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UNG uracil DNA glycosylase [ Homo sapiens (human) ]

Gene ID: 7374, updated on 13-Jan-2019

Summary

Official Symbol
UNGprovided by HGNC
Official Full Name
uracil DNA glycosylaseprovided by HGNC
Primary source
HGNC:HGNC:12572
See related
Ensembl:ENSG00000076248 MIM:191525
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
DGU; UDG; UNG1; UNG2; HIGM4; HIGM5; UNG15
Summary
This gene encodes one of several uracil-DNA glycosylases. One important function of uracil-DNA glycosylases is to prevent mutagenesis by eliminating uracil from DNA molecules by cleaving the N-glycosylic bond and initiating the base-excision repair (BER) pathway. Uracil bases occur from cytosine deamination or misincorporation of dUMP residues. Alternative promoter usage and splicing of this gene leads to two different isoforms: the mitochondrial UNG1 and the nuclear UNG2. The UNG2 term was used as a previous symbol for the CCNO gene (GeneID 10309), which has been confused with this gene, in the literature and some databases. [provided by RefSeq, Nov 2010]
Annotation information
Note: Due to a common symbol (UNG2) for the specific nuclear isoform of the UNG gene (GeneID 7374) and as a previous symbol for the CCNO gene (GeneID 10309), incorrect attributions of uracil DNA glycosylase activity have been made for CCNO in the scientific literature and some databases. CCNO was correctly identified as a cyclin protein family member in PubMed ID: 8419333. [13 Feb 2013]
Expression
Ubiquitous expression in adrenal (RPKM 23.4), testis (RPKM 16.9) and 25 other tissues See more
Orthologs

Genomic context

See UNG in Genome Data Viewer
Location:
12q24.11
Exon count:
7
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 12 NC_000012.12 (109097594..109110993)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (109535399..109548798)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene ubiquitin specific peptidase 30 Neighboring gene RNA, 5S ribosomal pseudogene 372 Neighboring gene alkB homolog 2, alpha-ketoglutarate dependent dioxygenase Neighboring gene uncharacterized LOC105369974 Neighboring gene acetyl-CoA carboxylase beta Neighboring gene forkhead box N4

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 replication is enhanced by UNG2 in monocyte derived macrophages PubMed
HIV-1 replication is enhanced by UNG2 in PBMCs by influencing the efficiency of reverse transcription PubMed
HIV-1 replication is enhanced by UNG2 (HeLa-CD4 cells and Jurkat T cells) as shown by shRNA mediated knockdown of UNG2 PubMed
Depletion of UNG2 by shRNA in HIV-1-producing 293T cells inhibits viral infectivity and replication PubMed

