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Protein

Nuclear factor of activated T-cells, cytoplasmic 3

Gene

NFATC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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-2.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi444 – 4518

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-2025928 Calcineurin activates NFAT
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-5607763 CLEC7A (Dectin-1) induces NFAT activation
SIGNORiQ12968

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:NFATC3
Synonyms:NFAT4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000072736.18
HGNCiHGNC:7777 NFATC3
MIMi602698 gene
neXtProtiNX_Q12968

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

Organism-specific databases

DisGeNETi4775
OpenTargetsiENSG00000072736
PharmGKBiPA247

Polymorphism and mutation databases

BioMutaiNFATC3
DMDMi9087155

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00002051802 – 1075Nuclear factor of activated T-cells, cytoplasmic 3Add BLAST1074

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylthreonine1 Publication1
Modified residuei344PhosphoserineBy similarity1
Modified residuei372PhosphoserineCombined sources1
Modified residuei1063PhosphoserineCombined sources1
Modified residuei1066PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ12968
MaxQBiQ12968
PaxDbiQ12968
PeptideAtlasiQ12968
PRIDEiQ12968
ProteomicsDBi59061
59062 [Q12968-2]
59063 [Q12968-3]
59064 [Q12968-4]
59065 [Q12968-5]
59066 [Q12968-6]

PTM databases

iPTMnetiQ12968
PhosphoSitePlusiQ12968

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000072736 Expressed in 214 organ(s), highest expression level in leukocyte
CleanExiHS_NFATC3
ExpressionAtlasiQ12968 baseline and differential
GenevisibleiQ12968 HS

Organism-specific databases

HPAiHPA050665

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.

Binary interactionsi

WithEntry#Exp.IntActNotes
RAF1P040492EBI-5278441,EBI-365996

Protein-protein interaction databases

BioGridi110848, 13 interactors
ELMiQ12968
IntActiQ12968, 5 interactors
MINTiQ12968
STRINGi9606.ENSP00000300659

Structurei

Secondary structure

11075
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ12968
SMRiQ12968
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati207 – 2231Add BLAST17
Repeati236 – 2522Add BLAST17
Repeati292 – 3083Add BLAST17
Domaini415 – 596RHDPROSITE-ProRule annotationAdd BLAST182

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni109 – 114Calcineurin-binding6
Regioni207 – 3083 X SP repeatsAdd BLAST102

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi273 – 275Nuclear localization signal3
Motifi686 – 688Nuclear localization signal3
Motifi1032 – 1041Nuclear export signal10

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi24 – 29Poly-Pro6

Domaini

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IIAD Eukaryota
ENOG4111EMW LUCA
GeneTreeiENSGT00550000074562
HOGENOMiHOG000231780
HOVERGENiHBG069754
InParanoidiQ12968
KOiK17333
OMAiTSISPNC
OrthoDBiEOG091G01QP
PhylomeDBiQ12968
TreeFamiTF326480

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
IPR008967 p53-like_TF_DNA-bd
IPR032397 RHD_dimer
IPR011539 RHD_DNA_bind_dom
IPR037059 RHD_DNA_bind_dom_sf
PANTHERiPTHR12533 PTHR12533, 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 (6+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 6 described isoforms and 6 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q12968-1) [UniParc]FASTAAdd to basket
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.

