Q12968 (NFAC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 134.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | 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 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 | 1075 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is further processed into a mature form. |
| Protein existence | Evidence at protein level |
General annotation (Comments)
| Function | 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. Ref.9 |
| Subunit structure | 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. |
| Subcellular location | Cytoplasm. Nucleus. Note: Cytoplasmic for the phosphorylated form and nuclear after activation that is controlled by calcineurin-mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to be one mechanism by which cells distinguish between sustained and transient calcium signals. The subcellular localization of NFATC plays a key role in the regulation of gene transcription. Ref.9 |
| Tissue specificity | 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. |
| Domain | Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors. |
| Post-translational modification | Phosphorylated by NFATC-kinase; dephosphorylated by calcineurin By similarity. |
| Sequence similarities | Contains 1 RHD (Rel-like) domain. |
Ontologies
Alternative products
| This entry describes 6 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q12968-1) 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. | ||||||
| Isoform 2 (identifier: Q12968-2) Also known as: X2; C; The sequence of this isoform differs from the canonical sequence as follows: 1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → DQFISDLEHQPSGSAEKWPNHSVLSCPAPFWRI | ||||||
| Isoform 3 (identifier: Q12968-3) Also known as: X3; The sequence of this isoform differs from the canonical sequence as follows: 1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → DLFTSNNFDLLQLRPTFWPVPAGRYLRNLE | ||||||
| Isoform 4 (identifier: Q12968-4) Also known as: X4; The sequence of this isoform differs from the canonical sequence as follows: 1036-1075: VNEIIGRDMSQISVSQGAGVSRQAPLPSPESLDLGRSDGL → GKFISDMFLK | ||||||
| Isoform 5 (identifier: Q12968-5) Also known as: A; The sequence of this isoform differs from the canonical sequence as follows: 700-1075: VLMKQEHREE...SLDLGRSDGL → GTRSHDGLL | ||||||
| Isoform 6 (identifier: Q12968-6) Also known as: B; The sequence of this isoform differs from the canonical sequence as follows: 717-1075: SLPVPHPAQT...SLDLGRSDGL → TLPQTSRQTLLGSQPPSASPPTV |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Initiator methionine | 1 | 1 | Removed Ref.6 | ||||||||
| Chain | 2 – 1075 | 1074 | Nuclear factor of activated T-cells, cytoplasmic 3 | PRO_0000205180 | |||||||
Regions | |||||||||||
| Repeat | 207 – 223 | 17 | 1 | ||||||||
| Repeat | 236 – 252 | 17 | 2 | ||||||||
| Repeat | 292 – 308 | 17 | 3 | ||||||||
| Domain | 415 – 596 | 182 | RHD | ||||||||
| DNA binding | 444 – 451 | 8 | |||||||||
| Region | 109 – 114 | 6 | Calcineurin-binding | ||||||||
| Region | 207 – 308 | 102 | 3 X SP repeats | ||||||||
| Motif | 273 – 275 | 3 | Nuclear localization signal | ||||||||
| Motif | 686 – 688 | 3 | Nuclear localization signal | ||||||||
| Motif | 1032 – 1041 | 10 | Nuclear export signal | ||||||||
| Compositional bias | 24 – 29 | 6 | Poly-Pro | ||||||||
Amino acid modifications | |||||||||||
| Modified residue | 2 | 1 | N-acetylthreonine Ref.6 | ||||||||
Natural variations | |||||||||||
| Alternative sequence | 700 – 1075 | 376 | VLMKQ…RSDGL → GTRSHDGLL in isoform 5. | VSP_005598 | |||||||
| Alternative sequence | 717 – 1075 | 359 | SLPVP…RSDGL → TLPQTSRQTLLGSQPPSASP PTV in isoform 6. | VSP_005599 | |||||||
| Alternative sequence | 1036 – 1075 | 40 | VNEII…RSDGL → DQFISDLEHQPSGSAEKWPN HSVLSCPAPFWRI in isoform 2. | VSP_005600 | |||||||
| Alternative sequence | 1036 – 1075 | 40 | VNEII…RSDGL → DLFTSNNFDLLQLRPTFWPV PAGRYLRNLE in isoform 3. | VSP_005601 | |||||||
| Alternative sequence | 1036 – 1075 | 40 | VNEII…RSDGL → GKFISDMFLK in isoform 4. | VSP_005602 | |||||||
