UNG uracil DNA glycosylase [Homo sapiens (human)] - Gene

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; AllianceGenome:HGNC:12572
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: mouse all
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Genomic context

Location:: 12q24.11

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (109097597..109110992)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (109072409..109086041)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (109535402..109548797)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Replication Protein A Enhances Kinetics of Uracil DNA Glycosylase on ssDNA and Across DNA Junctions: Explored with a DNA Repair Complex Produced with SpyCatcher/SpyTag Ligation.
Title: Replication Protein A Enhances Kinetics of Uracil DNA Glycosylase on ssDNA and Across DNA Junctions: Explored with a DNA Repair Complex Produced with SpyCatcher/SpyTag Ligation.
Uracil-DNA glycosylase efficiency is modulated by substrate rigidity.
Title: Uracil-DNA glycosylase efficiency is modulated by substrate rigidity.
FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation.
Title: FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation.
The N-terminal domain of uracil-DNA glycosylase: Roles for disordered regions.
Title: The N-terminal domain of uracil-DNA glycosylase: Roles for disordered regions.
Modulation of the Apurinic/Apyrimidinic Endonuclease Activity of Human APE1 and of Its Natural Polymorphic Variants by Base Excision Repair Proteins.
Title: Modulation of the Apurinic/Apyrimidinic Endonuclease Activity of Human APE1 and of Its Natural Polymorphic Variants by Base Excision Repair Proteins.
Macromolecular crowding induces compaction and DNA binding in the disordered N-terminal domain of hUNG2.
Title: Macromolecular crowding induces compaction and DNA binding in the disordered N-terminal domain of hUNG2.
A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers.
Title: A common SNP in the UNG gene decreases ovarian cancer risk in BRCA2 mutation carriers.
We identified a distinct UNG1 isoform variant that is targeted to the cell nucleus where it supports antibody class switching and repairs genomic uracil. We propose that the nuclear UNG1 variant, which in contrast to UNG2 lacks a PCNA-binding motif, may be specialized to act on ssDNA through its ability to bind RPA
Title: Uracil-DNA glycosylase UNG1 isoform variant supports class switch recombination and repairs nuclear genomic uracil.
Data indicate that patients with a combined profile of uracil DNA glycosylase (UDG)/breast cancer 1, early onset protein (BRCA1) had the poorest outcome.
Title: High UDG and BRCA1 expression is associated with adverse outcome in patients with pemetrexed treated non-small cell lung Cancer.
Findings indicate that the of N-terminal domain (NTD) of human uracil DNA glycosylase (hUNG2) targets the enzyme to ssDNA-dsDNA junctions using replication protein A (RPA)-dependent and RPA-independent mechanisms.
Title: N-terminal domain of human uracil DNA glycosylase (hUNG2) promotes targeting to uracil sites adjacent to ssDNA-dsDNA junctions.

Submit: New GeneRIF Correction See all GeneRIFs (88)

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

Associated conditions

Description	Tests
Hyper-IgM syndrome type 5 MedGen: C1720958 OMIM: 608106 GeneReviews: Not available	Compare labs

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
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

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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

RH15692 (e-PCR)
- UniSTS:4613

UNG_288 (e-PCR)
- UniSTS:277856

RH75801 (e-PCR)
- UniSTS:86470

WI-19583 (e-PCR)
- UniSTS:47820

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables damaged DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables ribosomal small subunit binding	IPI Inferred from Physical Interaction more info	PubMed
enables uracil DNA N-glycosylase activity	IBA Inferred from Biological aspect of Ancestor more info
enables uracil DNA N-glycosylase activity	NAS Non-traceable Author Statement more info	PubMed
enables uracil DNA N-glycosylase activity	TAS Traceable Author Statement more info

Process	Evidence Code	Pubs
involved_in base-excision repair, AP site formation via deaminated base removal	IBA Inferred from Biological aspect of Ancestor more info
involved_in base-excision repair, AP site formation via deaminated base removal	IDA Inferred from Direct Assay more info	PubMed
involved_in depyrimidination	TAS Traceable Author Statement more info
involved_in isotype switching	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in somatic hypermutation of immunoglobulin genes	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay 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	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: uracil-DNA glycosylase

Names: uracil-DNA glycosylase 1, uracil-DNA glycosylase 2

NP_003353.1

EC 3.2.2.27

NP_550433.1

EC 3.2.2.27

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.

Genomic

NG_007284.1 RefSeqGene

Range

4985..18384

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_124

mRNA and Protein(s)

NM_003362.4 → NP_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/TrEMBL

A0A8V8TQ66, E5KTA6

Related

ENSP00000337398.2, ENST00000336865.6

Conserved Domains (1) summary

TIGR00628
Location:87 → 296

ung; uracil-DNA glycosylase
NM_080911.3 → NP_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

A8K5M6, B2R8Y1, O00637, O00719, P13051, Q93028

UniProtKB/TrEMBL

A0A8V8TQ66, E5KTA5, Q6FHS8

Related

ENSP00000242576.3, ENST00000242576.7

Conserved Domains (1) summary

TIGR00628
Location:96 → 305

ung; uracil-DNA glycosylase