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Description:
Uracil-DNA glycosylase (EC 3.2.2.-) (UDG).
Molecular weight: 34645
View which proteins in this organism that is involved with DNA Repair;
classified after biological processes (using data from the GOA project):
DNA repair( GO:0006281 ) base-excision repair( GO:0006284 )
Important dates:
01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
10-OCT-2003, sequence version 2.
07-MAR-2006, entry version 70.
Phylogenetic order:
Eukaryota Metazoa Chordata Craniata Vertebrata Euteleostomi Mammalia Eutheria Euarchontoglires Primates Catarrhini Hominidae Homo.
To calculate the pI (Isoelectric point - the pH where a protein has a neutral charge),
go to this page and enter the protein ID (e.g 3MG_ECOLI): http://us.expasy.org/tools/pi_tool.html
Links to references in other databases for protein UNG_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | X15653 | CAA33679.1 | - |
| EMBL | X89398 | CAA61579.1 | - |
| EMBL | X89398 | CAA61578.1 | - |
| EMBL | Y09008 | CAA70211.1 | - |
| EMBL | AF526277 | AAM77695.1 | - |
| EMBL | BC015205 | AAH15205.1 | - |
| EMBL | BC050634 | AAH50634.1 | - |
| PIR | S05964 | A60472. | |
| PDB | 1AKZ | X-ray | @=94-313. |
| PDB | 1DPU | NMR | B=73-88. |
| PDB | 1EMH | X-ray | A=94-313. |
| PDB | 1EMJ | X-ray | A=94-313. |
| PDB | 1Q3F | X-ray | A=94-313. |
| PDB | 1SSP | X-ray | E=94-313. |
| PDB | 1UGH | X-ray | E=94-313. |
| PDB | 1YUO | X-ray | A=94-313. |
| PDB | 2SSP | X-ray | E=94-313. |
| PDB | 4SKN | X-ray | E=94-313. |
| Ensembl | ENSG00000076248 | Homo sapiens.1 | |
| H-InvDB | HIX0010973 | -.1 | |
| HGNC | HGNC:12572 | UNG.1 | |
| MIM | 191525 | gene. | |
| MIM | 608106 | phenotype. | |
| LinkHub | P13051 | -.1 | |
| GO | GO:0005634 | C:nucleus | NAS. |
| GO | GO:0004844 | F:uracil DNA N-glycosylase activity | NAS. |
| GO | GO:0006284 | P:base-excision repair | TAS. |
| InterPro | IPR003249 | U_glycsylse_notp. | |
| InterPro | IPR002043 | UDNA_glycsylse. | |
| InterPro | IPR005122 | UDNA_glycsylseSF. | |
| PANTHER | PTHR11264 | U_glycsylse_notp.1 | 1. |
| Pfam | PF03167 | UDG | 1. |
| ProDom | PD001589 | U_glycsylse_notp | 1. |
| TIGRFAMs | TIGR00628 | ung | 1. |
| PROSITE | PS00130 | U_DNA_GLYCOSYLASE | 1. |
Keywords:
3D-structure; Alternative splicing; Direct protein sequencing; Disease mutation; DNA damage; DNA repair; Glycosidase; Hydrolase; Mitochondrion; Nuclear protein; Phosphorylation; Transit peptide.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1), AND PROTEIN SEQUENCE OF 87-113.
RC TISSUE=Placenta;
RX MEDLINE=90059899; PubMed=2555154;
RA Olsen L.C., Aasland R., Wittwer C.U., Krokan H.E., Helland D.E.;
RT "Molecular cloning of human uracil-DNA glycosylase, a highly conserved
RT DNA repair enzyme.";
RL EMBO J. 8:3121-3125(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE (ISOFORM 1).
RX MEDLINE=95010790; PubMed=7926048; DOI=10.1016/0014-5793(94)01042-0;
RA Haug T., Skorpen F., Lund H., Krokan H.E.;
RT "Structure of the gene for human uracil-DNA glycosylase and analysis
RT of the promoter function.";
RL FEBS Lett. 353:180-184(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM 2), AND ALTERNATIVE SPLICING.
