Reviewed, UniProtKB/Swiss-Prot P28340 (DPOD1_HUMAN)

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) [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	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).
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.
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.

Ontologies

Keywords
Biological process	DNA replication
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Domain	Zinc-finger
Ligand	DNA-binding Metal-binding Zinc
Molecular function	DNA-directed DNA polymerase Exonuclease Hydrolase Nuclease Nucleotidyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA synthesis during DNA repair Inferred from direct assay. Source: UniProtKB S phase of mitotic cell cycle Inferred from direct assay. Source: UniProtKB nucleotide-excision repair, DNA gap filling Inferred from Experiment. Source: Reactome response to UV Traceable author statement. Source: ProtInc
Cellular component	nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	DNA binding Inferred from direct assay. Source: UniProtKB DNA-directed DNA polymerase activity Inferred from mutant phenotype. Source: UniProtKB chromatin binding Inferred from direct assay. Source: UniProtKB exonuclease activity Inferred from electronic annotation. Source: UniProtKB-KW nucleotide binding Inferred from electronic annotation. Source: InterPro protein binding Ref.5 Ref.6 Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ABL1	P00519	1	EBI-716569,EBI-375543
FYN	P06241	1	EBI-716569,EBI-515315
GRB2	P62993	1	EBI-716569,EBI-401755
PCNA	P12004	1	EBI-716569,EBI-358311
POLD2	P49005	1	EBI-716569,EBI-372354
POLD4	Q9HCU8	2	EBI-716569,EBI-864968
PTP4A3	O75365	1	EBI-716569,EBI-1043866
SRC	P12931	1	EBI-716569,EBI-621482

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	C4-type Potential
	Zinc finger	1058 – 1076	19	C4-type Potential
	Motif	4 – 19	16	Nuclear localization signal Potential
Amino acid modifications
	Modified residue	914	1	Phosphoserine Ref.7
	Modified residue	917	1	Phosphoserine Ref.7
	Modified residue	1007	1	N6-acetyllysine Ref.9
Natural variations
	Natural variant	5	1	R → W: dbSNP rs9282830.		VAR_048878
	Natural variant	19	1	R → H: dbSNP rs3218773. Ref.3		VAR_019340
	Natural variant	21	1	G → C: dbSNP rs9282831.		VAR_048879
	Natural variant	30	1	R → W: dbSNP rs3218772. Ref.3 Ref.1		VAR_016146
	Natural variant	119	1	R → H: dbSNP rs1726801. Ref.3 Ref.2 Ref.4		VAR_019341
	Natural variant	173	1	S → N: dbSNP rs1726803. Ref.3 Ref.2		VAR_019342
	Natural variant	177	1	R → H: dbSNP rs3218750. Ref.3		VAR_019343
	Natural variant	347	1	P → L: dbSNP rs2230243.		VAR_048880
	Natural variant	849	1	R → H: dbSNP rs3218775. Ref.3		VAR_019344
	Natural variant	1086	1	R → Q: dbSNP rs3219457. Ref.3		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)
	P28340-1 [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: 1722322] [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: 1542570] [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: 15489334] [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: 15670210] [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: 16510448] [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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-914 AND SER-917, MASS SPECTROMETRY.
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-1007, MASS SPECTROMETRY.
+	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_002682.2.
UniGene	Hs.279413
3D structure databases
SMR	P28340. Positions 119-973.
ModBase	Search...
Protein-protein interaction databases
IntAct	P28340. 16 interactions.
STRING	P28340.
PTM databases
PhosphoSite	P28340.
Proteomic databases
PRIDE	P28340.
Genome annotation databases
Ensembl	ENST00000262266; ENSP00000262266; ENSG00000062822; Homo sapiens. [Genome view] ENST00000440232; ENSP00000406046; ENSG00000062822; Homo sapiens. [Genome view]
GeneID	5424.
KEGG	hsa:5424.
UCSC	uc002psb.2. human.
Organism-specific databases
CTD	5424.
GeneCards	GC19P055582.
HGNC	HGNC:9175. POLD1.
HPA	CAB004375.
MIM	174761. gene.
PharmGKB	PA33496.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12117.
HOVERGEN	P28340.
OrthoDB	EOG976NKK.
PhylomeDB	P28340.
Enzyme and pathway databases
BRENDA	2.7.7.7. 247.
Reactome	REACT_152. Cell Cycle, Mitotic. REACT_216. DNA Repair. REACT_383. DNA Replication. REACT_7970. Telomere Maintenance.
Gene expression databases
ArrayExpress	P28340.
Bgee	P28340.
CleanEx	HS_POLD1.
Genevestigator	P28340.
GermOnline	ENSG00000062822. Homo sapiens.
Family and domain databases
InterPro	IPR006172. DNA-dir_DNA_pol_B. IPR006134. DNA-dir_DNA_pol_B_cons-reg. IPR017966. DNA-dir_DNA_pol_B_cons_reg2. IPR017964. DNA-dir_DNA_pol_B_CS. IPR006133. DNA-dir_DNA_pol_B_exonuc. IPR004578. DNA-dir_DNA_pol_B_pol2. IPR012337. PolynucTfrase_RNaseH_fold. [Graphical view]
PANTHER	PTHR10322. DNA_pol_B. 1 hit.
Pfam	PF00136. DNA_pol_B. 1 hit. PF03104. DNA_pol_B_exo. 1 hit. [Graphical view]
PRINTS	PR00106. DNAPOLB.
SMART	SM00486. POLBc. 1 hit. [Graphical view]
TIGRFAMs	TIGR00592. pol2. 1 hit.
PROSITE	PS00116. DNA_POLYMERASE_B. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
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:	February 9, 2010
This is version 100 of the entry and version 2 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.