ID NUB1_HUMAN Reviewed; 615 AA. AC Q9Y5A7; O95422; Q75MR9; Q8IX22; Q9BXR2; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 26-SEP-2003, sequence version 2. DT 05-OCT-2010, entry version 99. DE RecName: Full=NEDD8 ultimate buster 1; DE AltName: Full=Negative regulator of ubiquitin-like proteins 1; DE AltName: Full=Renal carcinoma antigen NY-REN-18; GN Name=NUB1; Synonyms=NYREN18; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND IDENTIFICATION AS A RENAL RP CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX MEDLINE=99438124; PubMed=10508479; RX DOI=10.1002/(SICI)1097-0215(19991112)83:4<456::AID-IJC4>3.0.CO;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal- RT cell carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH NEDD8, RP SUBCELLULAR LOCATION, AND INDUCTION BY INTERFERONS. RC TISSUE=Heart; RX MEDLINE=21282873; PubMed=11259415; DOI=10.1074/jbc.M100920200; RA Kito K., Yeh E.T.H., Kamitani T.; RT "NUB1, a NEDD8-interacting protein, is induced by interferon and down- RT regulates the NEDD8 expression."; RL J. Biol. Chem. 276:20603-20609(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), CHARACTERIZATION, AND RP MUTAGENESIS OF ALA-448; LEU-453; LEU-464; LEU-468; LEU-587 AND RP LEU-591. RC TISSUE=Testis; RX MEDLINE=22817890; PubMed=12816948; DOI=10.1074/jbc.M212057200; RA Tanaka T., Kawashima H., Yeh E.T.H., Kamitani T.; RT "Regulation of the NEDD8 conjugation system by a splicing variant, RT NUB1L."; RL J. Biol. Chem. 278:32905-32913(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=22737999; PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Testis; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-365. RA Rump A., Rosenthal A., Drescher B., Weber J., Schattevoy R., RA Korenberg J.; RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases. RN [7] RP INTERACTION WITH PSMD4. RX MEDLINE=21588229; PubMed=11585840; DOI=10.1074/jbc.M108636200; RA Kamitani T., Kito K., Fukuda-Kamitani T., Yeh E.T.H.; RT "Targeting of NEDD8 and its conjugates for proteasomal degradation by RT NUB1."; RL J. Biol. Chem. 276:46655-46660(2001). RN [8] RP INTERACTION WITH AIPL1. RC TISSUE=Retina; RX PubMed=12374762; DOI=10.1093/hmg/11.22.2723; RA Akey D.T., Zhu X., Dyer M., Li A., Sorensen A., Blackshaw S., RA Fukuda-Kamitani T., Daiger S.P., Craft C.M., Kamitani T., RA Sohocki M.M.; RT "The inherited blindness associated protein AIPL1 interacts with the RT cell cycle regulator protein NUB1."; RL Hum. Mol. Genet. 11:2723-2733(2002). RN [9] RP INTERACTION WITH UBD. RX PubMed=14757770; DOI=10.1074/jbc.M310114200; RA Hipp M.S., Raasi S., Groettrup M., Schmidtke G.; RT "NEDD8 ultimate buster-1L interacts with the ubiquitin-like protein RT FAT10 and accelerates its degradation."; RL J. Biol. Chem. 279:16503-16510(2004). RN [10] RP FUNCTION, INTERACTION WITH UBD AND PROTEASOME, AND INDUCTION BY TNFA RP AND IFNG. RX PubMed=16707496; DOI=10.1074/jbc.M603063200; RA Schmidtke G., Kalveram B., Weber E., Bochtler P., Lukasiak S., RA Hipp M.S., Groettrup M.; RT "The UBA domains of NUB1L are required for binding but not for RT accelerated degradation of the ubiquitin-like modifier FAT10."; RL J. Biol. Chem. 281:20045-20054(2006). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [12] RP STRUCTURE BY NMR OF 75-161. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of N-terminal ubiquitin-like domain of human NEDD8 RT ultimate buster-1."; RL Submitted (JAN-2006) to the PDB data bank. CC -!- FUNCTION: Specific down-regulator of the NEDD8 conjugation system. CC Recruits NEDD8, UBD, and their conjugates to the proteasome for CC degradation. Isoform 1 promotes the degradation of NEDD8 more CC efficiently than isoform 2. CC -!- SUBUNIT: Directly interacts with NEDD8 and PSMD4/S5a, a member of CC the regulatory subunit of the 26S proteasome. Isoform 1 binds to CC NEDD8 more efficiently than isoform 2. Interacts with AIPL1. The CC interaction with UBD via UBA domains facilitates the linking of CC UBD-conjugated target protein to the proteasome complex and CC accelerates UBD degradation and that of its conjugates. CC -!- SUBCELLULAR LOCATION: Nucleus. Note=Predominantly nuclear. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=NUB1L; CC IsoId=Q9Y5A7-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9Y5A7-2; Sequence=VSP_008335; CC -!