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Reviewed, UniProtKB/Swiss-Prot Q13469 (NFAC2_HUMAN)

Last modified January 19, 2010. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Nuclear factor of activated T-cells, cytoplasmic 2
Alternative name(s):
    T-cell transcription factor NFAT1
    NFAT pre-existing subunit
      Short name=NF-ATp
Gene names
Name: NFATC2
Synonyms: NFAT1, NFATP
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length925 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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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.

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 By similarity.

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 thymus, spleen, heart, testis, brain, placenta, muscle and pancreas.

Induction

Inducibly expressed in T-lymphocytes upon activation of the T-cell receptor (TCR) complex. Induced after co-addition of phorbol 12-myristate 13-acetate (PMA) and ionomycin.

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 99-363 region. Upon cell stimulation, all these sites except Ser-243 are dephosphorylated by calcineurin. Dephosphorylation induces a conformational change that simultaneously exposes an NLS and masks an NES, which results in nuclear localization. Simultaneously, Ser-53 or Ser-56 is phosphorylated; which is required for full transcriptional activity. Ref.4 Ref.5 Ref.6

Sequence similarities

Contains 1 RHD (Rel-like) domain.

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Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processtranscription

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentnucleus Ref.1

Traceable author statement. Source: UniProtKB

   Molecular functionprotein binding

Inferred from physical interaction. Source: UniProtKB

transcription activator activity

Inferred from direct assay. Source: MGI

transcription factor activity Ref.1

Traceable author statement. Source: UniProtKB

Complete GO annotation...

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Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform C (identifier: Q13469-1)

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: Q13469-2)

The sequence of this isoform differs from the canonical sequence as follows:
     908-925: VNEIIRKEFSGPPARNQT → ELIDTHLSWIQNIL

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 925925Nuclear factor of activated T-cells, cytoplasmic 2
PRO_0000205178

Regions

Repeat184 – 200171
Repeat213 – 229172
Repeat272 – 286153; approximate
Domain392 – 574183RHD
DNA binding421 – 4288
Region111 – 1166Calcineurin-binding
Region119 – 19981Trans-activation domain A (TAD-A)
Region161 – 17515Required for cytoplasmic retention of the phosphorylated form By similarity
Region184 – 2861033 X approximate SP repeats
Motif251 – 2533Nuclear localization signal
Motif664 – 6663Nuclear localization signal
Motif904 – 91310Nuclear export signal

Amino acid modifications

Modified residue531Phosphoserine By similarity
Modified residue561Phosphoserine By similarity
Modified residue991Phosphoserine By similarity
Modified residue1101Phosphoserine By similarity
Modified residue1681Phosphoserine By similarity
Modified residue1711Phosphoserine By similarity
Modified residue1721Phosphoserine By similarity
Modified residue1741Phosphoserine By similarity
Modified residue1751Phosphoserine By similarity
Modified residue1771Phosphoserine By similarity
Modified residue1801Phosphoserine By similarity
Modified residue2131Phosphoserine By similarity
Modified residue2171Phosphoserine By similarity
Modified residue2211Phosphoserine By similarity
Modified residue2361Phosphoserine By similarity
Modified residue2431Phosphoserine By similarity
Modified residue2681Phosphoserine By similarity
Modified residue2741Phosphoserine By similarity
Modified residue2761Phosphoserine By similarity
Modified residue2801Phosphoserine By similarity
Modified residue3261Phosphoserine Ref.4
Modified residue3301Phosphoserine Ref.4 Ref.6
Modified residue3631Phosphoserine By similarity
Modified residue5851Phosphothreonine Ref.5
Modified residue5991Phosphothreonine Ref.5
Modified residue6051Phosphoserine Ref.5
Modified residue7551Phosphoserine Ref.6
Modified residue7591Phosphoserine Ref.6
Modified residue8561Phosphoserine Ref.6
Modified residue8591Phosphoserine Ref.6

Natural variations

Alternative sequence908 – 92518VNEII…ARNQT → ELIDTHLSWIQNIL in isoform B.
VSP_005595
Natural variant4461H → R: dbSNP rs12479626.
VAR_051783

Experimental info

Sequence conflict651L → M in AAC50886. Ref.1
Sequence conflict651L → M in AAC50887. Ref.1

Secondary structure

1 .............................................. 925
Helix Strand Turn

Details...

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Sequences

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

Last modified July 5, 2005. Version 2.
Checksum: 8DAE86855CCB58D3

FASTA925100,146
        10         20         30         40         50         60 
MNAPERQPQP DGGDAPGHEP GGSPQDELDF SILFDYEYLN PNEEEPNAHK VASPPSGPAY 

        70         80         90        100        110        120 
PDDVLDYGLK PYSPLASLSG EPPGRFGEPD RVGPQKFLSA AKPAGASGLS PRIEITPSHE 

       130        140        150        160        170        180 
LIQAVGPLRM RDAGLLVEQP PLAGVAASPR FTLPVPGFEG YREPLCLSPA SSGSSASFIS 

       190        200        210        220        230        240 
DTFSPYTSPC VSPNNGGPDD LCPQFQNIPA HYSPRTSPIM SPRTSLAEDS CLGRHSPVPR 

       250        260        270        280        290        300 
PASRSSSPGA KRRHSCAEAL VALPPGASPQ RSRSPSPQPS SHVAPQDHGS PAGYPPVAGS 

       310        320        330        340        350        360 
AVIMDALNSL ATDSPCGIPP KMWKTSPDPS PVSAAPSKAG LPRHIYPAVE FLGPCEQGER 

       370        380        390        400        410        420 
RNSAPESILL VPPTWPKPLV PAIPICSIPV TASLPPLEWP LSSQSGSYEL RIEVQPKPHH 

