."
Luoma J.I., Zirpel L.
J. Neurosci. 28:3159-3169(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"The interleukin-1 receptor associated kinase 1 contributes to the regulation of NFAT."
Wang D., Fasciano S., Li L.
Mol. Immunol. 45:3902-3908(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-168 AND SER-170.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF283284 mRNA. Translation: AAF98174.1.
AF309389, AF309388 Genomic DNA. Translation: AAG39446.1.
EU887656 mRNA. Translation: ACG55676.1.
EU887657 mRNA. Translation: ACG55677.1.
AK159078 mRNA. Translation: BAE34797.1.
CH466535 Genomic DNA. Translation: EDL36234.1.
BC028928 mRNA. Translation: AAH28928.1.
CCDSCCDS27132.1. [Q8K120-1]
CCDS49500.1. [Q8K120-2]
RefSeqNP_001161818.1. NM_001168346.1. [Q8K120-2]
NP_076188.3. NM_023699.3. [Q8K120-1]
UniGeneMm.27908.

3D structure databases

ProteinModelPortalQ8K120.
SMRQ8K120. Positions 405-691.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid215821. 2 interactions.

PTM databases

PhosphoSiteQ8K120.

Proteomic databases

PRIDEQ8K120.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000024179; ENSMUSP00000024179; ENSMUSG00000023411. [Q8K120-1]
ENSMUST00000172271; ENSMUSP00000132763; ENSMUSG00000023411. [Q8K120-2]
GeneID73181.
KEGGmmu:73181.
UCSCuc007uax.2. mouse. [Q8K120-1]
uc011zlq.1. mouse. [Q8K120-2]

Organism-specific databases

CTD4776.
MGIMGI:1920431. Nfatc4.

Phylogenomic databases

eggNOGNOG70055.
GeneTreeENSGT00550000074562.
HOGENOMHOG000231780.
HOVERGENHBG104364.
InParanoidQ3TXW7.
KOK17334.
OMAWTPDDPW.
OrthoDBEOG79PJND.
PhylomeDBQ8K120.
TreeFamTF326480.

Gene expression databases

BgeeQ8K120.
GenevestigatorQ8K120.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR008366. NFAT.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]
PANTHERPTHR12533. PTHR12533. 1 hit.
PfamPF00554. RHD. 1 hit.
PF01833. TIG. 1 hit.
[Graphical view]
PRINTSPR01789. NUCFACTORATC.
SMARTSM00429. IPT. 1 hit.
[Graphical view]
SUPFAMSSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEPS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio337621.
PROQ8K120.
SOURCESearch...

Entry information

Entry nameNFAC4_MOUSE
AccessionPrimary (citable) accession number: Q8K120
Secondary accession number(s): B5B2X2, Q3TXW7, Q9EP91
Entry history
Integrated into UniProtKB/Swiss-Prot: March 24, 2009
Last sequence update: March 24, 2009
Last modified: July 9, 2014
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot