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    UBA3 ubiquitin like modifier activating enzyme 3 [ Homo sapiens (human) ]

    Gene ID: 9039, updated on 14-Nov-2024

    Summary

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    Official Symbol
    UBA3provided by HGNC
    Official Full Name
    ubiquitin like modifier activating enzyme 3provided by HGNC
    Primary source
    HGNC:HGNC:12470
    See related
    Ensembl:ENSG00000144744 MIM:603172; AllianceGenome:HGNC:12470
    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
    NAE2; UBE1C; hUBA3
    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 E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in heart (RPKM 24.5), lymph node (RPKM 24.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See UBA3 in Genome Data Viewer
    Location:
    3p14.1
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (69054730..69080373, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (69091517..69117165, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (69103881..69129524, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14514 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14515 Neighboring gene EGF domain specific O-linked N-acetylglucosamine transferase Neighboring gene EOGT divergent transcript Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20050 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14517 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14516 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14518 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20051 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20052 Neighboring gene TATA element modulatory factor 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20053 Neighboring gene microRNA 3136 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:69152971-69154170 Neighboring gene NANOG hESC enhancer GRCh37_chr3:69160043-69160544 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:69170601-69171800 Neighboring gene ARF like GTPase 6 interacting protein 5 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:69193854-69194511 Neighboring gene leiomodin 3 Neighboring gene FERM domain containing 4B Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:69280094-69280858 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:69284177-69284678 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:69284679-69285178 Neighboring gene NANOG hESC enhancer GRCh37_chr3:69298106-69298630 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:69337315-69338305 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20054 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:69434706-69435316 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:69441946-69442574 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:69469827-69470328 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:69470329-69470828 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:69511585-69512085 Neighboring gene RNA binding motif protein 43 pseudogene 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 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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    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway.
      Title: UBA3 promotes the occurrence and metastasis of intrahepatic cholangiocarcinoma through MAPK signaling pathway.
    2. The NEDD8-activating enzyme E1 UBA3 orchestrates the immunosuppressive microenvironment in lung adenocarcinoma via the NF-small ka, CyrillicB pathway.
      Title: The NEDD8-activating enzyme E1 UBA3 orchestrates the immunosuppressive microenvironment in lung adenocarcinoma via the NF-кB pathway.
    3. UBE1C is upregulated and promotes neddylation of p53 in lung cancer.
      Title: UBE1C is upregulated and promotes neddylation of p53 in lung cancer.
    4. The study demonstrated that two mutations in UBA3 which were not previously reported confer MLN4924 resistance to MLN4924, a selective NEDD8-activating enzyme inhibitor.
      Title: Mutations in UBA3 confer resistance to the NEDD8-activating enzyme inhibitor MLN4924 in human leukemic cells.
    5. E1 (NAE1 and UBA3) and E2 (UBC12) enzymes, as well as global NEDD8 conjugation, were upregulated in over 2/3 of human intrahepatic cholangiocarcinoma
      Title: Neddylation pathway is up-regulated in human intrahepatic cholangiocarcinoma and serves as a potential therapeutic target.
    6. Report role for neddylation via Nedd8-activating enzyme in the regulation of tumor angiogenesis.
      Title: Suppression of tumor angiogenesis by targeting the protein neddylation pathway.
    7. Demonstrated that Uba3-betaGD is an independently folded domain in solution and that residues involved in E2 binding are absent from the NMR spectrum, indicating that the E2-binding surface on Uba3-betaGD interconverts between multiple conformations.
      Title: E2-binding surface on Uba3 β-grasp domain undergoes a conformational transition.
    8. X-ray crystallographic analysis of APPBP1-UBA3-NEDD8 shows that APPBP1-UBA3's preference for NEDD8's Ala72 appears to be indirect, due to proper positioning of UBA3's Arg190.
      Title: Structural dissection of a gating mechanism preventing misactivation of ubiquitin by NEDD8's E1.
    9. Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.
      Title: Conservation in the mechanism of Nedd8 activation by the human AppBp1-Uba3 heterodimer.
    10. structure and mutational analysis of human APPBP1-UBA3, the heterodimeric E1 enzyme for NEDD8
      Title: Insights into the ubiquitin transfer cascade from the structure of the activating enzyme for NEDD8.
    Submit: New GeneRIF Correction See all GeneRIFs (12)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of ubiquitin-like modifier activating enzyme 3 (UBA3) by siRNA inhibits HIV-1 replication in CD4+/CCR5+/CXCR4+ TZM-bl HeLa 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

