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UniProtKB/Swiss-Prot Q12968 (NFAC3_HUMAN)
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January 19, 2010.
Version 104.
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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents
Names and origin
| Protein names | Recommended name: Nuclear factor of activated T-cells, cytoplasmic 3 Short name=NF-ATc3 Short name=NFATc3 Alternative name(s): T-cell transcription factor NFAT4 Short name=NF-AT4 NFATx | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete 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 | Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2. |
| 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. |
| 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. Ref.9 |
| Sequence similarities | Contains 1 RHD (Rel-like) domain. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Transcription Transcription regulation |
| Cellular component | Cytoplasm Nucleus |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Domain | Repeat |
| Ligand | DNA-binding |
| Molecular function | Activator |
| PTM | Acetylation Phosphoprotein |
| Technical term | Complete proteome Direct protein sequencing |
| Gene Ontology (GO) | |
| Biological process | inflammatory response Ref.2 Traceable author statement. Source: ProtInc transcription from RNA polymerase II promoter Ref.2Traceable author statement. Source: ProtInc |
| Cellular component | cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleusInferred from electronic annotation. Source: UniProtKB-SubCell |
| Complete GO annotation... | |
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 | ||||||
| Modified residue | 163 | 1 | Phosphoserine Ref.9 | ||||||
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: dbSNP rs2230092. | VAR_051784 | |||||
| Natural variant | 94 | 1 | E → A: dbSNP rs3743736. | VAR_051785 | |||||
| Natural variant | 100 | 1 | L → S: dbSNP rs2230093. | VAR_051786 | |||||
| Natural variant | 136 | 1 | P → L: dbSNP rs2230094. | VAR_051787 | |||||
| Natural variant | 382 | 1 | P → S: dbSNP rs2230095. | 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 | ||||||
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: 7749981] [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: 7739550] [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: 9759864] [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: 10493829] [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: 15489334] [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: 9630228] [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: 10089876] [Abstract] Cited for: REVIEW. |
| [9] | "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-163, MASS SPECTROMETRY. Tissue: T-cell. |
| + | 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. NP_775186.1. NP_775187.1. NP_775188.1. |
| UniGene | Hs.632209 |
3D structure databases | |
| SMR | Q12968. Positions 415-700. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q12968. |
PTM databases | |
| PhosphoSite | Q12968. |
Proteomic databases | |
| PRIDE | Q12968. |
Genome annotation databases | |
| Ensembl | ENST00000346183; ENSP00000300659; ENSG00000072736; Homo sapiens. [Genome view] |
| GeneID | 4775. |
| KEGG | hsa:4775. |
| UCSC | uc002evk.1. human. uc002evm.1. human. uc002evn.1. human. uc002evo.1. human. |
Organism-specific databases | |
| CTD | 4775. |
| GeneCards | GC16P066676. |
| H-InvDB | HIX0013169. |
| HGNC | HGNC:7777. NFATC3. |
| HPA | CAB004514. HPA023844. |
| MIM | 602698. gene. |
| PharmGKB | PA247. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG18409. |
| HOGENOM | HBG717170. |
| HOVERGEN | Q12968. |
| InParanoid | Q12968. |
| OMA | HSTQAQS. |
| 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. |
Gene expression databases | |
| ArrayExpress | Q12968. |
| Bgee | Q12968. |
| CleanEx | HS_NFATC3. |
| Genevestigator | Q12968. |
| GermOnline | ENSG00000072736. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR013783. Ig-like_fold. IPR014756. Ig_E-set. IPR002909. IPT_TIG_rcpt. IPR008366. NFAT. IPR018286. NFAT_sbgrp. IPR008967. p53-like_TF_DNA-bd. IPR011539. RHD. [Graphical view] |
| Gene3D | G3DSA:2.60.40.10. Ig-like_fold. 1 hit. |
| PANTHER | PTHR12533. NFAT. 1 hit. |
| Pfam | PF00554. RHD. 1 hit. PF01833. TIG. 1 hit. [Graphical view] |
| PRINTS | PR01789. NUCFACTORATC. |
| SMART | SM00429. IPT. 1 hit. [Graphical view] |
| PROSITE | PS01204. REL_1. False negative. PS50254. REL_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 18410. |
| SOURCE | Search... |
Entry information
| Entry name | NFAC3_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q12968 Secondary accession number(s): O75211  Q99842 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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 |
| SIMILARITY comments Index of protein domains and families |
