Q9UNA4 (POLI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA polymerase iota
EC=2.7.7.7

Alternative name(s):
Eta2
RAD30 homolog B

Gene names

Name:	POLI
Synonyms:	RAD30B

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	740 AA.
Sequence status	Complete.
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.7 Ref.8 Ref.9 Ref.10 Ref.12 Ref.13 Ref.14
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Cofactor	Magnesium.
Subunit structure	Interacts with REV1 By similarity. Interacts with POLH. Ref.11
Subcellular location	Nucleus. Note: Accumulates at replication forks after DNA damage. Ref.11
Tissue specificity	Ubiquitous. Highly expressed in testis. Ref.3 Ref.9
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.
Sequence caution	The sequence AAD50381.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAF63383.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAH32662.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence AAM11872.1 differs from that shown. Reason: Erroneous gene model prediction. The sequence CAB66605.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

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 Reference proteome
Gene Ontology (GO)
Biological process	DNA repair Traceable author statement. Source: ProtInc DNA replication Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	nucleoplasm Traceable author statement. Source: ProtInc
Molecular function	DNA-directed DNA polymerase activity Traceable author statement. Source: ProtInc damaged DNA binding Inferred from electronic annotation. Source: InterPro metal 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	3	EBI-741774,EBI-724310

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 740

740

DNA polymerase iota

PRO_0000173988

Regions

Domain

55 – 268

214

UmuC

Region

325 – 332

8

DNA binding

Region

368 – 386

19

DNA binding

Compositional bias

589 – 617

29

Ser-rich

Sites

Active site

152

1

Proton acceptor Potential

Metal binding

59

1

Magnesium

Metal binding

151

1

Magnesium

Binding site

64

1

dNTP

Binding site

96

1

dNTP

Natural variations

Natural variant

96

1

R → G. Ref.1
Corresponds to variant rs3218778 [ dbSNP | Ensembl ].

VAR_021239

Natural variant

261

1

I → M. Ref.1
Corresponds to variant rs3218784 [ dbSNP | Ensembl ].

VAR_021240

Natural variant

276

1

E → K. Ref.1
Corresponds to variant rs3218783 [ dbSNP | Ensembl ].

VAR_021241

Natural variant

474

1

H → R. Ref.1
Corresponds to variant rs3730823 [ dbSNP | Ensembl ].

VAR_021242

Natural variant

532

1

F → S. Ref.1 Ref.4
Corresponds to variant rs3218786 [ dbSNP | Ensembl ].

VAR_021243

Natural variant

560

1

C → R. Ref.1
Corresponds to variant rs3218787 [ dbSNP | Ensembl ].

VAR_021244

Natural variant

731

1

A → T. Ref.3 Ref.6
Corresponds to variant rs8305 [ dbSNP | Ensembl ].

VAR_021245

Experimental info

Sequence conflict

15

1

Missing in AAD50381. Ref.3

Sequence conflict

15

1

Missing in CAB66605. Ref.4

Sequence conflict

15

1

Missing in AAF63383. Ref.6

Sequence conflict

337

1

S → T in CAB66605. Ref.4

Sequence conflict

433

1

V → A in AAF63383. Ref.6

Sequence conflict

514

1

D → G in AAF63383. Ref.6

Secondary structure

1

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740

Helix Strand Turn

Details...

