Nuclear factor of activated T cell gene transcriptions (NFAT)

# Nuclear factor of activated T cell genes
Gene ID: 4772 is NFATC1 nuclear factor of activated T cells 1 (aka NFAT2) on 18q23: "The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as cyclosporin A. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes."
- NP_001265598.1 nuclear factor of activated T-cells, cytoplasmic 1 isoform F: "Transcript Variant: This variant (6) encodes the longest isoform (F)."
- NP_001265599.1 nuclear factor of activated T-cells, cytoplasmic 1 isoform G: "Transcript Variant: This variant (7) lacks an in-frame exon in the 3' coding region, compared to variant 6. The encoded isoform (G) lacks an internal segment in the C-terminal region, compared to isoform F."
- NP_001265601.1 nuclear factor of activated T-cells, cytoplasmic 1 isoform H: "Transcript Variant: This variant (8) has an alternate 5' terminal exon, which results in a different 5' UTR and 5' coding region, and lacks an in-frame exon in the 3' coding region, compared to variant 6. The encoded isoform (H) is shorter; it has a distinct N-terminus and lacks an internal segment in the C-terminal region, compared to isoform F."
- NP_001265602.1 nuclear factor of activated T-cells, cytoplasmic 1 isoform J: "Transcript Variant: This variant (10) has an alternate 5' terminal exon and lacks an internal exon in the 5' region, which results in a downstream translation start codon, compared to variant 6. The encoded isoform (J) is shorter at the N-terminus, compared to isoform F."
- NP_001265604.1 nuclear factor of activated T-cells, cytoplasmic 1 isoform I: "Transcript Variant: This variant (9) has multiple differences, compared to variant 6. These differences result in distinct 5' and 3' UTRs and 5' and 3' terminal coding regions, compared to variant 6. The encoded isoform (I) is shorter and has distinct N- and C-termini, compared to isoform F."
- NP_006153.2 nuclear factor of activated T-cells, cytoplasmic 1 isoform B: "Transcript Variant: This variant (2) uses an alternate splice site in the 3' coding region, compared to variant 6. The encoded isoform (B) is truncated at the C-terminus, compared to isoform F."
- NP_765975.1 nuclear factor of activated T-cells, cytoplasmic 1 isoform C: "Transcript Variant: This variant (3) has an alternate 5' terminal exon, which results in a different 5' UTR and 5' coding region, compared to variant 6. The encoded isoform (C) is shorter and has a distinct N-terminus, compared to isoform F."
- NP_765976.1 nuclear factor of activated T-cells, cytoplasmic 1 isoform D: "Transcript Variant: This variant (4) lacks an internal exon in the 5' region, which results in a downstream translation start codon, and has an alternate splice site in the 3' coding region, compared to variant 6. The encoded isoform (D) is shorter at both the N- and C- termini, compared to isoform F."
- NP_765977.1 nuclear factor of activated T-cells, cytoplasmic 1 isoform E: "Transcript Variant: This variant (5) has an alternate 5' terminal exon, which results in a different 5' UTR and 5' coding region, and uses an alternate splice site in the 3' coding region, compared to variant 6. The encoded isoform (E, also known as C.b) is shorter; it has a distinct N-terminus and is truncated at the C-terminus, compared to isoform F."
- NP_765978.1  nuclear factor of activated T-cells, cytoplasmic 1 isoform A: "Transcript Variant: This variant (1) lacks two exons and its transcription extends past a splice site that is used in variant 6, which results in a novel 3' coding region and 3' UTR, compared to variant 6. The encoded isoform (A) is shorter and has a distinct C-terminus, compared to isoform F."
Gene ID: 4773 is NFATC2 nuclear factor of activated T cells 2 (aka NFAT1) on 20q13.2. "This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants encoding different isoforms have been characterized."
- NP_001129493.1 nuclear factor of activated T-cells, cytoplasmic 2 isoform D: "Transcript Variant: This variant (3) uses an alternate first exon and contains an alternate exon in the 3' end compared to variant 2, that causes a frameshift. The resulting isoform (D) has shorter and distinct N- and C-termini compared to isoform C."
- NP_001245221.1 nuclear factor of activated T-cells, cytoplasmic 2 isoform E: "Transcript Variant: This variant (4) uses an alternate first exon compared to variant 2. The resulting isoform (E) has a shorter and distinct N-terminus compared to isoform C."
- NP_001245223.1 nuclear factor of activated T-cells, cytoplasmic 2 isoform F: "Transcript Variant: This variant (5) has an alternate first exon, an alternate exon in the 3' end, and uses an alternate splice junction at the 5' end of a coding exon compared to variant 2. The resulting isoform (F) is shorter at the N-terminus and has a shorter and distinct C-terminus compared to isoform C. Variants 5 and 7 both encode the same isoform (F)."
- NP_001245224.1 nuclear factor of activated T-cells, cytoplasmic 2 isoform G: "Transcript Variant: This variant (6) has an alternate first exon and uses an alternate splice junction at the 5' end of a coding exon compared to variant 2. The resulting isoform (G) is shorter at the N-terminus compared to isoform C. Variants 6 and 8 both encode the same isoform (G)."
- NP_001245225.1 nuclear factor of activated T-cells, cytoplasmic 2 isoform F: "Transcript Variant: This variant (7) uses an alternate splice junction at the 5' end of a coding exon and contains an alternate exon in the 3' end compared to variant 2, that causes a frameshift. The resulting isoform (F) is shorter at the N-terminus and has a shorter and distinct C-terminus compared to isoform C. Variants 5 and 7 both encode the same isoform (F)."