- TISSUE SPECIFICITY: Widely expressed with lowest expression in the CC pancreas for isoform 1 and in leukocytes, liver, prostate and CC skeletal muscle for isoform 2. CC -!- INDUCTION: By TNF, IFNG/IFN-gamma and IFNB1/IFN-beta. CC -!- SIMILARITY: Contains 3 UBA domains. CC -!- SEQUENCE CAUTION: CC Sequence=AAD42865.1; Type=Frameshift; Positions=365, 393; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF155099; AAD42865.1; ALT_FRAME; mRNA. DR EMBL; AF300717; AAK21001.1; -; mRNA. DR EMBL; AF459743; AAO14547.1; -; mRNA. DR EMBL; AY129295; AAN01355.1; -; mRNA. DR EMBL; AC005486; AAS02030.1; -; Genomic_DNA. DR EMBL; BC046354; AAH46354.1; -; mRNA. DR EMBL; AF108083; AAC82474.2; -; Genomic_DNA. DR IPI; IPI00157365; -. DR IPI; IPI00377271; -. DR RefSeq; NP_057202.2; -. DR UniGene; Hs.647082; -. DR UniGene; Hs.662237; -. DR PDB; 1WJU; NMR; -; A=75-161. DR PDBsum; 1WJU; -. DR ProteinModelPortal; Q9Y5A7; -. DR SMR; Q9Y5A7; 470-544. DR MINT; MINT-268296; -. DR STRING; Q9Y5A7; -. DR PhosphoSite; Q9Y5A7; -. DR PRIDE; Q9Y5A7; -. DR Ensembl; ENST00000355851; ENSP00000348110; ENSG00000013374. DR GeneID; 51667; -. DR KEGG; hsa:51667; -. DR UCSC; uc003wjw.1; human. DR UCSC; uc003wjx.1; human. DR CTD; 51667; -. DR GeneCards; GC07P151038; -. DR HGNC; HGNC:17623; NUB1. DR MIM; 607981; gene. DR eggNOG; prNOG05872; -. DR HOGENOM; HBG445703; -. DR HOVERGEN; HBG045600; -. DR InParanoid; Q9Y5A7; -. DR OMA; QLGKTLE; -. DR OrthoDB; EOG9DRCXG; -. DR PhylomeDB; Q9Y5A7; -. DR NextBio; 55660; -. DR ArrayExpress; Q9Y5A7; -. DR Bgee; Q9Y5A7; -. DR CleanEx; HS_NUB1; -. DR Genevestigator; Q9Y5A7; -. DR GermOnline; ENSG00000013374; Homo sapiens. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquiti...; IMP:UniProtKB. DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB. DR GO; GO:0034341; P:response to interferon-gamma; IEP:UniProtKB. DR GO; GO:0034612; P:response to tumor necrosis factor; IEP:UniProtKB. DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IMP:UniProtKB. DR InterPro; IPR009060; UBA-like. DR InterPro; IPR000449; UBA/transl_elong_EF1B_N. DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk. DR Pfam; PF00627; UBA; 2. DR SMART; SM00165; UBA; 3. DR SUPFAM; SSF46934; UBA_like; 2. DR PROSITE; PS50030; UBA; 3. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Complete proteome; KW Nucleus; Polymorphism; Repeat. FT CHAIN 1 615 NEDD8 ultimate buster 1. FT /FTId=PRO_0000210992. FT DOMAIN 374 413 UBA 1. FT DOMAIN 424 470 UBA 2. FT DOMAIN 489 529 UBA 3. FT REGION 427 474 NEDD8-binding 1. FT REGION 550 598 NEDD8-binding 2. FT COILED 36 70 Potential. FT COILED 152 203 Potential. FT MOTIF 414 431 Nuclear localization signal (Probable). FT VAR_SEQ 452 465 Missing (in isoform 2). FT /FTId=VSP_008335. FT VARIANT 13 13 Q -> R (in dbSNP:rs2302131). FT /FTId=VAR_057369. FT MUTAGEN 448 448 A->V: No effect on NEDD8-binding. FT MUTAGEN 453 453 L->A: Partial inhibition of NEDD8- FT binding. FT MUTAGEN 464 464 L->A: Partial inhibition of NEDD8- FT binding. FT MUTAGEN 468 468 L->A: Partial inhibition of NEDD8- FT binding. FT MUTAGEN 587 587 L->A: Suppression of NEDD8-binding; when FT associated with A-464; A-468 and A-591. FT Suppression of NEDD8-buster function; FT when associated with A-591. FT MUTAGEN 591 591 L->A: Suppression of NEDD8-binding; when FT associated with A-464; A-468 and A-587. FT Suppression of NEDD8-buster function; FT when associated with A-587. FT STRAND 76 78 FT STRAND 82 88 FT STRAND 96 108 FT HELIX 109 119 FT STRAND 128 131 FT HELIX 142 145 FT STRAND 149 156 SQ SEQUENCE 615 AA; 70538 MW; D70FD6B21F4CD42E CRC64; MAQKKYLQAK LTQFLREDRI QLWKPPYTDE NKKVGLALKD LAKQYSDRLE CCENEVEKVI EEIRCKAIER GTGNDNYRTT GIATIEVFLP PRLKKDRKNL LETRLHITGR ELRSKIAETF GLQENYIKIV INKKQLQLGK TLEEQGVAHN VKAMVLELKQ SEEDARKNFQ LEEEEQNEAK LKEKQIQRTK RGLEILAKRA AETVVDPEMT PYLDIANQTG RSIRIPPSER KALMLAMGYH EKGRAFLKRK EYGIALPCLL DADKYFCECC RELLDTVDNY AVLQLDIVWC YFRLEQLECL DDAEKKLNLA QKCFKNCYGE NHQRLVHIKG NCGKEKVLFL RLYLLQGIRN YHSGNDVEAY EYLNKARQLF KELYIDPSKV DNLLQLGFTA QEARLGLRAC DGNVDHAATH ITNRREELAQ IRKEEKEKKR RRLENIRFLK GMGYSTHAAQ QVLHAASGNL DEALKILLSN PQMWWLNDSN PETDNRQESP SQENIDRLVY MGFDALVAEA ALRVFRGNVQ LAAQTLAHNG GSLPPELPLS PEDSLSPPAT SPSDSAGTSS ASTDEDMETE AVNEILEDIP EHEEDYLDST LEDEEIIIAE YLSYVENRKS ATKKN //