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    UBR5 ubiquitin protein ligase E3 component n-recognin 5 [ Homo sapiens (human) ]

    Gene ID: 51366, updated on 27-Nov-2024

    Summary

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    Official Symbol
    UBR5provided by HGNC
    Official Full Name
    ubiquitin protein ligase E3 component n-recognin 5provided by HGNC
    Primary source
    HGNC:HGNC:16806
    See related
    Ensembl:ENSG00000104517 MIM:608413; AllianceGenome:HGNC:16806
    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
    DD5; EDD; HYD; EDD1
    Summary
    This gene encodes a progestin-induced protein, which belongs to the HECT (homology to E6-AP carboxyl terminus) family. The HECT family proteins function as E3 ubiquitin-protein ligases, targeting specific proteins for ubiquitin-mediated proteolysis. This gene is localized to chromosome 8q22 which is disrupted in a variety of cancers. This gene potentially has a role in regulation of cell proliferation or differentiation. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in testis (RPKM 18.7), lymph node (RPKM 11.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See UBR5 in Genome Data Viewer
    Location:
    8q22.3
    Exon count:
    60
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 8 NC_000008.11 (102252273..102412700, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 8 NC_060932.1 (103378173..103538611, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 8 NC_000008.10 (103264501..103424928, complement)

    Chromosome 8 - NC_000008.11Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:103240735-103241235 Neighboring gene ReSE screen-validated silencer GRCh37_chr8:103243938-103244157 Neighboring gene ribonucleotide reductase regulatory TP53 inducible subunit M2B Neighboring gene MED14-independent group 3 enhancer GRCh37_chr8:103248510-103249709 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27747 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19436 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27748 Neighboring gene SUMO2 pseudogene 19 Neighboring gene UBR5 divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27749 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27750 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:103329370-103329870 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr8:103335870-103336617 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27751 Neighboring gene uncharacterized LOC124902086 Neighboring gene Sharpr-MPRA regulatory region 4694 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27752 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19437 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27753 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:103423320-103424098 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:103424099-103424877 Neighboring gene uncharacterized LOC105375683 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19440 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27755 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27756 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 27757 Neighboring gene RNA, U6atac small nuclear 8, pseudogene Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:103446806-103447531 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr8:103447532-103448256 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:103449587-103450136 Neighboring gene H3K27ac hESC enhancer GRCh37_chr8:103450137-103450684 Neighboring gene heat shock protein family E (Hsp10) member 1 pseudogene 14

    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. UBR5 promotes tumor immune evasion through enhancing IFN-γ-induced PDL1 transcription in triple negative breast cancer. Wu B, et al. Theranostics, 2022. PMID 35836797, Free PMC Article
    2. BoxCar and shotgun proteomic analyses reveal molecular networks regulated by UBR5 in prostate cancer. Yan Y, et al. Proteomics, 2022 Feb. PMID 34897998, Free PMC Article
    3. EDD enhances cell survival and cisplatin resistance and is a therapeutic target for epithelial ovarian cancer. Bradley A, et al. Carcinogenesis, 2014 May. PMID 24379240, Free PMC Article
    4. The E3 ubiquitin ligase EDD regulates S-phase and G(2)/M DNA damage checkpoints. Munoz MA, et al. Cell Cycle, 2007 Dec 15. PMID 18073532
    5. Systems level-based RNAi screening by high content analysis identifies UBR5 as a regulator of estrogen receptor-α protein levels and activity. Bolt MJ, et al. Oncogene, 2015 Jan 8. PMID 24441042, Free PMC Article