RX MEDLINE=97169285; PubMed=9016624; DOI=10.1093/nar/25.4.750;
RA Nilsen H., Solum K., Haug T., Krokan H.E.;
RT "Nuclear and mitochondrial uracil-DNA glycosylases are generated by
RT alternative splicing and transcription from different positions in the
RT UNG gene.";
RL Nucleic Acids Res. 25:750-755(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W.,
RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D.,
RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.;
RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department
RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899;
RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G.,
RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D.,
RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K.,
RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F.,
RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L.,
RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E.,
RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C.,
RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J.,
RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H.,
RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W.,
RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A.,
RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A.,
RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G.,
RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C.,
RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M.,
RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E.,
RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.;
RT "Generation and initial analysis of more than 15,000 full-length human
RT and mouse cDNA sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002).
RN [6]
RP SUBCELLULAR LOCATION.
RX MEDLINE=93324318; PubMed=8332455;
RA Slupphaug G., Markussen F.-H., Olsen L.C., Aasland R., Aarsaether N.,
RA Bakke O., Krokan H.E., Helland D.E.;
RT "Nuclear and mitochondrial forms of human uracil-DNA glycosylase are
RT encoded by the same gene.";
RL Nucleic Acids Res. 21:2579-2584(1993).
RN [7]
RP SUBCELLULAR LOCATION.
RX MEDLINE=98428639; PubMed=9753728; DOI=10.1093/nar/26.20.4611;
RA Otterlei M., Haug T., Nagelhus T.A., Slupphaug G., Lindmo T.,
RA Krokan H.E.;
RT "Nuclear and mitochondrial splice forms of human uracil-DNA
RT glycosylase contain a complex nuclear localisation signal and a strong
RT classical mitochondrial localisation signal, respectively.";
RL Nucleic Acids Res. 26:4611-4617(1998).
RN [8]
RP PHOSPHORYLATION SITE THR-60.
RX PubMed=15302935; DOI=10.1073/pnas.0404720101;
RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J.,
RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.;
RT "Large-scale characterization of HeLa cell nuclear phosphoproteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX MEDLINE=95211838; PubMed=7697717; DOI=10.1016/0092-8674(95)90290-2;
RA Mol C.D., Arvai A.S., Slupphaug G., Kavli B., Alseth I., Krohan H.E.,
RA Tainer J.A.;
RT "Crystal structure and mutational analysis of human uracil-DNA
RT glycosylase: structural basis for specificity and catalysis.";
RL Cell 80:869-878(1995).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
RX MEDLINE=95401260; PubMed=7671300; DOI=10.1016/0092-8674(95)90467-0;
RA Mol C.D., Arvai A.S., Sanderson R.J., Slupphaug G., Kavli B.,
RA Krokan H.E., Mosbaugh D.W., Tainer J.A.;
RT "Crystal structure of human uracil-DNA glycosylase in complex with a
RT protein inhibitor: protein mimicry of DNA.";
RL Cell 82:701-708(1995).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS).
RX MEDLINE=97055940; PubMed=8900285; DOI=10.1038/384087a0;
RA Slupphaug G., Mol C.D., Kavli B., Arvai A.S., Krohan H.E.,
RA Tainer J.A.;
RT "A nucleotide-flipping mechanism from the structure of human uracil-
RT DNA glycosylase bound to DNA.";
RL Nature 384:87-92(1996).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 94-313.
RX MEDLINE=98393562; PubMed=9724657; DOI=10.1093/emboj/17.17.5214;
RA Parikh S.S., Mol C.D., Slupphaug G., Bharati S., Krokan H.E.,
RA Tainer J.A.;
RT "Base excision repair initiation revealed by crystal structures and
RT binding kinetics of human uracil-DNA glycosylase with DNA.";
RL EMBO J. 17:5214-5226(1998).
RN [13]
RP MUTAGENESIS.
RX MEDLINE=96283644; PubMed=8670846;
RA Kavli B., Slupphaug G., Mol C.D., Arvai A.S., Petersen S.B.,
RA Tainer J.A., Krohan H.E.;
RT "Excision of cytosine and thymine from DNA by mutants of human uracil-
RT DNA glycosylase.";
RL EMBO J. 15:3442-3447(1996).
