O95644 (NFAC1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear factor of activated T-cells, cytoplasmic 1
Short name=NF-ATc1
Short name=NFATc1

Alternative name(s):
NFAT transcription complex cytosolic component
Short name=NF-ATc
Short name=NFATc

Gene names

Name:	NFATC1
Synonyms:	NFAT2, NFATC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	943 AA.
Sequence status	Complete.
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 or IL-4 gene transcription. Also controls gene expression in embryonic cardiac cells. Could regulate not only the activation and proliferation but also the differentiation and programmed death of T-lymphocytes as well as lymphoid and non-lymphoid cells.
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	Expressed in thymus, peripheral leukocytes as T-cells and spleen. Isoforms A are preferentially expressed in effector T-cells (thymus and peripheral leukocytes) whereas isoforms B and isoforms C are preferentially expressed in naive T-cells (spleen). Isoforms B are expressed in naive T-cells after first antigen exposure and isoforms A are expressed in effector T-cells after second antigen exposure.
Induction	Only isoforms A are 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. Also induced after co-addition of 12-O-tetradecanoylphorbol-13-acetate (TPA) and ionomycin. Weakly induced with PMA, ionomycin and cyclosporin A.
Domain	Rel Similarity Domain (RSD) allows DNA-binding and cooperative interactions with AP1 factors. The N-terminal transactivation domain (TAD-A) binds to and is activated by Cbp/p300. The dephosphorylated form contains two unmasked nuclear localization signals (NLS), which allow translocation of the protein to the nucleus. Isoforms C have a C-terminal part with an additional trans-activation domain, TAD-B, which acts as a transcriptional activator. Isoforms B have a shorter C-terminal part without complete TAD-B which acts as a transcriptional repressor.
Post-translational modification	Phosphorylated by NFATC-kinase and GSK3B; phosphorylation induces NFATC1 nuclear exit and dephosphorylation by calcineurin promotes nuclear import. Ref.5 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 initiation Alternative splicing Polymorphism
Domain	Repeat
Ligand	DNA-binding
Molecular function	Activator Repressor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from direct assay. Source: MGI positive regulation of transcription, DNA-dependent Inferred from direct assay. Source: UniProtKB transcription from RNA polymerase II promoter Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Traceable author statement. Source: ProtInc nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	FK506 binding Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: UniProtKB sequence-specific DNA binding transcription factor activity Traceable author statement. Source: ProtInc transcription regulatory region DNA binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 9 isoforms produced by alternative splicing and alternative initiation. [Align] [Select]

Note: Isoform C-alpha and isoform C-beta are the strongest activator of gene transcription, followed by isoform A-alpha and isoform A-beta, whereas isoform B-alpha and isoform B-beta are the weakest. Isoform B-alpha, isoform B-beta, isoform C-alpha and isoform C-beta, both present in T-cells, can modulate their transcriptional activity.

Isoform C-alpha (identifier: O95644-1)

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 A-alpha (identifier: O95644-2)

The sequence of this isoform differs from the canonical sequence as follows:
     698-716: VPIIKTEPTDDYEPAPTCG → GNAIFLTVSREHERVGCFF
     717-943: Missing.

Isoform A-beta (identifier: O95644-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MPSTSFPVPSKFPLGPAAAVFGRGETLGPAPRAGGTMKSAEE → MTGLEDQEFDFEFLFEFNQRDEGAAAAAP
     698-716: VPIIKTEPTDDYEPAPTCG → GNAIFLTVSREHERVGCFF
     717-943: Missing.

Isoform B-alpha (identifier: O95644-4)

The sequence of this isoform differs from the canonical sequence as follows:
     826-943: Missing.

Isoform B-beta (identifier: O95644-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MPSTSFPVPSKFPLGPAAAVFGRGETLGPAPRAGGTMKSAEE → MTGLEDQEFDFEFLFEFNQRDEGAAAAAP
     826-943: Missing.

Isoform C-beta (identifier: O95644-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: MPSTSFPVPSKFPLGPAAAVFGRGETLGPAPRAGGTMKSAEE → MTGLEDQEFDFEFLFEFNQRDEGAAAAAP

Isoform C-alpha' (identifier: O95644-7)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.

Note: Produced by alternative initiation at Met-37 of isoform C-alpha. No experimental confirmation available.

Isoform A-alpha' (identifier: O95644-8)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
     698-716: VPIIKTEPTDDYEPAPTCG → GNAIFLTVSREHERVGCFF
     717-943: Missing.

