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    NUB1 negative regulator of ubiquitin like proteins 1 [ Homo sapiens (human) ]

    Gene ID: 51667, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NUB1provided by HGNC
    Official Full Name
    negative regulator of ubiquitin like proteins 1provided by HGNC
    Primary source
    HGNC:HGNC:17623
    See related
    Ensembl:ENSG00000013374 MIM:607981; AllianceGenome:HGNC:17623
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    BS4; NUB1L; NYREN18
    Summary
    This gene encodes a protein that functions as a negative regulator of NEDD8, a ubiquitin-like protein that conjugates with cullin family members in order to regulate vital biological events. The protein encoded by this gene regulates the NEDD8 conjugation system post-transcriptionally by recruiting NEDD8 and its conjugates to the proteasome for degradation. This protein interacts with the product of the AIPL1 gene, which is associated with Leber congenital amaurosis, an inherited retinopathy, and mutations in that gene can abolish interaction with this protein, which may contribute to the pathogenesis. This protein is also known to accumulate in Lewy bodies in Parkinson's disease and dementia with Lewy bodies, and in glial cytoplasmic inclusions in multiple system atrophy, with this abnormal accumulation being specific to alpha-synucleinopathy lesions. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2011]
    Expression
    Ubiquitous expression in lymph node (RPKM 24.3), testis (RPKM 24.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NUB1 in Genome Data Viewer
    Location:
    7q36.1
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (151341812..151378449)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (152514799..152551295)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (151038898..151075535)

    Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene MED14-independent group 3 enhancer GRCh37_chr7:150936637-150937836 Neighboring gene uncharacterized LOC124901779 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150938593-150939094 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150941724-150942298 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150942299-150942872 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150942873-150943447 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150943448-150944021 Neighboring gene Sharpr-MPRA regulatory region 13648 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18809 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150949301-150950210 Neighboring gene chondroitin polymerizing factor 2 Neighboring gene SWI/SNF related BAF chromatin remodeling complex subunit D3 Neighboring gene microRNA 671 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150953220-150953720 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150953721-150954221 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150971756-150972555 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:150974709-150975418 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:151000420-151001278 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26856 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26857 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26858 Neighboring gene H3K27ac hESC enhancer GRCh37_chr7:151038519-151039020 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18812 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26859 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18813 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 18814 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:151084439-151085101 Neighboring gene WD repeat domain 86 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:151107690-151108322 Neighboring gene WDR86 antisense RNA 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr7:151125597-151126116 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26860 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26861 Neighboring gene uncharacterized LOC124901780 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26862 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 26863 Neighboring gene microRNA 3907 Neighboring gene crystallin gamma N

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. NUB1, an interferon-inducible protein, mediates anti-proliferative actions and apoptosis in renal cell carcinoma cells through cell-cycle regulation. Hosono T, et al. Br J Cancer, 2010 Mar 2. PMID 20160729, Free PMC Article
    2. Degradation of FAT10 by the 26S proteasome is independent of ubiquitylation but relies on NUB1L. Schmidtke G, et al. FEBS Lett, 2009 Feb 4. PMID 19166848
    3. Phosphorylated NUB1 distinguishes α-synuclein in Lewy bodies from that in glial cytoplasmic inclusions in multiple system atrophy. Tanji K, et al. Brain Pathol, 2019 Nov. PMID 31006160, Free PMC Article
    4. NUB1-mediated targeting of the ubiquitin precursor UbC1 for its C-terminal hydrolysis. Tanaka T, et al. Eur J Biochem, 2004 Mar. PMID 15009209
    5. Synphilin-1-binding protein NUB1 is colocalized with nonfibrillar, proteinase K-resistant α-synuclein in presynapses in Lewy body disease. Tanji K, et al. J Neuropathol Exp Neurol, 2011 Oct. PMID 21937912, Free PMC Article

