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    UBE4A ubiquitination factor E4A [ Homo sapiens (human) ]

    Gene ID: 9354, updated on 27-Nov-2024

    Summary

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    Official Symbol
    UBE4Aprovided by HGNC
    Official Full Name
    ubiquitination factor E4Aprovided by HGNC
    Primary source
    HGNC:HGNC:12499
    See related
    Ensembl:ENSG00000110344 MIM:603753; AllianceGenome:HGNC:12499
    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; UBOX2; NEDHMS
    Summary
    This gene encodes a member of the U-box ubiquitin ligase family. The encoded protein is involved in multiubiquitin chain assembly and plays a critical role in chromosome condensation and separation through the polyubiquitination of securin. Autoantibodies against the encoded protein may be markers for scleroderma and Crohn's disease. A pseudogene of this gene is located on the long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2011]
    Expression
    Ubiquitous expression in brain (RPKM 15.5), appendix (RPKM 14.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See UBE4A in Genome Data Viewer
    Location:
    11q23.3
    Exon count:
    20
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (118359600..118399211)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (118375859..118415462)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (118230315..118269926)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr11:118220212-118221411 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5590 Neighboring gene CD3 delta subunit of T-cell receptor complex Neighboring gene CD3 gamma subunit of T-cell receptor complex Neighboring gene uncharacterized LOC100131626 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 5591 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:118272182-118273045 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:118273504-118274094 Neighboring gene ATP synthase membrane subunit g Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr11:118306179-118307176 and GRCh37_chr11:118307177-118308175 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:118308176-118309173 Neighboring gene Sharpr-MPRA regulatory region 11577 Neighboring gene lysine methyltransferase 2A Neighboring gene ReSE screen-validated silencer GRCh37_chr11:118358704-118358932 Neighboring gene TTC36 and KMT2A antisense RNA 1

    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. Biallelic UBE4A loss-of-function variants cause intellectual disability and global developmental delay. Melo US, et al. Genet Med, 2021 Apr. PMID 33420346
    2. Autoantibodies against ubiquitination factor E4A (UBE4A) are associated with severity of Crohn's disease. Sakiyama T, et al. Inflamm Bowel Dis, 2008 Mar. PMID 18069675
    3. Expression analysis of the gene encoding for the U-box-type ubiquitin ligase UBE4A in human tissues. Contino G, et al. Gene, 2004 Mar 17. PMID 15019985
    4. The ubiquitin ligase UBE4A inhibits prostate cancer progression by targeting interleukin-like EMT inducer (ILEI). Sun Y, et al. IUBMB Life, 2017 Jan. PMID 27862841
    5. SLAP displays tumour suppressor functions in colorectal cancer via destabilization of the SRC substrate EPHA2. Naudin C, et al. Nat Commun, 2014. PMID 24457997

