NUPR1_RAT
ID NUPR1_RAT Reviewed; 80 AA.
AC O54842;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 125.
DE RecName: Full=Nuclear protein 1 {ECO:0000305};
DE AltName: Full=Protein p8 {ECO:0000303|PubMed:9405444};
GN Name=Nupr1 {ECO:0000312|RGD:69363};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Pancreas;
RX PubMed=9405444; DOI=10.1074/jbc.272.51.32360;
RA Mallo G.V., Fiedler F., Calvo E.L., Ortiz E.M., Vasseur S., Keim V.,
RA Morisset J., Iovanna J.L.;
RT "Cloning and expression of the rat p8 cDNA, a new gene activated in
RT pancreas during the acute phase of pancreatitis, pancreatic development,
RT and regeneration, and which promotes cellular growth.";
RL J. Biol. Chem. 272:32360-32369(1997).
RN [2]
RP INDUCTION, AND FUNCTION.
RX PubMed=20181828; DOI=10.1091/mbc.e09-09-0818;
RA Kong D.K., Georgescu S.P., Cano C., Aronovitz M.J., Iovanna J.L.,
RA Patten R.D., Kyriakis J.M., Goruppi S.;
RT "Deficiency of the transcriptional regulator p8 results in increased
RT autophagy and apoptosis, and causes impaired heart function.";
RL Mol. Biol. Cell 21:1335-1349(2010).
RN [3]
RP INDUCTION BY METHAMPHETAMINE, AND FUNCTION.
RX PubMed=27031958; DOI=10.1038/cddis.2016.67;
RA Cai D., Huang E., Luo B., Yang Y., Zhang F., Liu C., Lin Z., Xie W.B.,
RA Wang H.;
RT "Nupr1/Chop signal axis is involved in mitochondrion-related endothelial
RT cell apoptosis induced by methamphetamine.";
RL Cell Death Dis. 7:E2161-E2161(2016).
RN [4]
RP INDUCTION BY CYCLOSPORIN A.
RX PubMed=27451286; DOI=10.1681/asn.2015080936;
RA Galichon P., Bataille A., Vandermeersch S., Wetzstein M., Xu-Dubois Y.C.,
RA Legouis D., Hertig A., Buob D., Placier S., Bige N., Lefevre G.,
RA Jouanneau C., Martin C., Iovanna J.L., Rondeau E.;
RT "Stress Response Gene Nupr1 Alleviates Cyclosporin A Nephrotoxicity In
RT Vivo.";
RL J. Am. Soc. Nephrol. 28:545-556(2017).
RN [5]
RP INDUCTION BY METHAMPHETAMINE, AND FUNCTION.
RX PubMed=28694771; DOI=10.3389/fnmol.2017.00203;
RA Xu X., Huang E., Tai Y., Zhao X., Chen X., Chen C., Chen R., Liu C.,
RA Lin Z., Wang H., Xie W.B.;
RT "Nupr1 Modulates Methamphetamine-Induced Dopaminergic Neuronal Apoptosis
RT and Autophagy through CHOP-Trib3-Mediated Endoplasmic Reticulum Stress
RT Signaling Pathway.";
RL Front. Mol. Neurosci. 10:203-203(2017).
CC -!- FUNCTION: Transcription regulator that converts stress signals into a
CC program of gene expression that empowers cells with resistance to the
CC stress induced by a change in their microenvironment. Thereby
CC participates in regulation of many process namely cell-cycle,
CC apoptosis, autophagy and DNA repair responses (PubMed:27031958,
CC PubMed:28694771, PubMed:20181828). Controls cell cycle progression and
CC protects cells from genotoxic stress induced by doxorubicin through the
CC complex formation with TP53 and EP300 that binds CDKN1A promoter
CC leading to transcriptional induction of CDKN1A (By similarity).
CC Protects pancreatic cancer cells from stress-induced cell death by
CC binding the RELB promoter and activating its transcription, leading to
CC IER3 transactivation (By similarity). Negatively regulates apoptosis
CC through interaction with PTMA (By similarity). Inhibits autophagy-
CC induced apoptosis in cardiac cells through FOXO3 interaction, inducing
CC cytoplasmic translocation of FOXO3 thereby preventing the FOXO3
CC association with the pro-autophagic BNIP3 promoter (PubMed:20181828).
CC Inhibits cell growth and facilitates programmed cell death by apoptosis
CC after adriamycin-induced DNA damage through transactivation of TP53 (By
CC similarity). Regulates methamphetamine-induced apoptosis and autophagy
CC through DDIT3-mediated endoplasmic reticulum stress pathway
CC (PubMed:28694771, PubMed:27031958). Participates in DNA repair
CC following gamma-irradiation by facilitating DNA access of the
CC transcription machinery through interaction with MSL1 leading to
CC inhibition of histone H4' Lys-16' acetylation (H4K16ac) (By
CC similarity). Coactivator of PAX2 transcription factor activity, both by
CC recruiting the EP300 cofactor to increase PAX2 transcription factor
CC activity and by binding PAXIP1 to suppress PAXIP1-induced inhibition on
CC PAX2 (By similarity). Positively regulates cell cycle progression
CC through interaction with COPS5 inducing cytoplasmic translocation of
CC CDKN1B leading to the CDKN1B degradation (By similarity). Coordinates,
CC through its interaction with EP300, the assiociation of MYOD1, EP300
CC and DDX5 to the MYOG promoter, leading to inhibition of cell-cycle
CC progression and myogenic differentiation promotion (By similarity).
CC Negatively regulates beta cell proliferation via inhibition of cell-
CC cycle regulatory genes expression through the suppression of their
CC promoter activities (By similarity). Also required for LHB expression
CC and ovarian maturation (By similarity). Exacerbates CNS inflammation
CC and demyelination upon cuprizone treatment (By similarity).