| Natural variant | 75 | 1 | S → L. Corresponds to variant rs2230092 [ dbSNP | Ensembl ]. | VAR_051784 | |||||||
| Natural variant | 94 | 1 | E → A. Corresponds to variant rs3743736 [ dbSNP | Ensembl ]. | VAR_051785 | |||||||
| Natural variant | 100 | 1 | L → S. Corresponds to variant rs2230093 [ dbSNP | Ensembl ]. | VAR_051786 | |||||||
| Natural variant | 136 | 1 | P → L. Corresponds to variant rs2230094 [ dbSNP | Ensembl ]. | VAR_051787 | |||||||
| Natural variant | 382 | 1 | P → S. Corresponds to variant rs2230095 [ dbSNP | Ensembl ]. | VAR_051788 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 702 | 1 | M → L in AAB46595. Ref.3 | ||||||||
| Sequence conflict | 702 | 1 | M → L in AAB46596. Ref.3 | ||||||||
| Sequence conflict | 702 | 1 | M → L in AAB46597. Ref.3 | ||||||||
| Sequence conflict | 831 | 1 | L → W in AAB46595. Ref.3 | ||||||||
| Sequence conflict | 831 | 1 | L → W in AAB46596. Ref.3 | ||||||||
| Sequence conflict | 831 | 1 | L → W in AAB46597. Ref.3 | ||||||||
| Sequence conflict | 899 | 1 | A → G in AAB46595. Ref.3 | ||||||||
| Sequence conflict | 899 | 1 | A → G in AAB46596. Ref.3 | ||||||||
| Sequence conflict | 899 | 1 | A → G in AAB46597. Ref.3 | ||||||||
| Sequence conflict | 923 | 1 | A → V in AAB46595. Ref.3 | ||||||||
| Sequence conflict | 923 | 1 | A → V in AAB46596. Ref.3 | ||||||||
| Sequence conflict | 923 | 1 | A → V in AAB46597. Ref.3 | ||||||||
| Sequence conflict | 935 | 1 | A → G in AAB46595. Ref.3 | ||||||||
| Sequence conflict | 935 | 1 | A → G in AAB46596. Ref.3 | ||||||||
| Sequence conflict | 935 | 1 | A → G in AAB46597. Ref.3 | ||||||||
| Sequence conflict | 947 | 1 | L → F in AAB46595. Ref.3 | ||||||||
| Sequence conflict | 947 | 1 | L → F in AAB46596. Ref.3 | ||||||||
| Sequence conflict | 947 | 1 | L → F in AAB46597. Ref.3 | ||||||||
| Sequence conflict | 960 | 1 | A → G in AAB46595. Ref.3 | ||||||||
| Sequence conflict | 960 | 1 | A → G in AAB46596. Ref.3 | ||||||||
| Sequence conflict | 960 | 1 | A → G in AAB46597. Ref.3 | ||||||||
Secondary structure | |||||||||||
Helix Strand Turn | |||||||||||
| Helix | 146 – 148 | 3 | |||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Isolation of two new members of the NF-AT gene family and functional characterization of the NF-AT proteins." Hoey T., Sun Y.-L., Williamson K., Xu X. Immunity 2:461-472(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 5 AND 6). Tissue: Skeletal muscle and T-cell. |
| [2] | "NFATx, a novel member of the nuclear factor of activated T cells family that is expressed predominantly in the thymus." Masuda E.S., Naito Y., Tokumitsu H., Campbell D., Saito F., Hannum C., Arai K., Arai N. Mol. Cell. Biol. 15:2697-2706(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: T-cell. |
| [3] | "Carboxy-terminal 15 amino acids sequence of NFATx1 is possibly created by tissue-specific splicing and is essential for transactivation activity in T cells." Imamura R., Masuda E.S., Naito Y., Imai S., Fujino T., Takano T., Arai K., Arai N. J. Immunol. 161:3455-3463(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4). Tissue: Fibroblast and T-cell. |
| [4] | "Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q." Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D. Genomics 60:295-308(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 4). |
| [5] | "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] (ISOFORM 1). Tissue: Kidney. |
| [6] | Bienvenut W.V., Waridel P., Quadroni M. Submitted (MAR-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-15; 468-488; 505-519 AND 579-594, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT THR-2, MASS SPECTROMETRY. Tissue: Embryonic kidney. |
| [7] | "Intramolecular masking of nuclear import signal on NF-AT4 by casein kinase I and MEKK1." Zhu J., Shibasaki F., Price R., Guillemot J.-C., Yano T., Doetsch V., Wagner G., Ferrara P., McKeon F. Cell 93:851-861(1998) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS. |