- NP_001245226.1 nuclear factor of activated T-cells, cytoplasmic 2 isoform G: "Transcript Variant: This variant (8) uses an alternate splice junction at the 5' end of a coding exon compared to variant 2. The resulting isoform (G) is shorter at the N-terminus compared to isoform C. Variants 6 and 8 both encode the same isoform (G)."
- NP_036472.2 nuclear factor of activated T-cells, cytoplasmic 2 isoform B: "Transcript Variant: This variant (1) contains an alternate exon in the 3' end compared to variant 2, that causes a frameshift. The resulting isoform (B) has a shorter and distinct C-terminus compared to isoform C."
- NP_775114.1 nuclear factor of activated T-cells, cytoplasmic 2 isoform C: "Transcript Variant: This variant (2) encodes the longest isoform (C)."
Gene ID: 4775 is NFATC3 nuclear factor of activated T cells 3 (aka NFAT4) on 16q22.1: "The product of this gene is a member of the nuclear factors of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation and an inducible nuclear component. Other members of this family participate to form this complex also. The product of this gene plays a role in the regulation of gene expression in T cells and immature thymocytes. Several transcript variants encoding distinct isoforms have been identified for this gene. "
- NP_004546.1 nuclear factor of activated T-cells, cytoplasmic 3 isoform 2: "Transcript Variant: This variant (2) contains an additional segment in the coding region, which causes a frameshift, compared to variant 1. The resulting isoform (2) contains a shorter and distinct C-terminus compared to isoform 1."
- NP_775186.1 nuclear factor of activated T-cells, cytoplasmic 3 isoform 3: "Transcript Variant: This variant (3) contains an additional segment in the coding region, which causes a frameshift, compared to variant 1. The resulting isoform (3) contains a shorter and distinct C-terminus compared to isoform 1."
- NP_775188.1 nuclear factor of activated T-cells, cytoplasmic 3 isoform 1: "Transcript Variant: This variant (1) encodes the longest isoform (1)."
Gene ID: 4776 is NFATC4 nuclear factor of activated T cells 4 (aka NFAT3) on 14q12: "This gene encodes a member of the nuclear factor of activated T cells (NFAT) protein family. The encoded protein is part of a DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor stimulation and an inducible nuclear component. NFAT proteins are activated by the calmodulin-dependent phosphatase, calcineurin. The encoded protein plays a role in the inducible expression of cytokine genes in T cells, especially in the induction of interleukin-2 and interleukin-4. Alternative splicing results in multiple transcript variants."
- NP_001129494.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 1 .
- NP_001185894.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 3 .
- NP_001185895.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 4 .
- NP_001185896.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 5 .
- NP_001275731.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 6 .
- NP_001306972.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 7 .
- NP_001350610.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 8 .
- NP_001350611.1 nuclear factor of activated T-cells, cytoplasmic 4 isoform 9 .
- NP_004545.2 nuclear factor of activated T-cells, cytoplasmic 4 isoform 2 .
Gene ID: 10725 is NFAT5 nuclear factor of activated T cells 5 on 16q22.1: "The product of this gene is a member of the nuclear factors of activated T cells family of transcription factors. Proteins belonging to this family play a central role in inducible gene transcription during the immune response. This protein regulates gene expression induced by osmotic stress in mammalian cells. Unlike monomeric members of this protein family, this protein exists as a homodimer and forms stable dimers with DNA elements. Multiple transcript variants encoding different isoforms have been found for this gene."
- NP_001106649.1 nuclear factor of activated T-cells 5 isoform d: "Transcript Variant: This variant (6) lacks an exon in the 5' region and uses an alternate in-frame splice site in the central coding region, compared to variant 1. These differences result in an isoform (d) with a longer N-terminus and lacking an internal aa, compared to isoform a."
- NP_001354638.1 nuclear factor of activated T-cells 5 isoform e .
- NP_006590.1 nuclear factor of activated T-cells 5 isoform c: "Transcript Variant: This variant (3) lacks two exons in the 5' region, compared to variant 1. This difference causes translation initiation at an upstream start codon and results in an isoform (c) with a longer N-terminus compared to isoform a."
- NP_619727.2 nuclear factor of activated T-cells 5 isoform b: "Transcript Variant: This variant (2) lacks an exon in the 5' region, compared to variant 1. This difference causes translation initiation at an upstream start codon and results in an isoform (b) with a longer N-terminus compared to isoform a."
- NP_619728.2 nuclear factor of activated T-cells 5 isoform a: "Transcript Variant: This variant (1) represents the longest transcript. This variant and variants 4 and 5 encode the same isoform (a)."
- NP_775321.1 nuclear factor of activated T-cells 5 isoform a: "Transcript Variant: This variant (4) lacks an exon in the 5' UTR, compared to variant 1. Variants 1, 4 and 5 encode the same isoform (a)."
- NP_775322.1 nuclear factor of activated T-cells 5 isoform a: "Transcript Variant: This variant (5) differs in the 5' and 3' UTRs, compared to variant 1. It encodes isoform a, which is also encoded by variants 1 and 4."

