NUPR1_MOUSE
ID NUPR1_MOUSE Reviewed; 80 AA.
AC Q9WTK0; Q9D756;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=Nuclear protein 1 {ECO:0000305};
DE AltName: Full=Protein p8 {ECO:0000303|Ref.1};
GN Name=Nupr1 {ECO:0000312|MGI:MGI:1891834};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE.
RA Vasseur S., Mallo G.V., Garcia-Montero A., Ortiz E.M., Fiedler F.,
RA Moreno S., Iovanna J.L.;
RT "Structural and functional characterization of the mouse p8 gene: promotion
RT of transcription by the C/EBPa and C/EBPb trans-acting factors involves a
RT C/EBP cis-acting element and other regions of the promoter.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Tongue;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE, INDUCTION, AND FUNCTION.
RX PubMed=11896600; DOI=10.1038/sj.onc.1205222;
RA Vasseur S., Hoffmeister A., Garcia-Montero A., Mallo G.V., Feil R.,
RA Kuehbandner S., Dagorn J.C., Iovanna J.L.;
RT "p8-deficient fibroblasts grow more rapidly and are more resistant to
RT adriamycin-induced apoptosis.";
RL Oncogene 21:1685-1694(2002).
RN [5]
RP INDUCTION, FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=16374777; DOI=10.1002/glia.20297;
RA Plant S.R., Wang Y., Vasseur S., Thrash J.C., McMahon E.J.,
RA Bergstralh D.T., Arnett H.A., Miller S.D., Carson M.J., Iovanna J.L.,
RA Ting J.P.;
RT "Upregulation of the stress-associated gene p8 in mouse models of
RT demyelination and in multiple sclerosis tissues.";
RL Glia 53:529-537(2006).
RN [6]
RP DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=18495683; DOI=10.1095/biolreprod.108.068304;
RA Million Passe C.M., White C.R., King M.W., Quirk P.L., Iovanna J.L.,
RA Quirk C.C.;
RT "Loss of the protein NUPR1 (p8) leads to delayed LHB expression, delayed
RT ovarian maturation, and testicular development of a sertoli-cell-only
RT syndrome-like phenotype in mice.";
RL Biol. Reprod. 79:598-607(2008).
RN [7]
RP INDUCTION, FUNCTION, AND INTERACTION WITH MYOD1; EP300 AND DDX5.
RX PubMed=19723804; DOI=10.1242/jcs.048678;
RA Sambasivan R., Cheedipudi S., Pasupuleti N., Saleh A., Pavlath G.K.,
RA Dhawan J.;
RT "The small chromatin-binding protein p8 coordinates the association of
RT anti-proliferative and pro-myogenic proteins at the myogenin promoter.";
RL J. Cell Sci. 122:3481-3491(2009).
RN [8]
RP 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 [9]
RP FUNCTION.
RX PubMed=22565310; DOI=10.1172/jci60144;
RA Hamidi T., Algul H., Cano C.E., Sandi M.J., Molejon M.I., Riemann M.,
RA Calvo E.L., Lomberk G., Dagorn J.C., Weih F., Urrutia R., Schmid R.M.,
RA Iovanna J.L.;
RT "Nuclear protein 1 promotes pancreatic cancer development and protects
RT cells from stress by inhibiting apoptosis.";
RL J. Clin. Invest. 122:2092-2103(2012).
RN [10]
RP FUNCTION.
RX PubMed=23900510; DOI=10.1007/s00125-013-3006-x;
RA Barbosa-Sampaio H.C., Liu B., Drynda R., Rodriguez de Ledesma A.M.,
RA King A.J., Bowe J.E., Malicet C., Iovanna J.L., Jones P.M., Persaud S.J.,
RA Muller D.S.;
RT "Nupr1 deletion protects against glucose intolerance by increasing beta
RT cell mass.";
RL Diabetologia 56:2477-2486(2013).
RN [11]
RP FUNCTION.
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).
