P28340 (DPOD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
DNA polymerase delta catalytic subunit
EC=2.7.7.7

Alternative name(s):
DNA polymerase subunit delta p125

Gene names

Name:	POLD1
Synonyms:	POLD

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1107 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades single stranded DNA in the 3'- to 5'-direction. Required with its accessory proteins (proliferating cell nuclear antigen (PCNA) and replication factor C (RFC) or activator 1) for leading strand synthesis. Also involved in completing Okazaki fragments initiated by the DNA polymerase alpha/primase complex.
Catalytic activity	Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
Cofactor	Binds 1 4Fe-4S cluster By similarity.
Subunit structure	Heterotetramer composed of subunits of 125 kDa, 50 kDa, 66 kDa and 12 kDa. The 125 kDa subunit contains the polymerase active site and most likely the active site for the 3'-5' exonuclease activity. Interacts with WRNIP1. Interacts with POLD4 and PCNA. Ref.5 Ref.6
Subcellular location	Nucleus.
Domain	The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes By similarity.
Miscellaneous	In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.
Sequence similarities	Belongs to the DNA polymerase type-B family. Contains 1 CysA-type zinc finger.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	4Fe-4S DNA-binding Iron Iron-sulfur Metal-binding Zinc
Molecular function	DNA-directed DNA polymerase Exonuclease Hydrolase Nuclease Nucleotidyltransferase Transferase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA replication proofreading Inferred from Biological aspect of Ancestor. Source: RefGenome DNA replication, removal of RNA primer Inferred from Biological aspect of Ancestor. Source: RefGenome DNA synthesis involved in DNA repair Inferred from direct assay PubMed 3335506. Source: UniProtKB S phase of mitotic cell cycle Inferred from direct assay PubMed 16762037. Source: UniProtKB base-excision repair, gap-filling Inferred from direct assay PubMed 10559260PubMed 10559261. Source: UniProtKB nucleotide-excision repair, DNA gap filling Inferred from mutant phenotype PubMed 20227374. Source: UniProtKB regulation of mitotic cell cycle Inferred from Biological aspect of Ancestor. Source: RefGenome response to UV Traceable author statement PubMed 3146346. Source: ProtInc telomere maintenance via recombination Traceable author statement. Source: Reactome telomere maintenance via semi-conservative replication Traceable author statement. Source: Reactome transcription-coupled nucleotide-excision repair Traceable author statement. Source: Reactome
Cellular_component	delta DNA polymerase complex Inferred from Biological aspect of Ancestor. Source: RefGenome nucleoplasm Traceable author statement. Source: Reactome nucleotide-excision repair complex Inferred from direct assay PubMed 20713449. Source: UniProtKB
Molecular_function	3'-5' exonuclease activity Inferred from Biological aspect of Ancestor. Source: RefGenome 4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW DNA binding Inferred from direct assay PubMed 16762037. Source: UniProtKB DNA-directed DNA polymerase activity Inferred from mutant phenotype PubMed 16762037. Source: UniProtKB chromatin binding Inferred from direct assay PubMed 16762037. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PCNA	P12004	2	EBI-716569,EBI-358311
POLD2	P49005	9	EBI-716569,EBI-372354
POLD4	Q9HCU8	10	EBI-716569,EBI-864968
WRNIP1	Q96S55	2	EBI-716569,EBI-2513471

