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UBE4B ubiquitination factor E4B [ Homo sapiens (human) ]

Gene ID: 10277, updated on 3-Apr-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
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Genomic context

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Location:
1p36.22
Exon count:
32
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (10032958..10181239)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (9576012..9724288)
105.20220307 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
  • 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. A novel protein encoded by circUBE4B promotes progression of esophageal squamous cell carcinoma by augmenting MAPK/ERK signaling. Lyu Y, et al. Cell Death Dis, 2023 Jun 1. PMID 37264022, Free PMC Article
  2. 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
  3. 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
  4. Expression and prognostic role of ubiquitination factor E4B in primary hepatocellular carcinoma. Zhang XF, et al. Mol Carcinog, 2016 Jan. PMID 25557723
  5. 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

See all (96) 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)

Genotypes

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 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_2023_10

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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