    See all (293) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The G1-S transition is promoted by Rb degradation via the E3 ligase UBR5.
      Title: The G(1)-S transition is promoted by Rb degradation via the E3 ligase UBR5.
    2. VIRMA promotes the progression of head and neck squamous cell carcinoma by regulating UBR5 mRNA and m6A levels.
      Title: VIRMA promotes the progression of head and neck squamous cell carcinoma by regulating UBR5 mRNA and m6A levels.
    3. SUB1 promotes colorectal cancer metastasis by activating NF-kappaB signaling via UBR5-mediated ubiquitination of UBXN1.
      Title: SUB1 promotes colorectal cancer metastasis by activating NF-κB signaling via UBR5-mediated ubiquitination of UBXN1.
    4. E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA.
      Title: E3 ubiquitin ligase UBR5 promotes gemcitabine resistance in pancreatic cancer by inducing O-GlcNAcylation-mediated EMT via destabilization of OGA.
    5. Spermatid perinuclear RNA-binding protein promotes UBR5-mediated proteolysis of Dicer to accelerate triple-negative breast cancer progression.
      Title: Spermatid perinuclear RNA-binding protein promotes UBR5-mediated proteolysis of Dicer to accelerate triple-negative breast cancer progression.
    6. The role of UBR5 in tumor proliferation and oncotherapy.
      Title: The role of UBR5 in tumor proliferation and oncotherapy.
    7. Structural snapshots along K48-linked ubiquitin chain formation by the HECT E3 UBR5.
      Title: Structural snapshots along K48-linked ubiquitin chain formation by the HECT E3 UBR5.
    8. Targeting UBR5 inhibits postsurgical breast cancer lung metastases by inducing CDC73 and p53 mediated apoptosis.
      Title: Targeting UBR5 inhibits postsurgical breast cancer lung metastases by inducing CDC73 and p53 mediated apoptosis.
    9. The role and molecular mechanism of metabolic reprogramming of colorectal cancer by UBR5 through PYK2 regulation of OXPHOS expression study.
      Title: The role and molecular mechanism of metabolic reprogramming of colorectal cancer by UBR5 through PYK2 regulation of OXPHOS expression study.
    10. Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5.
      Title: Cryo-EM structure of the chain-elongating E3 ubiquitin ligase UBR5.
    Submit: New GeneRIF Correction See all GeneRIFs (77)

    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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    Replication interactions

    Interaction Pubs
    Knockdown of ubiquitin protein ligase E3 component n-recognin 5 (UBR5) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Vpr vpr The interaction of HIV-1 Vpr with the EDVP E3 ligase complex (EDD, DDB1, and VPRBP) promotes Vpr-mediated downregulation of TERT protein PubMed
    vpr The interaction of Vpr with DDB1 facilitates the formation of complexes containing Cul4A-Roc1 E3 ubiquitin ligase. The association of Vpr with DDB1-containing E3 ligase mediates the degradation of UNG2 and SMUG1 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ11310, KIAA0896, MGC57263

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin protein ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin-ubiquitin ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin-ubiquitin ligase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables zinc ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in DNA damage response IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in DNA repair IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in DNA repair-dependent chromatin remodeling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cytoplasm protein quality control IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in cytoplasm protein quality control by the ubiquitin-proteasome system IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in heterochromatin boundary formation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of smoothened signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in nuclear protein quality control by the ubiquitin-proteasome system IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in positive regulation of canonical Wnt signaling pathway IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    acts_upstream_of_or_within positive regulation of gene expression IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of protein import into nucleus IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in progesterone receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K11-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K29-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K48-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein branched polyubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein polyubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein polyubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in membrane HDA PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in perinuclear region of cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    E3 ubiquitin-protein ligase UBR5
    Names
    E3 identified by differential display
    E3 ubiquitin-protein ligase, HECT domain-containing 1
    HECT-type E3 ubiquitin transferase UBR5
    hyperplastic discs protein homolog
    progestin-induced protein
    NP_001269802.1
    NP_056986.2
    XP_005251019.1
    XP_024302946.1
    XP_024302947.1
    XP_047277803.1
    XP_047277804.1
    XP_047277805.1
    XP_054216598.1
    XP_054216599.1
    XP_054216600.1
    XP_054216601.1
    XP_054216602.1
    XP_054216603.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_047152.1 RefSeqGene

      Range
      4990..165417
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001282873.2 → NP_001269802.1  E3 ubiquitin-protein ligase UBR5 isoform 2

      See identical proteins and their annotated locations for NP_001269802.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AB020703, AL833555, AP002907, AP002981, BC037843
      Consensus CDS
      CCDS64946.1
      UniProtKB/Swiss-Prot
      O95071
      Related
      ENSP00000220959.4, ENST00000220959.8
      Conserved Domains (4) summary
      smart00517
      Location:2389 → 2452
      PolyA; C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein
      smart00119
      Location:2500 → 2795
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
      cd14423
      Location:184 → 230
      CUE_UBR5; CUE domain found in E3 ubiquitin-protein ligase UBR5 and similar proteins
      cd19675
      Location:1171 → 1246
      UBR-box_UBR5; UBR-box found in HECT-type E3 ubiquitin-protein ligase UBR5 and similar proteins

    2. NM_015902.6 → NP_056986.2  E3 ubiquitin-protein ligase UBR5 isoform 1

      See identical proteins and their annotated locations for NP_056986.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AB020703, AP002907, AP002981, BX489192
      Consensus CDS
      CCDS34933.1
      UniProtKB/Swiss-Prot
      B2RP24, J3KMW7, O94970, O95071, Q9NPL3
      Related
      ENSP00000429084.1, ENST00000520539.6
      Conserved Domains (4) summary
      smart00396
      Location:1177 → 1244
      ZnF_UBR1; Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway
      smart00517
      Location:2389 → 2452
      PolyA; C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein
      smart00119
      Location:2501 → 2796
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
      cd14423
      Location:184 → 230
      CUE_UBR5; CUE domain found in E3 ubiquitin-protein ligase UBR5 and similar proteins

    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_000008.11 Reference GRCh38.p14 Primary Assembly

      Range
      102252273..102412700 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047421849.1 → XP_047277805.1  E3 ubiquitin-protein ligase UBR5 isoform X5

    2. XM_047421848.1 → XP_047277804.1  E3 ubiquitin-protein ligase UBR5 isoform X4

    3. XM_024447179.2 → XP_024302947.1  E3 ubiquitin-protein ligase UBR5 isoform X3

      Conserved Domains (3) summary
      smart00396
      Location:923 → 990
      ZnF_UBR1; Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway
      smart00517
      Location:2137 → 2200
      PolyA; C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein
      smart00119
      Location:2249 → 2544
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

    4. XM_047421847.1 → XP_047277803.1  E3 ubiquitin-protein ligase UBR5 isoform X2

    5. XM_024447178.2 → XP_024302946.1  E3 ubiquitin-protein ligase UBR5 isoform X1

      Conserved Domains (3) summary
      smart00396
      Location:929 → 996
      ZnF_UBR1; Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway
      smart00517
      Location:2143 → 2206
      PolyA; C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein
      smart00119
      Location:2255 → 2550
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with

    6. XM_005250962.6 → XP_005251019.1  E3 ubiquitin-protein ligase UBR5 isoform X6

      Conserved Domains (4) summary
      smart00396
      Location:187 → 254
      ZnF_UBR1; Putative zinc finger in N-recognin, a recognition component of the N-end rule pathway
      smart00517
      Location:1401 → 1464
      PolyA; C-terminal domain of Poly(A)-binding protein. Present also in Drosophila hyperplastics discs protein
      smart00119
      Location:1513 → 1808
      HECTc; Domain Homologous to E6-AP Carboxyl Terminus with
      pfam00632
      Location:1513 → 1811
      HECT; HECT-domain (ubiquitin-transferase)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060932.1 Alternate T2T-CHM13v2.0

      Range
      103378173..103538611 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054360627.1 → XP_054216602.1  E3 ubiquitin-protein ligase UBR5 isoform X5

    2. XM_054360626.1 → XP_054216601.1  E3 ubiquitin-protein ligase UBR5 isoform X4

    3. XM_054360625.1 → XP_054216600.1  E3 ubiquitin-protein ligase UBR5 isoform X3

    4. XM_054360624.1 → XP_054216599.1  E3 ubiquitin-protein ligase UBR5 isoform X2

    5. XM_054360623.1 → XP_054216598.1  E3 ubiquitin-protein ligase UBR5 isoform X1

    6. XM_054360628.1 → XP_054216603.1  E3 ubiquitin-protein ligase UBR5 isoform X6

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95071.2 GenPept UniProtKB/Swiss-Prot:O95071

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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