# NFAT samplings
Copying an apparent consensus sequence for the NFAT GGAAAA and putting it in "F" finds none located between ZSCAN22 and one between ZNF497 and A1BG as can be found by the computer programs.
For the Basic programs testing consensus sequence GGAAAA (starting with SuccessablesNFAT.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), the programs are, are looking for, and found:
- negative strand, negative direction, looking for GGAAAA, 0.
- positive strand, negative direction, looking for GGAAAA, 3, GGAAAA at 2968, GGAAAA at 2927, GGAAAA at 2459.
- positive strand, positive direction, looking for GGAAAA, 1, GGAAAA at 135.
- negative strand, positive direction, looking for GGAAAA, 1, GGAAAA at 291.
- complement, negative strand, negative direction, looking for CCTTTT, 3, CCTTTT at 2968, CCTTTT at 2927, CCTTTT at 2459.
- complement, positive strand, negative direction, looking for CCTTTT, 0.
- complement, positive strand, positive direction, looking for CCTTTT, 1, CCTTTT at 291.
- complement, negative strand, positive direction, looking for CCTTTT, 1, CCTTTT at 135.
- inverse complement, negative strand, negative direction, looking for TTTTCC, 4, TTTTCC at 3441, TTTTCC at 3345, TTTTCC at 1107, TTTTCC at 105.
- inverse complement, positive strand, negative direction, looking for TTTTCC, 0.
- inverse complement, positive strand, positive direction, looking for TTTTCC, 0.
- inverse complement, negative strand, positive direction, looking for TTTTCC, 0.
- inverse negative strand, negative direction, looking for AAAAGG, 0.
- inverse positive strand, negative direction, looking for AAAAGG, 4, AAAAGG at 3441, AAAAGG at 3345, AAAAGG at 1107, AAAAGG at 105.
- inverse positive strand, positive direction, looking for AAAAGG, 0.
- inverse negative strand, positive direction, looking for AAAAGG, 0.

