O94916 (NFAT5_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 135.
History...
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | 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 protein Short name=TonE-binding protein Short name=TonEBP | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Reference proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo![]() |
Protein attributes
| Sequence length | 1531 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | Plays a role in the inducible expression of genes. Regulates hypertonicity-induced cellular accumulation of osmolytes. |
| Subunit structure | Homodimer when bound to DNA, completely encircles its DNA target. Does not bind with Fos and Jun transcription factors. Ref.10 |
| Subcellular location | |
| Tissue specificity | Highest levels in skeletal muscle, brain, heart and peripheral blood leukocytes. Also expressed in placenta, lung, liver, kidney, pancreas, spleen, thymus, prostate, testis, ovary, small intestine and colon. |
| Post-translational modification | Phosphorylated at Thr-135 by CDK5 in response to osmotic stress; this phosphorylation mediates its rapid nuclear localization. Ref.11 |
| Sequence similarities | Contains 1 RHD (Rel-like) domain. |
| Sequence caution | The sequence BAA74850.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened. The sequence CAB09693.1 differs from that shown. Reason: Frameshift at position 1164. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transcription Transcription regulation |
| Cellular component | Nucleus |
| Coding sequence diversity | Alternative splicing |
| Ligand | DNA-binding |
| Molecular function | Activator |
| PTM | Phosphoprotein |
| Technical term | 3D-structure Complete proteome Reference proteome |
| Gene Ontology (GO) | |
| Biological_process | excretion Traceable author statement Ref.3. Source: ProtInc signal transductionNon-traceable author statement Ref.2. Source: ProtInc transcription from RNA polymerase II promoterTraceable author statement Ref.3. Source: ProtInc |
| Cellular_component | nucleus Traceable author statement Ref.3. Source: ProtInc |
| Molecular_function | DNA binding Inferred from electronic annotation. Source: UniProtKB-KW sequence-specific DNA binding transcription factor activityTraceable author statement Ref.3. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| DDX17 | Q92841 | 3 | EBI-308320,EBI-746012 | |
| DDX5 | P17844 | 4 | EBI-308320,EBI-351962 |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] Note: Experimental confirmation may be lacking for some isoforms. | ||||||
| Isoform C (identifier: O94916-1) 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. | ||||||
| Isoform A (identifier: O94916-2) The sequence of this isoform differs from the canonical sequence as follows: 1-76: Missing. | ||||||
| Isoform B (identifier: O94916-3) The sequence of this isoform differs from the canonical sequence as follows: 1-47: Missing. | ||||||
| Isoform D (identifier: O94916-4) The sequence of this isoform differs from the canonical sequence as follows: 24-24: R → RDSLKLHPSQNFHRAGLLE 546-546: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1531 | 1531 | Nuclear factor of activated T-cells 5 | PRO_0000205183 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Domain | 264 – 443 | 180 | RHD | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DNA binding | 293 – 300 | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compositional bias | 69 – 100 | 32 | Ser-rich | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compositional bias | 739 – 743 | 5 | Poly-Gln | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compositional bias | 879 – 888 | 10 | Poly-Gln | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compositional bias | 966 – 971 | 6 | Poly-Thr | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Compositional bias | 1248 – 1266 | 19 | Poly-Gln | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Amino acid modifications | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 120 | 1 | Phosphoserine Ref.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 134 | 1 | Phosphoserine Ref.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 135 | 1 | Phosphothreonine; by CDK5 Ref.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Modified residue | 155 | 1 | Phosphoserine Ref.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 76 | 76 | Missing in isoform A. | VSP_005605 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 1 – 47 | 47 | Missing in isoform B. | VSP_005606 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 24 | 1 | R → RDSLKLHPSQNFHRAGLLE in isoform D. | VSP_043840 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