       430        440        450        460        470        480 
RAHYETEGSR GAVKAPTGGH PVVQLHGYME NKPLGLQIFI GTADERILKP HAFYQVHRIT 

       490        500        510        520        530        540 
GKTVTTTSYE KIVGNTKVLE IPLEPKNNMR ATIDCAGILK LRNADIELRK GETDIGRKNT 

       550        560        570        580        590        600 
RVRLVFRVHI PESSGRIVSL QTASNPIECS QRSAHELPMV ERQDTDSCLV YGGQQMILTG 

       610        620        630        640        650        660 
QNFTSESKVV FTEKTTDGQQ IWEMEATVDK DKSQPNMLFV EIPEYRNKHI RTPVKVNFYV 

       670        680        690        700        710        720 
INGKRKRSQP QHFTYHPVPA IKTEPTDEYD PTLICSPTHG GLGSQPYYPQ HPMVAESPSC 

       730        740        750        760        770        780 
LVATMAPCQQ FRTGLSSPDA RYQQQNPAAV LYQRSKSLSP SLLGYQQPAL MAAPLSLADA 

       790        800        810        820        830        840 
HRSVLVHAGS QGQSSALLHP SPTNQQASPV IHYSPTNQQL RCGSHQEFQH IMYCENFAPG 

       850        860        870        880        890        900 
TTRPGPPPVS QGQRLSPGSY PTVIQQQNAT SQRAAKNGPP VSDQKEVLPA GVTIKQEQNL 

       910        920 
DQTYLDDVNE IIRKEFSGPP ARNQT

« Hide

Isoform B.

Checksum: 71C45C9B348AE9C8
Show »

FASTA92199,784

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References

« Hide 'large scale' references
[1]"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: 8668213] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
[2]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed: 11780052] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT."
Crabtree G.R.
Cell 96:611-614(1999) [PubMed: 10089876] [Abstract]
Cited for: REVIEW.
[4]"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry."
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C.
Anal. Chem. 76:2763-2772(2004) [PubMed: 15144186] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326 AND SER-330, MASS SPECTROMETRY.
Tissue: T-cell.
[5]"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry."
Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.
Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-585; THR-599 AND SER-605, MASS SPECTROMETRY.
[6]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-330; SER-755; SER-759; SER-856 AND SER-859, MASS SPECTROMETRY.
Tissue: T-cell.
+Additional computationally mapped references.

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		U43341 mRNA. Translation: AAC50886.1.
U43342 mRNA. Translation: AAC50887.1.
AL132866 Genomic DNA. Translation: CAC00528.2.
AL035682, AL035684, AL132866 Genomic DNA. Translation: CAI18852.1.
AL035682, AL035684, AL132866 Genomic DNA. Translation: CAI18853.1.
AL035684, AL035682, AL132866 Genomic DNA. Translation: CAI19205.1.
AL035684, AL035682, AL132866 Genomic DNA. Translation: CAI19206.1.
AL132866, AL035682, AL035684 Genomic DNA. Translation: CAI23549.1.
IPIIPI00247309.
IPI00297845.
PIRG02326.
RefSeqNP_036472.2.
NP_775114.1.
UniGeneHs.713650

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A02X-ray2.70N396-678[»]
1OWRX-ray3.00M/N/P/Q396-678[»]
1P7HX-ray2.60L/M/N/O396-678[»]
1PZUX-ray3.10B/D/H/I/L/M396-678[»]
1S9KX-ray3.10C399-678[»]
2AS5X-ray2.70M/N392-678[»]
2O93X-ray3.05L/M/O396-678[»]
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-27630N.
IntActQ13469. 4 interactions.
STRINGQ13469.

PTM databases

PhosphoSiteQ13469.

Genome annotation databases

EnsemblENST00000396009; ENSP00000379330; ENSG00000101096; Homo sapiens. [Genome view]
GeneID4773.
UCSCuc002xwc.1. human.
uc002xwd.1. human.

Organism-specific databases

CTD4773.
GeneCardsGC20M049442.
H-InvDBHIX0040626.
HGNCHGNC:7776. NFATC2.
HPACAB018567.
HPA008789.
HPA024369.
MIM600490. gene.
PharmGKBPA31583.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG14740.
HOVERGENQ13469.
InParanoidQ13469.
OMAKMWKTSP.
PhylomeDBQ13469.

Enzyme and pathway databases

Pathway_Interaction_DBnfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.
tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
wnt_calcium_pathway. Noncanonical Wnt signaling pathway.
nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes.

Gene expression databases

ArrayExpressQ13469.
BgeeQ13469.
CleanExHS_NFATC2.
GenevestigatorQ13469.
GermOnlineENSG00000101096. Homo sapiens.

Family and domain databases

InterProIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT_TIG_rcpt.
IPR008366. NFAT.
IPR018286. NFAT_sbgrp.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]
Gene3DG3DSA:2.60.40.10. Ig-like_fold. 1 hit.
G3DSA:2.60.40.340. RHD. 1 hit.
PANTHERPTHR12533. NFAT. 1 hit.
PfamPF00554. RHD. 1 hit.
PF01833. TIG. 1 hit.
[Graphical view]
PRINTSPR01789. NUCFACTORATC.
SMARTSM00429. IPT. 1 hit.
[Graphical view]
PROSITEPS01204. REL_1. False negative.
PS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio18400.
SOURCESearch...

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Entry information

Entry nameNFAC2_HUMAN
AccessionPrimary (citable) accession number: Q13469
Secondary accession number(s): Q13468 expand/collapse secondary AC list , Q5TFW7, Q5TFW8, Q9NPX6, Q9NQH3, Q9UJR2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: July 5, 2005
Last modified: January 19, 2010
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Relevant documents

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents