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Protein

Nuclear factor of activated T-cells 5

Gene

NFAT5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcription factor involved, among others, in the transcriptional regulation of osmoprotective and inflammatory genes. Mediates the transcriptional response to hypertonicity (PubMed:10051678). Positively regulates the transcription of LCN2 and S100A4 genes; optimal transactivation of these genes requires the presence of DDX5/DDX17 (PubMed:22266867). Binds the DNA consensus sequence 5'-[ACT][AG]TGGAAA[CAT]A[TA][ATC][CA][ATG][GT][GAC][CG][CT]-3' (PubMed:10377394).3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi293 – 3008

GO - Molecular functioni

GO - Biological processi

  • cytokine production Source: Ensembl
  • excretion Source: ProtInc
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • regulation of calcineurin-NFAT signaling cascade Source: Ensembl
  • response to osmotic stress Source: Ensembl
  • signal transduction Source: ProtInc
  • transcription from RNA polymerase II promoter Source: ProtInc

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

SIGNORiO94916.

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear factor of activated T-cells 5
Short name:
NF-AT5
Alternative name(s):
T-cell transcription factor NFAT5
Tonicity-responsive enhancer-binding protein1 Publication
Short name:
TonE-binding protein1 Publication
Short name:
TonEBP1 Publication
Gene namesi
Name:NFAT5
Synonyms:KIAA0827, TONEBP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000102908.20.
HGNCiHGNC:7774. NFAT5.

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi120S → A: Normal nuclear localization. 1 Publication1
Mutagenesisi134S → A: Reduced nuclear localization. 1 Publication1
Mutagenesisi135T → A: Reduced nuclear localization. 1 Publication1
Mutagenesisi155S → A: Increased nuclear localization. 1 Publication1

Organism-specific databases

DisGeNETi10725.
OpenTargetsiENSG00000102908.
PharmGKBiPA31581.

Polymorphism and mutation databases

BioMutaiNFAT5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002051831 – 1531Nuclear factor of activated T-cells 5Add BLAST1531

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei120Phosphoserine1 Publication1
Modified residuei122N6-acetyllysineBy similarity1
Modified residuei134Phosphoserine1 Publication1
Modified residuei135Phosphothreonine; by CDK5Combined sources1 Publication1
Modified residuei155Phosphoserine1 Publication1
Cross-linki556Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki556Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei561PhosphoserineCombined sources1
Cross-linki603Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Isoform D (identifier: O94916-4)
Cross-linki573Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Phosphorylated (PubMed:10377394). Phosphorylated at Thr-135 by CDK5 in response to osmotic stress; this phosphorylation mediates its rapid nuclear localization (PubMed:21209322).2 Publications

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO94916.
MaxQBiO94916.
PaxDbiO94916.
PeptideAtlasiO94916.
PRIDEiO94916.

PTM databases

iPTMnetiO94916.
PhosphoSitePlusiO94916.

Expressioni

Tissue specificityi

Widely expressed, with highest levels in skeletal muscle, brain, heart and peripheral blood leukocytes.2 Publications

Gene expression databases

BgeeiENSG00000102908.
CleanExiHS_NFAT5.
ExpressionAtlasiO94916. baseline and differential.
GenevisibleiO94916. HS.

Organism-specific databases

HPAiHPA057304.
HPA069711.

Interactioni

Subunit structurei

Homodimer when bound to DNA, completely encircles its DNA target. Interacts with CIDEC; this interaction is direct and retains NFAT5 in the cytoplasm (By similarity). Does not bind with Fos and Jun transcription factors. Interacts with DDX5 and DDX17; this interaction leads to DDX5/DDX17 recruitment to LNC2 and S100A4 promoters and NFAT5-mediated DDX5/DDX17-enhanced transactivation (PubMed:22266867).By similarity2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi115949. 5 interactors.
DIPiDIP-58524N.
IntActiO94916. 7 interactors.
STRINGi9606.ENSP00000396538.

