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Protein

Nuclear factor of activated T-cells, cytoplasmic 1

Gene

Nfatc1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:102469 Nfatc1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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). Interacts with HOMER2 and HOMER3 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Q913V32EBI-8073353,EBI-10053030From Hepatitis C virus genotype 1b (isolate HCR6).

GO - Molecular functioni

Protein-protein interaction databases

IntActiO88942, 2 interactors
MINTiO88942
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

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
InterProiView protein in InterPro
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR002909 IPT_dom
IPR008366 NFAT
IPR015647 NFAT1
IPR008967 p53-like_TF_DNA-bd
IPR032397 RHD_dimer
IPR011539 RHD_DNA_bind_dom
IPR037059 RHD_DNA_bind_dom_sf
PANTHERiPTHR12533 PTHR12533, 1 hit
PTHR12533:SF5 PTHR12533:SF5, 1 hit
PfamiView protein in Pfam
PF16179 RHD_dimer, 1 hit
PF00554 RHD_DNA_bind, 1 hit
PRINTSiPR01789 NUCFACTORATC
SMARTiView protein in SMART
SM00429 IPT, 1 hit
SUPFAMiSSF49417 SSF49417, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS50254 REL_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

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

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B5B2N2B5B2N2_MOUSE
Nuclear factor of activated T-cells...
Nfatc1
939Annotation score:
Q6P7T9Q6P7T9_MOUSE
Nuclear factor of activated T-cells...
Nfatc1
827Annotation score:
Q9DBQ6Q9DBQ6_MOUSE
Nuclear factor of activated T-cells...
Nfatc1
703Annotation score:
B5B2N7B5B2N7_MOUSE
Nuclear factor of activated T-cells...
Nfatc1
925Annotation score:

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

Similar proteinsi

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
MINTiO88942
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

PROiPR:O88942
SOURCEiSearch...

Family and domain databases

Gene3Di2.60.40.10, 1 hit
2.60.40.340, 1 hit
InterProiView protein in InterPro
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR002909 IPT_dom
IPR008366 NFAT
IPR015647 NFAT1
IPR008967 p53-like_TF_DNA-bd
IPR032397 RHD_dimer
IPR011539 RHD_DNA_bind_dom
IPR037059 RHD_DNA_bind_dom_sf
PANTHERiPTHR12533 PTHR12533, 1 hit
PTHR12533:SF5 PTHR12533:SF5, 1 hit
PfamiView protein in Pfam
PF16179 RHD_dimer, 1 hit
PF00554 RHD_DNA_bind, 1 hit
PRINTSiPR01789 NUCFACTORATC
SMARTiView protein in SMART
SM00429 IPT, 1 hit
SUPFAMiSSF49417 SSF49417, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS50254 REL_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNFAC1_MOUSE
AccessioniPrimary (citable) accession number: O88942
Secondary accession number(s): O70345
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1998
Last modified: November 7, 2018
This is version 169 of the entry and version 1 of the sequence. See 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
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Main funding by: National Institutes of Health

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