    See all (69) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage.
      Title: UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage.
    2. PTBP3 modulates P53 expression and promotes colorectal cancer cell proliferation by maintaining UBE4A mRNA stability.
      Title: PTBP3 modulates P53 expression and promotes colorectal cancer cell proliferation by maintaining UBE4A mRNA stability.
    3. Biallelic UBE4A loss-of-function variants cause intellectual disability and global developmental delay.
      Title: Biallelic UBE4A loss-of-function variants cause intellectual disability and global developmental delay.
    4. UBE4A's recruitment to sites of DNA damage is dependent on primary E3 ligases in the DDR and promotes enhancement and sustainment of K48- and K63-linked ubiquitin chains at these sites. This step is required for timely recruitment of the RAP80 and BRCA1 proteins and proper organization of RAP80- and BRCA1-associated protein complexes at DSB sites.
      Title: The Ubiquitin E3/E4 Ligase UBE4A Adjusts Protein Ubiquitylation and Accumulation at Sites of DNA Damage, Facilitating Double-Strand Break Repair.
    5. UBE4A targets PCBP1 for proteasomal degradation and that UBE4A expression can serve as a novel biomarker in thyroid cancer patients.
      Title: Poly r(C) binding protein (PCBP) 1 expression is regulated by the E3 ligase UBE4A in thyroid carcinoma.
    6. Ectopic overexpression of UBE4A, but not UBE3C, in cells was downregulated in vitro migration and invasion in these cells. Cumulatively, our data reveals a novel post-translational regulatory mechanism of regulating ILEI1 expression, a protein required for metastatic progression in prostate cancer cells
      Title: The ubiquitin ligase UBE4A inhibits prostate cancer progression by targeting interleukin-like EMT inducer (ILEI).
    7. Identified an intestinal cDNA clone encoding ubiquitination factor E4A (UBE4A), a U-box-type ubiquitin-protein ligase. The prevalence of anti-UBE4A IgG in patients with CD was significantly higher than that in patients with UC or healthy controls
      Title: Autoantibodies against ubiquitination factor E4A (UBE4A) are associated with severity of Crohn's disease.
    8. UBE4A was over-expressed in ovarian serous cystadenocarcinoma tissues, suggesting that the activity of ubiquitin-proteasome system is enhanced in ovarian cancer.
      Title: [Differential expression of USP2, USP14 and UBE4A between ovarian serous cystadenocarcinoma and adjacent normal tissues].
    9. In these studies, we define Ufd2 (a novel E4 polyubiquitylating enzyme) as a new autoantigen in scleroderma, and show that it regulates chromosome condensation and separation during mitosis in human cells.
      Title: Ufd2, a novel autoantigen in scleroderma, regulates sister chromatid separation.
    10. UBE4A is expressed in different tissues in a pattern that seems to be dependent from cell type and cell cycle and that UBE4A might have a specific role in different biochemical processes other than ubiquitination, including growth or differentiation.
      Title: Expression analysis of the gene encoding for the U-box-type ubiquitin ligase UBE4A in human tissues.
    Submit: New GeneRIF Correction

    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

    Associated conditions

    Description Tests
    Neurodevelopmental disorder with hypotonia and gross motor and speech delay
    MedGen: C5562031 OMIM: 619639 GeneReviews: Not available
    		not available

    EBI GWAS Catalog

    Description
    Genes linked to energy metabolism and immunoregulatory mechanisms are associated with subcutaneous adipose tissue distribution in HIV-infected men.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • KIAA0126, MGC133315

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    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 protein polyubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ubiquitin-dependent protein catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of ubiquitin ligase complex IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    ubiquitin conjugation factor E4 A
    Names
    RING-type E3 ubiquitin transferase E4 A
    ubiquitination factor E4A (UFD2 homolog, yeast)
    NP_001191006.1
    NP_004779.2

    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_047106.1 RefSeqGene

      Range
      5020..44631
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001204077.2 → NP_001191006.1  ubiquitin conjugation factor E4 A isoform 2

      See identical proteins and their annotated locations for NP_001191006.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site in the coding region, but maintains the reading frame, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
      Source sequence(s)
      AP001267, AW021567, BC039240, BC112367, DB068702
      Consensus CDS
      CCDS55790.1
      UniProtKB/Swiss-Prot
      B0YJB6, Q14139, Q2M1H0, Q6P5T4, Q7Z639
      UniProtKB/TrEMBL
      B4DK32
      Related
      ENSP00000252108.4, ENST00000252108.8
      Conserved Domains (2) summary
      pfam10408
      Location:330 → 971
      Ufd2P_core; Ubiquitin elongating factor core
      cd16657
      Location:990 → 1059
      RING-Ubox_UBE4A; U-box domain, a modified RING finger, found in ubiquitin conjugation factor E4 A (UBE4A) and similar proteins

    2. NM_004788.4 → NP_004779.2  ubiquitin conjugation factor E4 A isoform 1

      See identical proteins and their annotated locations for NP_004779.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
      Source sequence(s)
      AP001267, AW021567, BC039240, BC062695, D50916, DB068702
      Consensus CDS
      CCDS8396.1
      UniProtKB/TrEMBL
      B4DK32
      Related
      ENSP00000387362.2, ENST00000431736.6
      Conserved Domains (3) summary
      COG5113
      Location:170 → 1068
      UFD2; Ubiquitin fusion degradation protein 2 [Posttranslational modification, protein turnover, chaperones]
      pfam04564
      Location:995 → 1067
      U-box; U-box domain
      pfam10408
      Location:337 → 978
      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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      118359600..118399211
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      118375859..118415462
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q14139.2 GenPept UniProtKB/Swiss-Prot:Q14139

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