Uracil-DNA glycosylase - Homo sapiens (Human)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Web resources

Cross-references

Entry information

Relevant documents

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

Alternative products

Sequence annotation (Features)

Sequences

References

Web resources

Cross-references

Entry information

Relevant documents

Molecule processing

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

With

Entry

#Exp.

IntAct

Notes

Molecule processing

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Protein names

Recommended name:
    Uracil-DNA glycosylase
      Short name=UDG
    EC=3.2.2.-

Gene names

Name:	UNG
Synonyms:	DGU, UNG1, UNG15

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Sequence length	313 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level.

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Function	Excises uracil residues from the DNA which can arise as a result of misincorporation of dUMP residues by DNA polymerase or due to deamination of cytosine.
Subunit structure	Monomer. Interacts with HIV-1 Vpr. Ref.10
Subcellular location	Isoform 1: Mitochondrion Ref.8 Ref.11. Isoform 2: Nucleus Ref.8 Ref.11.
Tissue specificity	Isoform 1 is widely expressed with the highest expression in skeletal muscle, heart and testicles. Isoform 2 has the highest expression levels in tissues containing proliferating cells.
Post-translational modification	Isoform 1 is processed by cleavage of a transit peptide.
Involvement in disease	Defects in UNG are a cause of immunodeficiency with hyper-IgM type 5 syndrome (HIGM5) [MIM:608106]. Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations. HIGM5 is associated with profound impairment in immunoglobulin (Ig) class-switch recombination (CSR) at a DNA precleavage step. Ref.24 Ref.25
Sequence similarities	Belongs to the uracil-DNA glycosylase family.

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Keywords
Biological process	DNA damage DNA repair Host-virus interaction
Cellular component	Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Molecular function	Glycosidase Hydrolase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	base-excision repair Traceable author statement. Source: ProtInc interspecies interaction between organisms Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Ref.3 Non-traceable author statement. Source: UniProtKB
Molecular function	protein binding Ref.21 Inferred from physical interaction. Source: IntAct uracil DNA N-glycosylase activity Ref.3 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

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With	Entry	#Exp.	IntAct	Notes
UGI	P14739	1	EBI-1025947,EBI-1025973	From a different organism.

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Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 313

313

Uracil-DNA glycosylase

PRO_0000176173

Active site

154

1

Proton acceptor By similarity

Modified residue

5

1

N6-acetyllysine Ref.19

Modified residue

12

1

Phosphoserine Ref.15 Ref.16

Modified residue

14

1

Phosphoserine Ref.15 Ref.16 Ref.18

Modified residue

23

1

Phosphoserine Ref.16 Ref.18 Ref.13 Ref.17

Modified residue

60

1

Phosphothreonine Ref.16 Ref.18 Ref.13 Ref.17 Ref.12 Ref.14

Modified residue

63

1

Phosphoserine Ref.16 Ref.17 Ref.14

Modified residue

64

1

Phosphoserine Ref.16 Ref.18 Ref.17

Modified residue

67

1

Phosphoserine Ref.17

Modified residue

295

1

N6-acetyllysine Ref.19

Alternative sequence

1 – 44

44

MIGQK…SGDAA → MGVFCLGPWGLGRKLRTPGK GPLQLLSRLCGDHLQ in isoform 1.

VSP_008513

Natural variant

4

1

Q → R: dbSNP rs7488798.

VAR_052697

Natural variant

251

1

F → S in HIGM5; fully active and stable when expressed in E. coli; mistargeted to mitochondria rather than the nucleus. Ref.24 Ref.25

VAR_017094

Mutagenesis

154

1

D → E or N: Loss of activity.

Mutagenesis

156

1

Y → A, C or S: Thymine-DNA glycosylase activity.

Mutagenesis

213

1

N → D: Cytosine-DNA glycosylase activity.

1

.

313

Helix Strand Turn

Details...

