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    UBE2E1 ubiquitin conjugating enzyme E2 E1 [ Homo sapiens (human) ]

    Gene ID: 7324, updated on 5-Mar-2024

    Summary

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    Official Symbol
    UBE2E1provided by HGNC
    Official Full Name
    ubiquitin conjugating enzyme E2 E1provided by HGNC
    Primary source
    HGNC:HGNC:12477
    See related
    Ensembl:ENSG00000170142 MIM:602916; AllianceGenome:HGNC:12477
    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
    UBCH6
    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 a member of the E2 ubiquitin-conjugating enzyme family. Three alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jan 2011]
    Expression
    Ubiquitous expression in lymph node (RPKM 26.5), brain (RPKM 25.3) and 25 other tissues See more
    Orthologs
    all
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    Genomic context

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    Location:
    3p24.2
    Exon count:
    7
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (23805955..23891640)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (23810731..23896417)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (23847446..23933131)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105376993 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:23696236-23696419 Neighboring gene uncharacterized LOC124909353 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:23709558-23710757 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:23712993-23713494 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:23713495-23713994 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:23743503-23744115 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_68903 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:23801884-23802520 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:23802521-23803157 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14139 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14140 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14141 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14142 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14143 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19600 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19601 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14144 Neighboring gene UBE2E1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19602 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19603 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19604 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19605 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:23906443-23907202 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:23924271-23924855 Neighboring gene ADP ribosylation factor like GTPase 4A pseudogene 4 Neighboring gene NFKB inhibitor interacting Ras like 1 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:23958136-23959335 Neighboring gene uncharacterized LOC124909354 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:23987327-23987868 Neighboring gene ribosomal protein L15

    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. Microarray-based analysis and clinical validation identify ubiquitin-conjugating enzyme E2E1 (UBE2E1) as a prognostic factor in acute myeloid leukemia. Luo H, et al. J Hematol Oncol, 2016 Nov 17. PMID 27855695, Free PMC Article
    2. The structure and conformation of Lys63-linked tetraubiquitin. Datta AB, et al. J Mol Biol, 2009 Oct 9. PMID 19664638, Free PMC Article
    3. Mechanisms underlying ubiquitination. Pickart CM. Annu Rev Biochem, 2001. PMID 11395416
    4. E3 ubiquitin-protein ligase TRIM21-mediated lysine capture by UBE2E1 reveals substrate-targeting mode of a ubiquitin-conjugating E2. Anandapadamanaban M, et al. J Biol Chem, 2019 Jul 26. PMID 31160341, Free PMC Article
    5. Functional characterizations of rare UBA1 variants in X-linked Spinal Muscular Atrophy. Balak CD, et al. F1000Res, 2017. PMID 29034082, Free PMC Article

    See all (153) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. found that critical UBE2E1 residues involved in the capture of the TRIM21 substrate lysine are conserved in ubiquitin-conjugating E2s, whereas residues critical for SUMOylation are not conserved
      Title: E3 ubiquitin-protein ligase TRIM21-mediated lysine capture by UBE2E1 reveals substrate-targeting mode of a ubiquitin-conjugating E2.
    2. OTUB1 depletion dramatically destabilizes the E2-conjugating enzyme UBE2E1 in both mouse and human OTUB1 knockout cell lines.
      Title: OTUB1 non-catalytically stabilizes the E2 ubiquitin-conjugating enzyme UBE2E1 by preventing its autoubiquitination.
    3. UBE2E1 expression was adversely correlated with AML survival; UBE2E1 expression was negatively correlated with patients' response to induction chemotherapy
      Title: Microarray-based analysis and clinical validation identify ubiquitin-conjugating enzyme E2E1 (UBE2E1) as a prognostic factor in acute myeloid leukemia.
    4. IPO11 provides protection in another way, the researchers found. The transport receptor also shuttles UBE2E1, an enzyme necessary for PTEN ubiquitination, into the nucleus. Thanks to IPO11, normal cells keep all of their UBE2E1 in the nucleus, allowing PTEN to continue functioning in the cytoplasm. In cells lacking IPO11, UBE2E1 remains in the cytoplasm and promotes the destruction of PTEN.
      Title: Protecting PTEN in the Nucleus.
    5. study reveals that UbE2E1 is an in vivo E2 for the PRC1 ligase complex and thus plays an important role in the regulation of H2A Lys-119 monoubiquitination
      Title: UbE2E1/UBCH6 Is a Critical in Vivo E2 for the PRC1-catalyzed Ubiquitination of H2A at Lys-119.
    6. Auto-ubiquitination of Ube2E1 is intramolecular.RNF4 enhances Ube2E1 self-ubiquitination.
      Title: RING E3-Catalyzed E2 Self-Ubiquitination Attenuates the Activity of Ube2E Ubiquitin-Conjugating Enzymes.
    7. USP7 is critical in maintaining the steady state levels of UbE2E1 in cells.
      Title: Ubiquitin-specific protease 7 is a regulator of ubiquitin-conjugating enzyme UbE2E1.
    8. Smallangle X-ray scattering experiments show that the Lys63 tetra-Ub chain is dynamic in solution, adopting an ensemble of conformations that are more compact than the extended form in the crystal.
      Title: The structure and conformation of Lys63-linked tetraubiquitin.
    9. isolated ISG15-modified and unmodified UbcH6 proteins, and analyzed their abilities to form thioester intermediates with ubiquitin
      Title: Link between the ubiquitin conjugation system and the ISG15 conjugation system: ISG15 conjugation to the UbcH6 ubiquitin E2 enzyme.
    10. E1 ligase of the proteasome is inhibitd by ziram and has a role in preventing dopaminergic cell damage
      Title: Ziram causes dopaminergic cell damage by inhibiting E1 ligase of the proteasome.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    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 three novel susceptibility loci for severe Acne vulgaris.
    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