« Hide
        10         20         30         40         50
MTTANCGAHD ELDFKLVFGE DGAPAPPPPG SRPADLEPDD CASIYIFNVD
60 70 80 90 100
PPPSTLTTPL CLPHHGLPSH SSVLSPSFQL QSHKNYEGTC EIPESKYSPL
110 120 130 140 150
GGPKPFECPS IQITSISPNC HQELDAHEDD LQINDPEREF LERPSRDHLY
160 170 180 190 200
LPLEPSYRES SLSPSPASSI SSRSWFSDAS SCESLSHIYD DVDSELNEAA
210 220 230 240 250
ARFTLGSPLT SPGGSPGGCP GEETWHQQYG LGHSLSPRQS PCHSPRSSVT
260 270 280 290 300
DENWLSPRPA SGPSSRPTSP CGKRRHSSAE VCYAGSLSPH HSPVPSPGHS
310 320 330 340 350
PRGSVTEDTW LNASVHGGSG LGPAVFPFQY CVETDIPLKT RKTSEDQAAI
360 370 380 390 400
LPGKLELCSD DQGSLSPARE TSIDDGLGSQ YPLKKDSCGD QFLSVPSPFT
410 420 430 440 450
WSKPKPGHTP IFRTSSLPPL DWPLPAHFGQ CELKIEVQPK THHRAHYETE
460 470 480 490 500
GSRGAVKAST GGHPVVKLLG YNEKPINLQM FIGTADDRYL RPHAFYQVHR
510 520 530 540 550
ITGKTVATAS QEIIIASTKV LEIPLLPENN MSASIDCAGI LKLRNSDIEL
560 570 580 590 600
RKGETDIGRK NTRVRLVFRV HIPQPSGKVL SLQIASIPVE CSQRSAQELP
610 620 630 640 650
HIEKYSINSC SVNGGHEMVV TGSNFLPESK IIFLEKGQDG RPQWEVEGKI
660 670 680 690 700
IREKCQGAHI VLEVPPYHNP AVTAAVQVHF YLCNGKRKKS QSQRFTYTPV
710 720 730 740 750
LMKQEHREEI DLSSVPSLPV PHPAQTQRPS SDSGCSHDSV LSGQRSLICS
760 770 780 790 800
IPQTYASMVT SSHLPQLQCR DESVSKEQHM IPSPIVHQPF QVTPTPPVGS
810 820 830 840 850
SYQPMQTNVV YNGPTCLPIN AASSQEFDSV LFQQDATLSG LVNLGCQPLS
860 870 880 890 900
SIPFHSSNSG STGHLLAHTP HSVHTLPHLQ SMGYHCSNTG QRSLSSPVAD
910 920 930 940 950
QITGQPSSQL QPITYGPSHS GSATTASPAA SHPLASSPLS GPPSPQLQPM
960 970 980 990 1000
PYQSPSSGTA SSPSPATRMH SGQHSTQAQS TGQGGLSAPS SLICHSLCDP
1010 1020 1030 1040 1050
ASFPPDGATV SIKPEPEDRE PNFATIGLQD ITLDDVNEII GRDMSQISVS
1060 1070
QGAGVSRQAP LPSPESLDLG RSDGL
Length:1,075
Mass (Da):115,594
Last modified:November 1, 1996 - v1
Checksum:i0B25D61A2B56D898
GO
Isoform 2 (identifier: Q12968-2) [UniParc]FASTAAdd to basket
Also known as: X2, C

The sequence of this isoform differs from the canonical sequence as follows:
     1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → DQFISDLEHQPSGSAEKWPNHSVLSCPAPFWRI

Show »
Length:1,068
Mass (Da):115,237
Checksum:iCD91817D06AD5D82
GO
Isoform 3 (identifier: Q12968-3) [UniParc]FASTAAdd to basket
Also known as: X3

The sequence of this isoform differs from the canonical sequence as follows:
     1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → DLFTSNNFDLLQLRPTFWPVPAGRYLRNLE

Show »
Length:1,065
Mass (Da):115,050
Checksum:iB827F1D5CE01D033
GO
Isoform 4 (identifier: Q12968-4) [UniParc]FASTAAdd to basket
Also known as: X4

The sequence of this isoform differs from the canonical sequence as follows:
     1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → GKFISDMFLK

Show »
Length:1,045
Mass (Da):112,642
Checksum:i44CE97FCF4A4EEAD
GO
Isoform 5 (identifier: Q12968-5) [UniParc]FASTAAdd to basket
Also known as: A

The sequence of this isoform differs from the canonical sequence as follows:
     700-1075: VLMKQEHREE...SLDLGRSDGL → GTRSHDGLL

Show »
Length:708
Mass (Da):77,181
Checksum:iD96C59AEC592D0E0
GO
Isoform 6 (identifier: Q12968-6) [UniParc]FASTAAdd to basket
Also known as: B

