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Description:
DNA polymerase iota (EC 2.7.7.7) (RAD30 homolog B) (Eta2).
Molecular weight: 80346
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 )
Important dates:
15-FEB-2005, integrated into UniProtKB/Swiss-Prot.
01-MAY-2000, sequence version 1.
07-MAR-2006, entry version 30.
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 POLI_HUMAN:
| Database | Pointer | Add. info#1 | Add. info#2 |
| EMBL | AF140501 | AAD50381.1 | - |
| EMBL | AF245438 | AAF63383.1 | - |
| EMBL | AL136670 | CAB66605.1 | - |
| EMBL | AY094607 | AAM11872.1 | - |
| EMBL | BC032662 | AAH32662.1 | - |
| PDB | 1T3N | X-ray | A/B=27-414. |
| PDB | 2ALZ | X-ray | A=25-414. |
| Ensembl | ENSG00000101751 | Homo sapiens.1 | |
| HGNC | HGNC:9182 | POLI.1 | |
| MIM | 605252 | gene. | |
| GO | GO:0005654 | C:nucleoplasm | TAS. |
| GO | GO:0016000 | F:iota DNA polymerase activity | TAS. |
| GO | GO:0006281 | P:DNA repair | TAS. |
| InterPro | IPR012246 | RAD30. | |
| InterPro | IPR001126 | UMUC_like. | |
| Pfam | PF00817 | IMS | 1. |
| PIRSF | PIRSF036574 | RAD30 | 1. |
| PROSITE | PS50173 | UMUC | 1. |
Keywords:
3D-structure; DNA damage; DNA repair; DNA replication; DNA synthesis; DNA-binding; DNA-directed DNA polymerase; Magnesium; Metal-binding; Mutator protein; Nuclear protein; Nucleotidyltransferase; Polymorphism; Schiff base; Transferase.
References:
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-706, AND TISSUE SPECIFICITY.
RC TISSUE=Umbilical vein endothelial cell;
RX MEDLINE=99389722; PubMed=10458907; DOI=10.1006/geno.1999.5906;
RA McDonald J.P., Rapic-Otrin V., Epstein J.A., Broughton B.C., Wang X.,
RA Lehmann A.R., Wolgemuth D.J., Woodgate R.;
RT "Novel human and mouse homologs of Saccharomyces cerevisiae DNA
RT polymerase eta.";
RL Genomics 60:20-30(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-507.
RA Poltoratsky V.P., Scharff M.D.;
RT "Human eta2 gene homologous to bacterial UmuC and Rev1 genes.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX MEDLINE=21154917; PubMed=11230166; DOI=10.1101/gr.154701;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H.,
RA Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N.,
RA Mewes H.-W., Ottenwaelder B., Obermaier B., Tampe J., Heubner D.,
RA Wambutt R., Korn B., Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and
RT analysis of 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLY-71; MET-236;
RP LYS-251; ARG-449; SER-507; ARG-535 AND ALA-706.
RA Rieder M.J., Braun A.C., Montoya M.A., Chung M.-W., Nguyen C.P.,
RA Nguyen D.A., Livingston R.J., 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 (APR-2002) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-706.
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 FUNCTION.
RX MEDLINE=20515644; PubMed=11013228; DOI=10.1093/emboj/19.19.5259;
RA Tissier A., Frank E.G., McDonald J.P., Iwai S., Hanaoka F.,
RA Woodgate R.;
RT "Misinsertion and bypass of thymine-thymine dimers by human DNA
RT polymerase iota.";
RL EMBO J. 19:5259-5266(2000).
RN [7]
RP FUNCTION, AND SCHIFF BASE FORMATION.
RX MEDLINE=21150573; PubMed=11251121; DOI=10.1126/science.1058386;
RA Bebenek K., Tissier A., Frank E.G., McDonald J.P., Prasad R.,
RA Wilson S.H., Woodgate R., Kunkel T.A.;
RT "5'-deoxyribose phosphate lyase activity of human DNA polymerase iota
RT in vitro.";
RL Science 291:2156-2159(2001).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX MEDLINE=21280813; PubMed=11387224; DOI=10.1093/emboj/20.11.2914;
RA Frank E.G., Tissier A., McDonald J.P., Rapic-Otrin V., Zeng X.,
RA Gearhart P.J., Woodgate R.;
RT "Altered nucleotide misinsertion fidelity associated with poliota-
RT dependent replication at the end of a DNA template.";
RL EMBO J. 20:2914-2922(2001).
