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Q12968 (NFAC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | 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 3

Short name=NF-ATc3
Short name=NFATc3
Alternative name(s):
NFATx
T-cell transcription factor NFAT4
Short name=NF-AT4
Gene names
Name:NFATC3
Synonyms:NFAT4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1075 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as a regulator of transcriptional activation. Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2. Ref.9

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.

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.9

Tissue specificity

Isoform 1 is predominantly expressed in thymus and is also found in peripheral blood leukocytes and kidney. Isoform 2 is predominantly expressed in skeletal muscle and is also found in thymus, kidney, testis, spleen, prostate, ovary, small intestine, heart, placenta and pancreas. Isoform 3 is expressed in thymus and kidney. Isoform 4 is expressed in thymus and skeletal muscle.

Domain

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

Post-translational modification

Phosphorylated by NFATC-kinase; dephosphorylated by calcineurin By similarity.

Sequence similarities

Contains 1 RHD (Rel-like) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

cellular respiration

Inferred from electronic annotation. Source: Ensembl

cellular response to lithium ion

Inferred from electronic annotation. Source: Ensembl

heart development

Inferred from electronic annotation. Source: Ensembl

inflammatory response

Traceable author statement Ref.2. Source: ProtInc

innate immune response

Traceable author statement. Source: Reactome

muscle cell development

Inferred from electronic annotation. Source: Ensembl

patterning of blood vessels

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.9. Source: UniProtKB

regulation of transcription from RNA polymerase II promoter

Traceable author statement Ref.1. Source: ProtInc

smooth muscle cell differentiation

Inferred from electronic annotation. Source: Ensembl

transcription from RNA polymerase II promoter

Traceable author statement Ref.2. Source: ProtInc

   Cellular_componentcytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleolus

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.9. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

chromatin binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction PubMed 24330068. Source: IntAct

sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RAF1P040492EBI-5278441,EBI-365996

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q12968-1)

Also known as: X1;

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 (identifier: Q12968-2)

Also known as: X2; C;

The sequence of this isoform differs from the canonical sequence as follows:
     1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → DQFISDLEHQPSGSAEKWPNHSVLSCPAPFWRI
Isoform 3 (identifier: Q12968-3)

Also known as: X3;

The sequence of this isoform differs from the canonical sequence as follows:
     1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → DLFTSNNFDLLQLRPTFWPVPAGRYLRNLE
Isoform 4 (identifier: Q12968-4)

Also known as: X4;

The sequence of this isoform differs from the canonical sequence as follows:
     1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → GKFISDMFLK
Isoform 5 (identifier: Q12968-5)

Also known as: A;

The sequence of this isoform differs from the canonical sequence as follows:
     700-1075: VLMKQEHREE...SLDLGRSDGL → GTRSHDGLL
Isoform 6 (identifier: Q12968-6)

Also known as: B;

The sequence of this isoform differs from the canonical sequence as follows:
     717-1075: SLPVPHPAQT...SLDLGRSDGL → TLPQTSRQTLLGSQPPSASPPTV

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.6
Chain2 – 10751074Nuclear factor of activated T-cells, cytoplasmic 3
PRO_0000205180

Regions

Repeat207 – 223171
Repeat236 – 252172
Repeat292 – 308173
Domain415 – 596182RHD
DNA binding444 – 4518
Region109 – 1146Calcineurin-binding
Region207 – 3081023 X SP repeats
Motif273 – 2753Nuclear localization signal
Motif686 – 6883Nuclear localization signal
Motif1032 – 104110Nuclear export signal
Compositional bias24 – 296Poly-Pro

Amino acid modifications

Modified residue21N-acetylthreonine Ref.6

Natural variations

Alternative sequence700 – 1075376VLMKQ…RSDGL → GTRSHDGLL in isoform 5.
VSP_005598
Alternative sequence717 – 1075359SLPVP…RSDGL → TLPQTSRQTLLGSQPPSASP PTV in isoform 6.
VSP_005599
Alternative sequence1036 – 107540VNEII…RSDGL → DQFISDLEHQPSGSAEKWPN HSVLSCPAPFWRI in isoform 2.
VSP_005600
Alternative sequence1036 – 107540VNEII…RSDGL → DLFTSNNFDLLQLRPTFWPV PAGRYLRNLE in isoform 3.
VSP_005601
Alternative sequence1036 – 107540VNEII…RSDGL → GKFISDMFLK in isoform 4.
VSP_005602
Natural variant751S → L.
Corresponds to variant rs2230092 [ dbSNP | Ensembl ].
VAR_051784
Natural variant941E → A.
Corresponds to variant rs3743736 [ dbSNP | Ensembl ].
VAR_051785
Natural variant1001L → S.
Corresponds to variant rs2230093 [ dbSNP | Ensembl ].
VAR_051786
Natural variant1361P → L.
Corresponds to variant rs2230094 [ dbSNP | Ensembl ].
VAR_051787
Natural variant3821P → S.
Corresponds to variant rs2230095 [ dbSNP | Ensembl ].
VAR_051788

