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Protein

Nuclear factor of activated T-cells, cytoplasmic 1

Gene

Nfatc1

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 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells (By similarity). Required for osteoclastogenesis and regulates many genes important for osteoclast differentiation and function (PubMed:26644563).1 PublicationBy similarity

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi440 – 447By similarity8

GO - Molecular functioni

  • chromatin binding Source: MGI
  • DNA binding Source: MGI
  • mitogen-activated protein kinase p38 binding Source: BHF-UCL
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II core promoter sequence-specific DNA binding Source: MGI
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II transcription factor binding Source: BHF-UCL
  • sequence-specific DNA binding Source: MGI
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding Source: BHF-UCL
  • transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: MGI
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • aortic valve morphogenesis Source: MGI
  • B-1a B cell differentiation Source: MGI
  • calcineurin-NFAT signaling cascade Source: MGI
  • calcium ion transport Source: MGI
  • epithelial to mesenchymal transition Source: MGI
  • G1/S transition of mitotic cell cycle Source: MGI
  • heart development Source: MGI
  • heart trabecula morphogenesis Source: MGI
  • heart valve morphogenesis Source: MGI
  • intracellular signal transduction Source: MGI
  • lymphangiogenesis Source: MGI
  • negative regulation of osteoblast differentiation Source: MGI
  • negative regulation of stem cell proliferation Source: MGI
  • negative regulation of transcription from RNA polymerase II promoter Source: MGI
  • osteoclast differentiation Source: MGI
  • patterning of lymph vessels Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • pulmonary valve morphogenesis Source: MGI
  • regulation of hair cycle Source: MGI
  • regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • transition between fast and slow fiber Source: MGI
  • ventricular septum morphogenesis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear factor of activated T-cells, cytoplasmic 1
Short name:
NF-ATc1
Short name:
NFATc1
Alternative name(s):
NFAT transcription complex cytosolic component
Short name:
NF-ATc
Short name:
NFATc
Gene namesi
Name:Nfatc1
Synonyms:Nfat2, Nfatc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:102469. Nfatc1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • nuclear chromatin Source: MGI
  • nucleus Source: UniProtKB
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL6034.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000303311 – 717Nuclear factor of activated T-cells, cytoplasmic 1Add BLAST717

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei235PhosphoserineCombined sources1
Modified residuei239PhosphoserineCombined sources1
Modified residuei247Phosphoserine; by PKABy similarity1
Modified residuei271Phosphoserine; by PKABy similarity1
Modified residuei296Phosphoserine; by PKABy similarity1

Post-translational modificationi

Phosphorylated by NFATC-kinase and GSK3B; phosphorylation induces NFATC1 nuclear exit and dephosphorylation by calcineurin promotes nuclear import. Phosphorylation by PKA and DYRK2 negatively modulates nuclear accumulation, and promotes subsequent phosphorylation by GSK3B or casein kinase 1 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiO88942.
PaxDbiO88942.
PRIDEiO88942.

PTM databases

iPTMnetiO88942.
PhosphoSitePlusiO88942.

Expressioni

Tissue specificityi

Expressed in spleen, lung, skeletal muscle, thymus and skin (PubMed:9388475). Weakly expressed in heart, brain, liver and kidney. Not expressed in testis (PubMed:10072529).2 Publications

Developmental stagei

Expression begins at E7 day and increases until E17 day. Strongly expressed in thymus, lung and submandibular gland and weakly in skeletal muscle and heart.1 Publication

Inductioni

Inducibly expressed in T-lymphocytes upon activation of the T-cell receptor (TCR) complex. Induced after addition of phorbol 12-myristate 13-acetate (PMA) (PubMed:9388475, PubMed:10072529). Expressed during osteoclastogenesis and its induction and activation is regulated by TNFSF11 (PubMed:26644563).3 Publications

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. NFATC proteins bind to DNA as monomers (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Q913V32EBI-8073353,EBI-10053030From a different organism.

GO - Molecular functioni

  • mitogen-activated protein kinase p38 binding Source: BHF-UCL
  • RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

IntActiO88942. 2 interactors.
MINTiMINT-6612506.
STRINGi10090.ENSMUSP00000129001.

Structurei

3D structure databases

ProteinModelPortaliO88942.
SMRiO88942.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati205 – 2211Add BLAST17
Repeati235 – 2512Add BLAST17
Repeati284 – 3003Add BLAST17
Domaini411 – 593RHDPROSITE-ProRule annotationAdd BLAST183

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni120 – 125Calcineurin-binding6
Regioni128 – 220Trans-activation domain A (TAD-A)Add BLAST93
Regioni205 – 3003 X SP repeatsAdd BLAST96

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi267 – 269Nuclear localization signal3
Motifi312 – 323Nuclear export signalAdd BLAST12
Motifi683 – 685Nuclear localization signal3

Domaini

Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors.By similarity
The N-terminal transactivation domain (TAD-A) binds to and is activated by Cbp/p300. The dephosphorylated form contains two unmasked nuclear localization signals (NLS), which allow translocation of the protein to the nucleus (By similarity).By similarity

Sequence similaritiesi

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IHFR. Eukaryota.
ENOG41105U2. LUCA.
HOGENOMiHOG000231780.
HOVERGENiHBG069754.
InParanoidiO88942.
PhylomeDBiO88942.