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of ubiquitin-conjugating enzyme E2E 1 (UBE2E1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells 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

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ISG15 transferase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ISG15 transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin conjugating enzyme activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ubiquitin conjugating enzyme activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables ubiquitin-protein transferase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in ISG15-protein conjugation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in ISG15-protein conjugation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of transcription by RNA polymerase II IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein K48-linked ubiquitination IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein K48-linked ubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein polyubiquitination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein ubiquitination 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
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of ubiquitin ligase complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    ubiquitin-conjugating enzyme E2 E1
    Names
    (E3-independent) E2 ubiquitin-conjugating enzyme E1
    E2 ubiquitin-conjugating enzyme E1
    ubiquitin carrier protein E1
    ubiquitin conjugating enzyme E2E 1
    ubiquitin-conjugating enzyme E2E 1 (UBC4/5 homolog, yeast)
    ubiquitin-conjugating enzyme E2E 1 (homologous to yeast UBC4/5)
    ubiquitin-protein ligase E1
    NP_001189405.1
    NP_003332.1
    NP_872607.1
    XP_005265488.1
    XP_054203712.1

    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_001202476.2 → NP_001189405.1  ubiquitin-conjugating enzyme E2 E1 isoform 3

      See identical proteins and their annotated locations for NP_001189405.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two exons from the 5' end and has an alternate 5' exon, as comapred to variant 1. The resulting isoform (3) has a shorter and distinct N-terminus, as compared to isoform 1.
      Source sequence(s)
      AC124914, DB499676
      Consensus CDS
      CCDS56244.1
      UniProtKB/TrEMBL
      H7C061
      Related
      ENSP00000411351.1, ENST00000424381.5
      Conserved Domains (1) summary
      pfam00179
      Location:18 → 155
      UQ_con; Ubiquitin-conjugating enzyme

    2. NM_003341.5 → NP_003332.1  ubiquitin-conjugating enzyme E2 E1 isoform 1

      See identical proteins and their annotated locations for NP_003332.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AC124914, AK314854, DB478686
      Consensus CDS
      CCDS2638.1
      UniProtKB/Swiss-Prot
      B2RBX4, C9J8K2, K4DI90, P51965
      Related
      ENSP00000303709.3, ENST00000306627.8
      Conserved Domains (1) summary
      pfam00179
      Location:51 → 188
      UQ_con; Ubiquitin-conjugating enzyme

    3. NM_182666.3 → NP_872607.1  ubiquitin-conjugating enzyme E2 E1 isoform 2

      See identical proteins and their annotated locations for NP_872607.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon and thus encodes a shorter isoform (2), as compared to variant 1.
      Source sequence(s)
      AC124914, BC009139, BI223271, DB478686
      Consensus CDS
      CCDS2639.1
      UniProtKB/Swiss-Prot
      P51965
      Related
      ENSP00000329113.4, ENST00000346855.7
      Conserved Domains (1) summary
      pfam00179
      Location:51 → 171
      UQ_con; Ubiquitin-conjugating enzyme

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      23805955..23891640
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005265431.6 → XP_005265488.1  ubiquitin-conjugating enzyme E2 E1 isoform X1

      See identical proteins and their annotated locations for XP_005265488.1

      UniProtKB/TrEMBL
      B7Z306
      Related
      ENSP00000475890.1, ENST00000467766.5
      Conserved Domains (1) summary
      pfam00179
      Location:18 → 128
      UQ_con; Ubiquitin-conjugating enzyme

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      23810731..23896417
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054347737.1 → XP_054203712.1  ubiquitin-conjugating enzyme E2 E1 isoform X1

      UniProtKB/TrEMBL
      B7Z306
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P51965.1 GenPept UniProtKB/Swiss-Prot:P51965

    Gene LinkOut

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

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