Structurei

Secondary structure

11531
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi275 – 277Combined sources3
Beta strandi280 – 286Combined sources7
Beta strandi310 – 312Combined sources3
Beta strandi315 – 320Combined sources6
Beta strandi325 – 337Combined sources13
Beta strandi342 – 348Combined sources7
Beta strandi358 – 362Combined sources5
Beta strandi365 – 372Combined sources8
Helixi374 – 376Combined sources3
Beta strandi379 – 381Combined sources3
Beta strandi384 – 389Combined sources6
Helixi392 – 396Combined sources5
Beta strandi410 – 420Combined sources11
Beta strandi422 – 424Combined sources3
Beta strandi426 – 432Combined sources7
Beta strandi446 – 451Combined sources6
Beta strandi454 – 456Combined sources3
Beta strandi462 – 468Combined sources7
Beta strandi475 – 482Combined sources8
Beta strandi489 – 492Combined sources4
Helixi496 – 498Combined sources3
Beta strandi501 – 507Combined sources7
Beta strandi520 – 528Combined sources9
Beta strandi537 – 542Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1IMHX-ray2.86C/D264-544[»]
ProteinModelPortaliO94916.
SMRiO94916.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94916.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini264 – 443RHDPROSITE-ProRule annotationAdd BLAST180

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi69 – 100Ser-richAdd BLAST32
Compositional biasi739 – 743Poly-Gln5
Compositional biasi879 – 888Poly-Gln10
Compositional biasi966 – 971Poly-Thr6
Compositional biasi1248 – 1266Poly-GlnAdd BLAST19

Phylogenomic databases

eggNOGiENOG410IGY4. Eukaryota.
ENOG41118Z9. LUCA.
GeneTreeiENSGT00550000074562.
HOGENOMiHOG000236245.
HOVERGENiHBG052612.
InParanoidiO94916.
KOiK17335.
OMAiFLFGIQN.
OrthoDBiEOG091G01QP.
PhylomeDBiO94916.
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.
IPR008366. NFAT.
IPR015646. NFAT5.
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:SF10. PTHR12533:SF10. 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 (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform C (identifier: O94916-1) [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
MPSDFISLLS ADLDLESPKS LYSRESVYDL LPKELQLPPS RETSVASMSQ
60 70 80 90 100
TSGGEAGSPP PAVVAADASS APSSSSMGGA CSSFTTSSSP TIYSTSVTDS
110 120 130 140 150
KAMQVESCSS AVGVSNRGVS EKQLTSNTVQ QHPSTPKRHT VLYISPPPED
