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

Gene ID: 51667, updated on 3-Apr-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
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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_2023_10 current GRCh38.p14 (GCF_000001405.40) 7 NC_000007.14 (151341812..151378449)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 7 NC_060931.1 (152514799..152551295)
105.20220307 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, matrix associated, actin dependent regulator of chromatin, subfamily d, member 3 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. 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
  2. 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
  3. 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
  4. 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
  5. NUB1-mediated targeting of the ubiquitin precursor UbC1 for its C-terminal hydrolysis. Tanaka T, et al. Eur J Biochem, 2004 Mar. PMID 15009209

See all (71) 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)

Genotypes

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_2023_10

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

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

  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

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

  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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