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

Gene ID: 9039, updated on 7-Apr-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
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Genomic context

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Location:
3p14.1
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (69054730..69080373, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (69091517..69117165, complement)
105.20220307 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 ADP ribosylation factor 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
  • 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. Mutations in UBA3 confer resistance to the NEDD8-activating enzyme inhibitor MLN4924 in human leukemic cells. Xu GW, et al. PLoS One, 2014. PMID 24691136, Free PMC Article
  2. Suppression of tumor angiogenesis by targeting the protein neddylation pathway. Yao WT, et al. Cell Death Dis, 2014 Feb 13. PMID 24525735, Free PMC Article
  3. E2-binding surface on Uba3 β-grasp domain undergoes a conformational transition. Elgin ES, et al. Proteins, 2012 Oct. PMID 22821745
  4. Evaluation of HZX-960, a novel DCN1-UBC12 interaction inhibitor, as a potential antifibrotic compound for liver fibrosis. Zhou W, et al. Biochem Cell Biol, 2022 Aug 1. PMID 35544948
  5. Dissecting Distinct Roles of NEDDylation E1 Ligase Heterodimer APPBP1 and UBA3 Reveals Potential Evolution Process for Activation of Ubiquitin-related Pathways. Malik-Chaudhry HK, et al. Sci Rep, 2018 Jul 4. PMID 29973603, Free PMC Article

See all (76) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. UBE1C is upregulated and promotes neddylation of p53 in lung cancer.
    Title: UBE1C is upregulated and promotes neddylation of p53 in lung cancer.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. crystal structure of a complex between the C-terminal domain from NEDD8's heterodimeric E1 (APPBP1-UBA3) and the catalytic core domain of NEDD8's E2 (Ubc12)
    Title: Structural basis for recruitment of Ubc12 by an E2 binding domain in NEDD8's E1.
Submit: New GeneRIF Correction See all GeneRIFs (11)

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)

Genotypes

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
  
enables NEDD8 activating enzyme activity IBA
Inferred from Biological aspect of Ancestor
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_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
    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

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