NUB1_HUMAN
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 03-AUG-2022, entry version 198.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 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-cell
RT carcinoma.";
RL Int. J. Cancer 83:456-464(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH NEDD8, SUBCELLULAR
RP LOCATION, AND INDUCTION BY INTERFERONS.
RC TISSUE=Heart;
RX 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 LEU-591.
RC TISSUE=Testis;
RX 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, NUB1L.";
RL J. Biol. Chem. 278:32905-32913(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX 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., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., 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., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA 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 project:
RT 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., Korenberg J.;
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP INTERACTION WITH PSMD4.
RX 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., Sohocki M.M.;
RT "The inherited blindness associated protein AIPL1 interacts with the cell
RT 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 FAT10
RT and accelerates its degradation.";
RL J. Biol. Chem. 279:16503-16510(2004).
RN [10]
RP FUNCTION, INTERACTION WITH UBD AND PROTEASOME, AND INDUCTION BY TNF AND
RP IFNG.
RX PubMed=16707496; DOI=10.1074/jbc.m603063200;
RA Schmidtke G., Kalveram B., Weber E., Bochtler P., Lukasiak S., Hipp M.S.,
RA Groettrup M.;
RT "The UBA domains of NUB1L are required for binding but not for accelerated
RT 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].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP INTERACTION WITH UBD.
RX PubMed=25422469; DOI=10.1073/pnas.1403383111;
RA Theng S.S., Wang W., Mah W.C., Chan C., Zhuo J., Gao Y., Qin H., Lim L.,
RA Chong S.S., Song J., Lee C.G.;
RT "Disruption of FAT10-MAD2 binding inhibits tumor progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E5282-E5291(2014).
RN [14]
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. {ECO:0000269|PubMed:16707496}.
CC -!- SUBUNIT: Directly interacts with NEDD8 and PSMD4/S5a, a member of the
CC regulatory subunit of the 26S proteasome. Isoform 1 binds to NEDD8 more
CC efficiently than isoform 2. Interacts with AIPL1. The interaction with
CC UBD via UBA domains facilitates the linking of UBD-conjugated target
CC protein to the proteasome complex and accelerates UBD degradation and
CC that of its conjugates. {ECO:0000269|PubMed:11259415,
CC ECO:0000269|PubMed:11585840, ECO:0000269|PubMed:12374762,
CC ECO:0000269|PubMed:14757770, ECO:0000269|PubMed:16707496,
CC ECO:0000269|PubMed:25422469}.
CC -!- INTERACTION:
CC Q9Y5A7; Q9NZN9: AIPL1; NbExp=2; IntAct=EBI-3936907, EBI-6557414;
CC Q9Y5A7; Q15427: SF3B4; NbExp=3; IntAct=EBI-3936907, EBI-348469;
CC Q9Y5A7; P54274: TERF1; NbExp=8; IntAct=EBI-3936907, EBI-710997;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11259415}.
CC 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 skeletal
CC muscle for isoform 2.
CC -!- INDUCTION: By TNF, IFNG/IFN-gamma and IFNB1/IFN-beta.
CC {ECO:0000269|PubMed:11259415, ECO:0000269|PubMed:16707496}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD42865.1; Type=Frameshift; Evidence={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; 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 CCDS; CCDS47751.2; -. [Q9Y5A7-2]
DR CCDS; CCDS59089.1; -. [Q9Y5A7-1]
DR CCDS; CCDS87565.1; -. [Q9Y5A7-1]
DR RefSeq; NP_001230280.1; NM_001243351.1. [Q9Y5A7-1]
DR RefSeq; NP_057202.3; NM_016118.4. [Q9Y5A7-2]
DR RefSeq; XP_005250068.1; XM_005250011.2.
DR RefSeq; XP_016867795.1; XM_017012306.1. [Q9Y5A7-2]
DR PDB; 1WJU; NMR; -; A=75-161.
DR PDBsum; 1WJU; -.
DR AlphaFoldDB; Q9Y5A7; -.
DR SMR; Q9Y5A7; -.
DR BioGRID; 119670; 35.
DR CORUM; Q9Y5A7; -.
DR IntAct; Q9Y5A7; 10.
DR MINT; Q9Y5A7; -.
DR STRING; 9606.ENSP00000454264; -.
DR iPTMnet; Q9Y5A7; -.
DR MetOSite; Q9Y5A7; -.
DR PhosphoSitePlus; Q9Y5A7; -.
DR BioMuta; NUB1; -.
DR DMDM; 37154888; -.
DR EPD; Q9Y5A7; -.
DR jPOST; Q9Y5A7; -.
DR MassIVE; Q9Y5A7; -.
DR MaxQB; Q9Y5A7; -.
DR PaxDb; Q9Y5A7; -.
DR PeptideAtlas; Q9Y5A7; -.
DR PRIDE; Q9Y5A7; -.
DR ProteomicsDB; 86324; -. [Q9Y5A7-1]
DR ProteomicsDB; 86325; -. [Q9Y5A7-2]
DR Antibodypedia; 33007; 373 antibodies from 31 providers.
DR DNASU; 51667; -.
