NFAC1_PIG
ID NFAC1_PIG Reviewed; 822 AA.
AC O77638;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 2.
DT 25-MAY-2022, entry version 127.
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;
DE AltName: Full=NFATmac;
GN Name=NFATC1; Synonyms=NFAT2, NFATC;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Alveolar macrophage;
RX PubMed=9677199; DOI=10.1126/science.281.5376.562;
RA Miskin J.E., Abrams C.C., Goatley L.C., Dixon L.K.;
RT "A viral mechanism for inhibition of the cellular phosphatase
RT calcineurin.";
RL Science 281:562-565(1998).
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. {ECO:0000250|UniProtKB:O88942, 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). {ECO:0000250,
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}.
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 EMBL; AF069996; AAC27301.2; -; mRNA.
DR RefSeq; NP_999326.1; NM_214161.1.
DR AlphaFoldDB; O77638; -.
DR SMR; O77638; -.
DR ELM; O77638; -.
DR STRING; 9823.ENSSSCP00000005229; -.
DR PaxDb; O77638; -.
DR PRIDE; O77638; -.
DR GeneID; 397318; -.
DR KEGG; ssc:397318; -.
DR CTD; 4772; -.
DR eggNOG; ENOG502QTX8; Eukaryota.
DR InParanoid; O77638; -.
DR OrthoDB; 277998at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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 2: Evidence at transcript level;
KW Activator; Cytoplasm; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation.
FT CHAIN 1..822
FT /note="Nuclear factor of activated T-cells, cytoplasmic 1"
FT /id="PRO_0000205177"
FT REPEAT 195..211
FT /note="1"
FT REPEAT 225..241
FT /note="2"
FT REPEAT 274..290
FT /note="3"
FT DOMAIN 400..582
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT DNA_BIND 429..436
FT /evidence="ECO:0000250"
FT REGION 110..115
FT /note="Calcineurin-binding"
FT REGION 118..210
FT /note="Trans-activation domain A (TAD-A)"
FT REGION 192..289
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 195..290
FT /note="3 X SP repeats"
FT REGION 772..822
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 257..259
FT /note="Nuclear localization signal"
FT MOTIF 302..313
FT /note="Nuclear export signal"
FT MOTIF 672..674
FT /note="Nuclear localization signal"
FT COMPBIAS 225..256
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..289
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 805..822
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 225
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O95644"
FT MOD_RES 229
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88942"
FT MOD_RES 237
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O95644"
FT MOD_RES 286
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:O95644"
SQ SEQUENCE 822 AA; 88010 MW; C891D851B3644833 CRC64;
MTGLEEDQEF DFDFLFEFNQ SDEGAAAAGA TAERYSYATT GISSALPLPT APPTLPAPCH
DQQASAAGIS AVGSAGHPAG YAGAVDGGPS GYFLPSGGVR PNGAPALESP RIEITSYLGL
HHNNGQFFHD VAVEDVLPNP RRSPSTATLS LPNLEAYRDP SCLSPASSLS SRSCNSEASS
YESSFSYPYA SPQTSPWQSP CVSPKTTDPE EGFPRGLGAC SLLGSPRHSP STSPRTSVTE
ESWLGARTSR PSSPCNKRKY GLNGRQLFCS PHASPTPSPH SSPRVSVTDD TWLGNTTQYT
SSAIVAAINA LSTDSSLDLG DGVPVKARKT ALDHSPSLAL KVEPAAEDLG ATPPTSDFPP
EEFPPFQHIR KGAFCDQYLS VPQHPYPWAR PRSPTPYASP SLPALDWQLP SHSGPYELRI
EVQPKSHHRA HYETEGSRGA VKASAGGHPS VQLHGYVESE PLTLQLFIGT ADDRLLRPHA
FYQVHRITGK TVSTTSHEAV LSNTKVLEIP LLPENNMRAI IDCAGILKLR NSDIELRKGE
TDIGRKNTRV RLVFRVHIPQ PNGRTLSLQV ASNPIECSQR SAQELPLVEK QSAASCPVLG
GKRMVLTGHN FLQDSKVVFV EKAPDGHHIW EMEAKTDGDL CKPNSLVVEI PPFRNQRITS
PVQVNFYVCN GKRKRSQYQH FTYLPANAPV IKTEPSDDYE PALTCGPVSQ GLNPLTKPCY
GPPLALPPDP SSCLVAGFPP CPQRSAVMSP PPSASPKLHD LSCAPYSKGM AGPGHLGLQR
PAGGVLGGQE APRPGGPHPG APQLHPLNLS QSIVTRLTEP QP