| Alternative sequence | 546 | 1 | Missing in isoform D. | VSP_043841 | |||||||||||||||||||||||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 120 | 1 | S → A: Normal nuclear localization. Ref.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 134 | 1 | S → A: Reduced nuclear localization. Ref.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 135 | 1 | T → A: Reduced nuclear localization. Ref.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Mutagenesis | 155 | 1 | S → A: Increased nuclear localization. Ref.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Sequence conflict | 1369 | 1 | E → D in CAB09693. Ref.8 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 275 – 277 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 280 – 286 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 310 – 312 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 315 – 320 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 325 – 337 | 13 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 342 – 348 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 358 – 362 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 365 – 372 | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 374 – 376 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 379 – 381 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 384 – 389 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 392 – 396 | 5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 410 – 420 | 11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 422 – 424 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 426 – 432 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 446 – 451 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 454 – 456 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 462 – 468 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 475 – 482 | 8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 489 – 492 | 4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Helix | 496 – 498 | 3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 501 – 507 | 7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 520 – 528 | 9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Beta strand | 537 – 542 | 6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro." Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:355-364(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C). Tissue: Brain. |
| [2] | "NFAT5, a constitutively nuclear NFAT protein that does not cooperate with Fos and Jun." Lopez-Rodriguez C., Aramburu J., Rakeman A.S., Rao A. Proc. Natl. Acad. Sci. U.S.A. 96:7214-7219(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). Tissue: Brain. |
| [3] | "Tonicity-responsive enhancer binding protein, a rel-like protein that stimulates transcription in response to hypertonicity." Miyakawa H., Woo S.K., Dahl S.C., Handler J.S., Kwon H.M. Proc. Natl. Acad. Sci. U.S.A. 96:2538-2542(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). |
| [4] | "NFAT5: the NF-AT family of transcription factors expands in a new direction." Lopez-Rodriguez C., Aramburu J., Rakeman A.S., Copeland N.G., Gilbert D.J., Thomas S., Disteche C., Jenkins N.A., Rao A. Cold Spring Harb. Symp. Quant. Biol. 64:517-526(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B). Tissue: Brain. |
| [5] | "The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. Pennacchio L.A.Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS C AND D). |
| [8] | "Isolation and characterization of novel CAG repeat containing genes expressed in human brain." Zuehlke C., Kiehl R., Johannsmeyer A., Grzeschik K.H., Schwinger E. DNA Seq. 10:1-6(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 675-1531. Tissue: Brain. |
| [9] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma. |
| [10] | "Structure of a TonEBP-DNA complex reveals DNA encircled by a transcription factor." Stroud J.C., Lopez-Rodriguez C., Rao A., Chen L. Nat. Struct. Biol. 9:90-94(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.86 ANGSTROMS) OF 264-544 IN COMPLEX WITH DNA, SUBUNIT. |