## NFAT (4560-2846) UTRs
- Negative strand, negative direction: TTTTCC at 3441, TTTTCC at 3345.
- Positive strand, negative direction: GGAAAA at 2968, GGAAAA at 2927.

## NFAT negative direction (2596-1) distal promoters
- Negative strand, negative direction: TTTTCC at 1107, TTTTCC at 105.
- Positive strand, negative direction: GGAAAA at 2459.

## NFAT positive direction (4050-1) distal promoters
- Negative strand, positive direction: GGAAAA at 291.
- Positive strand, positive direction: GGAAAA at 135.

# Response element random dataset samplings
- NFATr0: 1, GGAAAA at 769.
- NFATr1: 1, GGAAAA at 1707.
- NFATr2: 1, GGAAAA at 2081.
- NFATr3: 3, GGAAAA at 2900, GGAAAA at 2846, GGAAAA at 762.
- NFATr4: 3, GGAAAA at 3904, GGAAAA at 3627, GGAAAA at 860.
- NFATr5: 2, GGAAAA at 4321, GGAAAA at 635.
- NFATr6: 1, GGAAAA at 746.
- NFATr7: 4, GGAAAA at 3883, GGAAAA at 3321, GGAAAA at 2063, GGAAAA at 1504.
- NFATr8: 6, GGAAAA at 3992, GGAAAA at 3407, GGAAAA at 3085, GGAAAA at 2164, GGAAAA at 2100, GGAAAA at 308.
- NFATr9: 4, GGAAAA at 3182, GGAAAA at 2909, GGAAAA at 2184, GGAAAA at 592.
- NFATr0ci: 1, TTTTCC at 4204.
- NFATr1ci: 8, TTTTCC at 4231, TTTTCC at 3839, TTTTCC at 3648, TTTTCC at 3034, TTTTCC at 2569, TTTTCC at 2290, TTTTCC at 2143, TTTTCC at 656.
- NFATr2ci: 4, TTTTCC at 4115, TTTTCC at 3560, TTTTCC at 449, TTTTCC at 410.
- NFATr3ci: 4, TTTTCC at 3540, TTTTCC at 2472, TTTTCC at 2360, TTTTCC at 151.
- NFATr4ci: 1, TTTTCC at 2076.
- NFATr5ci: 5, TTTTCC at 3495, TTTTCC at 2357, TTTTCC at 1450, TTTTCC at 862, TTTTCC at 834.
- NFATr6ci: 4, TTTTCC at 4184, TTTTCC at 3674, TTTTCC at 3355, TTTTCC at 3291.
- NFATr7ci: 4, TTTTCC at 3582, TTTTCC at 3259, TTTTCC at 2840, TTTTCC at 351.
- NFATr8ci: 1, TTTTCC at 2122.
- NFATr9ci: 2, TTTTCC at 2315, TTTTCC at 136.

## NFATr arbitrary (evens) (4560-2846) UTRs
- NFATr4: GGAAAA at 3904, GGAAAA at 3627.
- NFATr8: GGAAAA at 3992, GGAAAA at 3407, GGAAAA at 3085.
- NFATr0ci: TTTTCC at 4204.
- NFATr2ci: TTTTCC at 4115, TTTTCC at 3560.
- NFATr6ci: TTTTCC at 4184, TTTTCC at 3674, TTTTCC at 3355, TTTTCC at 3291.

## NFATr alternate (odds) (4560-2846) UTRs
- NFATr5: GGAAAA at 4321.
- NFATr7: GGAAAA at 3883, GGAAAA at 3321.
- NFATr9: 4GGAAAA at 3182, GGAAAA at 2909.
- NFATr1ci: TTTTCC at 4231, TTTTCC at 3839, TTTTCC at 3648, TTTTCC at 3034.
- NFATr3ci: TTTTCC at 3540.
- NFATr5ci: TTTTCC at 3495.
- NFATr7ci: TTTTCC at 3582, TTTTCC at 3259.

