Reviewed, UniProtKB/Swiss-Prot Q9UNA4 (POLI_HUMAN)

Names and origin

Protein names

Recommended name:
    DNA polymerase iota
    EC=2.7.7.7
Alternative name(s):
    RAD30 homolog B
    Eta2

Gene names

Name:	POLI
Synonyms:	RAD30B

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

Protein attributes

Sequence length	715 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Cofactor	Magnesium.
Subunit structure	Binds REV1L By similarity. Binds POLH.
Subcellular location	Nucleus. Note: Accumulates at replication forks after DNA damage. Ref.10
Tissue specificity	Ubiquitous. Highly expressed in testis. Ref.8 Ref.1
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.
Sequence similarities	Belongs to the DNA polymerase type-Y family. Contains 1 umuC domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair DNA replication DNA synthesis
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Ligand	DNA-binding Magnesium Metal-binding Schiff base
Molecular function	DNA-directed DNA polymerase Mutator protein Nucleotidyltransferase Transferase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	DNA repair Ref.1 Traceable author statement. Source: ProtInc DNA replication Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleoplasm Ref.1 Traceable author statement. Source: ProtInc
Molecular function	DNA-directed DNA polymerase activity Ref.1 Traceable author statement. Source: ProtInc damaged DNA binding Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DAZAP2	Q15038	2	EBI-741774,EBI-724310

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 715

715

DNA polymerase iota

PRO_0000173988

Regions

Domain

30 – 243

214

UmuC

Region

300 – 307

8

DNA binding

Region

343 – 361

19

DNA binding

Compositional bias

564 – 592

29

Ser-rich

Sites

Active site

127

1

Proton acceptor Potential

Metal binding

34

1

Magnesium

Metal binding

126

1

Magnesium

Binding site

39

1

dNTP

Binding site

71

1

dNTP

Natural variations

Natural variant

71

1

R → G: dbSNP rs3218778. Ref.4

VAR_021239

Natural variant

236

1

I → M: dbSNP rs3218784. Ref.4

VAR_021240

Natural variant

251

1

E → K: dbSNP rs3218783. Ref.4

VAR_021241

Natural variant

449

1

H → R: dbSNP rs3730823. Ref.4

VAR_021242

Natural variant

507

1

F → S: dbSNP rs3218786. Ref.4 Ref.2

VAR_021243

Natural variant

535

1

C → R: dbSNP rs3218787. Ref.4

VAR_021244

Natural variant

706

1

T → A: dbSNP rs8305. Ref.1 Ref.4 Ref.5

VAR_021245

Experimental info

Sequence conflict

312

1

S → T in CAB66605. Ref.3

Sequence conflict

408

1

V → A in AAF63383. Ref.2

Sequence conflict

489

1

D → G in AAF63383. Ref.2

Secondary structure

1

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715

Helix Strand Turn

Details...