Experimental info

Sequence conflict7021M → L in AAB46595. Ref.3
Sequence conflict7021M → L in AAB46596. Ref.3
Sequence conflict7021M → L in AAB46597. Ref.3
Sequence conflict8311L → W in AAB46595. Ref.3
Sequence conflict8311L → W in AAB46596. Ref.3
Sequence conflict8311L → W in AAB46597. Ref.3
Sequence conflict8991A → G in AAB46595. Ref.3
Sequence conflict8991A → G in AAB46596. Ref.3
Sequence conflict8991A → G in AAB46597. Ref.3
Sequence conflict9231A → V in AAB46595. Ref.3
Sequence conflict9231A → V in AAB46596. Ref.3
Sequence conflict9231A → V in AAB46597. Ref.3
Sequence conflict9351A → G in AAB46595. Ref.3
Sequence conflict9351A → G in AAB46596. Ref.3
Sequence conflict9351A → G in AAB46597. Ref.3
Sequence conflict9471L → F in AAB46595. Ref.3
Sequence conflict9471L → F in AAB46596. Ref.3
Sequence conflict9471L → F in AAB46597. Ref.3
Sequence conflict9601A → G in AAB46595. Ref.3
Sequence conflict9601A → G in AAB46596. Ref.3
Sequence conflict9601A → G in AAB46597. Ref.3

Secondary structure

... 1075
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (X1) [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 0B25D61A2B56D898

FASTA1,075115,594
        10         20         30         40         50         60 
MTTANCGAHD ELDFKLVFGE DGAPAPPPPG SRPADLEPDD CASIYIFNVD PPPSTLTTPL 

        70         80         90        100        110        120 
CLPHHGLPSH SSVLSPSFQL QSHKNYEGTC EIPESKYSPL GGPKPFECPS IQITSISPNC 

       130        140        150        160        170        180 
HQELDAHEDD LQINDPEREF LERPSRDHLY LPLEPSYRES SLSPSPASSI SSRSWFSDAS 

       190        200        210        220        230        240 
SCESLSHIYD DVDSELNEAA ARFTLGSPLT SPGGSPGGCP GEETWHQQYG LGHSLSPRQS 

       250        260        270        280        290        300 
PCHSPRSSVT DENWLSPRPA SGPSSRPTSP CGKRRHSSAE VCYAGSLSPH HSPVPSPGHS 

       310        320        330        340        350        360 
PRGSVTEDTW LNASVHGGSG LGPAVFPFQY CVETDIPLKT RKTSEDQAAI LPGKLELCSD 

       370        380        390        400        410        420 
DQGSLSPARE TSIDDGLGSQ YPLKKDSCGD QFLSVPSPFT WSKPKPGHTP IFRTSSLPPL 

       430        440        450        460        470        480 
DWPLPAHFGQ CELKIEVQPK THHRAHYETE GSRGAVKAST GGHPVVKLLG YNEKPINLQM 

       490        500        510        520        530        540 
FIGTADDRYL RPHAFYQVHR ITGKTVATAS QEIIIASTKV LEIPLLPENN MSASIDCAGI 

       550        560        570        580        590        600 
LKLRNSDIEL RKGETDIGRK NTRVRLVFRV HIPQPSGKVL SLQIASIPVE CSQRSAQELP 

       610        620        630        640        650        660 
HIEKYSINSC SVNGGHEMVV TGSNFLPESK IIFLEKGQDG RPQWEVEGKI IREKCQGAHI 

       670        680        690        700        710        720 
VLEVPPYHNP AVTAAVQVHF YLCNGKRKKS QSQRFTYTPV LMKQEHREEI DLSSVPSLPV 

       730        740        750        760        770        780 
PHPAQTQRPS SDSGCSHDSV LSGQRSLICS IPQTYASMVT SSHLPQLQCR DESVSKEQHM 

       790        800        810        820        830        840 
IPSPIVHQPF QVTPTPPVGS SYQPMQTNVV YNGPTCLPIN AASSQEFDSV LFQQDATLSG 

       850        860        870        880        890        900 
LVNLGCQPLS SIPFHSSNSG STGHLLAHTP HSVHTLPHLQ SMGYHCSNTG QRSLSSPVAD 

       910        920        930        940        950        960 
QITGQPSSQL QPITYGPSHS GSATTASPAA SHPLASSPLS GPPSPQLQPM PYQSPSSGTA 

       970        980        990       1000       1010       1020 
SSPSPATRMH SGQHSTQAQS TGQGGLSAPS SLICHSLCDP ASFPPDGATV SIKPEPEDRE 

      1030       1040       1050       1060       1070 
PNFATIGLQD ITLDDVNEII GRDMSQISVS QGAGVSRQAP LPSPESLDLG RSDGL 

« Hide

Isoform 2 (X2) (C) [UniParc].

Checksum: CD91817D06AD5D82
Show »

FASTA1,068115,237
Isoform 3 (X3) [UniParc].