| [11] | "High NaCl-induced activation of CDK5 increases phosphorylation of the osmoprotective transcription factor TonEBP/OREBP at threonine 135, which contributes to its rapid nuclear localization." Gallazzini M., Heussler G.E., Kunin M., Izumi Y., Burg M.B., Ferraris J.D. Mol. Biol. Cell 22:703-714(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-120; SER-134; THR-135 AND SER-155, MUTAGENESIS OF SER-120; SER-134; THR-135 AND SER-155. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | AB020634 mRNA. Translation: BAA74850.2. Different initiation. AF134870 mRNA. Translation: AAD38360.1. AF089824 mRNA. Translation: AAD18136.1. AF163836 mRNA. Translation: AAD48441.1. 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. Z97016 mRNA. Translation: CAB09693.1. Frameshift. | ||||||||||||
| IPI | IPI00217710. IPI00218771. IPI00218772. | ||||||||||||
| RefSeq | NP_001106649.1. NM_001113178.2. NP_006590.1. NM_006599.3. NP_619727.2. NM_138713.3. NP_619728.2. NM_138714.3. NP_775321.1. NM_173214.2. NP_775322.1. NM_173215.2. | ||||||||||||
| UniGene | Hs.371987. | ||||||||||||
3D structure databases | |||||||||||||
| PDBe RCSB PDB PDBj |
| ||||||||||||
| ProteinModelPortal | O94916. | ||||||||||||
| ModBase | Search... | ||||||||||||
Protein-protein interaction databases | |||||||||||||
| DIP | DIP-58524N. | ||||||||||||
| IntAct | O94916. 5 interactions. | ||||||||||||
| STRING | 9606.ENSP00000396538. | ||||||||||||
PTM databases | |||||||||||||
| PhosphoSite | O94916. | ||||||||||||
Proteomic databases | |||||||||||||
| PaxDb | O94916. | ||||||||||||
| PRIDE | O94916. | ||||||||||||
Protocols and materials databases | |||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||
Genome annotation databases | |||||||||||||
| Ensembl | ENST00000349945; ENSP00000338806; ENSG00000102908. ENST00000354436; ENSP00000346420; ENSG00000102908. ENST00000393742; ENSP00000377343; ENSG00000102908. ENST00000566899; ENSP00000455628; ENSG00000102908. ENST00000567239; ENSP00000457593; ENSG00000102908. | ||||||||||||
| GeneID | 10725. | ||||||||||||
| KEGG | hsa:10725. | ||||||||||||
| UCSC | uc002exi.3. human. | ||||||||||||
Organism-specific databases | |||||||||||||
| CTD | 10725. | ||||||||||||
| GeneCards | GC16P069599. | ||||||||||||
| HGNC | HGNC:7774. NFAT5. | ||||||||||||
| MIM | 604708. gene. | ||||||||||||
| neXtProt | NX_O94916. | ||||||||||||
| PharmGKB | PA31581. | ||||||||||||
| HUGE | Search... | ||||||||||||
| GenAtlas | Search... | ||||||||||||
Phylogenomic databases | |||||||||||||
| eggNOG | NOG85658. | ||||||||||||
| HOGENOM | HOG000236245. | ||||||||||||
| HOVERGEN | HBG052612. | ||||||||||||
| InParanoid | O94916. | ||||||||||||
| KO | K04446. | ||||||||||||
| OrthoDB | EOG48GW2P. | ||||||||||||
Gene expression databases | |||||||||||||
| ArrayExpress | O94916. | ||||||||||||
| Bgee | O94916. | ||||||||||||
| CleanEx | HS_NFAT5. | ||||||||||||
| Genevestigator | O94916. | ||||||||||||
| GermOnline | ENSG00000102908. Homo sapiens. | ||||||||||||
Family and domain databases | |||||||||||||
| Gene3D | 2.60.40.10. 1 hit. 2.60.40.340. 1 hit. | ||||||||||||
| InterPro | IPR013783. Ig-like_fold. IPR014756. Ig_E-set. IPR002909. IPT_TIG_rcpt. IPR008366. NFAT. IPR015646. NFAT5. IPR008967. p53-like_TF_DNA-bd. IPR011539. RHD. [Graphical view] | ||||||||||||
| PANTHER | PTHR12533. PTHR12533. 1 hit. PTHR12533:SF1. PTHR12533:SF1. 1 hit. | ||||||||||||
| Pfam | PF00554. RHD. 1 hit. [Graphical view] | ||||||||||||
| PRINTS | PR01789. NUCFACTORATC. | ||||||||||||
| SMART | SM00429. IPT. 1 hit. [Graphical view] | ||||||||||||
| SUPFAM | SSF81296. Ig_E-set. 1 hit. SSF49417. P53_like_DNA_bnd. 1 hit. | ||||||||||||
| PROSITE | PS01204. REL_1. False negative. PS50254. REL_2. 1 hit. [Graphical view] | ||||||||||||
| ProtoNet | Search... | ||||||||||||
Other | |||||||||||||
| ChiTaRS | NFAT5. human. | ||||||||||||
| EvolutionaryTrace | O94916. | ||||||||||||
| GenomeRNAi | 10725. | ||||||||||||
| NextBio | 40713. | ||||||||||||
| SOURCE | Search... | ||||||||||||
Entry information
| Entry name | NFAT5_HUMAN | ||||||||
| Accession | Primary (citable) accession number: O94916 Secondary accession number(s): A2RRB4 Q9UN18 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation program | Chordata Protein Annotation Program | ||||||||
| Disclaimer | Any 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. | ||||||||
Relevant documents
| Human chromosome 16 Human chromosome 16: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| SIMILARITY comments Index of protein domains and families |

Clusters with