| [8] | "Generic signals and specific outcomes: signaling through Ca2+, calcineurin, and NF-AT." Crabtree G.R. Cell 96:611-614(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW. |
| [9] | "CHP2 activates the calcineurin/nuclear factor of activated T cells signaling pathway and enhances the oncogenic potential of HEK293 cells." Li G.D., Zhang X., Li R., Wang Y.D., Wang Y.L., Han K.J., Qian X.P., Yang C.G., Liu P., Wei Q., Chen W.F., Zhang J., Zhang Y. J. Biol. Chem. 283:32660-32668(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| EMBL GenBank DDBJ | 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. | ||||||||||||||||||
| IPI | IPI00005240. IPI00030369. IPI00215624. IPI00215625. IPI00215626. IPI00215627. | ||||||||||||||||||
| PIR | A57377. | ||||||||||||||||||
| RefSeq | NP_004546.1. NM_004555.3. NP_775186.1. NM_173163.2. NP_775188.1. NM_173165.2. | ||||||||||||||||||
| UniGene | Hs.436585. | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| PDBe RCSB PDB PDBj |
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| ProteinModelPortal | Q12968. | ||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| IntAct | Q12968. 1 interaction. | ||||||||||||||||||
| STRING | 9606.ENSP00000300659. | ||||||||||||||||||
PTM databases | |||||||||||||||||||
| PhosphoSite | Q12968. | ||||||||||||||||||
Polymorphism databases | |||||||||||||||||||
| DMDM | 9087155. | ||||||||||||||||||
Proteomic databases | |||||||||||||||||||
| PaxDb | Q12968. | ||||||||||||||||||
| PRIDE | Q12968. | ||||||||||||||||||
Protocols and materials databases | |||||||||||||||||||
| DNASU | 4775. | ||||||||||||||||||
| StructuralBiologyKnowledgebase | Search... | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENST00000329524; ENSP00000331324; ENSG00000072736. ENST00000346183; ENSP00000300659; ENSG00000072736. ENST00000349223; ENSP00000264008; ENSG00000072736. | ||||||||||||||||||
| GeneID | 4775. | ||||||||||||||||||
| KEGG | hsa:4775. | ||||||||||||||||||
| UCSC | uc002evn.2. human. uc002evo.2. human. | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| CTD | 4775. | ||||||||||||||||||
| GeneCards | GC16P068119. | ||||||||||||||||||
| HGNC | HGNC:7777. NFATC3. | ||||||||||||||||||
| HPA | CAB004514. HPA023844. | ||||||||||||||||||
| MIM | 602698. gene. | ||||||||||||||||||
| neXtProt | NX_Q12968. | ||||||||||||||||||
| PharmGKB | PA247. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| eggNOG | NOG70055. | ||||||||||||||||||
| HOGENOM | HOG000231780. | ||||||||||||||||||
| HOVERGEN | HBG069754. | ||||||||||||||||||
| InParanoid | Q12968. | ||||||||||||||||||
| KO | K04446. | ||||||||||||||||||
| OMA | ASSQEFD. | ||||||||||||||||||
| PhylomeDB | Q12968. | ||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||
| Pathway_Interaction_DB | nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes. tcrcalciumpathway. Calcium signaling in the CD4+ TCR pathway. cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells. nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes. | ||||||||||||||||||
| Reactome | REACT_118664. Calcineurin Dephosphorylates NFATC1/2/3. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | Q12968. | ||||||||||||||||||
| Bgee | Q12968. | ||||||||||||||||||
| CleanEx | HS_NFATC3. | ||||||||||||||||||
| Genevestigator | Q12968. | ||||||||||||||||||
| GermOnline | ENSG00000072736. 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. IPR008967. p53-like_TF_DNA-bd. IPR011539. RHD. [Graphical view] | ||||||||||||||||||
| PANTHER | PTHR12533. PTHR12533. 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 | NFATC3. human. | ||||||||||||||||||
| GenomeRNAi | 4775. | ||||||||||||||||||
| NextBio | 18410. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
Entry information
| Entry name | NFAC3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q12968 Secondary accession number(s): O75211 Q99842 | ||||||||
| Entry history |
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| 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 |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| 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
