O60356 (NUPR1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Nuclear protein 1

Alternative name(s):
Candidate of metastasis 1
Protein p8

Gene names

Name:	NUPR1
Synonyms:	COM1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	82 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Chromatin-binding protein that converts stress signals into a program of gene expression that empowers cells with resistance to the stress induced by a change in their microenvironment. Interacts with MSL1 and inhibits its activity on histone H4 'Lys-16' acetylation (H4K16ac). Binds the RELB promoter and activates its transcription, leading to the transactivation of IER3. The NUPR1/RELB/IER3 survival pathway may provide pancreatic ductal adenocarcinoma with remarkable resistance to cell stress, such as starvation or gemcitabine treatment. In breast cancer cells, NUPR1 overexpression leads to the activation of PI3K/AKT signaling pathway, CDKN1A/p21 phosphorylation and relocalization from the nucleus to the cytoplasm, leading to resistance to chemotherapeutic agents, such as doxorubicin. Ref.10 Ref.11 Ref.12
Subunit structure	Monomer. Directly interacts with MSL1 and binds MORF4L1, two components of histone acetyltransferase complex; the interaction with MORF4L1 may be mediated by MSL1. Ref.10
Subcellular location	Nucleus Ref.1.
Tissue specificity	Widely expressed, with high levels in liver, pancreas, prostate, ovary, colon, thyroid, spinal cord, trachea and adrenal gland, moderate levels in heart, placenta, lung, skeletal muscle, kidney, testis, small intestine, stomach and lymph node, and low levels in brain, spleen, thymus and bone marrow. Not detected in peripheral blood leukocytes. Ref.1
Induction	Up-regulated by stress agents, such as nutrient deprivation (at protein level). Up-regulation by gamma-irradiation is eventually followed by down-regulation. Ref.10 Ref.12
Domain	Has been proposed to exhibit the features of HMG-I(Y) proteins (Ref.9).
Post-translational modification	Phosphorylated in vitro by PKA and CK. Phosphorylation promotes DNA-binding activity. Ref.9
Sequence similarities	Belongs to the NUPR family.
Sequence caution	The sequence AAC05335.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Nucleus
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	acute inflammatory response Inferred from electronic annotation. Source: Compara cell growth Inferred from direct assay Ref.1. Source: UniProtKB induction of apoptosis Non-traceable author statement. Source: UniProtKB intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from electronic annotation. Source: Compara male gonad development Inferred from electronic annotation. Source: Compara negative regulation of cell cycle Inferred from electronic annotation. Source: Compara negative regulation of fibroblast proliferation Inferred from electronic annotation. Source: Compara positive regulation of protein modification process Inferred from electronic annotation. Source: Compara protein acetylation Inferred from electronic annotation. Source: Compara protein complex assembly Inferred from electronic annotation. Source: Compara regulation of female gonad development Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to toxin Inferred from electronic annotation. Source: Compara skeletal muscle cell differentiation Inferred from electronic annotation. Source: Compara transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.1. Source: UniProtKB
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW chromatin binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 82	82	Nuclear protein 1		PRO_0000058007
Regions
	Motif	65 – 82	18	Nuclear localization signal Potential
Experimental info
	Sequence conflict	47	1	K → N in BAG35071. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O60356 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 596E342D10F87AF3	FASTA	82	8,873
	10 20 30 40 50 60 MATFPPATSA PQQPPGPEDE DSSLDESDLY SLAHSYLGGG GRKGRTKREA AANTNRPSPG 70 80 GHERKLVTKL QNSERKKRGA RR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of the human p8, a nuclear protein with mitogenic activity." Vasseur S., Mallo G.V., Fiedler F., Boedeker H., Canepa E., Moreno S., Iovanna J.L. Eur. J. Biochem. 259:670-675(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Pancreas.
[2]	"Expression of a novel factor in human breast cancer cells with metastatic potential." Ree A.H., Tvermyr M., Engebraaten O., Rooman M., Rosok O., Hovig E., Meza-Zepeda L.A., Bruland O.S., Fodstad O. Cancer Res. 59:4675-4680(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Mammary cancer.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q." Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D. Genomics 60:295-308(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[9]	"Human p8 is a HMG-I/Y-like protein with DNA binding activity enhanced by phosphorylation." Encinar J.A., Mallo G.V., Mizyrycki C., Giono L., Gonzalez-Ros J.M., Rico M., Canepa E., Moreno S., Neira J.L., Iovanna J.L. J. Biol. Chem. 276:2742-2751(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DNA-BINDING, MONOMER, PHOSPHORYLATION.
[10]	"p8/nupr1 regulates DNA-repair activity after double-strand gamma irradiation-induced DNA damage." Gironella M., Malicet C., Cano C., Sandi M.J., Hamidi T., Tauil R.M., Baston M., Valaco P., Moreno S., Lopez F., Neira J.L., Dagorn J.C., Iovanna J.L. J. Cell. Physiol. 221:594-602(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH MSL1 AND MORF4L1, INDUCTION BY GAMMA-IRRADIATION.
[11]	"Cytoplasmic translocation of p21 mediates NUPR1-induced chemoresistance: NUPR1 and p21 in chemoresistance." Vincent A.J., Ren S., Harris L.G., Devine D.J., Samant R.S., Fodstad O., Shevde L.A. FEBS Lett. 586:3429-3434(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[12]	"Nuclear protein 1 promotes pancreatic cancer development and protects cells from stress by inhibiting apoptosis." Hamidi T., Algul H., Cano C.E., Sandi M.J., Molejon M.I., Riemann M., Calvo E.L., Lomberk G., Dagorn J.C., Weih F., Urrutia R., Schmid R.M., Iovanna J.L. J. Clin. Invest. 122:2092-2103(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INDUCTION BY NUTRIENT DEPRIVATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF069073 mRNA. Translation: AAC19384.1. AF069074 Genomic DNA. Translation: AAC19385.1. AF135266 mRNA. Translation: AAD49221.1. AK312135 mRNA. Translation: BAG35071.1. BT006896 mRNA. Translation: AAP35542.1. CR542144 mRNA. Translation: CAG46941.1. AC002425 Genomic DNA. Translation: AAC05336.1. AC002425 Genomic DNA. Translation: AAC05335.1. Sequence problems. CH471279 Genomic DNA. Translation: EAW52274.1. BC002434 mRNA. Translation: AAH02434.1.
IPI	IPI00029073.
RefSeq	NP_001035948.1. NM_001042483.1. NP_036517.1. NM_012385.2.
UniGene	Hs.513463.
3D structure databases
DisProt	DP00510.
ProteinModelPortal	O60356.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60356. 4 interactions.
STRING	9606.ENSP00000379003.
PTM databases
PhosphoSite	O60356.
Proteomic databases
PaxDb	O60356.
PRIDE	O60356.
Protocols and materials databases
DNASU	26471.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000324873; ENSP00000315559; ENSG00000176046. ENST00000395641; ENSP00000379003; ENSG00000176046.
GeneID	26471.
KEGG	hsa:26471.
UCSC	uc002dqd.1. human.
Organism-specific databases
CTD	26471.
GeneCards	GC16M028548.
HGNC	HGNC:29990. NUPR1.
MIM	614812. gene.
neXtProt	NX_O60356.
PharmGKB	PA165450395.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG314223.
HOGENOM	HOG000007609.
HOVERGEN	HBG052704.
KO	K15626.
OrthoDB	EOG4SN1QG.
PhylomeDB	O60356.
Gene expression databases
ArrayExpress	O60356.
Bgee	O60356.
Genevestigator	O60356.
GermOnline	ENSG00000176046. Homo sapiens.
Family and domain databases
InterPro	IPR018792. Nuclear_phosphoprot_p8_DNA-bd. [Graphical view]
Pfam	PF10195. Phospho_p8. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	26471.
NextBio	35467489.
SOURCE	Search...

Entry information

Entry name

NUPR1_HUMAN

Accession

Primary (citable) accession number: O60356
Secondary accession number(s): B2R5C4, O60357, Q6FGG3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 93 of the entry and version 1 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.