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Sequence		Length	Mass (Da)
Isoform 2 (UNG2) [UniParc]. Last modified October 10, 2003. Version 2. Checksum: A4B27E6198AFE9C0 Show »	FASTA	313	34,645
10 20 30 40 50 60 MIGQKTLYSF FSPSPARKRH APSPEPAVQG TGVAGVPEES GDAAAIPAKK APAGQEEPGT 70 80 90 100 110 120 PPSSPLSAEQ LDRIQRNKAA ALLRLAARNV PVGFGESWKK HLSGEFGKPY FIKLMGFVAE 130 140 150 160 170 180 ERKHYTVYPP PHQVFTWTQM CDIKDVKVVI LGQDPYHGPN QAHGLCFSVQ RPVPPPPSLE 190 200 210 220 230 240 NIYKELSTDI EDFVHPGHGD LSGWAKQGVL LLNAVLTVRA HQANSHKERG WEQFTDAVVS 250 260 270 280 290 300 WLNQNSNGLV FLLWGSYAQK KGSAIDRKRH HVLQTAHPSP LSVYRGFFGC RHFSKTNELL 310 QKSGKKPIDW KEL « Hide
Isoform 1 (UNG1). Checksum: 32998C244E47B215 Show »	FASTA	304	33,924
10 20 30 40 50 60 MGVFCLGPWG LGRKLRTPGK GPLQLLSRLC GDHLQAIPAK KAPAGQEEPG TPPSSPLSAE 70 80 90 100 110 120 QLDRIQRNKA AALLRLAARN VPVGFGESWK KHLSGEFGKP YFIKLMGFVA EERKHYTVYP 130 140 150 160 170 180 PPHQVFTWTQ MCDIKDVKVV ILGQDPYHGP NQAHGLCFSV QRPVPPPPSL ENIYKELSTD 190 200 210 220 230 240 IEDFVHPGHG DLSGWAKQGV LLLNAVLTVR AHQANSHKER GWEQFTDAVV SWLNQNSNGL 250 260 270 280 290 300 VFLLWGSYAQ KKGSAIDRKR HHVLQTAHPS PLSVYRGFFG CRHFSKTNEL LQKSGKKPID WKEL « Hide