    See all (74) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. FAT10 and NUB1L cooperate to activate the 26S proteasome.
      Title: FAT10 and NUB1L cooperate to activate the 26S proteasome.
    2. SNHG12 regulates biological behaviors of ox-LDL-induced HA-VSMCs through upregulation of SPRY2 and NUB1.
      Title: SNHG12 regulates biological behaviors of ox-LDL-induced HA-VSMCs through upregulation of SPRY2 and NUB1.
    3. Overexpression of negative regulator of ubiquitin-like proteins 1 (NUB1) inhibits proliferation and invasion of gastric cancer cells through upregulation of p27Kip1 and inhibition of epithelial-mesenchymal transition.
      Title: Overexpression of negative regulator of ubiquitin-like proteins 1 (NUB1) inhibits proliferation and invasion of gastric cancer cells through upregulation of p27Kip1 and inhibition of epithelial-mesenchymal transition.
    4. Authors created a series of phosphomimic mutants of NUB1 and found that phosphorylation of NUB1 at S46 (P-NUB46) efficiently degrades aggregates using a cell-based assay.
      Title: Phosphorylated NUB1 distinguishes α-synuclein in Lewy bodies from that in glial cytoplasmic inclusions in multiple system atrophy.
    5. Mdm2 acts as a positive regulator of NUB1 function, by modulating NUB1 ubiquitination on lysine 159.
      Title: Regulation of NUB1 Activity through Non-Proteolytic Mdm2-Mediated Ubiquitination.
    6. data suggest that NUB1 participates in telomere maintenance by regulating the levels of TRF1 at telomeres through both NEDD8-dependent and NEDD8-independent pathways.
      Title: NEDD8 ultimate buster-1 regulates the abundance of TRF1 at telomeres by promoting its proteasomal degradation.
    7. NUB1L suppresses atypical neddylation and promotes the degradation of misfolded proteins by the proteasome
      Title: NEDD8 Ultimate Buster 1 Long (NUB1L) Protein Suppresses Atypical Neddylation and Promotes the Proteasomal Degradation of Misfolded Proteins.
    8. Based on biochemical features of the VBM motifs, we also identified NUB1L (NEDD8 ultimate buster-1 long) as a novel VBM-containing protein, which is involved in proteasomal degradation of NEDD8 through the P97 pathway.
      Title: Structural and mechanistic insights into the arginine/lysine-rich peptide motifs that interact with P97/VCP.
    9. In coordination with the P97-UFD1-NPL4 complex (P97(UFD1/NPL4)), NUB1L promotes transfer of NEDD8 to proteasome for degradation.
      Title: NEDD8 ultimate buster-1 long (NUB1L) protein promotes transfer of NEDD8 to proteasome for degradation through the P97UFD1/NPL4 complex.
    10. This study identified genes modifying endogenous mHTT using high-throughput screening and demonstrate NUB1 as an exemplar entry point for therapeutic intervention of Huntington's disease.
      Title: Identification of NUB1 as a suppressor of mutant Huntington toxicity via enhanced protein clearance.
    Submit: New GeneRIF Correction See all GeneRIFs (21)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    capsid gag The interaction of HIV-1 CA with human cellular negative regulator of ubiquitin-like protein 1 (NUB1) is identified by yeast two-hybrid screen PubMed

    Go to the HIV-1, Human Interaction Database

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein ubiquitination IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of ubiquitin-dependent protein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to tumor necrosis factor IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in response to type II interferon IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    NEDD8 ultimate buster 1
    Names
    NEDD8 ultimate buster-1
    renal carcinoma antigen NY-REN-18

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029746.2 RefSeqGene

      Range
      5052..41689
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243351.2 → NP_001230280.2  NEDD8 ultimate buster 1 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (2, also known as NUB1L).
      Source sequence(s)
      AC005486
      Consensus CDS
      CCDS87565.1
      UniProtKB/Swiss-Prot
      O95422, Q75MR9, Q8IX22, Q9BXR2, Q9Y5A7
      UniProtKB/TrEMBL
      H3BM74
      Related
      ENSP00000454264.2, ENST00000568733.6
      Conserved Domains (4) summary
      cd14291
      Location:376 → 411
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      cd14292
      Location:435 → 468
      UBA2_NUB1; UBA2 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      pfam18037
      Location:70 → 163
      Ubiquitin_5; Ubiquitin-like domain
      cl21463
      Location:493 → 528
      UBA_like_SF; UBA domain-like superfamily

    2. NM_001363529.2 → NP_001350458.1  NEDD8 ultimate buster 1 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC005486
      Consensus CDS
      CCDS87565.1
      UniProtKB/Swiss-Prot
      O95422, Q75MR9, Q8IX22, Q9BXR2, Q9Y5A7
      UniProtKB/TrEMBL
      H3BM74
      Related
      ENSP00000418234.2, ENST00000470229.6
      Conserved Domains (4) summary
      cd14291
      Location:376 → 411
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      cd14292
      Location:435 → 468
      UBA2_NUB1; UBA2 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      pfam18037
      Location:70 → 163
      Ubiquitin_5; Ubiquitin-like domain
      cl21463
      Location:493 → 528
      UBA_like_SF; UBA domain-like superfamily

