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Protein

Nuclear factor of activated T-cells, cytoplasmic 2

Gene

Nfatc2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi423 – 4308

GO - Molecular functioni

  • chromatin binding Source: MGI
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: BHF-UCL
  • sequence-specific DNA binding Source: MGI
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: MGI
  • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription factor activity, sequence-specific DNA binding Source: MGI
  • transcription factor binding Source: MGI
  • transcription regulatory region DNA binding Source: UniProtKB
  • transcription regulatory region sequence-specific DNA binding Source: BHF-UCL

GO - Biological processi

  • B cell receptor signaling pathway Source: MGI
  • calcineurin-NFAT signaling cascade Source: MGI
  • cell migration Source: UniProtKB
  • cellular response to DNA damage stimulus Source: MGI
  • cytokine production Source: MGI
  • myotube cell development Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • positive regulation of B cell proliferation Source: MGI
  • positive regulation of gene expression Source: UniProtKB
  • positive regulation of myoblast fusion Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • response to drug Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-2871809. FCERI mediated Ca+2 mobilization.
R-MMU-5607763. CLEC7A (Dectin-1) induces NFAT activation.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:Nfatc2
Synonyms:Nfat1, Nfatp
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:102463. Nfatc2.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication

  • 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.

GO - Cellular componenti

  • actin cytoskeleton Source: MGI
  • cytoplasm Source: MGI
  • cytosol Source: MGI
  • intracellular ribonucleoprotein complex Source: MGI
  • nuclear chromatin Source: BHF-UCL
  • nuclear transcription factor complex Source: MGI
  • nucleoplasm Source: MGI
  • nucleus Source: UniProtKB
  • plasma membrane Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi112R → A: Lowers dephosphorylation. 1 Publication1
Mutagenesisi114E → A: Lowers dephosphorylation. 1 Publication1
Mutagenesisi116T → A: No dephosphorylation. 1 Publication1
Mutagenesisi164R → A: Induces aberrant nuclear localization of the phosphorylated form. 1 Publication1
Mutagenesisi423R → A: Decrease in binding to DNA. 1 Publication1
Mutagenesisi425H → A: No change in binding to DNA. 1 Publication1
Mutagenesisi426Y → A: Decrease in binding to DNA. 1 Publication1
Mutagenesisi428T → A: No change in binding to DNA. 1 Publication1
Mutagenesisi428T → C: No change in binding to DNA and confers DNA-binding sensitivity to sulfhydryl modifications. 1 Publication1
Mutagenesisi429E → A: Decrease in binding to DNA. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002051791 – 927Nuclear factor of activated T-cells, cytoplasmic 2Add BLAST927

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei23PhosphoserineBy similarity1
Modified residuei53PhosphoserineCurated1
Modified residuei54PhosphoserineCurated1
Modified residuei56PhosphoserineCurated1
Modified residuei99Phosphoserine1 Publication1
Modified residuei107PhosphoserineBy similarity1
Modified residuei110PhosphoserineBy similarity1
Modified residuei136PhosphoserineCombined sources1 Publication1
Modified residuei150PhosphoserineBy similarity1
Modified residuei170Phosphoserine1 Publication1
Modified residuei173Phosphoserine1 Publication1
Modified residuei174Phosphoserine1 Publication1
Modified residuei176Phosphoserine1 Publication1
Modified residuei177Phosphoserine1 Publication1
Modified residuei179Phosphoserine1 Publication1
Modified residuei182Phosphoserine1 Publication1
Modified residuei215Phosphoserine1 Publication1
Modified residuei219Phosphoserine1 Publication1
Modified residuei223Phosphoserine1 Publication1
Modified residuei238Phosphoserine1 Publication1
Modified residuei245Phosphoserine1 Publication1
Modified residuei257PhosphoserineCombined sources1
Modified residuei270Phosphoserine1 Publication1
Modified residuei276Phosphoserine1 Publication1
Modified residuei278Phosphoserine1 Publication1
Modified residuei282Phosphoserine1 Publication1
Modified residuei328Phosphoserine1 Publication1
Modified residuei365PhosphoserineCombined sources1 Publication1
Modified residuei757PhosphoserineBy similarity1
Modified residuei759PhosphoserineBy similarity1
Modified residuei761PhosphoserineBy similarity1
Modified residuei860PhosphoserineBy similarity1

Post-translational modificationi

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.1 Publication
Ubiquitinated in endothelial cells by RNF213 downstream of the non-canonical Wnt signaling pathway, leading to its degradation by the proteasome.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ60591.
PaxDbiQ60591.
PeptideAtlasiQ60591.
PRIDEiQ60591.

PTM databases

iPTMnetiQ60591.
PhosphoSitePlusiQ60591.

Expressioni

Tissue specificityi

Expressed in thymus, spleen, heart, testis, brain, placenta, muscle and pancreas.1 Publication

Gene expression databases

BgeeiENSMUSG00000027544.
ExpressionAtlasiQ60591. baseline and differential.
GenevisibleiQ60591. MM.