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	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of human uracil-DNA glycosylase, a highly conserved DNA repair enzyme." Olsen L.C., Aasland R., Wittwer C.U., Krokan H.E., Helland D.E. EMBO J. 8:3121-3125(1989) [PubMed: 2555154] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 87-113. Tissue: Placenta.
[2]	"Structure of the gene for human uracil-DNA glycosylase and analysis of the promoter function." Haug T., Skorpen F., Lund H., Krokan H.E. FEBS Lett. 353:180-184(1994) [PubMed: 7926048] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Nuclear and mitochondrial uracil-DNA glycosylases are generated by alternative splicing and transcription from different positions in the UNG gene." Nilsen H., Solum K., Haug T., Krokan H.E. Nucleic Acids Res. 25:750-755(1997) [PubMed: 9016624] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
[4]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Tongue.
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Uterus.
[8]	"Nuclear and mitochondrial forms of human uracil-DNA glycosylase are encoded by the same gene." Slupphaug G., Markussen F.-H., Olsen L.C., Aasland R., Aarsaether N., Bakke O., Krokan H.E., Helland D.E. Nucleic Acids Res. 21:2579-2584(1993) [PubMed: 8332455] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Excision of cytosine and thymine from DNA by mutants of human uracil-DNA glycosylase." Kavli B., Slupphaug G., Mol C.D., Arvai A.S., Petersen S.B., Tainer J.A., Krohan H.E. EMBO J. 15:3442-3447(1996) [PubMed: 8670846] [Abstract] Cited for: MUTAGENESIS.
[10]	"Human immunodeficiency virus type 1 Vpr protein binds to the uracil DNA glycosylase DNA repair enzyme." Bouhamdan M., Benichou S., Rey F., Navarro J.-M., Agostini I., Spire B., Camonis J., Slupphaug G., Vigne R., Benarous R., Sire J. J. Virol. 70:697-704(1996) [PubMed: 8551605] [Abstract] Cited for: INTERACTION WITH HIV-1 VPR.
[11]	"Nuclear and mitochondrial splice forms of human uracil-DNA glycosylase contain a complex nuclear localisation signal and a strong classical mitochondrial localisation signal, respectively." Otterlei M., Haug T., Nagelhus T.A., Slupphaug G., Lindmo T., Krokan H.E. Nucleic Acids Res. 26:4611-4617(1998) [PubMed: 9753728] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-60, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23 AND THR-60, MASS SPECTROMETRY. Tissue: Epithelium.
[14]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-60 AND SER-63, MASS SPECTROMETRY.
[15]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12 AND SER-14, MASS SPECTROMETRY.
[16]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-12; SER-14; SER-23; THR-60; SER-63 AND SER-64, MASS SPECTROMETRY.
[17]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-23; THR-60; SER-63; SER-64 AND SER-67, MASS SPECTROMETRY.
[18]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-23; THR-60 AND SER-64, MASS SPECTROMETRY. Tissue: T-cell.
[19]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-5 AND LYS-295, MASS SPECTROMETRY.
[20]	"Crystal structure and mutational analysis of human uracil-DNA glycosylase: structural basis for specificity and catalysis." Mol C.D., Arvai A.S., Slupphaug G., Kavli B., Alseth I., Krohan H.E., Tainer J.A. Cell 80:869-878(1995) [PubMed: 7697717] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
[21]	"Crystal structure of human uracil-DNA glycosylase in complex with a protein inhibitor: protein mimicry of DNA." Mol C.D., Arvai A.S., Sanderson R.J., Slupphaug G., Kavli B., Krokan H.E., Mosbaugh D.W., Tainer J.A. Cell 82:701-708(1995) [PubMed: 7671300] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[22]	"A nucleotide-flipping mechanism from the structure of human uracil-DNA glycosylase bound to DNA." Slupphaug G., Mol C.D., Kavli B., Arvai A.S., Krohan H.E., Tainer J.A. Nature 384:87-92(1996) [PubMed: 8900285] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
[23]	"Base excision repair initiation revealed by crystal structures and binding kinetics of human uracil-DNA glycosylase with DNA." Parikh S.S., Mol C.D., Slupphaug G., Bharati S., Krokan H.E., Tainer J.A. EMBO J. 17:5214-5226(1998) [PubMed: 9724657] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 94-313.
[24]	"Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination." Imai K., Slupphaug G., Lee W.-I., Revy P., Nonoyama S., Catalan N., Yel L., Forveille M., Kavli B., Krokan H.E., Ochs H.D., Fischer A., Durandy A. Nat. Immunol. 4:1023-1028(2003) [PubMed: 12958596] [Abstract] Cited for: VARIANT HIGM5 SER-251.
[25]	"B cells from hyper-IgM patients carrying UNG mutations lack ability to remove uracil from ssDNA and have elevated genomic uracil." Kavli B., Andersen S., Otterlei M., Liabakk N.B., Imai K., Fischer A., Durandy A., Krokan H.E., Slupphaug G. J. Exp. Med. 201:2011-2021(2005) [PubMed: 15967827] [Abstract] Cited for: CHARACTERIZATION OF VARIANT HIGM5 SER-251.
+	Additional computationally mapped references.

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GeneReviews

NIEHS-SNPs

UNGbase

UNG mutation db

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EMBL
GenBank
DDBJ

X15653 mRNA. Translation: CAA33679.1.
X89398 Genomic DNA. Translation: CAA61578.1.
X89398 Genomic DNA. Translation: CAA61579.1.
Y09008 mRNA. Translation: CAA70211.1.
AF526277 Genomic DNA. Translation: AAM77695.1.
AK291341 mRNA. Translation: BAF84030.1.
AK313552 mRNA. Translation: BAG36328.1.
CH471054 Genomic DNA. Translation: EAW97846.1.
CH471054 Genomic DNA. Translation: EAW97847.1.
BC015205 mRNA. Translation: AAH15205.1.
BC050634 mRNA. Translation: AAH50634.1.