Note: Produced by alternative initiation at Met-37 of isoform A-alpha. No experimental confirmation available.

Isoform B-alpha' (identifier: O95644-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-36: Missing.
     826-943: Missing.

Note: Produced by alternative initiation at Met-37 of isoform B-alpha. No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 943

943

Nuclear factor of activated T-cells, cytoplasmic 1

PRO_0000030329

Regions

Repeat

203 – 219

17

1

Repeat

233 – 249

17

2

Repeat

282 – 298

17

3

Domain

410 – 592

183

RHD

DNA binding

439 – 446

8

Region

118 – 123

6

Calcineurin-binding

Region

126 – 218

93

Trans-activation domain A (TAD-A)

Region

203 – 298

96

3 X SP repeats

Region

703 – 943

241

Trans-activation domain B (TAD-B)

Motif

265 – 267

3

Nuclear localization signal

Motif

310 – 321

12

Nuclear export signal

Motif

682 – 684

3

Nuclear localization signal

Motif

924 – 933

10

Nuclear export signal

Amino acid modifications

Modified residue

233

1

Phosphoserine Ref.9

Natural variations

Alternative sequence

1 – 42

42

MPSTS…KSAEE → MTGLEDQEFDFEFLFEFNQR DEGAAAAAP in isoform A-beta, isoform B-beta and isoform C-beta.

VSP_005590

Alternative sequence

1 – 36

36

Missing in isoform A-alpha', isoform B-alpha' and isoform C-alpha'.

VSP_018978

Alternative sequence

698 – 716

19

VPIIK…APTCG → GNAIFLTVSREHERVGCFF in isoform A-alpha, isoform A-alpha' and isoform A-beta.

VSP_005591

Alternative sequence

717 – 943

227

Missing in isoform A-alpha, isoform A-alpha' and isoform A-beta.

VSP_005592

Alternative sequence

826 – 943

118

Missing in isoform B-alpha, isoform B-alpha' and isoform B-beta.

VSP_005593

Natural variant

68

1

P → T.
Corresponds to variant rs1051978 [ dbSNP | Ensembl ].

VAR_057145

Natural variant

315

1

A → T in a colorectal cancer sample; somatic mutation. Ref.12

VAR_036529

Natural variant

751

1

C → G.
Corresponds to variant rs754093 [ dbSNP | Ensembl ].

VAR_057146

Experimental info

Mutagenesis

169

1

S → A: No effect on subcellular localization.

Mutagenesis

172

1

S → A: Partial nuclear translocation. Ref.8

Mutagenesis

187

1

S → A: No effect on subcellular localization. Ref.8

Sequence conflict

232

1

G → S in AAC50869. Ref.2

Sequence conflict

235

1

R → Q in AAA19601. Ref.1

Secondary structure

1

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943

Helix Strand Turn

Details...

