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    UBE4B ubiquitination factor E4B [ Homo sapiens (human) ]

    Gene ID: 10277, updated on 2-Nov-2024

    Summary

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    Official Symbol
    UBE4Bprovided by HGNC
    Official Full Name
    ubiquitination factor E4Bprovided by HGNC
    Primary source
    HGNC:HGNC:12500
    See related
    Ensembl:ENSG00000130939 MIM:613565; AllianceGenome:HGNC:12500
    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
    E4; UFD2; HDNB1; UBOX3; UFD2A
    Summary
    The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes an additional conjugation factor, E4, which is involved in multiubiquitin chain assembly. This gene is also the strongest candidate in the neuroblastoma tumor suppressor genes. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in thyroid (RPKM 12.1), skin (RPKM 10.9) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See UBE4B in Genome Data Viewer
    Location:
    1p36.22
    Exon count:
    32
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (10032958..10181239)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (9576012..9724288)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (10093016..10241297)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene nicotinamide nucleotide adenylyltransferase 1 Neighboring gene Sharpr-MPRA regulatory region 14190 Neighboring gene basic salivary proline-rich protein 2-like Neighboring gene microRNA 5697 Neighboring gene MPRA-validated peak62 silencer Neighboring gene MPRA-validated peak63 silencer Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:10092788-10093442 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 141 Neighboring gene retinol binding protein 7 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:10119257-10120187 Neighboring gene ribosomal protein L21 pseudogene 21 Neighboring gene phosphoglycerate mutase 1 pseudogene 11 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:10149775-10150276 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:10150277-10150776 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:10168782-10169282 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:10215211-10215412 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 142 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 143 Neighboring gene RNA, U6 small nuclear 828, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 144 Neighboring gene Sharpr-MPRA regulatory region 4147 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 242 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 243 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:10271761-10272416 Neighboring gene MPRA-validated peak64 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:10304177-10304678 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:10304679-10305178 Neighboring gene kinesin family member 1B Neighboring gene MPRA-validated peak65 silencer Neighboring gene MPRA-validated peak66 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 145 Neighboring gene RNA, U6 small nuclear 37, pseudogene Neighboring gene RNA, 7SL, cytoplasmic 731, pseudogene

    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 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. Low UBE4B expression increases sensitivity of chemoresistant neuroblastoma cells to EGFR and STAT5 inhibition. Memarzadeh K, et al. Cancer Biol Ther, 2019. PMID 31475882, Free PMC Article
    2. UBE4B levels are correlated with clinical outcomes in neuroblastoma patients and with altered neuroblastoma cell proliferation and sensitivity to epidermal growth factor receptor inhibitors. Zage PE, et al. Cancer, 2013 Feb 15. PMID 22990745, Free PMC Article
    3. The MPAC domain is a novel mitotically regulated domain, removed by apoptotic protease cleavage during cell death. Spinette S, et al. Biochem Biophys Res Commun, 2006 Sep 8. PMID 16870146
    4. Upregulated UBE4B expression correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma. Shao X, et al. Aging (Albany NY), 2022 Dec 5. PMID 36470669, Free PMC Article
    5. Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line. Ohira M, et al. Oncogene, 2000 Aug 31. PMID 10980605

    See all (104) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. UBE4B regulates p27 expression in A549 NSCLC cells through regulating the interaction of HuR and the p27 5' UTR.
      Title: UBE4B regulates p27 expression in A549 NSCLC cells through regulating the interaction of HuR and the p27 5' UTR.
    2. UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis.
      Title: UBE4B interacts with the ITCH E3 ubiquitin ligase to induce Ku70 and c-FLIPL polyubiquitination and enhanced neuroblastoma apoptosis.
    3. A novel protein encoded by circUBE4B promotes progression of esophageal squamous cell carcinoma by augmenting MAPK/ERK signaling.
      Title: A novel protein encoded by circUBE4B promotes progression of esophageal squamous cell carcinoma by augmenting MAPK/ERK signaling.
    4. Upregulated UBE4B expression correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma.
      Title: Upregulated UBE4B expression correlates with poor prognosis and tumor immune infiltration in hepatocellular carcinoma.
    5. UBE4B promotes the development of lung adenocarcinoma by enhancing proliferation, migration and glycolysis via PP2A/AKT signaling.
      Title: UBE4B promotes the development of lung adenocarcinoma by enhancing proliferation, migration and glycolysis via PP2A/AKT signaling.
    6. UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation.
      Title: UBE4B, a microRNA-9 target gene, promotes autophagy-mediated Tau degradation.
    7. neuroblastoma cells with low UBE4B levels were significantly more sensitive to combined EGFR and STAT5 inhibition than parental cells. These findings may have potential therapeutic implications for patients with 1p36 chromosome LOH and low tumor UBE4B expression.
      Title: Low UBE4B expression increases sensitivity of chemoresistant neuroblastoma cells to EGFR and STAT5 inhibition.
    8. Phosphatase PGAM5 (phosphoglycerate mutase 5) and deubiquitinase OTUB1 (ovarian tumor domain containing ubiquitin aldehyde binding protein 1) were confirmed as E4B substrates, and beta-catenin and CDK4 (cyclin-dependent kinase 4) were confirmed as CHIP substrates.
      Title: Identifying the substrate proteins of U-box E3s E4B and CHIP by orthogonal ubiquitin transfer.
    9. miR-1301 functions as a tumor suppressor that inhibits tumor cell migration and invasion in multiple human cancer cells by regulating the UBE4B-p53 pathway.
      Title: MicroRNA-1301 suppresses tumor cell migration and invasion by targeting the p53/UBE4B pathway in multiple human cancer cells.
    10. UBE4B promotes endogenous phospho-p53(S15) and phospho-p53(S392) degradation in response to gamma irradiation. UBE4B plays an important role in regulating phosphorylated p53 following DNA damage.
      Title: UBE4B targets phosphorylated p53 at serines 15 and 392 for degradation.
    Submit: New GeneRIF Correction See all GeneRIFs (23)