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1107	1107	DNA polymerase delta catalytic subunit		PRO_0000046442
Regions
	Zinc finger	1012 – 1029	18	CysA-type
	Motif	4 – 19	16	Nuclear localization signal Potential
	Motif	1058 – 1076	19	CysB motif
Sites
	Metal binding	1012	1	Zinc By similarity
	Metal binding	1015	1	Zinc By similarity
	Metal binding	1026	1	Zinc By similarity
	Metal binding	1029	1	Zinc By similarity
	Metal binding	1058	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	1061	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	1071	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	1076	1	Iron-sulfur (4Fe-4S) By similarity
Amino acid modifications
	Modified residue	1007	1	N6-acetyllysine Ref.8
Natural variations
	Natural variant	5	1	R → W. Corresponds to variant rs9282830 [ dbSNP | Ensembl ].		VAR_048878
	Natural variant	19	1	R → H. Ref.3 Corresponds to variant rs3218773 [ dbSNP | Ensembl ].		VAR_019340
	Natural variant	21	1	G → C. Corresponds to variant rs9282831 [ dbSNP | Ensembl ].		VAR_048879
	Natural variant	30	1	R → W. Ref.1 Ref.3 Corresponds to variant rs3218772 [ dbSNP | Ensembl ].		VAR_016146
	Natural variant	119	1	R → H. Ref.2 Ref.3 Ref.4 Corresponds to variant rs1726801 [ dbSNP | Ensembl ].		VAR_019341
	Natural variant	173	1	S → N. Ref.2 Ref.3 Corresponds to variant rs1726803 [ dbSNP | Ensembl ].		VAR_019342
	Natural variant	177	1	R → H. Ref.3 Corresponds to variant rs3218750 [ dbSNP | Ensembl ].		VAR_019343
	Natural variant	347	1	P → L. Corresponds to variant rs2230243 [ dbSNP | Ensembl ].		VAR_048880
	Natural variant	849	1	R → H. Ref.3 Corresponds to variant rs3218775 [ dbSNP | Ensembl ].		VAR_019344
	Natural variant	1086	1	R → Q. Ref.3 Corresponds to variant rs3219457 [ dbSNP | Ensembl ].		VAR_019345
Experimental info
	Sequence conflict	472	1	Y → H in AAA58439. Ref.1
	Sequence conflict	776	1	R → G in AAA35768. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P28340 [UniParc]. Last modified July 19, 2004. Version 2. Checksum: 9D04D34AB4AEE810	FASTA	1,107	123,631
	10 20 30 40 50 60 MDGKRRPGPG PGVPPKRARG GLWDDDDAPR PSQFEEDLAL MEEMEAEHRL QEQEEEELQS 70 80 90 100 110 120 VLEGVADGQV PPSAIDPRWL RPTPPALDPQ TEPLIFQQLE IDHYVGPAQP VPGGPPPSRG 130 140 150 160 170 180 SVPVLRAFGV TDEGFSVCCH IHGFAPYFYT PAPPGFGPEH MGDLQRELNL AISRDSRGGR 190 200 210 220 230 240 ELTGPAVLAV ELCSRESMFG YHGHGPSPFL RITVALPRLV APARRLLEQG IRVAGLGTPS 250 260 270 280 290 300 FAPYEANVDF EIRFMVDTDI VGCNWLELPA GKYALRLKEK ATQCQLEADV LWSDVVSHPP 310 320 330 340 350 360 EGPWQRIAPL RVLSFDIECA GRKGIFPEPE RDPVIQICSL GLRWGEPEPF LRLALTLRPC 370 380 390 400 410 420 APILGAKVQS YEKEEDLLQA WSTFIRIMDP DVITGYNIQN FDLPYLISRA QTLKVQTFPF 430 440 450 460 470 480 LGRVAGLCSN IRDSSFQSKQ TGRRDTKVVS MVGRVQMDML QVLLREYKLR SYTLNAVSFH 490 500 510 520 530 540 FLGEQKEDVQ HSIITDLQNG NDQTRRRLAV YCLKDAYLPL RLLERLMVLV NAVEMARVTG 550 560 570 580 590 600 VPLSYLLSRG QQVKVVSQLL RQAMHEGLLM PVVKSEGGED YTGATVIEPL KGYYDVPIAT 610 620 630 640 650 660 LDFSSLYPSI MMAHNLCYTT LLRPGTAQKL GLTEDQFIRT PTGDEFVKTS VRKGLLPQIL 670 680 690 700 710 720 ENLLSARKRA KAELAKETDP LRRQVLDGRQ LALKVSANSV YGFTGAQVGK LPCLEISQSV 730 740 750 760 770 780 TGFGRQMIEK TKQLVESKYT VENGYSTSAK VVYGDTDSVM CRFGVSSVAE AMALGREAAD 790 800 810 820 830 840 WVSGHFPSPI RLEFEKVYFP YLLISKKRYA GLLFSSRPDA HDRMDCKGLE AVRRDNCPLV 850 860 870 880 890 900 ANLVTASLRR LLIDRDPEGA VAHAQDVISD LLCNRIDISQ LVITKELTRA ASDYAGKQAH 910 920 930 940 950 960 VELAERMRKR DPGSAPSLGD RVPYVIISAA KGVAAYMKSE DPLFVLEHSL PIDTQYYLEQ 970 980 990 1000 1010 1020 QLAKPLLRIF EPILGEGRAE AVLLRGDHTR CKTVLTGKVG GLLAFAKRRN CCIGCRTVLS 1030 1040 1050 1060 1070 1080 HQGAVCEFCQ PRESELYQKE VSHLNALEER FSRLWTQCQR CQGSLHEDVI CTSRDCPIFY 1090 1100 MRKKVRKDLE DQEQLLRRFG PPGPEAW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of the catalytic subunit of human DNA polymerase delta and chromosomal location of the gene." Chung D.W., Zhang J., Tan C.-K., Davie E.W., So A.G., Downey K.M. Proc. Natl. Acad. Sci. U.S.A. 88:11197-11201(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT TRP-30.