Beta strand

426 – 432

7

Beta strand

443 – 445

3

Beta strand

454 – 456

3

Beta strand

460 – 465

6

Beta strand

468 – 470

3

Beta strand

472 – 480

9

Beta strand

483 – 485

3

Beta strand

509 – 511

3

Beta strand

514 – 521

8

Beta strand

523 – 525

3

Helix

541 – 545

5

Beta strand

559 – 570

12

Turn

571 – 573

3

Beta strand

574 – 586

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform C-alpha [UniParc]. Last modified December 1, 2000. Version 3. Checksum: E72FAB10ECEB2D66	FASTA	943	101,243
	10 20 30 40 50 60 MPSTSFPVPS KFPLGPAAAV FGRGETLGPA PRAGGTMKSA EEEHYGYASS NVSPALPLPT 70 80 90 100 110 120 AHSTLPAPCH NLQTSTPGII PPADHPSGYG AALDGGPAGY FLSSGHTRPD GAPALESPRI 130 140 150 160 170 180 EITSCLGLYH NNNQFFHDVE VEDVLPSSKR SPSTATLSLP SLEAYRDPSC LSPASSLSSR 190 200 210 220 230 240 SCNSEASSYE SNYSYPYASP QTSPWQSPCV SPKTTDPEEG FPRGLGACTL LGSPRHSPST 250 260 270 280 290 300 SPRASVTEES WLGARSSRPA SPCNKRKYSL NGRQPPYSPH HSPTPSPHGS PRVSVTDDSW 310 320 330 340 350 360 LGNTTQYTSS AIVAAINALT TDSSLDLGDG VPVKSRKTTL EQPPSVALKV EPVGEDLGSP 370 380 390 400 410 420 PPPADFAPED YSSFQHIRKG GFCDQYLAVP QHPYQWAKPK PLSPTSYMSP TLPALDWQLP 430 440 450 460 470 480 SHSGPYELRI EVQPKSHHRA HYETEGSRGA VKASAGGHPI VQLHGYLENE PLMLQLFIGT 490 500 510 520 530 540 ADDRLLRPHA FYQVHRITGK TVSTTSHEAI LSNTKVLEIP LLPENSMRAV IDCAGILKLR 550 560 570 580 590 600 NSDIELRKGE TDIGRKNTRV RLVFRVHVPQ PSGRTLSLQV ASNPIECSQR SAQELPLVEK 610 620 630 640 650 660 QSTDSYPVVG GKKMVLSGHN FLQDSKVIFV EKAPDGHHVW EMEAKTDRDL CKPNSLVVEI 670 680 690 700 710 720 PPFRNQRITS PVHVSFYVCN GKRKRSQYQR FTYLPANVPI IKTEPTDDYE PAPTCGPVSQ 730 740 750 760 770 780 GLSPLPRPYY SQQLAMPPDP SSCLVAGFPP CPQRSTLMPA APGVSPKLHD LSPAAYTKGV 790 800 810 820 830 840 ASPGHCHLGL PQPAGEAPAV QDVPRPVATH PGSPGQPPPA LLPQQVSAPP SSSCPPGLEH 850 860 870 880 890 900 SLCPSSPSPP LPPATQEPTC LQPCSPACPP ATGRPQHLPS TVRRDESPTA GPRLLPEVHE 910 920 930 940 DGSPNLAPIP VTVKREPEEL DQLYLDDVNE IIRNDLSSTS THS
	Isoform A-alpha [UniParc]. Checksum: C02F3B03F2019BB1	FASTA	716	77,785
	10 20 30 40 50 60 MPSTSFPVPS KFPLGPAAAV FGRGETLGPA PRAGGTMKSA EEEHYGYASS NVSPALPLPT 70 80 90 100 110 120 AHSTLPAPCH NLQTSTPGII PPADHPSGYG AALDGGPAGY FLSSGHTRPD GAPALESPRI 130 140 150 160 170 180 EITSCLGLYH NNNQFFHDVE VEDVLPSSKR SPSTATLSLP SLEAYRDPSC LSPASSLSSR 190 200 210 220 230 240 SCNSEASSYE SNYSYPYASP QTSPWQSPCV SPKTTDPEEG FPRGLGACTL LGSPRHSPST 250 260 270 280 290 300 SPRASVTEES WLGARSSRPA SPCNKRKYSL NGRQPPYSPH HSPTPSPHGS PRVSVTDDSW 310 320 330 340 350 360 LGNTTQYTSS AIVAAINALT TDSSLDLGDG VPVKSRKTTL EQPPSVALKV EPVGEDLGSP 370 380 390 400 410 420 PPPADFAPED YSSFQHIRKG GFCDQYLAVP QHPYQWAKPK PLSPTSYMSP TLPALDWQLP 430 440 450 460 470 480 SHSGPYELRI EVQPKSHHRA HYETEGSRGA VKASAGGHPI VQLHGYLENE PLMLQLFIGT 490 500 510 520 530 540 ADDRLLRPHA FYQVHRITGK TVSTTSHEAI LSNTKVLEIP LLPENSMRAV IDCAGILKLR 550 560 570 580 590 600 NSDIELRKGE TDIGRKNTRV RLVFRVHVPQ PSGRTLSLQV ASNPIECSQR SAQELPLVEK 610 620 630 640 650 660 QSTDSYPVVG GKKMVLSGHN FLQDSKVIFV EKAPDGHHVW EMEAKTDRDL CKPNSLVVEI 670 680 690 700 710 PPFRNQRITS PVHVSFYVCN GKRKRSQYQR FTYLPANGNA IFLTVSREHE RVGCFF
	Isoform A-beta [UniParc]. Checksum: 57650B6E2A9A219C	FASTA	703	76,879
	10 20 30 40 50 60 MTGLEDQEFD FEFLFEFNQR DEGAAAAAPE HYGYASSNVS PALPLPTAHS TLPAPCHNLQ 70 80 90 100 110 120 TSTPGIIPPA DHPSGYGAAL DGGPAGYFLS SGHTRPDGAP ALESPRIEIT SCLGLYHNNN 130 140 150 160 170 180 QFFHDVEVED VLPSSKRSPS TATLSLPSLE AYRDPSCLSP ASSLSSRSCN SEASSYESNY 190 200 210 220 230 240 SYPYASPQTS PWQSPCVSPK TTDPEEGFPR GLGACTLLGS PRHSPSTSPR ASVTEESWLG 250 260 270 280 290 300 ARSSRPASPC NKRKYSLNGR QPPYSPHHSP TPSPHGSPRV SVTDDSWLGN TTQYTSSAIV 310 320 330 340 350 360 AAINALTTDS SLDLGDGVPV KSRKTTLEQP PSVALKVEPV GEDLGSPPPP ADFAPEDYSS 370 380 390 400 410 420 FQHIRKGGFC DQYLAVPQHP YQWAKPKPLS PTSYMSPTLP ALDWQLPSHS GPYELRIEVQ 430 440 450 460 470 480 PKSHHRAHYE TEGSRGAVKA SAGGHPIVQL HGYLENEPLM LQLFIGTADD RLLRPHAFYQ 490 500 510 520 530 540 VHRITGKTVS TTSHEAILSN TKVLEIPLLP ENSMRAVIDC AGILKLRNSD IELRKGETDI 550 560 570 580 590 600 GRKNTRVRLV FRVHVPQPSG RTLSLQVASN PIECSQRSAQ ELPLVEKQST DSYPVVGGKK 610 620 630 640 650 660 MVLSGHNFLQ DSKVIFVEKA PDGHHVWEME AKTDRDLCKP NSLVVEIPPF RNQRITSPVH 670 680 690 700 VSFYVCNGKR KRSQYQRFTY LPANGNAIFL TVSREHERVG CFF
	Isoform B-alpha [UniParc]. Checksum: 28469C5BE89B00CC	FASTA	825	88,763
	10 20 30 40 50 60 MPSTSFPVPS KFPLGPAAAV FGRGETLGPA PRAGGTMKSA EEEHYGYASS NVSPALPLPT 70 80 90 100 110 120 AHSTLPAPCH NLQTSTPGII PPADHPSGYG AALDGGPAGY FLSSGHTRPD GAPALESPRI 130 140 150 160 170 180 EITSCLGLYH NNNQFFHDVE VEDVLPSSKR SPSTATLSLP SLEAYRDPSC LSPASSLSSR 190 200 210 220 230 240 SCNSEASSYE SNYSYPYASP QTSPWQSPCV SPKTTDPEEG FPRGLGACTL LGSPRHSPST 250 260 270 280 290 300 SPRASVTEES WLGARSSRPA SPCNKRKYSL NGRQPPYSPH HSPTPSPHGS PRVSVTDDSW 310 320 330 340 350 360 LGNTTQYTSS AIVAAINALT TDSSLDLGDG VPVKSRKTTL EQPPSVALKV EPVGEDLGSP 370 380 390 400 410 420 PPPADFAPED YSSFQHIRKG GFCDQYLAVP QHPYQWAKPK PLSPTSYMSP TLPALDWQLP 430 440 450 460 470 480 SHSGPYELRI EVQPKSHHRA HYETEGSRGA VKASAGGHPI VQLHGYLENE PLMLQLFIGT 490 500 510 520 530 540 ADDRLLRPHA FYQVHRITGK TVSTTSHEAI LSNTKVLEIP LLPENSMRAV IDCAGILKLR 550 560 570 580 590 600 NSDIELRKGE TDIGRKNTRV RLVFRVHVPQ PSGRTLSLQV ASNPIECSQR SAQELPLVEK 610 620 630 640 650 660 QSTDSYPVVG GKKMVLSGHN FLQDSKVIFV EKAPDGHHVW EMEAKTDRDL CKPNSLVVEI 670 680 690 700 710 720 PPFRNQRITS PVHVSFYVCN GKRKRSQYQR FTYLPANVPI IKTEPTDDYE PAPTCGPVSQ 730 740 750 760 770 780 GLSPLPRPYY SQQLAMPPDP SSCLVAGFPP CPQRSTLMPA APGVSPKLHD LSPAAYTKGV 790 800 810 820 ASPGHCHLGL PQPAGEAPAV QDVPRPVATH PGSPGQPPPA LLPQQ
	Isoform B-beta [UniParc]. Checksum: DBF68E35846E998D	FASTA	812	87,857
	10 20 30 40 50 60 MTGLEDQEFD FEFLFEFNQR DEGAAAAAPE HYGYASSNVS PALPLPTAHS TLPAPCHNLQ 70 80 90 100 110 120 TSTPGIIPPA DHPSGYGAAL DGGPAGYFLS SGHTRPDGAP ALESPRIEIT SCLGLYHNNN 130 140 150 160 170 180 QFFHDVEVED VLPSSKRSPS TATLSLPSLE AYRDPSCLSP ASSLSSRSCN SEASSYESNY 190 200 210 220 230 240 SYPYASPQTS PWQSPCVSPK TTDPEEGFPR GLGACTLLGS PRHSPSTSPR ASVTEESWLG 250 260 270 280 290 300 ARSSRPASPC NKRKYSLNGR QPPYSPHHSP TPSPHGSPRV SVTDDSWLGN TTQYTSSAIV 310 320 330 340 350 360 AAINALTTDS SLDLGDGVPV KSRKTTLEQP PSVALKVEPV GEDLGSPPPP ADFAPEDYSS 370 380 390 400 410 420 FQHIRKGGFC DQYLAVPQHP YQWAKPKPLS PTSYMSPTLP ALDWQLPSHS GPYELRIEVQ 430 440 450 460 470 480 PKSHHRAHYE TEGSRGAVKA SAGGHPIVQL HGYLENEPLM LQLFIGTADD RLLRPHAFYQ 490 500 510 520 530 540 VHRITGKTVS TTSHEAILSN TKVLEIPLLP ENSMRAVIDC AGILKLRNSD IELRKGETDI 550 560 570 580 590 600 GRKNTRVRLV FRVHVPQPSG RTLSLQVASN PIECSQRSAQ ELPLVEKQST DSYPVVGGKK 610 620 630 640 650 660 MVLSGHNFLQ DSKVIFVEKA PDGHHVWEME AKTDRDLCKP NSLVVEIPPF RNQRITSPVH 670 680 690 700 710 720 VSFYVCNGKR KRSQYQRFTY LPANVPIIKT EPTDDYEPAP TCGPVSQGLS PLPRPYYSQQ 730 740 750 760 770 780 LAMPPDPSSC LVAGFPPCPQ RSTLMPAAPG VSPKLHDLSP AAYTKGVASP GHCHLGLPQP 790 800 810 AGEAPAVQDV PRPVATHPGS PGQPPPALLP QQ
	Isoform C-beta [UniParc]. Checksum: 8708706F1C8938AC	FASTA	930	100,336
	10 20 30 40 50 60 MTGLEDQEFD FEFLFEFNQR DEGAAAAAPE HYGYASSNVS PALPLPTAHS TLPAPCHNLQ 70 80 90 100 110 120 TSTPGIIPPA DHPSGYGAAL DGGPAGYFLS SGHTRPDGAP ALESPRIEIT SCLGLYHNNN 130 140 150 160 170 180 QFFHDVEVED VLPSSKRSPS TATLSLPSLE AYRDPSCLSP ASSLSSRSCN SEASSYESNY 190 200 210 220 230 240 SYPYASPQTS PWQSPCVSPK TTDPEEGFPR GLGACTLLGS PRHSPSTSPR ASVTEESWLG 250 260 270 280 290 300 ARSSRPASPC NKRKYSLNGR QPPYSPHHSP TPSPHGSPRV SVTDDSWLGN TTQYTSSAIV 310 320 330 340 350 360 AAINALTTDS SLDLGDGVPV KSRKTTLEQP PSVALKVEPV GEDLGSPPPP ADFAPEDYSS 370 380 390 400 410 420 FQHIRKGGFC DQYLAVPQHP YQWAKPKPLS PTSYMSPTLP ALDWQLPSHS GPYELRIEVQ 430 440 450 460 470 480 PKSHHRAHYE TEGSRGAVKA SAGGHPIVQL HGYLENEPLM LQLFIGTADD RLLRPHAFYQ 490 500 510 520 530 540 VHRITGKTVS TTSHEAILSN TKVLEIPLLP ENSMRAVIDC AGILKLRNSD IELRKGETDI 550 560 570 580 590 600 GRKNTRVRLV FRVHVPQPSG RTLSLQVASN PIECSQRSAQ ELPLVEKQST DSYPVVGGKK 610 620 630 640 650 660 MVLSGHNFLQ DSKVIFVEKA PDGHHVWEME AKTDRDLCKP NSLVVEIPPF RNQRITSPVH 670 680 690 700 710 720 VSFYVCNGKR KRSQYQRFTY LPANVPIIKT EPTDDYEPAP TCGPVSQGLS PLPRPYYSQQ 730 740 750 760 770 780 LAMPPDPSSC LVAGFPPCPQ RSTLMPAAPG VSPKLHDLSP AAYTKGVASP GHCHLGLPQP 790 800 810 820 830 840 AGEAPAVQDV PRPVATHPGS PGQPPPALLP QQVSAPPSSS CPPGLEHSLC PSSPSPPLPP 850 860 870 880 890 900 ATQEPTCLQP CSPACPPATG RPQHLPSTVR RDESPTAGPR LLPEVHEDGS PNLAPIPVTV 910 920 930 KREPEELDQL YLDDVNEIIR NDLSSTSTHS
	Isoform C-alpha' [UniParc]. Checksum: 0D4DE170925A1500	FASTA	907	97,734
	10 20 30 40 50 60 MKSAEEEHYG YASSNVSPAL PLPTAHSTLP APCHNLQTST PGIIPPADHP SGYGAALDGG 70 80 90 100 110 120 PAGYFLSSGH TRPDGAPALE SPRIEITSCL GLYHNNNQFF HDVEVEDVLP SSKRSPSTAT 130 140 150 160 170 180 LSLPSLEAYR DPSCLSPASS LSSRSCNSEA SSYESNYSYP YASPQTSPWQ SPCVSPKTTD 190 200 210 220 230 240 PEEGFPRGLG ACTLLGSPRH SPSTSPRASV TEESWLGARS SRPASPCNKR KYSLNGRQPP 250 260 270 280 290 300 YSPHHSPTPS PHGSPRVSVT DDSWLGNTTQ YTSSAIVAAI NALTTDSSLD LGDGVPVKSR 310 320 330 340 350 360 KTTLEQPPSV ALKVEPVGED LGSPPPPADF APEDYSSFQH IRKGGFCDQY LAVPQHPYQW 370 380 390 400 410 420 AKPKPLSPTS YMSPTLPALD WQLPSHSGPY ELRIEVQPKS HHRAHYETEG SRGAVKASAG 430 440 450 460 470 480 GHPIVQLHGY LENEPLMLQL FIGTADDRLL RPHAFYQVHR