NEDD8_MOUSE
ID NEDD8_MOUSE Reviewed; 81 AA.
AC P29595;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=NEDD8;
DE AltName: Full=Neddylin;
DE AltName: Full=Neural precursor cell expressed developmentally down-regulated protein 8;
DE Short=NEDD-8;
DE AltName: Full=Ubiquitin-like protein Nedd8;
DE Flags: Precursor;
GN Name=Nedd8; Synonyms=Nedd-8;
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 [MRNA].
RC TISSUE=Brain;
RX PubMed=1378265; DOI=10.1016/0006-291x(92)91747-e;
RA Kumar S., Tomooka Y., Noda M.;
RT "Identification of a set of genes with developmentally down-regulated
RT expression in the mouse brain.";
RL Biochem. Biophys. Res. Commun. 185:1155-1161(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], SEQUENCE REVISION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8395831; DOI=10.1006/bbrc.1993.2056;
RA Kumar S., Yoshida Y., Noda M.;
RT "Cloning of a cDNA which encodes a novel ubiquitin-like protein.";
RL Biochem. Biophys. Res. Commun. 195:393-399(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 DEVELOPMENTAL STAGE.
RX PubMed=9353319; DOI=10.1074/jbc.272.45.28557;
RA Kamitani T., Kito K., Nguyen H.P., Yeh E.T.H.;
RT "Characterization of NEDD8, a developmentally down-regulated ubiquitin-like
RT protein.";
RL J. Biol. Chem. 272:28557-28562(1997).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=10597293; DOI=10.1038/sj.onc.1203093;
RA Hori T., Osaka F., Chiba T., Miyamoto C., Okabayashi K., Shimbara N.,
RA Kato S., Tanaka K.;
RT "Covalent modification of all members of human cullin family proteins by
RT NEDD8.";
RL Oncogene 18:6829-6834(1999).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=11696557; DOI=10.1083/jcb.200104035;
RA Tateishi K., Omata M., Tanaka K., Chiba T.;
RT "The NEDD8 system is essential for cell cycle progression and morphogenetic
RT pathway in mice.";
RL J. Cell Biol. 155:571-580(2001).
RN [7]
RP INTERACTION WITH AHR, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=12215427; DOI=10.1074/jbc.m202413200;
RA Antenos M., Casper R.F., Brown T.J.;
RT "Interaction with Nedd8, a ubiquitin-like protein, enhances the
RT transcriptional activity of the aryl hydrocarbon receptor.";
RL J. Biol. Chem. 277:44028-44034(2002).
RN [8]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=15183309; DOI=10.1016/j.modgep.2004.01.005;
RA Carrabino S., Carminati E., Talarico D., Pardi R., Bianchi E.;
RT "Expression pattern of the JAB1/CSN5 gene during murine embryogenesis:
RT colocalization with NEDD8.";
RL Gene Expr. Patterns 4:423-431(2004).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=23806337; DOI=10.1016/j.molcel.2013.06.001;
RA Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y.,
RA Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.;
RT "SIRT5-mediated lysine desuccinylation impacts diverse metabolic
RT pathways.";
RL Mol. Cell 50:919-930(2013).
CC -!- FUNCTION: Ubiquitin-like protein which plays an important role in cell
CC cycle control and embryogenesis via its conjugation to a limited number
CC of cellular proteins, such as cullins or p53/TP53 (PubMed:11696557).
CC Attachment of NEDD8 to cullins is critical for the recruitment of E2 to
CC the cullin-RING-based E3 ubiquitin-protein ligase complex, thus
CC facilitating polyubiquitination and proteasomal degradation of cyclins
CC and other regulatory proteins. Attachment of NEDD8 to p53/TP53 inhibits
CC p53/TP53 transcriptional activity. Covalent attachment to its
CC substrates requires prior activation by the E1 complex UBE1C-APPBP1 and
CC linkage to the E2 enzyme UBE2M (By similarity).
CC {ECO:0000250|UniProtKB:Q15843, ECO:0000269|PubMed:11696557}.
CC -!- SUBUNIT: Interacts with AHR; interaction is direct. Interacts with
CC NUB1; interaction is direct. {ECO:0000250|UniProtKB:Q15843}.
CC -!- INTERACTION:
CC P29595; A0A0F6B423: sseL; Xeno; NbExp=2; IntAct=EBI-13953910, EBI-13953897;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12215427}.
CC Note=Mainly nuclear. {ECO:0000269|PubMed:12215427}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed (at protein level).
CC {ECO:0000269|PubMed:15183309, ECO:0000269|PubMed:8395831}.
CC -!- DEVELOPMENTAL STAGE: According to PubMed:1378265 and PubMed:15183309,
CC down-regulated during embryonic development, but according to
CC PubMed:10597293, expression does not change during embryonic
CC development. Between 10 dpc and 12 dpc, expressed in heart and spinal
CC ganglia. Between 13.5 dpc and 16.5 dpc, strongly expressed in spinal
CC and sympathetic ganglia, neural epithelium of the retina, oral and
CC olfactory epithelia and thymus. {ECO:0000269|PubMed:10597293,
CC ECO:0000269|PubMed:12215427, ECO:0000269|PubMed:15183309,
CC ECO:0000269|PubMed:9353319}.