Beta strand

30 – 35

6

Helix

38 – 46

9

Helix

48 – 50

3

Beta strand

56 – 59

4

Beta strand

62 – 66

5

Turn

68 – 70

3

Helix

71 – 73

3

Helix

81 – 86

6

Helix

100 – 116

17

Beta strand

120 – 123

4

Turn

124 – 126

3

Beta strand

127 – 131

5

Helix

133 – 142

10

Beta strand

155 – 157

3

Helix

168 – 191

24

Beta strand

195 – 202

8

Helix

203 – 210

8

Beta strand

218 – 220

3

Helix

223 – 225

3

Helix

226 – 231

6

Helix

236 – 238

3

Helix

244 – 251

8

Turn

252 – 254

3

Helix

258 – 263

6

Helix

266 – 273

8

Helix

275 – 285

11

Beta strand

304 – 306

3

Beta strand

313 – 315

3

Helix

318 – 335

18

Beta strand

341 – 345

5

Beta strand

359 – 363

5

Beta strand

366 – 368

3

Helix

376 – 379

4

Helix

380 – 393

14

Beta strand

406 – 409

4

Sequences

	Sequence		Length	Mass (Da)
	Q9UNA4-1 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: 3C223ED26CFDE4DB	FASTA	715	80,346
	10 20 30 40 50 60 MELADVGAAA SSQGVHDQVL PTPNASSRVI VHVDLDCFYA QVEMISNPEL KDKPLGVQQK 70 80 90 100 110 120 YLVVTCNYEA RKLGVKKLMN VRDAKEKCPQ LVLVNGEDLT RYREMSYKVT ELLEEFSPVV 130 140 150 160 170 180 ERLGFDENFV DLTEMVEKRL QQLQSDELSA VTVSGHVYNN QSINLLDVLH IRLLVGSQIA 190 200 210 220 230 240 AEMREAMYNQ LGLTGCAGVA SNKLLAKLVS GVFKPNQQTV LLPESCQHLI HSLNHIKEIP 250 260 270 280 290 300 GIGYKTAKCL EALGINSVRD LQTFSPKILE KELGISVAQR IQKLSFGEDN SPVILSGPPQ 310 320 330 340 350 360 SFSEEDSFKK CSSEVEAKNK IEELLASLLN RVCQDGRKPH TVRLIIRRYS SEKHYGRESR 370 380 390 400 410 420 QCPIPSHVIQ KLGTGNYDVM TPMVDILMKL FRNMVNVKMP FHLTLLSVCF CNLKALNTAK 430 440 450 460 470 480 KGLIDYYLMP SLSTTSRSGK HSFKMKDTHM EDFPKDKETN RDFLPSGRIE STRTRESPLD 490 500 510 520 530 540 TTNFSKEKDI NEFPLCSLPE GVDQEVFKQL PVDIQEEILS GKSREKFQGK GSVSCPLHAS 550 560 570 580 590 600 RGVLSFFSKK QMQDIPINPR DHLSSSKQVS SVSPCEPGTS GFNSSSSSYM SSQKDYSYYL 610 620 630 640 650 660 DNRLKDERIS QGPKEPQGFH FTNSNPAVSA FHSFPNLQSE QLFSRNHTTD SHKQTVATDS 670 680 690 700 710 HEGLTENREP DSVDEKITFP SDIDPQVFYE LPEAVQKELL AEWKRTGSDF HIGHK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel human and mouse homologs of Saccharomyces cerevisiae DNA polymerase eta." McDonald J.P., Rapic-Otrin V., Epstein J.A., Broughton B.C., Wang X., Lehmann A.R., Wolgemuth D.J., Woodgate R. Genomics 60:20-30(1999) [PubMed: 10458907] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-706, TISSUE SPECIFICITY. Tissue: Umbilical vein endothelial cell.
[2]	"Human eta2 gene homologous to bacterial UmuC and Rev1 genes." Poltoratsky V.P., Scharff M.D. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT SER-507.
[3]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	NIEHS SNPs program Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-71; MET-236; LYS-251; ARG-449; SER-507; ARG-535 AND ALA-706.
[5]	"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], VARIANT ALA-706. Tissue: Uterus.
[6]	"Misinsertion and bypass of thymine-thymine dimers by human DNA polymerase iota." Tissier A., Frank E.G., McDonald J.P., Iwai S., Hanaoka F., Woodgate R. EMBO J. 19:5259-5266(2000) [PubMed: 11013228] [Abstract] Cited for: FUNCTION.
[7]	"5'-deoxyribose phosphate lyase activity of human DNA polymerase iota in vitro." Bebenek K., Tissier A., Frank E.G., McDonald J.P., Prasad R., Wilson S.H., Woodgate R., Kunkel T.A. Science 291:2156-2159(2001) [PubMed: 11251121] [Abstract] Cited for: FUNCTION, SCHIFF BASE FORMATION.
[8]	"Altered nucleotide misinsertion fidelity associated with poliota-dependent replication at the end of a DNA template." Frank E.G., Tissier A., McDonald J.P., Rapic-Otrin V., Zeng X., Gearhart P.J., Woodgate R. EMBO J. 20:2914-2922(2001) [PubMed: 11387224] [Abstract] Cited for: FUNCTION, TISSUE SPECIFICITY.
[9]	"Induction of somatic hypermutation in immunoglobulin genes is dependent on DNA polymerase iota." Faili A., Aoufouchi S., Flatter E., Gueranger Q., Reynaud C.-A., Weill J.-C. Nature 419:944-947(2002) [PubMed: 12410315] [Abstract] Cited for: FUNCTION.
[10]	"Localization of DNA polymerases eta and iota to the replication machinery is tightly co-ordinated in human cells." Kannouche P.L., Fernandez de Henestrosa A.R., Coull B., Vidal A.E., Gray C., Zicha D., Woodgate R., Lehmann A.R. EMBO J. 22:1223-1233(2003) [PubMed: 12606586] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH POLH.
[11]	"A mechanism for the exclusion of low-fidelity human Y-family DNA polymerases from base excision repair." Haracska L., Prakash L., Prakash S. Genes Dev. 17:2777-2785(2003) [PubMed: 14630940] [Abstract] Cited for: FUNCTION, SCHIFF BASE FORMATION.
[12]	"Efficient and error-free replication past a minor-groove DNA adduct by the sequential action of human DNA polymerases iota and kappa." Washington M.T., Minko I.G., Johnson R.E., Wolfle W.T., Harris T.M., Lloyd R.S., Prakash S., Prakash L. Mol. Cell. Biol. 24:5687-5693(2004) [PubMed: 15199127] [Abstract] Cited for: FUNCTION.
[13]	"Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing." Nair D.T., Johnson R.E., Prakash S., Prakash L., Aggarwal A.K. Nature 430:377-380(2004) [PubMed: 15254543] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 27-414 IN COMPLEX WITH DNA AND NUCLEOTIDE, FUNCTION.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF140501 mRNA. Translation: AAD50381.1.
AF245438 mRNA. Translation: AAF63383.1.
AL136670 mRNA. Translation: CAB66605.1.
AY094607 Genomic DNA. Translation: AAM11872.1.
BC032662 mRNA. Translation: AAH32662.1.