ITGKTVSTTS HEAILSNTKV 490 500 510 520 530 540 LEIPLLPENS MRAVIDCAGI LKLRNSDIEL RKGETDIGRK NTRVRLVFRV HVPQPSGRTL 550 560 570 580 590 600 SLQVASNPIE CSQRSAQELP LVEKQSTDSY PVVGGKKMVL SGHNFLQDSK VIFVEKAPDG 610 620 630 640 650 660 HHVWEMEAKT DRDLCKPNSL VVEIPPFRNQ RITSPVHVSF YVCNGKRKRS QYQRFTYLPA 670 680 690 700 710 720 NVPIIKTEPT DDYEPAPTCG PVSQGLSPLP RPYYSQQLAM PPDPSSCLVA GFPPCPQRST 730 740 750 760 770 780 LMPAAPGVSP KLHDLSPAAY TKGVASPGHC HLGLPQPAGE APAVQDVPRP VATHPGSPGQ 790 800 810 820 830 840 PPPALLPQQV SAPPSSSCPP GLEHSLCPSS PSPPLPPATQ EPTCLQPCSP ACPPATGRPQ 850 860 870 880 890 900 HLPSTVRRDE SPTAGPRLLP EVHEDGSPNL APIPVTVKRE PEELDQLYLD DVNEIIRNDL SSTSTHS
	Isoform A-alpha' [UniParc]. Checksum: D9D7060FEB4E81DF	FASTA	680	74,276
	10 20 30 40 50 60 MKSAEEEHYG YASSNVSPAL PLPTAHSTLP APCHNLQTST PGIIPPADHP SGYGAALDGG 70 80 90 100 110 120 PAGYFLSSGH TRPDGAPALE SPRIEITSCL GLYHNNNQFF HDVEVEDVLP SSKRSPSTAT 130 140 150 160 170 180 LSLPSLEAYR DPSCLSPASS LSSRSCNSEA SSYESNYSYP YASPQTSPWQ SPCVSPKTTD 190 200 210 220 230 240 PEEGFPRGLG ACTLLGSPRH SPSTSPRASV TEESWLGARS SRPASPCNKR KYSLNGRQPP 250 260 270 280 290 300 YSPHHSPTPS PHGSPRVSVT DDSWLGNTTQ YTSSAIVAAI NALTTDSSLD LGDGVPVKSR 310 320 330 340 350 360 KTTLEQPPSV ALKVEPVGED LGSPPPPADF APEDYSSFQH IRKGGFCDQY LAVPQHPYQW 370 380 390 400 410 420 AKPKPLSPTS YMSPTLPALD WQLPSHSGPY ELRIEVQPKS HHRAHYETEG SRGAVKASAG 430 440 450 460 470 480 GHPIVQLHGY LENEPLMLQL FIGTADDRLL RPHAFYQVHR ITGKTVSTTS HEAILSNTKV 490 500 510 520 530 540 LEIPLLPENS MRAVIDCAGI LKLRNSDIEL RKGETDIGRK NTRVRLVFRV HVPQPSGRTL 550 560 570 580 590 600 SLQVASNPIE CSQRSAQELP LVEKQSTDSY PVVGGKKMVL SGHNFLQDSK VIFVEKAPDG 610 620 630 640 650 660 HHVWEMEAKT DRDLCKPNSL VVEIPPFRNQ RITSPVHVSF YVCNGKRKRS QYQRFTYLPA 670 680 NGNAIFLTVS REHERVGCFF
	Isoform B-alpha' [UniParc]. Checksum: D3EF411D7B8C2C82	FASTA	789	85,254
	10 20 30 40 50 60 MKSAEEEHYG YASSNVSPAL PLPTAHSTLP APCHNLQTST PGIIPPADHP SGYGAALDGG 70 80 90 100 110 120 PAGYFLSSGH TRPDGAPALE SPRIEITSCL GLYHNNNQFF HDVEVEDVLP SSKRSPSTAT 130 140 150 160 170 180 LSLPSLEAYR DPSCLSPASS LSSRSCNSEA SSYESNYSYP YASPQTSPWQ SPCVSPKTTD 190 200 210 220 230 240 PEEGFPRGLG ACTLLGSPRH SPSTSPRASV TEESWLGARS SRPASPCNKR KYSLNGRQPP 250 260 270 280 290 300 YSPHHSPTPS PHGSPRVSVT DDSWLGNTTQ YTSSAIVAAI NALTTDSSLD LGDGVPVKSR 310 320 330 340 350 360 KTTLEQPPSV ALKVEPVGED LGSPPPPADF APEDYSSFQH IRKGGFCDQY LAVPQHPYQW 370 380 390 400 410 420 AKPKPLSPTS YMSPTLPALD WQLPSHSGPY ELRIEVQPKS HHRAHYETEG SRGAVKASAG 430 440 450 460 470 480 GHPIVQLHGY LENEPLMLQL FIGTADDRLL RPHAFYQVHR ITGKTVSTTS HEAILSNTKV 490 500 510 520 530 540 LEIPLLPENS MRAVIDCAGI LKLRNSDIEL RKGETDIGRK NTRVRLVFRV HVPQPSGRTL 550 560 570 580 590 600 SLQVASNPIE CSQRSAQELP LVEKQSTDSY PVVGGKKMVL SGHNFLQDSK VIFVEKAPDG 610 620 630 640 650 660 HHVWEMEAKT DRDLCKPNSL VVEIPPFRNQ RITSPVHVSF YVCNGKRKRS QYQRFTYLPA 670 680 690 700 710 720 NVPIIKTEPT DDYEPAPTCG PVSQGLSPLP RPYYSQQLAM PPDPSSCLVA GFPPCPQRST 730 740 750 760 770 780 LMPAAPGVSP KLHDLSPAAY TKGVASPGHC HLGLPQPAGE APAVQDVPRP VATHPGSPGQ PPPALLPQQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"NF-AT components define a family of transcription factors targeted in T-cell activation." Northrop J.P., Ho S.N., Chen L., Thomas D.J., Timmerman L.A., Nolan G.P., Admon A., Crabtree G.R. Nature 369:497-502(1994) [PubMed: 8202141] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A-ALPHA). Tissue: Peripheral blood lymphocyte and T-cell.
