U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

UBE4A ubiquitination factor E4A [ Homo sapiens (human) ]

Gene ID: 9354, updated on 11-Apr-2024

Summary

Go to the top of the page Help
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
NEW
Try the new Gene table
Try the new Transcript table

Genomic context

Go to the top of the page Help
Location:
11q23.3
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (118359600..118399211)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (118375859..118415462)
105.20220307 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

Go to the top of the page Help

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help
  • 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

Go to the top of the pageHelp

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. UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage. Hu X, et al. Biochim Biophys Acta Gene Regul Mech, 2023 Jun. PMID 37084817
  5. 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

See all (65) 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

Go to the top of the page Help

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

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Interactions

Go to the top of the page Help
Products Interactant Other Gene Complex Source Pubs Description

General gene information

Go to the top of the page Help

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

Go to the top of the page Help
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)

Go to the top of the page Help

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_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_2023_10

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

Gene LinkOut

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

Chemical Information
Molecular Biology Databases
Research Materials
Tools
Miscellaneous