CC -!- PTM: Cleavage of precursor form by UCHL3 or SENP8 is necessary for
CC function. {ECO:0000250|UniProtKB:Q15843}.
CC -!- DISRUPTION PHENOTYPE: Mice die in utero at the periimplantation stage
CC due to impaired cell cycle progression (PubMed:11696557). Embryos show
CC selective apoptosis of the inner cell mass but not of trophoblastic
CC cells (PubMed:11696557). However, trophoblastic cells do not enter the
CC S phase of the endoreduplication cycle (PubMed:11696557).
CC {ECO:0000269|PubMed:11696557}.
CC -!- SIMILARITY: Belongs to the ubiquitin family. {ECO:0000305}.
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DR EMBL; D10918; BAA01719.1; -; mRNA.
DR EMBL; BC004625; AAH04625.1; -; mRNA.
DR CCDS; CCDS49498.1; -.
DR PIR; JN0710; JN0710.
DR RefSeq; NP_032709.1; NM_008683.3.
DR AlphaFoldDB; P29595; -.
DR BMRB; P29595; -.
DR SMR; P29595; -.
DR BioGRID; 201725; 31.
DR IntAct; P29595; 2.
DR STRING; 10090.ENSMUSP00000010520; -.
DR iPTMnet; P29595; -.
DR PhosphoSitePlus; P29595; -.
DR CPTAC; non-CPTAC-4051; -.
DR EPD; P29595; -.
DR jPOST; P29595; -.
DR PaxDb; P29595; -.
DR PeptideAtlas; P29595; -.
DR PRIDE; P29595; -.
DR ProteomicsDB; 286177; -.
DR Antibodypedia; 22753; 504 antibodies from 38 providers.
DR DNASU; 18002; -.
DR Ensembl; ENSMUST00000010520; ENSMUSP00000010520; ENSMUSG00000010376.
DR Ensembl; ENSMUST00000163750; ENSMUSP00000130492; ENSMUSG00000010376.
DR GeneID; 18002; -.
DR KEGG; mmu:18002; -.
DR UCSC; uc007uac.1; mouse.
DR CTD; 4738; -.
DR MGI; MGI:97301; Nedd8.
DR VEuPathDB; HostDB:ENSMUSG00000010376; -.
DR eggNOG; KOG0005; Eukaryota.
DR GeneTree; ENSGT00940000155856; -.
DR HOGENOM; CLU_010412_6_4_1; -.
DR InParanoid; P29595; -.
DR OMA; YAGKQMA; -.
DR OrthoDB; 1536766at2759; -.
DR PhylomeDB; P29595; -.
DR TreeFam; TF300072; -.
DR Reactome; R-MMU-2173789; TGF-beta receptor signaling activates SMADs.
DR Reactome; R-MMU-5689603; UCH proteinases.
DR Reactome; R-MMU-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-MMU-8951664; Neddylation.
DR Reactome; R-MMU-917937; Iron uptake and transport.
DR BioGRID-ORCS; 18002; 29 hits in 70 CRISPR screens.
DR ChiTaRS; Nedd8; mouse.
DR PRO; PR:P29595; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P29595; protein.
DR Bgee; ENSMUSG00000010376; Expressed in dentate gyrus of hippocampal formation granule cell and 268 other tissues.
DR ExpressionAtlas; P29595; baseline and differential.
DR Genevisible; P29595; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0031386; F:protein tag; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0019941; P:modification-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0008104; P:protein localization; IDA:MGI.
DR GO; GO:0045116; P:protein neddylation; ISS:MGI.
DR GO; GO:0030162; P:regulation of proteolysis; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0014070; P:response to organic cyclic compound; ISO:MGI.
DR CDD; cd01806; Ubl_NEDD8; 1.
DR InterPro; IPR038738; Nedd8-like.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR InterPro; IPR019954; Ubiquitin_CS.
DR InterPro; IPR019956; Ubiquitin_dom.
DR Pfam; PF00240; ubiquitin; 1.
DR PRINTS; PR00348; UBIQUITIN.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS00299; UBIQUITIN_1; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Isopeptide bond; Nucleus; Reference proteome;
KW Ubl conjugation pathway.
FT CHAIN 1..76
FT /note="NEDD8"
FT /id="PRO_0000042769"
FT PROPEP 77..81
FT /evidence="ECO:0000250|UniProtKB:Q15843"
FT /id="PRO_0000042770"
FT REGION 70..72
FT /note="Interaction with UBE1C"
FT /evidence="ECO:0000250|UniProtKB:Q15843"
FT SITE 8
FT /note="Interaction with UBE1C"
FT /evidence="ECO:0000250|UniProtKB:Q15843"
FT SITE 44
FT /note="Interaction with UBE1C"
FT /evidence="ECO:0000250|UniProtKB:Q15843"
FT MOD_RES 48
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23806337"
FT CROSSLNK 76
FT /note="Glycyl lysine isopeptide (Gly-Lys) (interchain with
FT K-? in acceptor proteins)"
SQ SEQUENCE 81 AA; 8972 MW; DC339102BE4725D2 CRC64;
MLIKVKTLTG KEIEIDIEPT DKVERIKERV EEKEGIPPQQ QRLIYSGKQM NDEKTAADYK
ILGGSVLHLV LALRGGGGLG Q