DR Ensembl; ENST00000413040.7; ENSP00000398644.3; ENSG00000013374.17. [Q9Y5A7-2]
DR Ensembl; ENST00000470229.6; ENSP00000418234.2; ENSG00000013374.17. [Q9Y5A7-1]
DR Ensembl; ENST00000568733.6; ENSP00000454264.2; ENSG00000013374.17. [Q9Y5A7-1]
DR GeneID; 51667; -.
DR KEGG; hsa:51667; -.
DR MANE-Select; ENST00000568733.6; ENSP00000454264.2; NM_001243351.2; NP_001230280.2.
DR CTD; 51667; -.
DR DisGeNET; 51667; -.
DR GeneCards; NUB1; -.
DR HGNC; HGNC:17623; NUB1.
DR HPA; ENSG00000013374; Low tissue specificity.
DR MIM; 607981; gene.
DR neXtProt; NX_Q9Y5A7; -.
DR OpenTargets; ENSG00000013374; -.
DR PharmGKB; PA147357533; -.
DR VEuPathDB; HostDB:ENSG00000013374; -.
DR eggNOG; KOG2561; Eukaryota.
DR GeneTree; ENSGT00390000010557; -.
DR InParanoid; Q9Y5A7; -.
DR OMA; AMDQFQV; -.
DR OrthoDB; 1339766at2759; -.
DR PhylomeDB; Q9Y5A7; -.
DR TreeFam; TF323449; -.
DR PathwayCommons; Q9Y5A7; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q9Y5A7; -.
DR BioGRID-ORCS; 51667; 8 hits in 1082 CRISPR screens.
DR ChiTaRS; NUB1; human.
DR EvolutionaryTrace; Q9Y5A7; -.
DR GeneWiki; NUB1; -.
DR GenomeRNAi; 51667; -.
DR Pharos; Q9Y5A7; Tbio.
DR PRO; PR:Q9Y5A7; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9Y5A7; protein.
DR Bgee; ENSG00000013374; Expressed in oviduct epithelium and 179 other tissues.
DR ExpressionAtlas; Q9Y5A7; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IMP:UniProtKB.
DR GO; GO:2000058; P:regulation of ubiquitin-dependent protein catabolic process; IBA:GO_Central.
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; IPR039749; NUB1.
DR InterPro; IPR041207; NUB1_ubiquitin-like_dom.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR015940; UBA.
DR InterPro; IPR009060; UBA-like_sf.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR12948; PTHR12948; 1.
DR Pfam; PF00627; UBA; 2.
DR Pfam; PF18037; Ubiquitin_5; 1.
DR SMART; SM00165; UBA; 3.
DR SUPFAM; SSF46934; SSF46934; 3.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS50030; UBA; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Nucleus;
KW Reference proteome; Repeat.
FT CHAIN 1..615
FT /note="NEDD8 ultimate buster 1"
FT /id="PRO_0000210992"
FT DOMAIN 374..413
FT /note="UBA 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 424..470
FT /note="UBA 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT DOMAIN 489..529
FT /note="UBA 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT REGION 427..474
FT /note="NEDD8-binding 1"
FT REGION 532..586
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 550..598
FT /note="NEDD8-binding 2"
FT COILED 36..70
FT /evidence="ECO:0000255"
FT COILED 152..203
FT /evidence="ECO:0000255"
FT MOTIF 414..431
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000305"
FT COMPBIAS 544..566
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..586
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 452..465
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10508479,
FT ECO:0000303|PubMed:11259415, ECO:0000303|PubMed:12816948,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_008335"
FT VARIANT 13
FT /note="Q -> R (in dbSNP:rs2302131)"
FT /id="VAR_057369"
FT MUTAGEN 448
FT /note="A->V: No effect on NEDD8-binding."
FT /evidence="ECO:0000269|PubMed:12816948"
FT MUTAGEN 453
FT /note="L->A: Partial inhibition of NEDD8-binding."
FT /evidence="ECO:0000269|PubMed:12816948"
FT MUTAGEN 464
FT /note="L->A: Partial inhibition of NEDD8-binding."
FT /evidence="ECO:0000269|PubMed:12816948"
FT MUTAGEN 468
FT /note="L->A: Partial inhibition of NEDD8-binding."
FT /evidence="ECO:0000269|PubMed:12816948"
FT MUTAGEN 587
FT /note="L->A: Suppression of NEDD8-binding; when associated
FT with A-464; A-468 and A-591. Suppression of NEDD8-buster
FT function; when associated with A-591."
FT /evidence="ECO:0000269|PubMed:12816948"
FT MUTAGEN 591
FT /note="L->A: Suppression of NEDD8-binding; when associated
FT with A-464; A-468 and A-587. Suppression of NEDD8-buster
FT function; when associated with A-587."
FT /evidence="ECO:0000269|PubMed:12816948"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:1WJU"
FT STRAND 82..88
FT /evidence="ECO:0007829|PDB:1WJU"
FT STRAND 96..108
FT /evidence="ECO:0007829|PDB:1WJU"
FT HELIX 109..119
FT /evidence="ECO:0007829|PDB:1WJU"
FT STRAND 128..131
FT /evidence="ECO:0007829|PDB:1WJU"
FT HELIX 142..145
FT /evidence="ECO:0007829|PDB:1WJU"
FT STRAND 149..156
FT /evidence="ECO:0007829|PDB:1WJU"
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