[2]	"Characterization of a new isoform of the NFAT (nuclear factor of activated T cells) gene family member NFATc." Park J., Takeuchi A., Sharma S. J. Biol. Chem. 271:20914-20921(1996) [PubMed: 8702849] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B-BETA). Tissue: B-cell.
[3]	Erratum Park J., Takeuchi A., Sharma S. J. Biol. Chem. 271:33705-33705(1996)
[4]	"Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells." Chuvpilo S., Zimmer M., Kerstan A., Gloeckner J., Avots A., Escher C., Fischer C., Inashkina I., Jankevics E., Berberich-Siebelt F., Schmitt E., Serfling E. Immunity 10:261-269(1999) [PubMed: 10072078] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A-ALPHA; B-ALPHA AND C-BETA). Tissue: B-cell lymphoma.
[5]	"Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3." Beals C.R., Sheridan C.M., Turck C.W., Gardner P., Crabtree G.R. Science 275:1930-1934(1997) [PubMed: 9072970] [Abstract] Cited for: PHOSPHORYLATION BY GSK3B.
[6]	"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.
[7]	"Multiple NF-ATc isoforms with individual transcriptional properties are synthesized in T lymphocytes." Chuvpilo S., Avots A., Berberich-Siebelt F., Gloeckner J., Fischer C., Kerstan A., Escher C., Inashkina I., Hlubek F., Jankevics E., Brabletz T., Serfling E. J. Immunol. 162:7294-7301(1999) [PubMed: 10358178] [Abstract] Cited for: ALTERNATIVE SPLICING, CHARACTERIZATION.
[8]	"Identification of amino acid residues and protein kinases involved in the regulation of NFATc subcellular localization." Porter C.M., Havens M.A., Clipstone N.A. J. Biol. Chem. 275:3543-3551(2000) [PubMed: 10652349] [Abstract] Cited for: MUTAGENESIS OF SER-172 AND SER-187.
[9]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-233, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"Unusual Rel-like architecture in the DNA-binding domain of the transcription factor NFATc." Wolfe S.A., Zhou P., Dotsch V., Chen L., You A., Ho S.N., Crabtree G.R., Wagner G., Verdine G.L. Nature 385:172-176(1997) [PubMed: 8990122] [Abstract] Cited for: STRUCTURE BY NMR OF 416-591.
[11]	"Solution structure of the core NFATC1/DNA complex." Zhou P., Sun L.J., Dotsch V., Wagner G., Verdine G.L. Cell 92:687-696(1998) [PubMed: 9506523] [Abstract] Cited for: STRUCTURE BY NMR OF 416-591 IN COMPLEX WITH DNA.
[12]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-315.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U08015 mRNA. Translation: AAA19601.1.
U59736 mRNA. Translation: AAC50869.1.
U80917 mRNA. Translation: AAD00450.1.
U80918 mRNA. Translation: AAD00451.1.
U80919 mRNA. Translation: AAD00452.1.