RN [14]
RP VARIANT HIGM5 SER-251.
RX MEDLINE=22877493; PubMed=12958596; DOI=10.1038/ni974;
RA Imai K., Slupphaug G., Lee W.-I., Revy P., Nonoyama S., Catalan N.,
RA Yel L., Forveille M., Kavli B., Krokan H.E., Ochs H.D., Fischer A.,
RA Durandy A.;
RT "Human uracil-DNA glycosylase deficiency associated with profoundly
RT impaired immunoglobulin class-switch recombination.";
RL Nat. Immunol. 4:1023-1028(2003).
Feature:
CHAIN 1 313 Uracil-DNA glycosylase.
/FTId=PRO_0000176173.
ACT_SITE 154 154 Proton acceptor (By similarity).
MOD_RES 60 60 Phosphothreonine.
VARSPLIC 1 44 MIGQKTLYSFFSPSPARKRHAPSPEPAVQGTGVAGVPEESG
DAA -> MGVFCLGPWGLGRKLRTPGKGPLQLLSRLCGDHL
Q (in isoform 1).
/FTId=VSP_008513.
VARIANT 251 251 F -> S (in HIGM5).
/FTId=VAR_017094.
MUTAGEN 154 154 D->E,N: Loss of activity.
MUTAGEN 156 156 Y->A,C,S: Thymine-DNA glycosylase
activity.
MUTAGEN 213 213 N->D: Cytosine-DNA glycosylase activity.
STRAND 75 76
HELIX 77 86
HELIX 96 106
TURN 107 107
STRAND 108 108
HELIX 109 124
STRAND 125 125
STRAND 127 129
HELIX 131 133
TURN 134 135
HELIX 136 138
TURN 139 139
STRAND 140 141
HELIX 143 145
STRAND 148 152
STRAND 154 154
STRAND 158 158
TURN 159 161
STRAND 164 165
TURN 166 167
TURN 171 172
STRAND 173 173
HELIX 177 189
STRAND 190 190
TURN 191 192
STRAND 197 198
HELIX 202 206
TURN 207 208
STRAND 209 215
STRAND 218 219
TURN 220 221
STRAND 222 222
TURN 223 228
STRAND 229 230
HELIX 231 245
STRAND 248 248
STRAND 250 255
HELIX 256 264
STRAND 265 265
TURN 267 269
STRAND 270 275
STRAND 278 279
TURN 280 282
HELIX 283 285
TURN 286 289
HELIX 292 302
TURN 303 304
TURN 310 311
Comments:
-!- 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: Monomer.
-!- SUBCELLULAR LOCATION: Mitochondrial (isoform 1). Nuclear (isoform
2).
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=2; Synonyms=UNG2;
IsoId=P13051-1; Sequence=Displayed;
Name=1; Synonyms=UNG1;
IsoId=P13051-2; Sequence=VSP_008513;
-!- 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.
-!- PTM: Isoform 1 is processed by cleavage of a transit peptide.
-!- 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.
-!- SIMILARITY: Belongs to the uracil-DNA glycosylase family.
-!- DATABASE: NAME=UNGbase; NOTE=UNG mutation db;
WWW="http://bioinf.uta.fi/UNGbase/".
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Sequence length: 313
MIGQKTLYSF FSPSPARKRH APSPEPAVQG TGVAGVPEES GDAAAIPAKK APAGQEEPGT
PPSSPLSAEQ LDRIQRNKAA ALLRLAARNV PVGFGESWKK HLSGEFGKPY FIKLMGFVAE
ERKHYTVYPP PHQVFTWTQM CDIKDVKVVI LGQDPYHGPN QAHGLCFSVQ RPVPPPPSLE
NIYKELSTDI EDFVHPGHGD LSGWAKQGVL LLNAVLTVRA HQANSHKERG WEQFTDAVVS
WLNQNSNGLV FLLWGSYAQK KGSAIDRKRH HVLQTAHPSP LSVYRGFFGC RHFSKTNELL
QKSGKKPIDW KEL