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:11896600,
CC PubMed:19723804, PubMed:23900510, PubMed:27451286, PubMed:22565310,
CC PubMed:20181828). Controls cell cycle progression and protects cells
CC from genotoxic stress induced by doxorubicin through the complex
CC formation with TP53 and EP300 that binds CDKN1A promoter leading to
CC transcriptional induction of CDKN1A (By similarity). Protects
CC pancreatic cancer cells from stress-induced cell death by binding the
CC RELB promoter and activating its transcription, leading to IER3
CC transactivation (PubMed:22565310). 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
CC (PubMed:11896600). Regulates methamphetamine-induced apoptosis and
CC autophagy through DDIT3-mediated endoplasmic reticulum stress pathway
CC (By similarity). Participates in DNA repair following gamma-irradiation
CC by facilitating DNA access of the transcription machinery through
CC interaction with MSL1 leading to inhibition of histone H4' Lys-16'
CC acetylation (H4K16ac) (By similarity). Coactivator of PAX2
CC transcription factor activity, both by recruiting the EP300 cofactor to
CC increase PAX2 transcription factor activity and by binding PAXIP1 to
CC suppress PAXIP1-induced inhibition on PAX2 (By similarity). Positively
CC regulates cell cycle progression through interaction with COPS5
CC inducing cytoplasmic translocation of CDKN1B leading to the CDKN1B
CC degradation (By similarity). Coordinates, through its interaction with
CC EP300, the assiociation of MYOD1, EP300 and DDX5 to the MYOG promoter,
CC leading to inhibition of cell-cycle progression and myogenic
CC differentiation promotion (PubMed:19723804). Negatively regulates beta
CC cell proliferation via inhibition of cell-cycle regulatory genes
CC expression through the suppression of their promoter activities
CC (PubMed:23900510). Also required for LHB expression and ovarian
CC maturation (PubMed:18495683). Exacerbates CNS inflammation and
CC demyelination upon cuprizone treatment (PubMed:16374777).
CC {ECO:0000250|UniProtKB:O54842, ECO:0000250|UniProtKB:O60356,
CC ECO:0000269|PubMed:11896600, ECO:0000269|PubMed:16374777,
CC ECO:0000269|PubMed:18495683, ECO:0000269|PubMed:19723804,
CC ECO:0000269|PubMed:20181828, ECO:0000269|PubMed:22565310,
CC ECO:0000269|PubMed:23900510, ECO:0000269|PubMed:27451286}.
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
CC (PubMed:19723804). Interacts with TP53; interaction is stress-
CC dependent. Forms a complex with EP300 and TP53; this complex binds
CC CDKN1A promoter leading to transcriptional induction of CDKN1A (By
CC similarity). {ECO:0000250|UniProtKB:O60356,
CC ECO:0000269|PubMed:19723804}.
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: Highly expressed in pancreas and both ovaries and
CC testes. {ECO:0000269|PubMed:18495683}.
CC -!- DEVELOPMENTAL STAGE: At 14 dpc, highly expressed in brain and the
CC highest level is detected at 16 dpc and 18 dpc. Following birth, levels
CC are barely detectable and stabilize at low levels starting at 20 pnd
CC through adulthood. {ECO:0000269|PubMed:16374777}.
CC -!- INDUCTION: Transiently induced in G1 phase (PubMed:19723804). Activated
CC in fibroblasts during growth arrest. Rapidly induced in response to
CC adriamycin-induced apoptosis. Inhibited by TP53 (PubMed:11896600). Up-
CC regulated during cuprizone-induced inflammation and demyelination
CC (PubMed:16374777). {ECO:0000269|PubMed:11896600,
CC ECO:0000269|PubMed:16374777, ECO:0000269|PubMed:19723804}.
CC -!- PTM: Phosphorylated. Phosphorylation promotes DNA-binding activity.
CC {ECO:0000250|UniProtKB:O60356}.
CC -!- PTM: Acetylated. {ECO:0000250|UniProtKB:O60356}.
CC -!- DISRUPTION PHENOTYPE: Knockout NUPR1 mice are viable and seem normal.
CC Mouse embryonic fibroblast grown more rapidly compared to wild type
CC (PubMed:11896600). Knockout NUPR1 mice are fertile. However female
CC present a delay in female sexual maturation and male develop a
CC phenotype similar to Sertoli-cell-only syndrome (SCOS)
CC (PubMed:18495683). {ECO:0000269|PubMed:11896600,
CC ECO:0000269|PubMed:18495683}.
CC -!- SIMILARITY: Belongs to the NUPR family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF131195; AAD41784.1; -; Genomic_DNA.
DR EMBL; AF131196; AAD41785.1; -; mRNA.
DR EMBL; AK009572; BAB26369.1; -; mRNA.
DR EMBL; BC002109; AAH02109.1; -; mRNA.
DR CCDS; CCDS40127.1; -.
DR RefSeq; NP_062712.1; NM_019738.1.
DR AlphaFoldDB; Q9WTK0; -.
DR BioGRID; 207894; 3.
DR STRING; 10090.ENSMUSP00000032961; -.
DR PhosphoSitePlus; Q9WTK0; -.
DR PaxDb; Q9WTK0; -.
DR PRIDE; Q9WTK0; -.
DR ProteomicsDB; 293908; -.
DR Antibodypedia; 13028; 154 antibodies from 26 providers.
DR DNASU; 56312; -.
DR Ensembl; ENSMUST00000032961; ENSMUSP00000032961; ENSMUSG00000030717.
DR GeneID; 56312; -.
DR KEGG; mmu:56312; -.
DR UCSC; uc009jsd.1; mouse.
DR CTD; 26471; -.
DR MGI; MGI:1891834; Nupr1.
DR VEuPathDB; HostDB:ENSMUSG00000030717; -.
DR eggNOG; KOG4319; Eukaryota.
DR GeneTree; ENSGT00530000064242; -.
DR HOGENOM; CLU_180450_1_0_1; -.
DR InParanoid; Q9WTK0; -.
DR OMA; RQNPAGH; -.
DR OrthoDB; 1609352at2759; -.
DR PhylomeDB; Q9WTK0; -.
DR TreeFam; TF324649; -.
DR BioGRID-ORCS; 56312; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Nupr1; mouse.
DR PRO; PR:Q9WTK0; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9WTK0; protein.
DR Bgee; ENSMUSG00000030717; Expressed in submandibular gland and 215 other tissues.
DR ExpressionAtlas; Q9WTK0; baseline and differential.
DR Genevisible; Q9WTK0; MM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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:MGI.
DR GO; GO:0010698; F:acetyltransferase activator activity; IMP:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IDA:MGI.
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; IMP:MGI.
DR GO; GO:0044346; P:fibroblast apoptotic process; IMP:MGI.
DR GO; GO:0048144; P:fibroblast proliferation; IMP:MGI.
DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IMP:MGI.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
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; ISS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IMP:MGI.
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; ISS:UniProtKB.
DR GO; GO:1904036; P:negative regulation of epithelial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IMP:MGI.
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; IMP:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISO:MGI.
DR GO; GO:2000271; P:positive regulation of fibroblast apoptotic process; IMP:MGI.
DR GO; GO:2001244; P:positive regulation of intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0150078; P:positive regulation of neuroinflammatory response; IMP:UniProtKB.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISS: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; IMP:MGI.
DR GO; GO:0006473; P:protein acetylation; IMP:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; IMP:MGI.
DR GO; GO:0010506; P:regulation of autophagy; ISS:UniProtKB.
DR GO; GO:2000194; P:regulation of female gonad development; IMP:MGI.
DR GO; GO:1905897; P:regulation of response to endoplasmic reticulum stress; ISS:UniProtKB.
DR GO; GO:0009636; P:response to toxic substance; IMP:MGI.
DR GO; GO:0035914; P:skeletal muscle cell differentiation; IMP:MGI.
DR InterPro; IPR018792; NUPR1-like.
DR PANTHER; PTHR17149; PTHR17149; 1.
DR Pfam; PF10195; Phospho_p8; 1.
PE 1: Evidence at protein level;
KW Activator; Cytoplasm; DNA-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..80
FT /note="Nuclear protein 1"
FT /id="PRO_0000058008"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 38..80
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 64..80
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 41
FT /note="G -> V (in Ref. 2; BAB26369)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 80 AA; 8901 MW; 8AF6CEF99F66ED67 CRC64;
MATLPPTANP SQQPLNLEDE DGILDEYDQY SLAHPCVVGG GRKGRTKREA AANTNRPSPG
GHERKLLTKF QNSERKKAWR