IPI

IPI00296840.

RefSeq

NP_009126.2.

UniGene

Hs.438533

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T3N	X-ray	2.30	A/B	27-414	[»]
1ZET	X-ray	2.30	A	27-414	[»]
2ALZ	X-ray	2.50	A	25-414	[»]
2DPI	X-ray	2.30	A	1-420	[»]
2DPJ	X-ray	2.30	A	1-420	[»]
2FLL	X-ray	2.60	A	1-420	[»]
2FLN	X-ray	2.50	A	1-420	[»]
2FLP	X-ray	2.40	A	1-420	[»]
3EPG	X-ray	2.50	A	1-420	[»]
3EPI	X-ray	2.90	A	1-420	[»]
3G6V	X-ray	2.20	A	1-420	[»]
3G6X	X-ray	2.08	A	1-420	[»]
3G6Y	X-ray	2.10	A	1-420	[»]
3GV5	X-ray	2.00	B/D	1-420	[»]
3GV7	X-ray	2.20	B	1-420	[»]
3GV8	X-ray	2.00	B	1-420	[»]
3H40	X-ray	2.30	A	26-414	[»]
3H4B	X-ray	2.85	A	25-414	[»]
3H4D	X-ray	2.20	A	25-414	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UNA4. 4 interactions.

STRING

Q9UNA4.

Proteomic databases

PRIDE

Q9UNA4.

Genome annotation databases

Ensembl

ENST00000217800; ENSP00000217800; ENSG00000101751; Homo sapiens. [Genome view]
ENST00000406285; ENSP00000385196; ENSG00000101751; Homo sapiens. [Genome view]

GeneID

11201.

KEGG

hsa:11201.

UCSC

uc002lfj.2. human.

Organism-specific databases

CTD

11201.

GeneCards

GC18P050049.

H-InvDB

HIX0014457.

HGNC

HGNC:9182. POLI.

HPA

HPA012000.

MIM

605252. gene.

PharmGKB

PA33502.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9UNA4.

HOVERGEN

Q9UNA4.

Enzyme and pathway databases

BRENDA

2.7.7.7. 247.

Gene expression databases

ArrayExpress

Q9UNA4.

Bgee

Q9UNA4.

CleanEx

HS_POLI.

Genevestigator

Q9UNA4.

GermOnline

ENSG00000101751. Homo sapiens.

Family and domain databases

InterPro

IPR017961. DNA_pol_Y-fam_little_finger.
IPR001126. DNA_repair_prot_UmuC-like.
IPR017963. DNA_repair_prot_UmuC-like_N.
[Graphical view]

PANTHER

PTHR11076. UMUC_like. 1 hit.

Pfam

PF00817. IMS. 1 hit.
[Graphical view]

PROSITE

PS50173. UMUC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

42637.

SOURCE

Search...

Entry information

Entry name

POLI_HUMAN

Accession

Primary (citable) accession number: Q9UNA4
Secondary accession number(s): Q8N590, Q9H0S1, Q9NYH6

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	May 1, 2000
Last modified:	November 24, 2009
This is version 76 of the entry and version 1 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.