RN [9]
RP FUNCTION.
RX PubMed=12410315; DOI=10.1038/nature01117;
RA Faili A., Aoufouchi S., Flatter E., Gueranger Q., Reynaud C.-A.,
RA Weill J.-C.;
RT "Induction of somatic hypermutation in immunoglobulin genes is
RT dependent on DNA polymerase iota.";
RL Nature 419:944-947(2002).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH POLH.
RX PubMed=12606586; DOI=10.1093/emboj/cdf618;
RA Kannouche P.L., Fernandez de Henestrosa A.R., Coull B., Vidal A.E.,
RA Gray C., Zicha D., Woodgate R., Lehmann A.R.;
RT "Localization of DNA polymerases eta and iota to the replication
RT machinery is tightly co-ordinated in human cells.";
RL EMBO J. 22:1223-1233(2003).
RN [11]
RP FUNCTION, AND SCHIFF BASE FORMATION.
RX PubMed=14630940; DOI=10.1101/gad.1146103;
RA Haracska L., Prakash L., Prakash S.;
RT "A mechanism for the exclusion of low-fidelity human Y-family DNA
RT polymerases from base excision repair.";
RL Genes Dev. 17:2777-2785(2003).
RN [12]
RP FUNCTION.
RX PubMed=15199127; DOI=10.1128/MCB.24.13.5687-5693.2004;
RA Washington M.T., Minko I.G., Johnson R.E., Wolfle W.T., Harris T.M.,
RA Lloyd R.S., Prakash S., Prakash L.;
RT "Efficient and error-free replication past a minor-groove DNA adduct
RT by the sequential action of human DNA polymerases iota and kappa.";
RL Mol. Cell. Biol. 24:5687-5693(2004).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 27-414 IN COMPLEX WITH DNA
RP AND NUCLEOTIDE, AND FUNCTION.
RX PubMed=15254543; DOI=10.1038/nature02692;
RA Nair D.T., Johnson R.E., Prakash S., Prakash L., Aggarwal A.K.;
RT "Replication by human DNA polymerase-iota occurs by Hoogsteen base-
RT pairing.";
RL Nature 430:377-380(2004).
Feature:
CHAIN 1 715 DNA polymerase iota.
/FTId=PRO_0000173988.
DOMAIN 30 243 UmuC.
REGION 300 307 DNA binding.
REGION 343 361 DNA binding.
COMPBIAS 564 592 Ser-rich.
ACT_SITE 127 127 Proton acceptor (Potential).
METAL 34 34 Magnesium.
METAL 126 126 Magnesium.
BINDING 39 39 dNTP.
BINDING 71 71 dNTP.
VARIANT 71 71 R -> G (in dbSNP:3218778).
/FTId=VAR_021239.
VARIANT 236 236 I -> M (in dbSNP:3218784).
/FTId=VAR_021240.
VARIANT 251 251 E -> K (in dbSNP:3218783).
/FTId=VAR_021241.
VARIANT 449 449 H -> R (in dbSNP:3730823).
/FTId=VAR_021242.
VARIANT 507 507 F -> S (in dbSNP:3218786).
/FTId=VAR_021243.
VARIANT 535 535 C -> R (in dbSNP:3218787).
/FTId=VAR_021244.
VARIANT 706 706 T -> A (in dbSNP:8305).
/FTId=VAR_021245.
CONFLICT 312 312 S -> T (in Ref. 3).
CONFLICT 408 408 V -> A (in Ref. 2).
CONFLICT 489 489 D -> G (in Ref. 2).