[2]	"Molecular cloning of the cDNA for the catalytic subunit of human DNA polymerase delta." Yang C.-L., Chang L.-S., Zhang P., Hao H., Zhu L., Toomey N.L., Lee M.Y.W.T. Nucleic Acids Res. 20:735-745(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS HIS-119 AND ASN-173.
[3]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS HIS-19; TRP-30; HIS-119; ASN-173; HIS-177; HIS-849 AND GLN-1086.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT HIS-119. Tissue: Lymph.
[5]	"Human Werner helicase interacting protein 1 (WRNIP1) functions as a novel modulator for DNA polymerase delta." Tsurimoto T., Shinozaki A., Yano M., Seki M., Enomoto T. Genes Cells 10:13-22(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH WRNIP1.
[6]	"Functional roles of p12, the fourth subunit of human DNA polymerase delta." Li H., Xie B., Zhou Y., Rahmeh A., Trusa S., Zhang S., Gao Y., Lee E.Y., Lee M.Y. J. Biol. Chem. 281:14748-14755(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH POLD4 AND PCNA.
[7]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1007, MASS SPECTROMETRY.
[9]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	M80397 mRNA. Translation: AAA58439.1. M81735 mRNA. Translation: AAA35768.1. AY129569 Genomic DNA. Translation: AAM76971.1. BC008800 mRNA. Translation: AAH08800.1.
IPI	IPI00002894.
PIR	A41618.
RefSeq	NP_001243778.1. NM_001256849.1. NP_002682.2. NM_002691.3.
UniGene	Hs.279413.
3D structure databases
ProteinModelPortal	P28340.
ModBase	Search...
Protein-protein interaction databases
IntAct	P28340. 13 interactions.
MINT	MINT-1414678.
STRING	9606.ENSP00000262266.
PTM databases
PhosphoSite	P28340.
Polymorphism databases
DMDM	50403732.
Proteomic databases
PaxDb	P28340.
PRIDE	P28340.
Protocols and materials databases
DNASU	5424.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000440232; ENSP00000406046; ENSG00000062822. ENST00000599857; ENSP00000473052; ENSG00000062822.
GeneID	5424.
KEGG	hsa:5424.
UCSC	uc002psb.4. human.
Organism-specific databases
CTD	5424.
GeneCards	GC19P050889.
H-InvDB	HIX0202825.
HGNC	HGNC:9175. POLD1.
HPA	CAB004375.
MIM	174761. gene.
neXtProt	NX_P28340.
PharmGKB	PA33496.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0417.
HOGENOM	HOG000036616.
HOVERGEN	HBG051395.
KO	K02327.
OMA	MIEQTKQ.
PhylomeDB	P28340.
Enzyme and pathway databases
Reactome	REACT_115566. Cell Cycle. REACT_216. DNA Repair. REACT_383. DNA Replication.
Gene expression databases
Bgee	P28340.
CleanEx	HS_POLD1.
Genevestigator	P28340.
GermOnline	ENSG00000062822. Homo sapiens.
Family and domain databases
Gene3D	3.90.1600.10. 2 hits.
InterPro	IPR006172. DNA-dir_DNA_pol_B. IPR017964. DNA-dir_DNA_pol_B_CS. IPR006133. DNA-dir_DNA_pol_B_exonuc. IPR006134. DNA-dir_DNA_pol_B_multi_dom. IPR004578. DNA-dir_DNA_pol_B_pol2. IPR023211. DNA_pol_palm_dom. IPR012337. RNaseH-like_dom. IPR025687. Znf-C4pol. [Graphical view]
Pfam	PF00136. DNA_pol_B. 1 hit. PF03104. DNA_pol_B_exo1. 1 hit. PF14260. zf-C4pol. 1 hit. [Graphical view]
PRINTS	PR00106. DNAPOLB.
SMART	SM00486. POLBc. 1 hit. [Graphical view]
SUPFAM	SSF53098. RNaseH_fold. 1 hit.
TIGRFAMs	TIGR00592. pol2. 1 hit.
PROSITE	PS00116. DNA_POLYMERASE_B. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P28340.
ChEMBL	CHEMBL2735.
GenomeRNAi	5424.
NextBio	20985.
PMAP-CutDB	P28340.
SOURCE	Search...

Entry information

Entry name

DPOD1_HUMAN

Accession

Primary (citable) accession number: P28340
Secondary accession number(s): Q8NER3, Q96H98

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 1992
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 133 of the entry and version 2 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.