    3. NM_001385353.1 → NP_001372282.1  NEDD8 ultimate buster 1 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC005486
      Consensus CDS
      CCDS47751.3
      UniProtKB/TrEMBL
      A0A090N8Q5, H3BM14
      Conserved Domains (3) summary
      cd14291
      Location:376 → 411
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      pfam18037
      Location:70 → 163
      Ubiquitin_5; Ubiquitin-like domain
      cl21463
      Location:479 → 514
      UBA_like_SF; UBA domain-like superfamily

    4. NM_001385354.1 → NP_001372283.1  NEDD8 ultimate buster 1 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC005486
      UniProtKB/TrEMBL
      H3BM14
      Conserved Domains (3) summary
      cd14291
      Location:375 → 410
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      pfam18037
      Location:70 → 163
      Ubiquitin_5; Ubiquitin-like domain
      cl21463
      Location:478 → 513
      UBA_like_SF; UBA domain-like superfamily

    5. NM_001385355.1 → NP_001372284.1  NEDD8 ultimate buster 1 isoform 4

      Status: REVIEWED

      Source sequence(s)
      AC005486
      UniProtKB/TrEMBL
      H3BM14
      Conserved Domains (3) summary
      cd14291
      Location:375 → 410
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      pfam18037
      Location:70 → 163
      Ubiquitin_5; Ubiquitin-like domain
      cl21463
      Location:478 → 513
      UBA_like_SF; UBA domain-like superfamily

    6. NM_001385356.1 → NP_001372285.1  NEDD8 ultimate buster 1 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC005486
      UniProtKB/TrEMBL
      H3BM14
      Conserved Domains (3) summary
      cd14291
      Location:376 → 411
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      pfam18037
      Location:70 → 163
      Ubiquitin_5; Ubiquitin-like domain
      cl21463
      Location:444 → 479
      UBA_like_SF; UBA domain-like superfamily

    7. NM_001385361.1 → NP_001372290.1  NEDD8 ultimate buster 1 isoform 5

      Status: REVIEWED

      Source sequence(s)
      AC005486
      UniProtKB/TrEMBL
      H3BM14
      Conserved Domains (3) summary
      cd14291
      Location:376 → 411
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      pfam18037
      Location:70 → 163
      Ubiquitin_5; Ubiquitin-like domain
      cl21463
      Location:444 → 479
      UBA_like_SF; UBA domain-like superfamily

    8. NM_016118.5 → NP_057202.4  NEDD8 ultimate buster 1 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 3' coding region, compared to variant 1, resulting in an isoform (2, also known as NUB1) that is shorter than isoform 1.
      Source sequence(s)
      AC005486
      Consensus CDS
      CCDS47751.3
      UniProtKB/TrEMBL
      A0A090N8Q5, H3BM14
      Related
      ENSP00000398644.3, ENST00000413040.7
      Conserved Domains (3) summary
      cd14291
      Location:376 → 411
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      pfam18037
      Location:70 → 163
      Ubiquitin_5; Ubiquitin-like domain
      cl21463
      Location:479 → 514
      UBA_like_SF; UBA domain-like superfamily

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000007.14 Reference GRCh38.p14 Primary Assembly

      Range
      151341812..151378449
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017012304.2 → XP_016867793.2  NEDD8 ultimate buster 1 isoform X1

      UniProtKB/TrEMBL
      H3BM74

    2. XM_017012308.2 → XP_016867797.2  NEDD8 ultimate buster 1 isoform X2

      UniProtKB/TrEMBL
      H3BM14

    3. XM_024446798.2 → XP_024302566.1  NEDD8 ultimate buster 1 isoform X3

      Conserved Domains (3) summary
      cd14291
      Location:223 → 258
      UBA1_NUB1_like; UBA1 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      cd14292
      Location:282 → 315
      UBA2_NUB1; UBA2 domain found in NEDD8 ultimate buster 1 (NUB1) and similar proteins
      cl21463
      Location:340 → 375
      UBA_like_SF; UBA domain-like superfamily

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060931.1 Alternate T2T-CHM13v2.0

      Range
      152514799..152551295
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054358390.1 → XP_054214365.1  NEDD8 ultimate buster 1 isoform X1

      UniProtKB/TrEMBL
      H3BM74

    2. XM_054358391.1 → XP_054214366.1  NEDD8 ultimate buster 1 isoform X2

      UniProtKB/TrEMBL
      H3BM14

    3. XM_054358392.1 → XP_054214367.1  NEDD8 ultimate buster 1 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9Y5A7.2 GenPept UniProtKB/Swiss-Prot:Q9Y5A7

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