STRAND 30 35
TURN 36 37
HELIX 38 46
STRAND 47 47
HELIX 48 50
TURN 51 52
STRAND 53 53
STRAND 56 59
TURN 60 61
STRAND 62 66
TURN 68 70
HELIX 71 73
TURN 76 77
STRAND 79 79
HELIX 81 86
TURN 87 87
TURN 89 90
STRAND 94 95
HELIX 100 116
STRAND 118 118
STRAND 120 123
TURN 124 126
STRAND 127 131
HELIX 133 142
STRAND 143 143
STRAND 145 146
TURN 147 148
STRAND 149 150
STRAND 155 157
TURN 158 159
STRAND 160 160
TURN 165 166
HELIX 168 191
STRAND 195 202
HELIX 203 210
TURN 211 211
STRAND 212 213
STRAND 215 216
STRAND 218 220
HELIX 223 231
TURN 232 232
STRAND 234 235
HELIX 236 238
STRAND 239 239
TURN 240 241
HELIX 244 251
TURN 252 254
STRAND 257 257
HELIX 258 263
STRAND 264 264
HELIX 266 273
HELIX 275 285
TURN 286 287
STRAND 298 298
STRAND 300 300
STRAND 304 306
STRAND 309 310
STRAND 313 315
HELIX 318 335
STRAND 338 339
STRAND 341 345
STRAND 351 351
TURN 352 353
STRAND 359 363
STRAND 366 368
TURN 369 370
STRAND 373 373
TURN 374 375
HELIX 376 393
TURN 394 394
TURN 396 397
STRAND 398 399
TURN 401 402
STRAND 403 404
STRAND 406 409
STRAND 413 414
Comments:
-!- FUNCTION: Error-prone DNA polymerase specifically involved in DNA
repair. Plays an important role in translesion synthesis, where
the normal high-fidelity DNA polymerases cannot proceed and DNA
synthesis stalls. Favors Hoogsteen base-pairing in the active
site. Inserts the correct base with high-fidelity opposite an
adenosine template. Exhibits low fidelity and efficiency opposite
a thymidine template, where it will preferentially insert
guanosine. May play a role in hypermutation of immunogobulin
genes. Forms a Schiff base with 5'-deoxyribose phosphate at abasic
sites, but may not have lyase activity.
-!- CATALYTIC ACTIVITY: Deoxynucleoside triphosphate + DNA(n) =
diphosphate + DNA(n+1).
-!- COFACTOR: Magnesium.
-!- SUBUNIT: Binds REV1L (By similarity). Binds POLH.
-!- SUBCELLULAR LOCATION: Nuclear. Accumulates at replication forks
after DNA damage.
-!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in testis.
-!- DOMAIN: The catalytic core consists of fingers, palm and thumb
subdomains, but the fingers and thumb subdomains are much smaller
than in high-fidelity polymerases; residues from five sequence
motifs of the Y-family cluster around an active site cleft that
can accommodate DNA and nucleotide substrates with relaxed
geometric constraints, with consequently higher rates of
misincorporation and low processivity.
-!- SIMILARITY: Belongs to the DNA polymerase type-Y family.
-!- SIMILARITY: Contains 1 umuC domain.
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Sequence length: 715
MELADVGAAA SSQGVHDQVL PTPNASSRVI VHVDLDCFYA QVEMISNPEL KDKPLGVQQK
YLVVTCNYEA RKLGVKKLMN VRDAKEKCPQ LVLVNGEDLT RYREMSYKVT ELLEEFSPVV
ERLGFDENFV DLTEMVEKRL QQLQSDELSA VTVSGHVYNN QSINLLDVLH IRLLVGSQIA
AEMREAMYNQ LGLTGCAGVA SNKLLAKLVS GVFKPNQQTV LLPESCQHLI HSLNHIKEIP
GIGYKTAKCL EALGINSVRD LQTFSPKILE KELGISVAQR IQKLSFGEDN SPVILSGPPQ
SFSEEDSFKK CSSEVEAKNK IEELLASLLN RVCQDGRKPH TVRLIIRRYS SEKHYGRESR
QCPIPSHVIQ KLGTGNYDVM TPMVDILMKL FRNMVNVKMP FHLTLLSVCF CNLKALNTAK
KGLIDYYLMP SLSTTSRSGK HSFKMKDTHM EDFPKDKETN RDFLPSGRIE STRTRESPLD
TTNFSKEKDI NEFPLCSLPE GVDQEVFKQL PVDIQEEILS GKSREKFQGK GSVSCPLHAS
RGVLSFFSKK QMQDIPINPR DHLSSSKQVS SVSPCEPGTS GFNSSSSSYM SSQKDYSYYL
DNRLKDERIS QGPKEPQGFH FTNSNPAVSA FHSFPNLQSE QLFSRNHTTD SHKQTVATDS
HEGLTENREP DSVDEKITFP SDIDPQVFYE LPEAVQKELL AEWKRTGSDF HIGHK