NFAC1_BOVIN
ID NFAC1_BOVIN Reviewed; 803 AA.
AC P98201;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 2.
DT 25-MAY-2022, entry version 123.
DE RecName: Full=Nuclear factor of activated T-cells, cytoplasmic 1;
DE Short=NF-ATc1;
DE Short=NFATc1;
DE AltName: Full=NFAT transcription complex cytosolic component;
DE Short=NF-ATc;
DE Short=NFATc;
GN Name=NFATC1 {ECO:0000250|UniProtKB:O95644};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19390049; DOI=10.1126/science.1169588;
RG The bovine genome sequencing and analysis consortium;
RT "The genome sequence of taurine cattle: a window to ruminant biology and
RT evolution.";
RL Science 324:522-528(2009).
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 415-430; 432-441; 518-534; 536-545; 554-560 AND
RP 612-615.
RC TISSUE=Thymus {ECO:0000269|PubMed:8202141};
RX PubMed=8202141; DOI=10.1038/369497a0;
RA Northrop J.P., Ho S.N., Chen L., Thomas D.J., Timmerman L.A., Nolan G.P.,
RA Admon A., Crabtree G.R.;
RT "NF-AT components define a family of transcription factors targeted in T-
RT cell activation.";
RL Nature 369:497-502(1994).
CC -!- FUNCTION: Plays a role in the inducible expression of cytokine genes in
CC T-cells, especially in the induction of the IL-2 or IL-4 gene
CC transcription. Also controls gene expression in embryonic cardiac
CC cells. Could regulate not only the activation and proliferation but
CC also the differentiation and programmed death of T-lymphocytes as well
CC as lymphoid and non-lymphoid cells. Required for osteoclastogenesis and
CC regulates many genes important for osteoclast differentiation and
CC function (By similarity). {ECO:0000250|UniProtKB:O88942,
CC ECO:0000250|UniProtKB:O95644}.
CC -!- SUBUNIT: Member of the multicomponent NFATC transcription complex that
CC consists of at least two components, a pre-existing cytoplasmic
CC component NFATC2 and an inducible nuclear component NFATC1. Other
CC members such as NFATC4, NFATC3 or members of the activating protein-1
CC family, MAF, GATA4 and Cbp/p300 can also bind the complex. NFATC
CC proteins bind to DNA as monomers (By similarity). Interacts with HOMER2
CC and HOMER3; this interaction may compete with calcineurin/PPP3CA-
CC binding and hence prevent NFATC1 dephosphorylation and activation (By
CC similarity). Interacts with TLE6/GRG6 (By similarity).
CC {ECO:0000250|UniProtKB:O88942, ECO:0000250|UniProtKB:O95644}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O95644}. Nucleus
CC {ECO:0000250|UniProtKB:O95644}. Note=Cytoplasmic for the phosphorylated
CC form and nuclear after activation that is controlled by calcineurin-
CC mediated dephosphorylation. Rapid nuclear exit of NFATC is thought to
CC be one mechanism by which cells distinguish between sustained and
CC transient calcium signals. The subcellular localization of NFATC plays
CC a key role in the regulation of gene transcription. Nuclear
CC translocation OF NFATC1 is enhanced in the presence of TNFSF11. Nuclear
CC translocation is decreased in the presence of FBN1 which can bind and
CC sequester TNFSF11. {ECO:0000250|UniProtKB:O88942,
CC ECO:0000250|UniProtKB:O95644}.
CC -!- DOMAIN: Rel Similarity Domain (RSD) allows DNA-binding and cooperative
CC interactions with AP1 factors. {ECO:0000250|UniProtKB:O95644}.
CC -!- DOMAIN: The N-terminal transactivation domain (TAD-A) binds to and is
CC activated by Cbp/p300. The dephosphorylated form contains two unmasked
CC nuclear localization signals (NLS), which allow translocation of the
CC protein to the nucleus (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by NFATC-kinase and GSK3B; phosphorylation induces
CC NFATC1 nuclear exit and dephosphorylation by calcineurin promotes
CC nuclear import. Phosphorylation by PKA and DYRK2 negatively modulates
CC nuclear accumulation, and promotes subsequent phosphorylation by GSK3B
CC or casein kinase 1 (By similarity). {ECO:0000250}.