    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

    EBI GWAS Catalog

    Description
    Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers.
    EBI GWAS Catalog

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    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

    • KIAA0684

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables enzyme binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin-ubiquitin ligase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    Process Evidence Code Pubs
    involved_in ERAD pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in granzyme-mediated apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    acts_upstream_of_or_within proteasome-mediated ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein polyubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in response to UV IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ubiquitin-dependent protein catabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of ubiquitin ligase complex TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    ubiquitin conjugation factor E4 B
    Names
    RING-type E3 ubiquitin transferase E4 B
    homologous to yeast UFD2
    homozygously deleted in neuroblastoma-1
    ubiquitin-fusion degradation protein 2
    ubiquitination factor E4B (UFD2 homolog, yeast)
    NP_001099032.1
    NP_001397673.1
    NP_006039.2
    XP_011538790.1
    XP_011538791.1
    XP_011538792.1
    XP_016855524.1
    XP_047283974.1
    XP_054189771.1
    XP_054189772.1
    XP_054189773.1
    XP_054189774.1
    XP_054189775.1

    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.

    mRNA and Protein(s)

    1. NM_001105562.3 → NP_001099032.1  ubiquitin conjugation factor E4 B isoform 1

      See identical proteins and their annotated locations for NP_001099032.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AB014584, AB028839, AF043117, AK292444, AL590639, BC093696, BQ001243
      Consensus CDS
      CCDS41245.1
      UniProtKB/Swiss-Prot
      A8K8S9, G0ZJH6, O75169, O95155, O95338, Q5SZ12, Q5SZ16, Q96QD4, Q9BYI7
      UniProtKB/TrEMBL
      B4E2Y2
      Related
      ENSP00000343001.6, ENST00000343090.11
      Conserved Domains (2) summary
      pfam04564
      Location:1228 → 1299
      U-box; U-box domain
      pfam10408
      Location:591 → 1211
      Ufd2P_core; Ubiquitin elongating factor core

    2. NM_001410744.1 → NP_001397673.1  ubiquitin conjugation factor E4 B isoform 3

      Status: REVIEWED

      Source sequence(s)
      AL096841, AL590639
      Consensus CDS
      CCDS90857.1
      Related
      ENSP00000500453.1, ENST00000672724.1

    3. NM_006048.5 → NP_006039.2  ubiquitin conjugation factor E4 B isoform 2

      See identical proteins and their annotated locations for NP_006039.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame coding exon in the middle region of the CDS, and thus encodes a shorter isoform (2), as compared to variant 1.
      Source sequence(s)
      AB014584, AB028839, AF043117, AK292444, AL590639, BC093696, BQ001243
      Consensus CDS
      CCDS110.1
      UniProtKB/TrEMBL
      B4E2Y2
      Related
      ENSP00000253251.8, ENST00000253251.12
      Conserved Domains (2) summary
      pfam04564
      Location:1099 → 1170
      U-box; U-box domain
      pfam10408
      Location:462 → 1082
      Ufd2P_core; Ubiquitin elongating factor core

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      10032958..10181239
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011540490.3 → XP_011538792.1  ubiquitin conjugation factor E4 B isoform X5

      Conserved Domains (1) summary
      pfam10408
      Location:642 → 1162
      Ufd2P_core; Ubiquitin elongating factor core

    2. XM_011540489.4 → XP_011538791.1  ubiquitin conjugation factor E4 B isoform X4

      Conserved Domains (1) summary
      pfam10408
      Location:642 → 1164
      Ufd2P_core; Ubiquitin elongating factor core

    3. XM_047428018.1 → XP_047283974.1  ubiquitin conjugation factor E4 B isoform X1

    4. XM_011540488.4 → XP_011538790.1  ubiquitin conjugation factor E4 B isoform X2

      UniProtKB/TrEMBL
      B4E2Y2
      Conserved Domains (2) summary
      pfam04564
      Location:1163 → 1234
      U-box; U-box domain
      pfam10408
      Location:526 → 1146
      Ufd2P_core; Ubiquitin elongating factor core

    5. XM_017000035.3 → XP_016855524.1  ubiquitin conjugation factor E4 B isoform X3

      UniProtKB/TrEMBL
      B4E2Y2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      9576012..9724288
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054333800.1 → XP_054189775.1  ubiquitin conjugation factor E4 B isoform X5

    2. XM_054333799.1 → XP_054189774.1  ubiquitin conjugation factor E4 B isoform X4

    3. XM_054333796.1 → XP_054189771.1  ubiquitin conjugation factor E4 B isoform X1

    4. XM_054333797.1 → XP_054189772.1  ubiquitin conjugation factor E4 B isoform X2

    5. XM_054333798.1 → XP_054189773.1  ubiquitin conjugation factor E4 B isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    O95155.1 GenPept UniProtKB/Swiss-Prot:O95155

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