IPI

IPI00032069.
IPI00221155.
IPI00221156.
IPI00221157.
IPI00221158.
IPI00336007.
IPI00395394.
IPI00759774.
IPI00759791.

PIR

S45262.

RefSeq

NP_006153.2. NM_006162.3.
NP_765975.1. NM_172387.1.
NP_765976.1. NM_172388.1.
NP_765977.1. NM_172389.1.
NP_765978.1. NM_172390.1.

UniGene

Hs.534074.
Hs.701518.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1A66	NMR	-	A	416-591	[»]
1NFA	NMR	-	A	416-591	[»]

ProteinModelPortal

O95644.

SMR

O95644. Positions 415-695.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-3319641.

STRING

O95644.

PTM databases

PhosphoSite

O95644.

Proteomic databases

PRIDE

O95644.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000415320; ENSP00000396667; ENSG00000131196.

GeneID

4772.

KEGG

hsa:4772.

UCSC

uc002lnc.1. human.
uc002lnd.1. human.
uc002lnf.1. human.
uc002lng.1. human.

Organism-specific databases

CTD

4772.

GeneCards

GC18P077208.

HGNC

HGNC:7775. NFATC1.

HPA

CAB004513.

MIM

600489. gene.

neXtProt

NX_O95644.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12664.

HOVERGEN

HBG069754.

OMA

HNNNQFF.

Enzyme and pathway databases

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.
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

O95644.

Bgee

O95644.

CleanEx

HS_NFATC1.

Genevestigator

O95644.

GermOnline

ENSG00000131196. Homo sapiens.

Family and domain databases

InterPro

IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT_TIG_rcpt.
IPR008366. NFAT.
IPR015647. NFAT1.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
G3DSA:2.60.40.340. RHD. 1 hit.

KO

K04446.

PANTHER

PTHR12533. NFAT. 1 hit.
PTHR12533:SF5. NFAT1. 1 hit.

Pfam

PF00554. RHD. 1 hit.
PF01833. TIG. 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

NextBio

18388.

SOURCE

Search...

Entry information

Entry name

NFAC1_HUMAN

Accession

Primary (citable) accession number: O95644
Secondary accession number(s): Q12865, Q15793

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	December 1, 2000
Last modified:	January 25, 2012
This is version 130 of the entry and version 3 of the sequence. [Complete history]

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.