Interactioni

Subunit structurei

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. Interacts with FOXP3 (By similarity).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
VRK2Q86Y07-12EBI-643104,EBI-1207633From a different organism.

GO - Molecular functioni

  • transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi201739. 1 interactor.
DIPiDIP-49476N.
IntActiQ60591. 11 interactors.
MINTiMINT-1565857.
STRINGi10090.ENSMUSP00000074198.

Structurei

3D structure databases

ProteinModelPortaliQ60591.
SMRiQ60591.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati186 – 2021Add BLAST17
Repeati215 – 2312Add BLAST17
Repeati274 – 2903; approximateAdd BLAST17
Domaini394 – 576RHDPROSITE-ProRule annotationAdd BLAST183

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni111 – 116Calcineurin-binding6
Regioni119 – 201Trans-activation domain A (TAD-A)Add BLAST83
Regioni163 – 177Required for cytoplasmic retention of the phosphorylated formAdd BLAST15
Regioni186 – 2923 X approximate SP repeatsAdd BLAST107

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi253 – 255Nuclear localization signal3

Domaini

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

Sequence similaritiesi

Contains 1 RHD (Rel-like) domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IHFR. Eukaryota.
ENOG41105U2. LUCA.
GeneTreeiENSGT00550000074562.
HOVERGENiHBG069754.
InParanoidiQ60591.
KOiK17332.
OMAiMWKTSPD.
OrthoDBiEOG091G01QP.
TreeFamiTF326480.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR008366. NFAT.
IPR008967. p53-like_TF_DNA-bd.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
[Graphical view]
PANTHERiPTHR12533. PTHR12533. 1 hit.
PfamiPF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
[Graphical view]
PRINTSiPR01789. NUCFACTORATC.
SMARTiSM00429. IPT. 1 hit.
[Graphical view]
SUPFAMiSSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS50254. REL_2. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform C (identifier: Q60591-3) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDVPEPQPDP DGGDGPGHEP GGSPQDELDF SILFDYDYLN PIEEEPIAHK
60 70 80 90 100
AISSPSGLAY PDDVLDYGLK PCNPLASLSG EPPGRFGEPD SIGFQNFLSP
110 120 130 140 150
VKPAGASGPS PRIEITPSHE LMQAGGALRG RDAGLSPEQP ALALAGVAAS
160 170 180 190 200
PRFTLPVPGY EGYREPLCLS PASSGSSASF ISDTFSPYTS PCVSPNNAGP
210 220 230 240 250
DDLCPQFQNI PAHYSPRTSP IMSPRTSLAE DSCLGRHSPV PRPASRSSSP
260 270 280 290 300
GAKRRHSCAE ALVAPLPAAS PQRSRSPSPQ PSPHVALQDD SIPAGYPPTA
310 320 330 340 350
GSAVLMDALN TLATDSPCGI PSKIWKTSPD PTPVSTAPSK AGLARHIYPT
360 370 380 390 400
VEFLGPCEQE ERRNSAPESI LLVPPTWPKQ LVPAIPICSI PVTASLPPLE
410 420 430 440 450
WPLSNQSGSY ELRIEVQPKP HHRAHYETEG SRGAVKAPTG GHPVVQLHGY
460 470 480 490 500
MENKPLGLQI FIGTADERIL KPHAFYQVHR ITGKTVTTTS YEKIVGNTKV
510 520 530 540 550
LEIPLEPKNN MRATIDCAGI LKLRNADIEL RKGETDIGRK NTRVRLVFRV
560 570 580 590 600
HVPEPSGRIV SLQAASNPIE CSQRSAHELP MVERQDMDSC LVYGGQQMIL
610 620 630 640 650
TGQNFTAESK VVFMEKTTDG QQIWEMEATV DKDKSQPNML FVEIPEYRNK
660 670 680 690 700
HIRVPVKVNF YVINGKRKRS QPQHFTYHPV PAIKTEPSDE YEPSLICSPA
710 720 730 740 750
HGGLGSQPYY PQHPMLAESP SCLVATMAPC QQFRSGLSSP DARYQQQSPA
760 770 780 790 800
AALYQRSKSL SPGLLGYQQP SLLAAPLGLA DAHRSVLVHA GSQGQGQGST
810 820 830 840 850
LPHTSSASQQ ASPVIHYSPT NQQLRGGGHQ EFQHIMYCEN FGPSSARPGP
860 870 880 890 900
PPINQGQRLS PGAYPTVIQQ QTAPSQRAAK NGPSDQKEAL PTGVTVKQEQ
910 920
NLDQTYLDDV NEIIRKEFSG PPSRNQT
Length:927
Mass (Da):100,020
Last modified:July 27, 2011 - v3
Checksum:iF21E7BABE7DBB40F
GO
Isoform B (identifier: Q60591-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     910-927: VNEIIRKEFSGPPSRNQT → ELIDTHLSWIQNIL