Checksum: B827F1D5CE01D033
Show »

FASTA1,065115,050
Isoform 4 (X4) [UniParc].

Checksum: 44CE97FCF4A4EEAD
Show »

FASTA1,045112,642
Isoform 5 (A) [UniParc].

Checksum: D96C59AEC592D0E0
Show »

FASTA70877,181
Isoform 6 (B) [UniParc].

Checksum: 8AB8BAFA1A319E50
Show »

FASTA73980,582

References

« Hide 'large scale' references
[1]"Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins."
Hoey T., Sun Y.-L., Williamson K., Xu X.
Immunity 2:461-472(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 5 AND 6).
Tissue: Skeletal muscle and T-cell.
[2]"NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus."
Masuda E.S., Naito Y., Tokumitsu H., Campbell D., Saito F., Hannum C., Arai K., Arai N.
Mol. Cell. Biol. 15:2697-2706(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: T-cell.
[3]"Carboxy-terminal 15 amino acids sequence of NFATx1 is possibly created by tissue-specific splicing and is essential for transactivation activity in T cells."
Imamura R., Masuda E.S., Naito Y., Imai S., Fujino T., Takano T., Arai K., Arai N.
J. Immunol. 161:3455-3463(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4).
Tissue: Fibroblast and T-cell.
[4]"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q."
Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D.
Genomics 60:295-308(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 4).
[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: Kidney.
[6]Bienvenut W.V., Waridel P., Quadroni M.
Submitted (MAR-2009) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-15; 468-488; 505-519 AND 579-594, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Embryonic kidney.
[7]"Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and MEKK1."
Zhu J., Shibasaki F., Price R., Guillemot J.-C., Yano T., Doetsch V., Wagner G., Ferrara P., McKeon F.
Cell 93:851-861(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[8]"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.
[9]"CHP2 activates the calcineurin/nuclear factor of activated T cells signaling pathway and enhances the oncogenic potential of HEK293 cells."
Li G.D., Zhang X., Li R., Wang Y.D., Wang Y.L., Han K.J., Qian X.P., Yang C.G., Liu P., Wei Q., Chen W.F., Zhang J., Zhang Y.
J. Biol. Chem. 283:32660-32668(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L41067 mRNA. Translation: AAA79174.1.
U14510 mRNA. Translation: AAA86308.1.
U85428 mRNA. Translation: AAB46595.1.
U85429 mRNA. Translation: AAB46596.1.
U85430 mRNA. Translation: AAB46597.1.
AC130462 Genomic DNA. No translation available.
BC001050 mRNA. Translation: AAH01050.1.
CCDSCCDS10860.1. [Q12968-1]
CCDS10861.1. [Q12968-3]
CCDS10862.1. [Q12968-2]
PIRA57377.
RefSeqNP_004546.1. NM_004555.3. [Q12968-2]
NP_775186.1. NM_173163.2. [Q12968-3]
NP_775188.1. NM_173165.2. [Q12968-1]
UniGeneHs.436585.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2XRWX-ray1.33B141-154[»]
2XS0X-ray2.60B141-154[»]
ProteinModelPortalQ12968.
SMRQ12968. Positions 419-700.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110848. 6 interactions.
IntActQ12968. 2 interactions.
STRING9606.ENSP00000300659.

PTM databases

PhosphoSiteQ12968.

Polymorphism databases

DMDM9087155.

Proteomic databases

MaxQBQ12968.
PaxDbQ12968.
PRIDEQ12968.

Protocols and materials databases

DNASU4775.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329524; ENSP00000331324; ENSG00000072736. [Q12968-2]
ENST00000346183; ENSP00000300659; ENSG00000072736. [Q12968-1]
ENST00000349223; ENSP00000264008; ENSG00000072736. [Q12968-3]
GeneID4775.
KEGGhsa:4775.
UCSCuc002evn.2. human. [Q12968-3]
uc002evo.2. human. [Q12968-1]

Organism-specific databases

CTD4775.
GeneCardsGC16P068119.
HGNCHGNC:7777. NFATC3.
HPACAB004514.
HPA023844.
HPA050665.
MIM602698. gene.
neXtProtNX_Q12968.
PharmGKBPA247.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG70055.
HOGENOMHOG000231780.
HOVERGENHBG069754.
InParanoidQ12968.
KOK17333.
OMAHINDPER.
PhylomeDBQ12968.
TreeFamTF326480.

Enzyme and pathway databases

ReactomeREACT_118664. Calcineurin dephosphorylates NFATC1,2,3.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressQ12968.
BgeeQ12968.
CleanExHS_NFATC3.
GenevestigatorQ12968.

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.
[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

ChiTaRSNFATC3. human.
GeneWikiNFATC3.
GenomeRNAi4775.
NextBio18410.
PROQ12968.
SOURCESearch...

Entry information

Entry nameNFAC3_HUMAN
AccessionPrimary (citable) accession number: Q12968
Secondary accession number(s): O75211 expand/collapse secondary AC list , Q14516, Q99840, Q99841, Q99842
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: July 9, 2014
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM