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Q60591 (NFAC2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. 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·Interactions·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 2

Short name=NF-ATc2
Short name=NFATc2
Alternative name(s):
NFAT pre-existing subunit
Short name=NF-ATp
T-cell transcription factor NFAT1
Gene names
Name:Nfatc2
Synonyms:Nfat1, Nfatp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length927 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, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway By similarity.

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. The phosphorylated form specifically interacts with XPO1; which mediates nuclear export. NFATC proteins bind to DNA as monomers. Interacts with NFATC2IP. Ref.7 Ref.10

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. Ref.10

Tissue specificity

Expressed in thymus, spleen, heart, testis, brain, placenta, muscle and pancreas. Ref.4

Domain

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

Post-translational modification

In resting cells, phosphorylated by NFATC-kinase on at least 18 sites in the 99-365 region. Upon cell stimulation, all these sites except Ser-245 are dephosphorylated by calcineurin. Dephosphorylation induces a conformational change that simultaneously exposes an NLS and masks an NES, which results in nuclear localization. Simultaneously, one site among Ser-53; Ser-54 and Ser-56 is phosphorylated; which is required for full transcriptional activity. Ref.10

Sequence similarities

Contains 1 RHD (Rel-like) domain.

Sequence caution

The sequence AAC52929.1 differs from that shown. Reason: Chimeric cDNA fused with Phyhd1 (Lrrc8a).

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from electronic annotation. Source: Ensembl

cytokine production

Inferred from direct assay PubMed 15790681. Source: MGI

positive regulation of B cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of gene expression

Inferred from mutant phenotype PubMed 19752193. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.3PubMed 15319455. Source: MGI

positive regulation of transcription, DNA-templated

Inferred from sequence orthology PubMed 15790681. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15319455. Source: MGI

response to drug

Inferred from electronic annotation. Source: Ensembl

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentactin cytoskeleton

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay PubMed 12091710PubMed 15319455PubMed 21709260. Source: MGI

cytosol

Inferred from direct assay PubMed 8973343. Source: MGI

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 19752193. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: Ensembl

ribonucleoprotein complex

Inferred from direct assay PubMed 21709260. Source: MGI

transcription factor complex

Inferred from physical interaction PubMed 19561615. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 10755616Ref.3PubMed 15319455. Source: MGI

sequence-specific DNA binding

Inferred from direct assay PubMed 8940147. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 15319455. Source: MGI

transcription regulatory region DNA binding

Inferred from direct assay PubMed 19752193. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

VRK2Q86Y07-12EBI-643104,EBI-1207633From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform C (identifier: Q60591-3)

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 B (identifier: Q60591-2)

The sequence of this isoform differs from the canonical sequence as follows:
     910-927: VNEIIRKEFSGPPSRNQT → ELIDTHLSWIQNIL
Isoform D (identifier: Q60591-4)

The sequence of this isoform differs from the canonical sequence as follows:
     619-806: DGQQIWEMEA...QGSTLPHTSS → GPAGTCETRP...PGSSLVLLAL
Isoform A (identifier: Q60591-1)

The sequence of this isoform is not available.
Note: Ref.2 (AAC52929) sequence is a chimeric cDNA.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 927927Nuclear factor of activated T-cells, cytoplasmic 2
PRO_0000205179

Regions

Repeat186 – 202171
Repeat215 – 231172
Repeat274 – 290173; approximate
Domain394 – 576183RHD
DNA binding423 – 4308
Region111 – 1166Calcineurin-binding
Region119 – 20183Trans-activation domain A (TAD-A)
Region163 – 17715Required for cytoplasmic retention of the phosphorylated form
Region186 – 2921073 X approximate SP repeats
Motif253 – 2553Nuclear localization signal

Amino acid modifications

Modified residue531Phosphoserine Probable
Modified residue541Phosphoserine Probable
Modified residue561Phosphoserine Probable
Modified residue991Phosphoserine Ref.10
Modified residue1361Phosphoserine Ref.10
Modified residue1501Phosphoserine By similarity
Modified residue1701Phosphoserine Probable
Modified residue1731Phosphoserine Probable
Modified residue1741Phosphoserine Probable
Modified residue1761Phosphoserine Probable
Modified residue1771Phosphoserine Probable
Modified residue1791Phosphoserine Probable
Modified residue1821Phosphoserine Probable
Modified residue2151Phosphoserine Ref.10
Modified residue2191Phosphoserine Ref.10
Modified residue2231Phosphoserine Ref.10
Modified residue2381Phosphoserine Ref.10
Modified residue2451Phosphoserine Ref.10
Modified residue2701Phosphoserine Ref.10
Modified residue2761Phosphoserine Ref.10
Modified residue2781Phosphoserine Ref.10
Modified residue2821Phosphoserine Ref.10
Modified residue3281Phosphoserine Ref.10
Modified residue3651Phosphoserine Ref.10
Modified residue7571Phosphoserine By similarity
Modified residue7591Phosphoserine By similarity
Modified residue7611Phosphoserine By similarity

Natural variations

Alternative sequence619 – 806188DGQQI…PHTSS → GPAGTCETRPLPISLISADR LSPWLSRLQRNPPGSVFRCS VLLPAPGSSLVLLAL in isoform D.
VSP_005597
Alternative sequence910 – 92718VNEII…SRNQT → ELIDTHLSWIQNIL in isoform B.
VSP_005596

Experimental info

Mutagenesis1121R → A: Lowers dephosphorylation. Ref.8
Mutagenesis1141E → A: Lowers dephosphorylation. Ref.8
Mutagenesis1161T → A: No dephosphorylation. Ref.8
Mutagenesis1641R → A: Induces aberrant nuclear localization of the phosphorylated form. Ref.10
Mutagenesis4231R → A: Decrease in binding to DNA. Ref.6
Mutagenesis4251H → A: No change in binding to DNA. Ref.6
Mutagenesis4261Y → A: Decrease in binding to DNA. Ref.6
Mutagenesis4281T → A: No change in binding to DNA. Ref.6
Mutagenesis4281T → C: No change in binding to DNA and confers DNA-binding sensitivity to sulfhydryl modifications. Ref.6
Mutagenesis4291E → A: Decrease in binding to DNA. Ref.6
Sequence conflict781L → P in AAK49895. Ref.3
Sequence conflict2871L → P in AAC52929. Ref.2
Sequence conflict2871L → P in AAC52930. Ref.2
Sequence conflict2871L → P in AAC52931. Ref.2
Sequence conflict8021P → R in AAC52929. Ref.2
Sequence conflict8021P → R in AAC52930. Ref.2
Sequence conflict8021P → R in AAC52931. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform C [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: F21E7BABE7DBB40F

FASTA927100,020
        10         20         30         40         50         60 
MDVPEPQPDP DGGDGPGHEP GGSPQDELDF SILFDYDYLN PIEEEPIAHK AISSPSGLAY 

        70         80         90        100        110        120 
PDDVLDYGLK PCNPLASLSG EPPGRFGEPD SIGFQNFLSP VKPAGASGPS PRIEITPSHE 

       130        140        150        160        170        180 
LMQAGGALRG RDAGLSPEQP ALALAGVAAS PRFTLPVPGY EGYREPLCLS PASSGSSASF 

       190        200        210        220        230        240 
ISDTFSPYTS PCVSPNNAGP DDLCPQFQNI PAHYSPRTSP IMSPRTSLAE DSCLGRHSPV 

       250        260        270        280        290        300 
PRPASRSSSP GAKRRHSCAE ALVAPLPAAS PQRSRSPSPQ PSPHVALQDD SIPAGYPPTA 

       310        320        330        340        350        360 
GSAVLMDALN TLATDSPCGI PSKIWKTSPD PTPVSTAPSK AGLARHIYPT VEFLGPCEQE 

       370        380        390        400        410        420 
ERRNSAPESI LLVPPTWPKQ LVPAIPICSI PVTASLPPLE WPLSNQSGSY ELRIEVQPKP 

       430        440        450        460        470        480 
HHRAHYETEG SRGAVKAPTG GHPVVQLHGY MENKPLGLQI FIGTADERIL KPHAFYQVHR 

       490        500        510        520        530        540 
ITGKTVTTTS YEKIVGNTKV LEIPLEPKNN MRATIDCAGI LKLRNADIEL RKGETDIGRK 

       550        560        570        580        590        600 
NTRVRLVFRV HVPEPSGRIV SLQAASNPIE CSQRSAHELP MVERQDMDSC LVYGGQQMIL 

       610        620        630        640        650        660 
TGQNFTAESK VVFMEKTTDG QQIWEMEATV DKDKSQPNML FVEIPEYRNK HIRVPVKVNF 

       670        680        690        700        710        720 
YVINGKRKRS QPQHFTYHPV PAIKTEPSDE YEPSLICSPA HGGLGSQPYY PQHPMLAESP 

       730        740        750        760        770        780 
SCLVATMAPC QQFRSGLSSP DARYQQQSPA AALYQRSKSL SPGLLGYQQP SLLAAPLGLA 

       790        800        810        820        830        840 
DAHRSVLVHA GSQGQGQGST LPHTSSASQQ ASPVIHYSPT NQQLRGGGHQ EFQHIMYCEN 

       850        860        870        880        890        900 
FGPSSARPGP PPINQGQRLS PGAYPTVIQQ QTAPSQRAAK NGPSDQKEAL PTGVTVKQEQ 

       910        920 
NLDQTYLDDV NEIIRKEFSG PPSRNQT 

« Hide

Isoform B [UniParc].

Checksum: A2B4B0476A75A83D
Show »

FASTA92399,642
Isoform D [UniParc].

Checksum: 1A8246FF98E219B8
Show »

FASTA79485,181
Isoform A (Sequence not available).