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.
IPR015647. NFAT1.
IPR008967. p53-like_TF_DNA-bd.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
[Graphical view]
PANTHERiPTHR12533. PTHR12533. 1 hit.
PTHR12533:SF5. PTHR12533:SF5. 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 (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform Alpha (identifier: O88942-1) [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
MPNTSFPVPS KFPLGPPAAV CGSGETLRPA PPSGGTMKAA EEEHYSYVSP
60 70 80 90 100
SVTSTLPLPT AHSALPAACH DLQTSTPGIS AVPSANHPPS YGGAVDSGPS
110 120 130 140 150
GYFLSSGNTR PNGAPTLESP RIEITSYLGL HHGSGQFFHD VEVEDVLPSC
160 170 180 190 200
KRSPSTATLH LPSLEAYRDP SCLSPASSLS SRSCNSEASS YESNYSYPYA
210 220 230 240 250
SPQTSPWQSP CVSPKTTDPE EGFPRSLGAC HLLGSPRHSP STSPRASITE
260 270 280 290 300
ESWLGARGSR PTSPCNKRKY SLNGRQPSCS PHHSPTPSPH GSPRVSVTED
310 320 330 340 350
TWLGNTTQYT SSAIVAAINA LTTDSTLDLG DGVPIKSRKT ALEHAPSVAL
360 370 380 390 400
KVEPAGEDLG TTPPTSDFPP EEYTFQHLRK GAFCEQYLSV PQASYQWAKP
410 420 430 440 450
KSLSPTSYMS PSLPALDWQL PSHSGPYELR IEVQPKSHHR AHYETEGSRG
460 470 480 490 500
AVKASAGGHP IVQLHGYLEN EPLTLQLFIG TADDRLLRPH AFYQVHRITG
510 520 530 540 550
KTVSTTSHEI ILSNTKVLEI PLLPENNMRA IIDCAGILKL RNSDIELRKG
560 570 580 590 600
ETDIGRKNTR VRLVFRVHIP QPNGRTLSLQ VASNPIECSQ RSAQELPLVE
610 620 630 640 650
KQSTDSYPVI GGKKMVLSGH NFLQDSKVIF VEKAPDGHHV WEMEAKTDRD
660 670 680 690 700
LCKPNSLVVE IPPFRNQRIT SPAQVSFYVC NGKRKRSQYQ RFTYLPANGN
710
SVFLTLSSES ELRGGFY
Length:717
Mass (Da):77,833
Last modified:November 1, 1998 - v1
Checksum:i58837C6CC085268D
GO
Isoform Beta (identifier: O88942-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MPNTSFPVPSKFPLGPPAAVCGSGETLRPAPPSGGTMKAAEE → MTGLEQDPEFDFDFLFEFDQSGGGAAAA

Show »
Length:703
Mass (Da):76,664
Checksum:iD737C9B87D8A8646
GO
Isoform Alpha' (identifier: O88942-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Note: Produced by alternative initiation at Met-37 of isoform Alpha. No experimental confirmation available.
Show »
Length:681
Mass (Da):74,328
Checksum:i8718DE5001750E2E
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0055941 – 42MPNTS…KAAEE → MTGLEQDPEFDFDFLFEFDQ SGGGAAAA in isoform Beta. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_0188671 – 36Missing in isoform Alpha'. CuratedAdd BLAST36

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF049606 mRNA. Translation: AAC05505.1.
AF087434 mRNA. Translation: AAC36725.1.
CCDSiCCDS29369.1. [O88942-2]
UniGeneiMm.329560.

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF049606 mRNA. Translation: AAC05505.1.
AF087434 mRNA. Translation: AAC36725.1.
CCDSiCCDS29369.1. [O88942-2]
UniGeneiMm.329560.

3D structure databases

ProteinModelPortaliO88942.
SMRiO88942.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO88942. 2 interactors.
MINTiMINT-6612506.
STRINGi10090.ENSMUSP00000129001.

Chemistry databases

ChEMBLiCHEMBL6034.

PTM databases

iPTMnetiO88942.
PhosphoSitePlusiO88942.

Proteomic databases

MaxQBiO88942.
PaxDbiO88942.
PRIDEiO88942.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:102469. Nfatc1.

Phylogenomic databases

eggNOGiENOG410IHFR. Eukaryota.
ENOG41105U2. LUCA.
HOGENOMiHOG000231780.
HOVERGENiHBG069754.
InParanoidiO88942.
PhylomeDBiO88942.

Miscellaneous databases

PROiO88942.
SOURCEiSearch...

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.
IPR015647. NFAT1.
IPR008967. p53-like_TF_DNA-bd.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
[Graphical view]
PANTHERiPTHR12533. PTHR12533. 1 hit.
PTHR12533:SF5. PTHR12533:SF5. 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 nameiNFAC1_MOUSE
AccessioniPrimary (citable) accession number: O88942
Secondary accession number(s): O70345
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1998
Last modified: November 2, 2016
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, 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.