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

Show »
Length:739
Mass (Da):80,582
Checksum:i8AB8BAFA1A319E50
GO

Computationally mapped potential isoform sequencesi

There are 6 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BRS1H3BRS1_HUMAN
Nuclear factor of-activated T-cells...
NFATC3
1,060Annotation score:
I3L3K7I3L3K7_HUMAN
Nuclear factor of-activated T-cells...
NFATC3
1,047Annotation score:
H3BR83H3BR83_HUMAN
Nuclear factor of-activated T-cells...
NFATC3
1,053Annotation score:
H3BU30H3BU30_HUMAN
Nuclear factor of-activated T-cells...
NFATC3
167Annotation score:
H3BRM3H3BRM3_HUMAN
Nuclear factor of-activated T-cells...
NFATC3
41Annotation score:
F8VPH9F8VPH9_HUMAN
Nuclear factor of-activated T-cells...
NFATC3
38Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti702M → L in AAB46595 (PubMed:9759864).Curated1
Sequence conflicti702M → L in AAB46596 (PubMed:9759864).Curated1
Sequence conflicti702M → L in AAB46597 (PubMed:9759864).Curated1
Sequence conflicti831L → W in AAB46595 (PubMed:9759864).Curated1
Sequence conflicti831L → W in AAB46596 (PubMed:9759864).Curated1
Sequence conflicti831L → W in AAB46597 (PubMed:9759864).Curated1
Sequence conflicti899A → G in AAB46595 (PubMed:9759864).Curated1
Sequence conflicti899A → G in AAB46596 (PubMed:9759864).Curated1
Sequence conflicti899A → G in AAB46597 (PubMed:9759864).Curated1
Sequence conflicti923A → V in AAB46595 (PubMed:9759864).Curated1
Sequence conflicti923A → V in AAB46596 (PubMed:9759864).Curated1
Sequence conflicti923A → V in AAB46597 (PubMed:9759864).Curated1
Sequence conflicti935A → G in AAB46595 (PubMed:9759864).Curated1
Sequence conflicti935A → G in AAB46596 (PubMed:9759864).Curated1
Sequence conflicti935A → G in AAB46597 (PubMed:9759864).Curated1
Sequence conflicti947L → F in AAB46595 (PubMed:9759864).Curated1
Sequence conflicti947L → F in AAB46596 (PubMed:9759864).Curated1
Sequence conflicti947L → F in AAB46597 (PubMed:9759864).Curated1
Sequence conflicti960A → G in AAB46595 (PubMed:9759864).Curated1
Sequence conflicti960A → G in AAB46596 (PubMed:9759864).Curated1
Sequence conflicti960A → G in AAB46597 (PubMed:9759864).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05178475S → L. Corresponds to variant dbSNP:rs2230092Ensembl.1
Natural variantiVAR_05178594E → A. Corresponds to variant dbSNP:rs3743736Ensembl.1
Natural variantiVAR_051786100L → S. Corresponds to variant dbSNP:rs2230093Ensembl.1
Natural variantiVAR_051787136P → L. Corresponds to variant dbSNP:rs2230094Ensembl.1
Natural variantiVAR_051788382P → S. Corresponds to variant dbSNP:rs2230095Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005598700 – 1075VLMKQ…RSDGL → GTRSHDGLL in isoform 5. 1 PublicationAdd BLAST376
Alternative sequenceiVSP_005599717 – 1075SLPVP…RSDGL → TLPQTSRQTLLGSQPPSASP PTV in isoform 6. 1 PublicationAdd BLAST359
Alternative sequenceiVSP_0056001036 – 1075VNEII…RSDGL → DQFISDLEHQPSGSAEKWPN HSVLSCPAPFWRI in isoform 2. 2 PublicationsAdd BLAST40
Alternative sequenceiVSP_0056011036 – 1075VNEII…RSDGL → DLFTSNNFDLLQLRPTFWPV PAGRYLRNLE in isoform 3. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_0056021036 – 1075VNEII…RSDGL → GKFISDMFLK in isoform 4. 1 PublicationAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS10860.1 [Q12968-1]
CCDS10861.1 [Q12968-3]
CCDS10862.1 [Q12968-2]
PIRiA57377
RefSeqiNP_004546.1, NM_004555.3 [Q12968-2]
NP_775186.1, NM_173163.2 [Q12968-3]
NP_775188.1, NM_173165.2 [Q12968-1]
UniGeneiHs.436585

Genome annotation databases

EnsembliENST00000329524; ENSP00000331324; ENSG00000072736 [Q12968-2]
ENST00000346183; ENSP00000300659; ENSG00000072736 [Q12968-1]
ENST00000349223; ENSP00000264008; ENSG00000072736 [Q12968-3]
GeneIDi4775
KEGGihsa:4775
UCSCiuc002evm.3 human [Q12968-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNFAC3_HUMAN
AccessioniPrimary (citable) accession number: Q12968
Secondary accession number(s): O75211
, Q14516, Q99840, Q99841, Q99842
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: November 1, 1996
Last modified: September 12, 2018
This is version 182 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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