## NFATr alternate negative direction (odds) (2846-2811) core promoters
- NFATr7ci: TTTTCC at 2840.

## NFATr arbitrary positive direction (odds) (4445-4265) core promoters
- NFATr5: GGAAAA at 4321.

## NFATr arbitrary positive direction (odds) (4265-4050) proximal promoters
- NFATr1ci: TTTTCC at 4231.

## NFATr alternate positive direction (evens) (4265-4050) proximal promoters
- NFATr0ci: TTTTCC at 4204.
- NFATr2ci: TTTTCC at 4115.
- NFATr6ci: TTTTCC at 4184.

## NFATr arbitrary negative direction (evens) (2596-1) distal promoters
- NFATr0: GGAAAA at 769.
- NFATr2: GGAAAA at 2081.
- NFATr4: GGAAAA at 860.
- NFATr6: GGAAAA at 746.
- NFATr8: GGAAAA at 2164, GGAAAA at 2100, GGAAAA at 308.
- NFATr2ci: TTTTCC at 449, TTTTCC at 410.
- NFATr4ci: TTTTCC at 2076.
- NFATr8ci: TTTTCC at 2122.

## NFATr alternate negative direction (odds) (2596-1) distal promoters
- NFATr5: GGAAAA at 635.
- NFATr7: GGAAAA at 2063, GGAAAA at 1504.
- NFATr9: GGAAAA at 2184, GGAAAA at 592.
- NFATr1ci: TTTTCC at 2569, TTTTCC at 2290, TTTTCC at 2143, TTTTCC at 656.
- NFATr3ci: TTTTCC at 2472, TTTTCC at 2360, TTTTCC at 151.
- NFATr5ci:TTTTCC at 2357, TTTTCC at 1450, TTTTCC at 862, TTTTCC at 834.
- NFATr7ci: TTTTCC at 351.
- NFATr9ci: TTTTCC at 2315, TTTTCC at 136.

## NFATr arbitrary positive direction (odds) (4050-1) distal promoters
- NFATr5: GGAAAA at 635.
- NFATr7: GGAAAA at 3883, GGAAAA at 3321, GGAAAA at 2063, GGAAAA at 1504.
- NFATr9: GGAAAA at 3182, GGAAAA at 2909, GGAAAA at 2184, GGAAAA at 592.
- NFATr1ci: TTTTCC at 3839, TTTTCC at 3648, TTTTCC at 3034, TTTTCC at 2569, TTTTCC at 2290, TTTTCC at 2143, TTTTCC at 656.
- NFATr3ci: TTTTCC at 3540, TTTTCC at 2472, TTTTCC at 2360, TTTTCC at 151.
- NFATr5ci: TTTTCC at 3495, TTTTCC at 2357, TTTTCC at 1450, TTTTCC at 862, TTTTCC at 834.
- NFATr7ci: TTTTCC at 3582, TTTTCC at 3259, TTTTCC at 2840, TTTTCC at 351.
- NFATr9ci: TTTTCC at 2315, TTTTCC at 136.

## NFATr alternate positive direction (evens) (4050-1) distal promoters
- NFATr0: GGAAAA at 769.
- NFATr2: GGAAAA at 2081.
- NFATr4: GGAAAA at 3904, GGAAAA at 3627, GGAAAA at 860.
- NFATr6: GGAAAA at 746.
- NFATr8: GGAAAA at 3992, GGAAAA at 3407, GGAAAA at 3085, GGAAAA at 2164, GGAAAA at 2100, GGAAAA at 308.
- NFATr2ci: TTTTCC at 3560, TTTTCC at 449, TTTTCC at 410.
- NFATr4ci: TTTTCC at 2076.
- NFATr6ci: TTTTCC at 3674, TTTTCC at 3355, TTTTCC at 3291.
- NFATr8ci: TTTTCC at 2122.

# NFAT analysis and results
"Some other cis-acting elements, such as pyrimidine boxes (GGTTTT) and TAT boxes (TATCCAT), are usually present in the vicinity of the GARE sequence of genes regulated by GA in cereal aleurone cells (Gubler and Jacobsen 1992; Cercos et al. 1999; Tsuji et al. 2006)."
Comparison:
The occurrences of real NFATs are greater than the randoms for the UTRs, within the randoms for the negative direction distals and below the randoms for the positive direction distals. This suggests that the real NFATs are likely active or activable, the negative direction distals are likely random.