160 170 180 190 200
LLDNSRMSCQ DEGCGLESEQ SCSMWMEDSP SNFSNMSTSS YNDNTEVPRK
210 220 230 240 250
SRKRNPKQRP GVKRRDCEES NMDIFDADSA KAPHYVLSQL TTDNKGNSKA
260 270 280 290 300
GNGTLENQKG TGVKKSPMLC GQYPVKSEGK ELKIVVQPET QHRARYLTEG
310 320 330 340 350
SRGSVKDRTQ QGFPTVKLEG HNEPVVLQVF VGNDSGRVKP HGFYQACRVT
360 370 380 390 400
GRNTTPCKEV DIEGTTVIEV GLDPSNNMTL AVDCVGILKL RNADVEARIG
410 420 430 440 450
IAGSKKKSTR ARLVFRVNIM RKDGSTLTLQ TPSSPILCTQ PAGVPEILKK
460 470 480 490 500
SLHSCSVKGE EEVFLIGKNF LKGTKVIFQE NVSDENSWKS EAEIDMELFH
510 520 530 540 550
QNHLIVKVPP YHDQHITLPV SVGIYVVTNA GRSHDVQPFT YTPDPAAAGA
560 570 580 590 600
LNVNVKKEIS SPARPCSFEE AMKAMKTTGC NLDKVNIIPN ALMTPLIPSS
610 620 630 640 650
MIKSEDVTPM EVTAEKRSST IFKTTKSVGS TQQTLENISN IAGNGSFSSP
660 670 680 690 700
SSSHLPSENE KQQQIQPKAY NPETLTTIQT QDISQPGTFP AVSASSQLPN
710 720 730 740 750
SDALLQQATQ FQTRETQSRE ILQSDGTVVN LSQLTEASQQ QQQSPLQEQA
760 770 780 790 800
QTLQQQISSN IFPSPNSVSQ LQNTIQQLQA GSFTGSTASG SSGSVDLVQQ
810 820 830 840 850
VLEAQQQLSS VLFSAPDGNE NVQEQLSADI FQQVSQIQSG VSPGMFSSTE
860 870 880 890 900
PTVHTRPDNL LPGRAESVHP QSENTLSNQQ QQQQQQQQVM ESSAAMVMEM
910 920 930 940 950
QQSICQAAAQ IQSELFPSTA SANGNLQQSP VYQQTSHMMS ALSTNEDMQM
960 970 980 990 1000
QCELFSSPPA VSGNETSTTT TQQVATPGTT MFQTSSSGDG EETGTQAKQI
1010 1020 1030 1040 1050
QNSVFQTMVQ MQHSGDNQPQ VNLFSSTKSM MSVQNSGTQQ QGNGLFQQGN
1060 1070 1080 1090 1100
EMMSLQSGNF LQQSSHSQAQ LFHPQNPIAD AQNLSQETQG SLFHSPNPIV
1110 1120 1130 1140 1150
HSQTSTTSSE QMQPPMFHSQ STIAVLQGSS VPQDQQSTNI FLSQSPMNNL
1160 1170 1180 1190 1200
QTNTVAQEAF FAAPNSISPL QSTSNSEQQA AFQQQAPISH IQTPMLSQEQ
1210 1220 1230 1240 1250
AQPPQQGLFQ PQVALGSLPP NPMPQSQQGT MFQSQHSIVA MQSNSPSQEQ
1260 1270 1280 1290 1300
QQQQQQQQQQ QQQQQQSILF SNQNTMATMA SPKQPPPNMI FNPNQNPMAN
1310 1320 1330 1340 1350
QEQQNQSIFH QQSNMAPMNQ EQQPMQFQSQ STVSSLQNPG PTQSESSQTP
1360 1370 1380 1390 1400
LFHSSPQIQL VQGSPSSQEQ QVTLFLSPAS MSALQTSINQ QDMQQSPLYS
1410 1420 1430 1440 1450
PQNNMPGIQG ATSSPQPQAT LFHNTAGGTM NQLQNSPGSS QQTSGMFLFG
1460 1470 1480 1490 1500
IQNNCSQLLT SGPATLPDQL MAISQPGQPQ NEGQPPVTTL LSQQMPENSP
1510 1520 1530
LASSINTNQN IEKIDLLVSL QNQGNNLTGS F
Length:1,531
Mass (Da):165,763
Last modified:May 1, 1999 - v1
Checksum:iA68C68088DABF69E
GO
Isoform A (identifier: O94916-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-76: Missing.