Protein interactions

Protein Gene Interaction Pubs
Tat tat The antiviral activity of UNG2 requires the integrity of its catalytic domain (residues 153 and 154). Depletion of endogenous UMG2 promotes Tat-mediated LTR transcription PubMed
Vpr vpr HIV-1 Vpr inhibits UNG (UNG2) activity when complexed with DDB1-DCAF1 by interfering with substrate (DNA) binding PubMed
vpr HIV-1 Vpr mimics DNA binding to UNG; UNG bind site for Vpr is identical to UNG-DNA; UNG uses Leu272 to insert into DNA minor groove whilst in the DDB1-DCAF1-Vpr-UNG complex , Leu272 inserts into Vpr cleft and Vpr insert loop mimics DNA phosphate backbone. PubMed
vpr HIV-1 Vpr depletes UNG (UNG2) in HIV-1 infected cells PubMed
vpr HIV-1 and SIVcpz Vpr targets UNG (UNG2) PubMed
vpr HIV-1 Vpr binds UNG2 and forms a trimolecular complex containing Vpr, UNG2 and RPA2 PubMed
vpr HIV-1 Vpr downregulates the gene expression of UNG2 and amino-acid residues A30/V31 are critical for the Vpr-mediated downregulation of UNG2 PubMed
vpr HIV-1 Vpr-induced reduction in uracil DNA glycosylase (UNG) is mediated through proteasomal degradation PubMed
vpr HIV-1 Vpr complexes with DCAF1, DDB1, CUL4A, CUL4B, and UNG2 proteins in the cullin4 (CUL4)-containing ubiquitin ligase complex in HEK293T cells PubMed
vpr Ubiquitination levels of UNG2 is upregulated in the presence of HIV-1 Vpr in the proviral backbone compared to the levels for control PubMed
vpr The coexpression of UNG2 with a dominant negative CUL4 molecule prevents UNG2 degradation from the presence of HIV-1 Vpr PubMed
vpr HIV-1 Vpr-mediated UNG2 degradation and constitutive UNG2 turnover are dependent on DCAF1 or DDB1 but not on CUL4a or CUL4B in the cullin4 (CUL4)-containing ubiquitin ligase complex in HEK293T cells PubMed
vpr HIV-1 Vpr-mediated degradation of UNG2 is dependent on CUL4A neddylation PubMed
vpr HIV-1 Vpr binding to UNG2 results in a rapid reduced level of UNG2 protein and a significant loss of uracil-DNA glycosylate activity PubMed
vpr Downregulation of UNG2 by Vpr is related to a transcriptional regulation and is independent of Vpr binding, Vpr-induced G2 arrest, and the proteasome degradation PubMed
vpr HIV-1 Vpr induces the ubiquitination of UNG and forms a complex with UNG PubMed
vpr Expression of exogenous HIV-1 Vpr inhibits class switch recombination (CSR) by competing with some endogenous factors for the WXXF site (residues 222-225) of uracil-DNA glycosylase PubMed
vpr High levels of HIV-1 Vpr expression leads to the accumulation of phosphorylated UNG2 and the redistribution of UNG2 into the cell nucleus PubMed
vpr HIV-1-Vpr induced upregulation of NKG2D ligands in HIV-infected T cells by activating UNG2-dependent repair of uridine-containing DNA PubMed
vpr W54R/S79A Vpr mutant impairs interaction with UNG2, but is still able to recruit DCAF1 PubMed
vpr In a yeast two-hybrid assay, tryptophan in position 54 of HIV-1 Vpr is critical for maintaining the interaction of Vpr with UNG2, and the WXXF motif (residues 231-234) of UNG2 is involved in this binding to Vpr PubMed
vpr The interaction of HIV-1 Vpr with UNG2 leads to virion incorporation of catalytically active UNG2, which is directly involved with Vpr in modulating the HIV-1 mutation rate PubMed
vpr DCAF1 interacts with DDB1 as well as the Vpr-UNG2 complex, which leads to polyubiquitination of UNG2 via Vpr PubMed
vpr One report indicates incorporation of uracil DNA glycosylase (UNG) into HIV-1 virions is mediated by binding of HIV-1 Vpr to UNG, however another indicates virion incorporation of UNG is independent of Vpr and is mediated by the HIV-1 Integrase protein PubMed
vpr HIV-1 Vpr (amino acids 15-77) binds to the uracil DNA glycosylase DNA repair enzyme (amino acids 222-225) and thereby modulates the HIV-1 mutation rate PubMed
integrase gag-pol HIV-1 L172A/K173A mutant virus is deficient for Uracil DNA Glycosylase (UNG2) incorporation into virions and is defective for replication due to a blockage at the stage of proviral DNA integration PubMed
gag-pol Uracil DNA Glycosylase (UNG2; amino acids 1-51) binds to HIV-1 integrase (amino acids 170-180) and is incorporated into HIV-1 particles by binding to the integrase domain of the HIV-1 Gag-Pol polyprotein PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Base Excision Repair, organism-specific biosystem (from REACTOME)
    Base Excision Repair, organism-specific biosystemOf the three major pathways involved in the repair of nucleotide damage in DNA, base excision repair (BER) involves the greatest number of individual enzymatic activities. This is the consequence of ...
  • Base excision repair, organism-specific biosystem (from KEGG)
    Base excision repair, organism-specific biosystemBase excision repair (BER) is the predominant DNA damage repair pathway for the processing of small base lesions, derived from oxidation and alkylation damages. BER is normally defined as DNA repair ...
  • Base excision repair, conserved biosystem (from KEGG)
    Base excision repair, conserved biosystemBase excision repair (BER) is the predominant DNA damage repair pathway for the processing of small base lesions, derived from oxidation and alkylation damages. BER is normally defined as DNA repair ...
  • Base-Excision Repair, AP Site Formation, organism-specific biosystem (from REACTOME)
    Base-Excision Repair, AP Site Formation, organism-specific biosystemBase excision repair is initiated by DNA glycosylases that hydrolytically cleave the base-deoxyribose glycosyl bond of a damaged nucleotide residue, releasing the damaged base (Lindahl and Wood 1999,...
  • Cleavage of the damaged pyrimidine, organism-specific biosystem (from REACTOME)
    Cleavage of the damaged pyrimidine, organism-specific biosystemDamaged pyrimidines are cleaved by pyrimide-specific glycosylases (Lindahl and Wood 1999).
  • DNA Repair, organism-specific biosystem (from REACTOME)
    DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
  • Depyrimidination, organism-specific biosystem (from REACTOME)
    Depyrimidination, organism-specific biosystemDepyrimidination of a damaged nucleotide in DNA is mediated by a pyrimidine-specific DNA glycosylase. The glycosylase cleaves the N-C1' glycosidic bond between the damaged DNA base and the deoxyribos...
  • Displacement of DNA glycosylase by APEX1, organism-specific biosystem (from REACTOME)
    Displacement of DNA glycosylase by APEX1, organism-specific biosystemFollowing cleavage of the damaged base, DNA glycosylase is displaced by APEX1, an AP endonuclease (Parikh et al. 1998).
  • Primary immunodeficiency, organism-specific biosystem (from KEGG)
    Primary immunodeficiency, organism-specific biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
  • Primary immunodeficiency, conserved biosystem (from KEGG)
    Primary immunodeficiency, conserved biosystemPrimary immunodeficiencies (PIs) are a heterogeneous group of disorders, which affect cellular and humoral immunity or non-specific host defense mechanisms mediated by complement proteins, and cells ...
  • Recognition and association of DNA glycosylase with site containing an affected pyrimidine, organism-specific biosystem (from REACTOME)
    Recognition and association of DNA glycosylase with site containing an affected pyrimidine, organism-specific biosystemBase excision repair is initiated by a DNA glycosylase which first recognizes and removes a damaged or incorrect (e.g. mismatched) base (Sokhansanj et al. 2002).
  • Resolution of Abasic Sites (AP sites), organism-specific biosystem (from REACTOME)
    Resolution of Abasic Sites (AP sites), organism-specific biosystemResolution of AP sites can occur through the single nucleotide replacement pathway or through the multiple nucleotide patch replacement pathway, also known as the long-patch base excision repair (BER...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp781L1143