References

« Hide 'large scale' references
[1]"Isolation of the cyclosporin-sensitive T cell transcription factor NFATp."
McCaffrey P.G., Luo C., Kerpolla T.K., Jain J., Badalian T.M., Ho A.M., Burgeon E., Lane W.S., Lambert J.N., Curran T., Verdine G.L., Rao A., Hogan P.G.
Science 262:750-754(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE (ISOFORM A).
[2]"Recombinant NFAT1 (NFATp) is regulated by calcineurin in T cells and mediates transcription of several cytokine genes."
Luo C., Burgeon E., Carew J.A., McCaffrey P.G., Badalian T.M., Lane W.S., Hogan P.G., Rao A.
Mol. Cell. Biol. 16:3955-3966(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A; B AND C).
[3]"Identification and characterization of a novel nuclear factor of activated T-cells-1 isoform expressed in mouse brain."
Plyte S., Boncristiano M., Fattori E., Galvagni F., Paccani S.R., Majolini M.B., Oliviero S., Ciliberto G., Telford J.L., Baldari C.T.
J. Biol. Chem. 276:14350-14358(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM D).
Strain: C57BL/6.
Tissue: Brain.
[4]"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] (ISOFORM C), ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
Strain: C57BL/6.
[5]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[6]"A similar DNA-binding motif in NFAT family proteins and the Rel homology region."
Jain J., Burgeon E., Badalian T.M., Hogan P.G., Rao A.
J. Biol. Chem. 270:4138-4145(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-423; HIS-425; TYR-426; THR-428 AND GLU-429.
[7]"NF-AT-driven interleukin-4 transcription potentiated by NIP45."
Hodge M.R., Chun H.J., Rengarajan J., Alt A., Lieberson R., Glimcher L.H.
Science 274:1903-1905(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFATC2IP.
[8]"Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFAT."
Aramburu J., Garcia-Cozar F., Raghavan A., Okamura H., Rao A., Hogan P.G.
Mol. Cell 1:627-637(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF ARG-112; GLU-114 AND THR-116.
[9]"Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT."
Crabtree G.R.
Cell 96:611-614(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[10]"Concerted dephosphorylation of the transcription factor NFAT1 induces a conformational switch that regulates transcriptional activity."
Okamura H., Aramburu J., Garcia-Rodriguez C., Viola J.P.B., Raghavan A., Tahiliani M., Zhang X., Qin J., Hogan P.G., Rao A.
Mol. Cell 6:539-550(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-99; SER-136; SER-170; SER-173; SER-174; SER-176; SER-177; SER-179; SER-182; SER-215; SER-219; SER-223; SER-238; SER-245; SER-270; SER-276; SER-278; SER-282; SER-328 AND SER-365, SUBCELLULAR LOCATION, INTERACTION WITH XPO1, MUTAGENESIS OF ARG-164, IDENTIFICATION BY MASS SPECTROMETRY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U02079 mRNA. Translation: AAC52929.1. Sequence problems.
U36575 mRNA. Translation: AAC52930.1.
U36576 mRNA. Translation: AAC52931.1.
AF289078 mRNA. Translation: AAK49895.1.
EU887588 mRNA. Translation: ACG55608.1.
AL840639, AL844575 Genomic DNA. Translation: CAM15662.1.
AL840639, AL844575 Genomic DNA. Translation: CAM15663.1.
AL844575 Genomic DNA. Translation: CAM15669.1.
AL844575, AL840639 Genomic DNA. Translation: CAM15670.1.
AL844575, AL840639 Genomic DNA. Translation: CAM15671.1.
PIRA48753.
RefSeqNP_001032254.1. NM_001037177.1.
NP_035029.2. NM_010899.2.
UniGeneMm.116802.

3D structure databases

ProteinModelPortalQ60591.
SMRQ60591. Positions 398-680.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201739. 1 interaction.
DIPDIP-49476N.
IntActQ60591. 9 interactions.
MINTMINT-1565857.

PTM databases

PhosphoSiteQ60591.

Proteomic databases

PRIDEQ60591.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000074618; ENSMUSP00000074198; ENSMUSG00000027544. [Q60591-3]
ENSMUST00000109184; ENSMUSP00000104812; ENSMUSG00000027544. [Q60591-2]
GeneID18019.
KEGGmmu:18019.
UCSCuc008oau.1. mouse. [Q60591-3]

Organism-specific databases

CTD4773.
MGIMGI:102463. Nfatc2.

Phylogenomic databases

eggNOGNOG84065.
GeneTreeENSGT00550000074562.
HOVERGENHBG069754.
InParanoidB5B2Q3.
KOK17332.
OMAPRHIYPA.
OrthoDBEOG79PJND.
TreeFamTF326480.

Enzyme and pathway databases

ReactomeREACT_118809. Calcineurin Dephosphorylates Nfatc2.

Gene expression databases

ArrayExpressQ60591.
BgeeQ60591.
GenevestigatorQ60591.

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

ChiTaRSNFATC2. mouse.
NextBio293063.
PROQ60591.
SOURCESearch...

Entry information

Entry nameNFAC2_MOUSE
AccessionPrimary (citable) accession number: Q60591
Secondary accession number(s): A2APK2 expand/collapse secondary AC list , A2APK3, A2AQC5, A2AQC6, A2AQC7, B5B2Q3, Q60984, Q60985, Q91Y65
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: July 27, 2011
Last modified: April 16, 2014
This is version 138 of the entry and version 3 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