    Clone Names

    • MGC22384, DKFZp566J164

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    contributes_to NEDD8 activating enzyme activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables NEDD8 activating enzyme activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables NEDD8 transferase activity TAS
    Traceable Author Statement
    more info
    		  
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in endomitotic cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in post-translational protein modification TAS
    Traceable Author Statement
    more info
    		  
    involved_in protein modification process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein neddylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein neddylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein neddylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in proteolysis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in regulation of cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol 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
    		  
    part_of protein-containing complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    NEDD8-activating enzyme E1 catalytic subunit
    Names
    NEDD8-activating enzyme E1 subunit 2
    NEDD8-activating enzyme E1C
    Nedd8-activating enzyme hUba3
    UBA3, ubiquitin-activating enzyme E1 homolog
    ubiquitin-activating enzyme 3
    ubiquitin-activating enzyme E1C (UBA3 homolog, yeast)
    ubiquitin-activating enzyme E1C (homologous to yeast UBA3)
    NP_001350790.1
    NP_003959.3
    NP_937838.1
    XP_011532512.1
    XP_054204301.1

    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_001363861.1 → NP_001350790.1  NEDD8-activating enzyme E1 catalytic subunit isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC092060, AC109587
      Consensus CDS
      CCDS87106.1
      UniProtKB/TrEMBL
      B2RBP3, F8W8D4
      Related
      ENSP00000400294.2, ENST00000415609.6
      Conserved Domains (2) summary
      cd01488
      Location:48 → 327
      Uba3_RUB; Ubiquitin activating enzyme (E1) subunit UBA3. UBA3 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...
      pfam08825
      Location:335 → 420
      E2_bind; E2 binding domain

    2. NM_003968.4 → NP_003959.3  NEDD8-activating enzyme E1 catalytic subunit isoform 1

      See identical proteins and their annotated locations for NP_003959.3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longer isoform (1).
      Source sequence(s)
      AK002159, AL117566, BC022853, CD700642
      Consensus CDS
      CCDS2909.1
      UniProtKB/Swiss-Prot
      A6NLB5, A8K027, O76088, Q8TBC4, Q9NTU3
      UniProtKB/TrEMBL
      B2RBP3
      Related
      ENSP00000354340.4, ENST00000361055.9
      Conserved Domains (2) summary
      cd01488
      Location:71 → 368
      Uba3_RUB; Ubiquitin activating enzyme (E1) subunit UBA3. UBA3 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...
      pfam08825
      Location:376 → 461
      E2_bind; E2 binding domain

    3. NM_198195.2 → NP_937838.1  NEDD8-activating enzyme E1 catalytic subunit isoform 2

      See identical proteins and their annotated locations for NP_937838.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the 5' coding region, as compared to variant 1. The encoded isoform (2) is thus missing an internal segment in the N-terminal region, as compared to isoform 1.
      Source sequence(s)
      AK002159, AL117566, CD700642
      Consensus CDS
      CCDS2910.1
      UniProtKB/TrEMBL
      B2RBP3
      Related
      ENSP00000340041.4, ENST00000349511.8
      Conserved Domains (2) summary
      cd01488
      Location:57 → 354
      Uba3_RUB; Ubiquitin activating enzyme (E1) subunit UBA3. UBA3 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...
      pfam08825
      Location:362 → 447
      E2_bind; E2 binding domain

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      69054730..69080373 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011534210.2 → XP_011532512.1  NEDD8-activating enzyme E1 catalytic subunit isoform X1

      See identical proteins and their annotated locations for XP_011532512.1

      UniProtKB/TrEMBL
      B2RBP3
      Conserved Domains (2) summary
      cd01488
      Location:62 → 341
      Uba3_RUB; Ubiquitin activating enzyme (E1) subunit UBA3. UBA3 is part of the heterodimeric activating enzyme (E1), specific for the Rub family of ubiquitin-like proteins (Ubls). E1 enzymes are part of a conjugation cascade to attach Ub or Ubls, covalently to ...
      pfam08825
      Location:349 → 434
      E2_bind; E2 binding domain

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      69091517..69117165 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054348326.1 → XP_054204301.1  NEDD8-activating enzyme E1 catalytic subunit isoform X1

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_198197.1: Suppressed sequence

      Description
      NM_198197.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q8TBC4.2 GenPept UniProtKB/Swiss-Prot:Q8TBC4

    Gene LinkOut

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

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