Gene Ontology Provided by GOA

Function Evidence Code Pubs
damaged DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ribosomal small subunit binding IPI
Inferred from Physical Interaction
more info
PubMed 
uracil DNA N-glycosylase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
uracil DNA N-glycosylase activity NAS
Non-traceable Author Statement
more info
PubMed 
uracil DNA N-glycosylase activity TAS
Traceable Author Statement
more info
 
Process Evidence Code Pubs
DNA repair TAS
Traceable Author Statement
more info
PubMed 
base-excision repair TAS
Traceable Author Statement
more info
PubMed 
base-excision repair, AP site formation via deaminated base removal IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
base-excision repair, AP site formation via deaminated base removal IDA
Inferred from Direct Assay
more info
PubMed 
depyrimidination TAS
Traceable Author Statement
more info
 
negative regulation of apoptotic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of isotype switching IEA
Inferred from Electronic Annotation
more info
 
somatic hypermutation of immunoglobulin genes IEA
Inferred from Electronic Annotation
more info
 
somatic recombination of immunoglobulin gene segments IEA
Inferred from Electronic Annotation
more info
 
viral process IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
NOT mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
NOT nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus NAS
Non-traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
uracil-DNA glycosylase
Names
uracil-DNA glycosylase 1, uracil-DNA glycosylase 2
NP_003353.1
NP_550433.1

NCBI Reference Sequences (RefSeq)

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_007284.1 RefSeqGene

    Range
    4985..18384
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_124

mRNA and Protein(s)

  1. NM_003362.3NP_003353.1  uracil-DNA glycosylase isoform UNG1 precursor

    See identical proteins and their annotated locations for NP_003353.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) uses the downstream promoter and a full-length exon 1B. It encodes the UNG1 isoform, which includes a mitochondrial targeting sequence.
    Source sequence(s)
    AC007637, BM928006, BU622689, DB045515
    Consensus CDS
    CCDS9125.1
    UniProtKB/Swiss-Prot
    P13051
    UniProtKB/TrEMBL
    E5KTA6
    Related
    ENSP00000337398.2, ENST00000336865.6
    Conserved Domains (1) summary
    TIGR00628
    Location:87296
    ung; uracil-DNA glycosylase
  2. NM_080911.2NP_550433.1  uracil-DNA glycosylase isoform UNG2

    See identical proteins and their annotated locations for NP_550433.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) uses an upstream promoter and an alternate splice site for exon 1B when compared to variant 1. It encodes the nuclear UNG2 isoform, which has a different N-terminal sequence than the UNG1 isoform.
    Source sequence(s)
    BQ950839, BU622689, Y09008
    Consensus CDS
    CCDS9124.1
    UniProtKB/Swiss-Prot
    P13051
    UniProtKB/TrEMBL
    E5KTA5
    Related
    ENSP00000242576.2, ENST00000242576.6
    Conserved Domains (1) summary
    TIGR00628
    Location:96305
    ung; uracil-DNA glycosylase

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000012.12 Reference GRCh38.p12 Primary Assembly

    Range
    109097594..109110993
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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