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FLASH GENE

Symbol

NFATC3

contributors: mct/npt - updated : 05-09-2016

HGNC name	nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 3
HGNC id	7777

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	16q22.1      Physical location : 68.119.374 - 68.260.837
Synonym name	nuclear factor of activated T-cells, cytoplasmic 3
	T cell transcription factor NFAT4
	cytoplasmic nuclear factor of activated T-cells 3
Synonym symbol(s)	NFAT4, NFATX, NFC3

DNA

TYPE	functioning gene
STRUCTURE	141.46 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D16S3031 - CBFB - CDH5 - HSD11B2 - CDH11 - LCAT LCAT - NFATC3 - E2F4 - AARS - CDH3 - D16S3095 - NQO1 - HP HP - qter
Authors	Gene Map (98)

Physical map

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_173165 10 splicing 3901 NP_775188 115.5 1075 - 2008 18675896 also called variant IB-deltaXa or variant 1 NM_004555 11 splicing 4005 NP_004546 115.1 1068 skeletal muscle, thymus, kidney, small intestine, heart, ovary, prostate, placenta, pancreas 2008 18675896 also called variant IB-Xa or variant 2 containing an additional segment in the coding region, which causes a frameshift, compared to variant 1 NM_173163 11 splicing 3990 NP_775186 114.9 1065 thymus, kidney, testis, spleen 2008 18675896 also called variant 3 containing an additional segment in the coding region, which causes a frameshift, compared to variant 1 NM_173164 9 splicing 3769 NP_775187 112.5 1045 thymus, skeletal muscle 2008 18675896 also called variant IB-IX or variant 4 having a distinct 3' UTR and 3' coding region compared to variant 1 variant 7 11 splicing - isoform 7 - 589 - 2008 18675896 also called IAL-Xa variant 5 10 splicing - isoform 5 - 596 - 2008 18675896 also called IAL-deltaXa variant 6 9 splicing - isoform 6 - 566 - 2008 18675896 also called IAL-IX variant 10 11 splicing - isoform 10 - 589 - 2008 18675896 also called IAS-Xa variant 8 10 splicing - isoform 8 - 596 - 2008 18675896 also called IAS-deltaXa variant 9 9 splicing - isoform 9 - 566 - 2008 18675896 also called IAS-IX variant 13 11 splicing - isoform 13 - 589 - 2008 18675896 also called variant IC-Xa variant 11 10 splicing - isoform 11 - 596 - 2008 18675896 also called IC-deltaXa variant 12 9 splicing - isoform 12 - 566 - 2008 18675896 also called variant IC-IX variant 16 11 splicing - isoform 16 - 589 - 2008 18675896 also called variant ID-Xa variant 14 10 splicing - isoform 14 - 596 - 2008 18675896 also called variant ID-deltaXa variant 15 9 splicing - isoform 15 - 566 - 2008 18675896 also called variant ID-IX variant 19 11 splicing - isoform 19 - 589 - 2008 18675896 also called variant IE-Xa variant 17 10 splicing - isoform 17 - 596 - 2008 18675896 also called variant IE-deltaXa variant 18 9 splicing - isoform 18 - 566 - 2008 18675896 also called variant IE-IX variant 22 11 splicing - isoform 22 - 589 - 2008 18675896 also called variant IF-Xa variant 20 10 splicing - isoform 20 - 596 - 2008 18675896 also called variant IF-deltaXa variant 21 9 splicing - isoform 21 - 566 - 2008 18675896 also called variant IF-IX

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular vessel artery       Homo sapiens Lymphoid/Immune lymph node       highly   thymus       highly   tonsils       highly Reproductive male system         Respiratory respiratory tract larynx     highly Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular smooth vessel   highly Homo sapiens Muscular striatum skeletal

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a calcineurin binding motif (targeting motif, PxIxIT) near at the N terminus of the regulatory domain
	a nuclear localization signal (NLS)
	a serine-rich region and three SP motifs
	a second calcineurin binding domain
	a central Rel-like, DNA binding domain
	a C terminal transactivation domain

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to rattus Nfatc3 (89.7 pc)
	homolog to murine Nfatc3 (89.6 pc)

Homologene

FAMILY

activated T-cell (NFAT) family of transcription factors

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	cytoplasmic phosphorylated form
	nuclear after activation controlled by calcineurin-mediated dephosphorylation
	undergoes rapid dephosphorylation and nuclear translocation that are essentially complete within 20 min depolarization

basic FUNCTION	acting as a putative regulator of gene expression in T cells and immature thymocytes and of cytokines to suppress local aberrant growth of vessels
	inducing chondrogenesis and chondrocyte gene expression
	required for cardiac development and mitochondrial function
	calcineurin/NFATC3 signaling pathway regulates the expression of the 1 subunit of Ca2+-activated K+ (BK) channel in arterial smooth muscle and plays a critical role in the development of angiotensin II-induced hypertension
	translocates to the nucleus in response both to a slow and to a fast-like pattern of activity (Calabria 2009)
	transcriptionally active in fast muscles, i.e., in response to less frequent calcium transients and, presumably, lower Calcineurin activity (Calabria 2009)
	transcription factor tightly regulated by the calcium/calmodulin-dependent phosphatase, calcineurin, activated in astrocytes applied with calcium ionophore or APP (
	positive feedback control between STIM1/SOCE and NFATC3 is required for efficient induction and progression of myoblast differentiation
	NFATC2, NFATC3 possess distinct nuclear localization dynamics in response to cell stimulation
	important and novel regulatory mechanisms of NFATC3 activation in in pulmonary arterial smooth muscle cells (PASMC) by ROS
	transcription factor NFATC3 binds to IRF7 and functions synergistically to enhance IRF7-mediated IFN expression in Plasmacytoid dendritic cells (pDCs)

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development

PATHWAY

metabolism

signaling

signal transduction

a component

INTERACTION

DNA	binding to promoters of cytokine genes

RNA

small molecule

protein	calcineurin substrate (calcineurin/NFATC3 activates BMP expression)
	RhoA/Rho kinase (ROK) increases actin polymerization, thus providing structural support for NFATC3 nuclear transport
	GPC6 is a novel NFATC1, NFATC2, NFATC3, NFATC4 target gene in breast cancer cells that promotes invasive migration through WNT5A signalling
	NFATC3 promotes BACE1 expression via direct interaction with the BACE1 promoter
	STIM1 regulates NFATC3 expression and its activity, and myotube formation
	regulates the expression levels of STIM1 and ORAI1, and the activity of SOCE in C2C12 myoblasts
	astrocyte MMP3 expression was induced by overexpression of a constitutively active form of NFATC3
	NR4A1 functionally interacts with NFATC3 and GATA4 and inhibits their transcriptional activities, which are critical for the development of cardiac hypertrophy
	NFATC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production

cell & other

REGULATION

activated by

calcineurin

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional       gain of function transiently up-regulated in the early phase of myoblast differentiation

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	is a marker of activation for a specific population of astrocytes in response to brain damage, which may have consequences for neuronal survival
Therapy target

ANIMAL & CELL MODELS