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DR AlphaFoldDB; P98201; -.
DR SMR; P98201; -.
DR STRING; 9913.ENSBTAP00000000859; -.
DR PaxDb; P98201; -.
DR PRIDE; P98201; -.
DR eggNOG; ENOG502QTX8; Eukaryota.
DR HOGENOM; CLU_010185_1_0_1; -.
DR InParanoid; P98201; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005667; C:transcription regulator complex; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 1.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR008366; NFAT.
DR InterPro; IPR015647; NFAT1.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR032397; RHD_dimer.
DR InterPro; IPR011539; RHD_DNA_bind_dom.
DR InterPro; IPR037059; RHD_DNA_bind_dom_sf.
DR PANTHER; PTHR12533; PTHR12533; 1.
DR PANTHER; PTHR12533:SF5; PTHR12533:SF5; 1.
DR Pfam; PF16179; RHD_dimer; 1.
DR Pfam; PF00554; RHD_DNA_bind; 1.
DR PRINTS; PR01789; NUCFACTORATC.
DR SMART; SM00429; IPT; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS50254; REL_2; 1.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; Direct protein sequencing; DNA-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..803
FT /note="Nuclear factor of activated T-cells, cytoplasmic 1"
FT /id="PRO_0000299065"
FT REPEAT 184..200
FT /note="1"
FT REPEAT 214..230
FT /note="2"
FT REPEAT 263..279
FT /note="3"
FT DOMAIN 389..571
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT DNA_BIND 418..425
FT /evidence="ECO:0000250"
FT REGION 101..106
FT /note="Calcineurin-binding"
FT /evidence="ECO:0000250"
FT REGION 109..199
FT /note="Trans-activation domain A (TAD-A)"
FT /evidence="ECO:0000250"
FT REGION 181..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 184..279
FT /note="3 X SP repeats"
FT REGION 723..803
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 246..248
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 291..302
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOTIF 661..663
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 215..245
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 777..795
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95644"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88942"
FT MOD_RES 226
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O95644"
FT MOD_RES 275
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O95644"
FT CONFLICT 439
FT /note="S -> I (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 803 AA; 85752 MW; 6B4237FD34A434F2 CRC64;
MTGLEEDQEF DFDFLFEFNQ SDEGAVAAPA EHYGYAAPGL GAGLPLSAAH PSLPAPCHDL
QSSAAGVSAV GYGGTVDSGP SGYFLSSGGI RPNGAPALES PRIEITSYLG LHHNSSQFLH
EVDVEDVLPK RSPSTATLNL PSLEAYRDPS CLSPASSLSS RSCNSEASSY ESSFSYPYAS
PQTSPWQSPC VSPKTTDPEE GFARGLGACG LLGSPRHSPS TSPRTSVTEE SWLGARTSRP
SSPCNKRKYG LNGRQLSCSP HPSPTPSPQG SPRVSVTDDT WLGNTTQYTS SAIVAAINAL
STDSSLDLGD GVPVKARKTT LDHSPAVALK VEPAGEDLGT TPPTPDFQPE EFAAFQHIRK
GAFCDQYLSV PQHPYPWARP RSPASYTSPS LPALDWQLPS HSGPYELRIE VQPKSHHRAH
YETEGSRGAV KASAGGHPSV QLHGYVESEP LTLQLFIGTA DDRLLRPHAF YQVHRITGKT
VSTASHEAVV CSTKVLEIPL LPENNMRATI DCAGILKLRN SDIELRKGET DIGRKNTRVR
LVFRVHIPQP NGRTLSLQVA SNPIECSQRS AQELPLVEKQ SAASGPVLGG KRMVLSGHNF
LQDSKVIFVE KAPDGHHIWE MEAKTEGDLC KPNSLVVEIP PFRNQRITSP VQVNFYVCNG
KRKRSQYQHF TYLPANVPII KTEPSDDYEP ALTCGPMSQG LSPLPKPCYG QPLALPPDPG
ACLMPGFPPR PQGSASPELH DLSCAPYGSA TAGPGHSPLG LPRPVGGVLA SQEAPRPSGV
PPGPPQPPPP TLLQPQVSPT SSG