Note: The transcript encoding this isoform contains an alternative coding exon 4 which contains 2 stop codons and could target the transcript to nonsense-mediated mRNA decay after the pioneer round of translation, as suggested by the decreased NFAT5 protein levels when the number of exon 4-containing transcripts increases. The insertion of exon 4 is stimulated in the presence of DDX5 and DDX17. Isoform A sequence described in this entry starts at the first methionine downstream of exon 4 last stop codon. An alternative protein sequence can be predicted from this transcript starting at Met-1. This isoform encodes an 81 amino acid-long protein.Curated1 Publication
Show »
Length:1,455
Mass (Da):157,983
Checksum:i4FA637348EAC0041
GO
Isoform B (identifier: O94916-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: R → RDSLKLHPSQNFHRAGLLE
     67-81: DASSAPSSSSMGGAC → GFASEAGSVCIKNDL
     82-1531: Missing.

Note: The transcript encoding this isoform contains an alternative coding exon 4 which contains 2 stop codons and could target the transcript to nonsense-mediated mRNA decay after the pioneer round of translation, as suggested by the decreased NFAT5 protein levels when the number of exon 4-containing transcripts increases. The insertion of exon 4 is stimulated in the presence of DDX5 and DDX17.Curated1 Publication
Show »
Length:99
Mass (Da):10,459
Checksum:i3E2BB95953579EE8
GO
Isoform D (identifier: O94916-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: R → RDSLKLHPSQNFHRAGLLE
     546-546: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:1,548
Mass (Da):167,737
Checksum:i48E5072E004F9C09
GO
Isoform E (identifier: O94916-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     24-24: R → RDSLKLHPSQNFHRAGLLE

Show »
Length:1,549
Mass (Da):167,808
Checksum:i12DBBD89C630E445
GO

Sequence cautioni

O94916: The sequence AAK91166 differs from that shown. Reason: Frameshift at position 20.Curated
O94916: The sequence AAK91166 differs from that shown. Reason: Erroneous translation.Curated
O94916: The sequence BAA74850 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
O94916: The sequence CAB09693 differs from that shown. Reason: Frameshift at position 1164.Curated
O94916: The sequence CAC42765 differs from that shown. Reason: Frameshift at position 20.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti666 – 667QP → HA in CAC42764 (PubMed:11528118).Curated2
Sequence conflicti666 – 667QP → HA in CAC42765 (PubMed:11528118).Curated2
Sequence conflicti1369E → D in CAB09693 (PubMed:10565538).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0587841 – 76Missing in isoform A. 3 PublicationsAdd BLAST76
Alternative sequenceiVSP_05878524R → RDSLKLHPSQNFHRAGLLE in isoform B, isoform D and isoform E. 2 Publications1 Publication1
Alternative sequenceiVSP_05878667 – 81DASSA…MGGAC → GFASEAGSVCIKNDL in isoform B. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_05878782 – 1531Missing in isoform B. 1 PublicationAdd BLAST1450
Alternative sequenceiVSP_058788546Missing in isoform D. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF089824 mRNA. Translation: AAD18136.1.
AF134870 mRNA. Translation: AAD38360.1.
AF346509 mRNA. Translation: AAK91166.1. Sequence problems.
AJ243298 mRNA. Translation: CAC42764.1.
AJ243299 mRNA. Translation: CAC42765.1. Frameshift.
AB020634 mRNA. Translation: BAA74850.2. Different initiation.
AC009032 Genomic DNA. No translation available.
AC012321 Genomic DNA. No translation available.
CH471092 Genomic DNA. Translation: EAW83281.1.
BC131509 mRNA. Translation: AAI31510.1.
BC146765 mRNA. Translation: AAI46766.1.
AF163836 mRNA. Translation: AAD48441.1.
Z97016 mRNA. Translation: CAB09693.1. Frameshift.
CCDSiCCDS10881.1. [O94916-1]
CCDS10882.1. [O94916-2]
CCDS45518.1. [O94916-5]
CCDS45519.1. [O94916-4]
RefSeqiNP_001106649.1. NM_001113178.2. [O94916-4]
NP_006590.1. NM_006599.3. [O94916-1]
NP_619727.2. NM_138713.3. [O94916-5]
NP_619728.2. NM_138714.3. [O94916-2]
NP_775321.1. NM_173214.2. [O94916-2]
NP_775322.1. NM_173215.2. [O94916-2]
XP_006721188.1. XM_006721125.3.
XP_011521120.1. XM_011522818.2. [O94916-2]
XP_016878359.1. XM_017022870.1. [O94916-2]
UniGeneiHs.371987.

Genome annotation databases

EnsembliENST00000349945; ENSP00000338806; ENSG00000102908. [O94916-2]
ENST00000354436; ENSP00000346420; ENSG00000102908. [O94916-1]
ENST00000393742; ENSP00000377343; ENSG00000102908. [O94916-2]
ENST00000426654; ENSP00000413126; ENSG00000102908. [O94916-3]
ENST00000566899; ENSP00000455628; ENSG00000102908. [O94916-2]
ENST00000567239; ENSP00000457593; ENSG00000102908. [O94916-4]
ENST00000627621; ENSP00000486610; ENSG00000102908. [O94916-5]
GeneIDi10725.
KEGGihsa:10725.
UCSCiuc002exi.4. human. [O94916-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiNFAT5_HUMAN
AccessioniPrimary (citable) accession number: O94916
Secondary accession number(s): A2RRB4
, A6H8V5, E9PHR7, O95693, Q7LA65, Q969Q8, Q96QH3, Q9UN18
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: May 1, 1999
Last modified: October 25, 2017
This is version 179 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, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references