CC {ECO:0000250|UniProtKB:O60356, ECO:0000250|UniProtKB:Q9WTK0,
CC ECO:0000269|PubMed:20181828, ECO:0000269|PubMed:27031958,
CC ECO:0000269|PubMed:28694771}.
CC -!- SUBUNIT: Monomer. Directly interacts with MSL1 and binds MORF4L1, two
CC components of histone acetyltransferase complex; the interaction with
CC MORF4L1 may be mediated by MSL1. Interacts with EP300; this interaction
CC enhances the effect of EP300 on PAX2 transcription factor activity.
CC Interacts with PAXIP1; this interaction prevents PAXIP1 inhibition of
CC PAX2 transcription factor activity. Interacts with COPS5; this
CC interaction allows COPS5-dependent CDKN1B nuclear to cytoplasm
CC translocation. Interacts with RNF2. Interacts with FOXO3; this
CC interaction represses FOXO3 transactivation. Interacts with PTMA;
CC regulates apoptotic process (By similarity). Interacts with MYOD1,
CC EP300 and DDX5; this interaction coordinates the association of anti-
CC proliferative and pro-myogenic proteins at the myogenin promoter (By
CC similarity). Interacts with TP53; interaction is stress-dependent.
CC Forms a complex with EP300 and TP53; this complex binds CDKN1A promoter
CC leading to transcriptional induction of CDKN1A (By similarity).
CC {ECO:0000250|UniProtKB:O60356, ECO:0000250|UniProtKB:Q9WTK0}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O60356}. Cytoplasm
CC {ECO:0000250|UniProtKB:O60356}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:O60356}.
CC -!- TISSUE SPECIFICITY: Strongly activated in pancreatic acinar cells
CC during the acute phase of pancreatitis, in developing pancreas and
CC during pancreatic regeneration.
CC -!- INDUCTION: Increased by methamphetamine (PubMed:28694771,
CC PubMed:27031958). Up-regulated by cyclosporin A (PubMed:27451286).
CC Induced by energy nd amino acid deprivation (PubMed:20181828).
CC {ECO:0000269|PubMed:20181828, ECO:0000269|PubMed:27031958,
CC ECO:0000269|PubMed:27451286, ECO:0000269|PubMed:28694771}.
CC -!- PTM: Phosphorylated. Phosphorylation promotes DNA-binding activity.
CC {ECO:0000250|UniProtKB:O60356}.
CC -!- PTM: Acetylated. {ECO:0000250|UniProtKB:O60356}.
CC -!- SIMILARITY: Belongs to the NUPR family. {ECO:0000305}.
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DR EMBL; AF014503; AAB94673.1; -; mRNA.
DR RefSeq; NP_446063.1; NM_053611.2.
DR AlphaFoldDB; O54842; -.
DR STRING; 10116.ENSRNOP00000025988; -.
DR iPTMnet; O54842; -.
DR PhosphoSitePlus; O54842; -.
DR PaxDb; O54842; -.
DR GeneID; 100912108; -.
DR KEGG; rno:100912108; -.
DR UCSC; RGD:69363; rat.
DR CTD; 26471; -.
DR RGD; 69363; Nupr1.
DR eggNOG; KOG4319; Eukaryota.
DR HOGENOM; CLU_180450_1_0_1; -.
DR InParanoid; O54842; -.
DR OMA; RQNPAGH; -.
DR OrthoDB; 1609352at2759; -.
DR PhylomeDB; O54842; -.
DR TreeFam; TF324649; -.
DR PRO; PR:O54842; -.
DR Proteomes; UP000002494; Unplaced.
DR Genevisible; O54842; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0032993; C:protein-DNA complex; ISO:RGD.
DR GO; GO:0010698; F:acetyltransferase activator activity; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; ISS:UniProtKB.
DR GO; GO:0002526; P:acute inflammatory response; ISO:RGD.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:1902902; P:negative regulation of autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; ISO:RGD.
DR GO; GO:0045820; P:negative regulation of glycolytic process; ISS:UniProtKB.
DR GO; GO:0062099; P:negative regulation of programmed necrotic cell death; ISS:UniProtKB.
DR GO; GO:1904691; P:negative regulation of type B pancreatic cell proliferation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISO:RGD.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0150078; P:positive regulation of neuroinflammatory response; ISS:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:1903862; P:positive regulation of oxidative phosphorylation; ISS:UniProtKB.
DR GO; GO:1901800; P:positive regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031401; P:positive regulation of protein modification process; ISO:RGD.
DR GO; GO:0006473; P:protein acetylation; ISO:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:RGD.
DR GO; GO:0010506; P:regulation of autophagy; IMP:UniProtKB.
DR GO; GO:2000194; P:regulation of female gonad development; ISO:RGD.
DR GO; GO:1905897; P:regulation of response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; ISO:RGD.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; ISO:RGD.
DR InterPro; IPR018792; NUPR1-like.
DR PANTHER; PTHR17149; PTHR17149; 1.
DR Pfam; PF10195; Phospho_p8; 1.
PE 2: Evidence at transcript level;
KW Cytoplasm; Nucleus; Reference proteome.
FT CHAIN 1..80
FT /note="Nuclear protein 1"
FT /id="PRO_0000058009"
FT REGION 40..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 64..80
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
SQ SEQUENCE 80 AA; 8955 MW; D250DAE379AC1573 CRC64;
MATLPPTAHT SQQPVNIEDE DGILDEYDQY SLAQSYVVGG GRKGRTKREA AANTNRPSPG
GHERKLLTKF QNSERKKAWR