Show »
Length:923
Mass (Da):99,642
Checksum:iA2B4B0476A75A83D
GO
Isoform D (identifier: Q60591-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     619-806: DGQQIWEMEA...QGSTLPHTSS → GPAGTCETRP...PGSSLVLLAL

Show »
Length:794
Mass (Da):85,181
Checksum:i1A8246FF98E219B8
GO
Isoform A (identifier: Q60591-1)
Sequence is not available
Note: PubMed:8668213 (AAC52929) sequence is a chimeric cDNA.
Length:
Mass (Da):

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti78L → P in AAK49895 (PubMed:11278367).Curated1
Sequence conflicti287L → P in AAC52929 (PubMed:8668213).Curated1
Sequence conflicti287L → P in AAC52930 (PubMed:8668213).Curated1
Sequence conflicti287L → P in AAC52931 (PubMed:8668213).Curated1
Sequence conflicti802P → R in AAC52929 (PubMed:8668213).Curated1
Sequence conflicti802P → R in AAC52930 (PubMed:8668213).Curated1
Sequence conflicti802P → R in AAC52931 (PubMed:8668213).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005597619 – 806DGQQI…PHTSS → GPAGTCETRPLPISLISADR LSPWLSRLQRNPPGSVFRCS VLLPAPGSSLVLLAL in isoform D. 1 PublicationAdd BLAST188
Alternative sequenceiVSP_005596910 – 927VNEII…SRNQT → ELIDTHLSWIQNIL in isoform B. 1 PublicationAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS17112.1. [Q60591-3]
CCDS50803.1. [Q60591-2]
PIRiA48753.
RefSeqiNP_035029.2. NM_010899.3. [Q60591-3]
UniGeneiMm.116802.

Genome annotation databases

EnsembliENSMUST00000074618; ENSMUSP00000074198; ENSMUSG00000027544. [Q60591-3]
ENSMUST00000109184; ENSMUSP00000104812; ENSMUSG00000027544. [Q60591-2]
GeneIDi18019.
KEGGimmu:18019.
UCSCiuc008oau.2. mouse. [Q60591-3]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS17112.1. [Q60591-3]
CCDS50803.1. [Q60591-2]
PIRiA48753.
RefSeqiNP_035029.2. NM_010899.3. [Q60591-3]
UniGeneiMm.116802.

3D structure databases

ProteinModelPortaliQ60591.
SMRiQ60591.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201739. 1 interactor.
DIPiDIP-49476N.
IntActiQ60591. 11 interactors.
MINTiMINT-1565857.
STRINGi10090.ENSMUSP00000074198.

PTM databases

iPTMnetiQ60591.
PhosphoSitePlusiQ60591.

Proteomic databases

EPDiQ60591.
PaxDbiQ60591.
PeptideAtlasiQ60591.
PRIDEiQ60591.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000074618; ENSMUSP00000074198; ENSMUSG00000027544. [Q60591-3]
ENSMUST00000109184; ENSMUSP00000104812; ENSMUSG00000027544. [Q60591-2]
GeneIDi18019.
KEGGimmu:18019.
UCSCiuc008oau.2. mouse. [Q60591-3]

Organism-specific databases

CTDi4773.
MGIiMGI:102463. Nfatc2.

Phylogenomic databases

eggNOGiENOG410IHFR. Eukaryota.
ENOG41105U2. LUCA.
GeneTreeiENSGT00550000074562.
HOVERGENiHBG069754.
InParanoidiQ60591.
KOiK17332.
OMAiMWKTSPD.
OrthoDBiEOG091G01QP.
TreeFamiTF326480.

Enzyme and pathway databases

ReactomeiR-MMU-2871809. FCERI mediated Ca+2 mobilization.
R-MMU-5607763. CLEC7A (Dectin-1) induces NFAT activation.

Miscellaneous databases

ChiTaRSiNfatc2. mouse.
PROiQ60591.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000027544.
ExpressionAtlasiQ60591. baseline and differential.
GenevisibleiQ60591. MM.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiIPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR008366. NFAT.
IPR008967. p53-like_TF_DNA-bd.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
[Graphical view]
PANTHERiPTHR12533. PTHR12533. 1 hit.
PfamiPF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
[Graphical view]
PRINTSiPR01789. NUCFACTORATC.
SMARTiSM00429. IPT. 1 hit.
[Graphical view]
SUPFAMiSSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNFAC2_MOUSE
AccessioniPrimary (citable) accession number: Q60591
Secondary accession number(s): A2APK2
, A2APK3, A2AQC5, A2AQC6, A2AQC7, B5B2Q3, Q60984, Q60985, Q91Y65
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: July 27, 2011
Last modified: November 30, 2016
This is version 165 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.