IPI

IPI00006516.
IPI00011069.

PIR

A60472. S05964.

RefSeq

NP_003353.1.
NP_550433.1.

UniGene

Hs.191334

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AKZ	X-ray	1.57	A	94-313	[»]
1DPU	NMR	-	B	73-88	[»]
1EMH	X-ray	1.80	A	94-313	[»]
1EMJ	X-ray	2.00	A	94-313	[»]
1Q3F	X-ray	1.90	A	94-304	[»]
1SSP	X-ray	1.90	E	94-313	[»]
1UGH	X-ray	1.90	E	94-313	[»]
1YUO	X-ray	1.95	A	94-313	[»]
2HXM	X-ray	1.30	A	94-313	[»]
2OXM	X-ray	2.50	A	94-313	[»]
2OYT	X-ray	2.00	A	94-313	[»]
2SSP	X-ray	2.25	E	94-313	[»]
3FCF	X-ray	1.84	A	94-313	[»]
3FCI	X-ray	1.27	A	94-313	[»]
3FCK	X-ray	1.64	B	94-313	[»]
3FCL	X-ray	1.70	A/B	94-313	[»]
4SKN	X-ray	2.90	E	94-313	[»]

ModBase

Search...

DIP

DIP-24194N.

IntAct

P13051. 2 interactions.

STRING

P13051.

PhosphoSite

P13051.

PRIDE

P13051.

Ensembl

ENST00000242576; ENSP00000242576; ENSG00000076248; Homo sapiens. [Genome view]

GeneID

7374.

KEGG

hsa:7374.

UCSC

uc001tnz.1. human.
uc001toa.1. human.

CTD

7374.

GeneCards

GC12P107998.

H-InvDB

HIX0010973.

HGNC

HGNC:12572. UNG.

HPA

CAB011605.

MIM

191525. gene.
608106. phenotype.

Orphanet

69712. Hyper-IgM syndrome.
101094. Hyper-IgM syndrome, autosomal recessive.

PharmGKB

PA364.

GenAtlas

Search...

eggNOG

prNOG08710.

HOGENOM

HBG605450.

HOVERGEN

P13051.

InParanoid

P13051.

OMA

MLWGNYA.

OrthoDB

EOG9MD0JN.

PhylomeDB

P13051.

ArrayExpress

P13051.

Bgee

P13051.

CleanEx

HS_UNG.

Genevestigator

P13051.

GermOnline

ENSG00000076248. Homo sapiens.

InterPro

IPR002043. UDNA_glycsylse.
IPR018085. Ura-DNA_Glyclase_AS.
IPR005122. Uracil-DNA_glycosylase-like.
[Graphical view]

Gene3D

G3DSA:3.40.470.10. Uracil-DNA_glycosylase-like. 1 hit.

PANTHER

PTHR11264. UDNA_glycsylse. 1 hit.

Pfam

PF03167. UDG. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00628. ung. 1 hit.

PROSITE

PS00130. U_DNA_GLYCOSYLASE. 1 hit.
[Graphical view]

ProtoNet

Search...

NextBio

28874.

SOURCE

Search...

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Entry name

UNG_HUMAN

Accession

Primary (citable) accession number: P13051
Secondary accession number(s): A8K5M6

Q93028

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	October 10, 2003
Last modified:	February 9, 2010
This is version 123 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 2 (identifier: P13051-1)

Also known as: UNG2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 1 (identifier: P13051-2)

Also known as: UNG1;

The sequence of this isoform differs from the canonical sequence as follows:
1-44: MIGQKTLYSF...GVPEESGDAA → MGVFCLGPWGLGRKLRTPGKGPLQLLSRLCGDHLQ