UniProt functional annotation for Q13469



	UniProt functional annotation for Q13469

UniProt code: Q13469.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway. {ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:21871017}.

Subunit: 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. The phosphorylated form specifically interacts with XPO1; which mediates nuclear export. NFATC proteins bind to DNA as monomers. Interacts with NFATC2IP (By similarity). Interacts with FOXP3 (PubMed:15790681). Interacts with TBX21 ('Thr-303' phosphorylated form) (By similarity). Interacts with KAT2A (By similarity). Interacts with HOMER2 and HOMER3; this interaction competes with calcineurin/PPP3CA-binding and hence prevents NFATC2 dephosphorylation and activation (PubMed:18218901). Interacts with protein phosphatase PPP3CA/calcineurin A (PubMed:26248042). {ECO:0000250|UniProtKB:Q60591, ECO:0000269|PubMed:15790681, ECO:0000269|PubMed:18218901, ECO:0000269|PubMed:21458306, ECO:0000269|PubMed:26248042}.

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: Expressed in thymus, spleen, heart, testis, brain, placenta, muscle and pancreas. Isoform 1 is highly expressed in the small intestine, heart, testis, prostate, thymus, placenta and thyroid. Isoform 3 is highly expressed in stomach, uterus, placenta, trachea and thyroid. {ECO:0000269|PubMed:8668213}.

Induction: Inducibly expressed in T-lymphocytes upon activation of the T-cell receptor (TCR) complex. Induced after co-addition of phorbol 12- myristate 13-acetate (PMA) and ionomycin.

Domain: the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000269|PubMed:17467953}.

Domain: Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors. {ECO:0000250}.

Ptm: In resting cells, phosphorylated by NFATC-kinase on at least 18 sites in the 99-363 region. Upon cell stimulation, all these sites except Ser-243 are dephosphorylated by calcineurin. Dephosphorylation induces a conformational change that simultaneously exposes an NLS and masks an NES, which results in nuclear localization. Simultaneously, Ser-53 or Ser-56 is phosphorylated; which is required for full transcriptional activity. {ECO:0000250|UniProtKB:Q60591}.

Ptm: Ubiquitinated in endothelial cells by RNF213 downstream of the non-canonical Wnt signaling pathway, leading to its degradation by the proteasome. {ECO:0000269|PubMed:26766444}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Plays a role in the inducible expression of cytokine genes in T-cells, especially in the induction of the IL-2, IL-3, IL-4, TNF-alpha or GM-CSF. Promotes invasive migration through the activation of GPC6 expression and WNT5A signaling pathway. {ECO:0000269\|PubMed:15790681, ECO:0000269\|PubMed:21871017}.


Subunit:		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. The phosphorylated form specifically interacts with XPO1; which mediates nuclear export. NFATC proteins bind to DNA as monomers. Interacts with NFATC2IP (By similarity). Interacts with FOXP3 (PubMed:15790681). Interacts with TBX21 ('Thr-303' phosphorylated form) (By similarity). Interacts with KAT2A (By similarity). Interacts with HOMER2 and HOMER3; this interaction competes with calcineurin/PPP3CA-binding and hence prevents NFATC2 dephosphorylation and activation (PubMed:18218901). Interacts with protein phosphatase PPP3CA/calcineurin A (PubMed:26248042). {ECO:0000250\|UniProtKB:Q60591, ECO:0000269\|PubMed:15790681, ECO:0000269\|PubMed:18218901, ECO:0000269\|PubMed:21458306, ECO:0000269\|PubMed:26248042}.
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:		Expressed in thymus, spleen, heart, testis, brain, placenta, muscle and pancreas. Isoform 1 is highly expressed in the small intestine, heart, testis, prostate, thymus, placenta and thyroid. Isoform 3 is highly expressed in stomach, uterus, placenta, trachea and thyroid. {ECO:0000269\|PubMed:8668213}.
Induction:		Inducibly expressed in T-lymphocytes upon activation of the T-cell receptor (TCR) complex. Induced after co-addition of phorbol 12- myristate 13-acetate (PMA) and ionomycin.
Domain:		the 9aaTAD motif is a transactivation domain present in a large number of yeast and animal transcription factors. {ECO:0000269\|PubMed:17467953}.
Domain:		Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors. {ECO:0000250}.
Ptm:		In resting cells, phosphorylated by NFATC-kinase on at least 18 sites in the 99-363 region. Upon cell stimulation, all these sites except Ser-243 are dephosphorylated by calcineurin. Dephosphorylation induces a conformational change that simultaneously exposes an NLS and masks an NES, which results in nuclear localization. Simultaneously, Ser-53 or Ser-56 is phosphorylated; which is required for full transcriptional activity. {ECO:0000250\|UniProtKB:Q60591}.
Ptm:		Ubiquitinated in endothelial cells by RNF213 downstream of the non-canonical Wnt signaling pathway, leading to its degradation by the proteasome. {ECO:0000269\|PubMed:26766444}.