Beta strand

55 – 60

6

Helix

63 – 71

9

Helix

73 – 75

3

Beta strand

81 – 84

4

Beta strand

87 – 91

5

Turn

93 – 95

3

Helix

96 – 98

3

Helix

106 – 111

6

Helix

125 – 141

17

Beta strand

145 – 148

4

Turn

149 – 151

3

Beta strand

152 – 156

5

Helix

158 – 167

10

Beta strand

180 – 182

3

Helix

193 – 216

24

Beta strand

220 – 227

8

Helix

228 – 235

8

Beta strand

243 – 245

3

Helix

248 – 250

3

Helix

251 – 256

6

Helix

261 – 263

3

Helix

269 – 276

8

Turn

277 – 279

3

Helix

283 – 288

6

Helix

291 – 298

8

Helix

300 – 310

11

Beta strand

329 – 331

3

Beta strand

338 – 340

3

Helix

343 – 360

18

Beta strand

366 – 370

5

Beta strand

384 – 388

5

Beta strand

391 – 393

3

Helix

401 – 404

4

Helix

405 – 418

14

Beta strand

431 – 434

4

Sequences

	Sequence		Length	Mass (Da)
	Q9UNA4 [UniParc]. Last modified April 5, 2011. Version 3. Checksum: C1A5BF0894E91FDF	FASTA	740	83,006
	10 20 30 40 50 60 MEKLGVEPEE EGGGDDDEED AEAWAMELAD VGAAASSQGV HDQVLPTPNA SSRVIVHVDL 70 80 90 100 110 120 DCFYAQVEMI SNPELKDKPL GVQQKYLVVT CNYEARKLGV KKLMNVRDAK EKCPQLVLVN 130 140 150 160 170 180 GEDLTRYREM SYKVTELLEE FSPVVERLGF DENFVDLTEM VEKRLQQLQS DELSAVTVSG 190 200 210 220 230 240 HVYNNQSINL LDVLHIRLLV GSQIAAEMRE AMYNQLGLTG CAGVASNKLL AKLVSGVFKP 250 260 270 280 290 300 NQQTVLLPES CQHLIHSLNH IKEIPGIGYK TAKCLEALGI NSVRDLQTFS PKILEKELGI 310 320 330 340 350 360 SVAQRIQKLS FGEDNSPVIL SGPPQSFSEE DSFKKCSSEV EAKNKIEELL ASLLNRVCQD 370 380 390 400 410 420 GRKPHTVRLI IRRYSSEKHY GRESRQCPIP SHVIQKLGTG NYDVMTPMVD ILMKLFRNMV 430 440 450 460 470 480 NVKMPFHLTL LSVCFCNLKA LNTAKKGLID YYLMPSLSTT SRSGKHSFKM KDTHMEDFPK 490 500 510 520 530 540 DKETNRDFLP SGRIESTRTR ESPLDTTNFS KEKDINEFPL CSLPEGVDQE VFKQLPVDIQ 550 560 570 580 590 600 EEILSGKSRE KFQGKGSVSC PLHASRGVLS FFSKKQMQDI PINPRDHLSS SKQVSSVSPC 610 620 630 640 650 660 EPGTSGFNSS SSSYMSSQKD YSYYLDNRLK DERISQGPKE PQGFHFTNSN PAVSAFHSFP 670 680 690 700 710 720 NLQSEQLFSR NHTTDSHKQT VATDSHEGLT ENREPDSVDE KITFPSDIDP QVFYELPEAV 730 740 QKELLAEWKR AGSDFHIGHK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	NIEHS SNPs program Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-96; MET-261; LYS-276; ARG-474; SER-532 AND ARG-560.
[2]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed: 16177791] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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] OF 4-740, VARIANT THR-731, TISSUE SPECIFICITY. Tissue: Umbilical vein endothelial cell.
[4]	"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] OF 10-740, VARIANT SER-532. Tissue: Brain.
[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] OF 12-740. Tissue: Uterus.
[6]	"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] OF 14-740, VARIANT THR-731.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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 52-439 IN COMPLEX WITH DNA AND NUCLEOTIDE, FUNCTION.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY094607 Genomic DNA. Translation: AAM11872.1. Sequence problems.
AC093462 Genomic DNA. No translation available.
AF140501 mRNA. Translation: AAD50381.1. Different initiation.
AL136670 mRNA. Translation: CAB66605.1. Different initiation.
BC032662 mRNA. Translation: AAH32662.1. Different initiation.
AF245438 mRNA. Translation: AAF63383.1. Different initiation.

IPI

IPI00296840.

RefSeq

NP_009126.2. NM_007195.2.

UniGene

Hs.438533.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T3N	X-ray	2.30	A/B	52-439	[»]
1ZET	X-ray	2.30	A	52-439	[»]
2ALZ	X-ray	2.50	A	50-439	[»]
2DPI	X-ray	2.30	A	26-445	[»]
2DPJ	X-ray	2.30	A	26-445	[»]
2FLL	X-ray	2.60	A	26-445	[»]
2FLN	X-ray	2.50	A	26-445	[»]
2FLP	X-ray	2.40	A	26-445	[»]
2KHU	NMR	-	A	699-740	[»]
2KHW	NMR	-	A	699-740	[»]
2KTF	NMR	-	B	704-732	[»]
2L0F	NMR	-	B	699-740	[»]
2L0G	NMR	-	A	704-732	[»]
3EPG	X-ray	2.50	A	26-445	[»]
3EPI	X-ray	2.90	A	26-445	[»]
3G6V	X-ray	2.20	A	26-445	[»]
3G6X	X-ray	2.08	A	26-445	[»]
3G6Y	X-ray	2.10	A	26-445	[»]
3GV5	X-ray	2.00	B/D	26-445	[»]
3GV7	X-ray	2.20	B	26-445	[»]
3GV8	X-ray	2.00	B	26-445	[»]
3H40	X-ray	2.30	A	51-439	[»]
3H4B	X-ray	2.85	A	50-439	[»]
3H4D	X-ray	2.20	A	50-439	[»]
3NGD	X-ray	2.80	A	26-445	[»]
3OSN	X-ray	1.90	A	26-445	[»]
3Q8P	X-ray	1.95	B	26-445	[»]
3Q8Q	X-ray	2.03	B	26-445	[»]
3Q8R	X-ray	2.45	B	26-445	[»]
3Q8S	X-ray	2.09	B	26-445	[»]

ProteinModelPortal

Q9UNA4.

SMR

Q9UNA4. Positions 6-439, 518-553, 701-732.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UNA4. 4 interactions.

MINT

MINT-1189678.

STRING

Q9UNA4.

Polymorphism databases

DMDM

59798440.

Proteomic databases

PRIDE

Q9UNA4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000217800; ENSP00000217800; ENSG00000101751.
ENST00000406285; ENSP00000385196; ENSG00000101751.

GeneID

11201.

KEGG

hsa:11201.

UCSC

uc002lfj.2. human.

Organism-specific databases

CTD

11201.

GeneCards

GC18P051731.

H-InvDB

HIX0014457.

HGNC

HGNC:9182. POLI.

HPA

HPA012000.

MIM

605252. gene.

neXtProt

NX_Q9UNA4.

PharmGKB

PA33502.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG10986.

GeneTree

ENSGT00530000062942.

HOGENOM

HBG717347.

HOVERGEN

HBG053634.

InParanoid

Q9UNA4.

OMA

QVEMISN.

OrthoDB

EOG46T310.

PhylomeDB

Q9UNA4.

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]

KO

K03510.

Pfam

PF00817. IMS. 1 hit.
PF11799. IMS_C. 1 hit.
[Graphical view]

SUPFAM

SSF100879. DNA_pol_Y-fam_little_finger. 1 hit.

PROSITE

PS50173. UMUC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

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:	April 5, 2011
Last modified:	January 25, 2012
This is version 95 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.