Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P28340 (DPOD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1107 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

Tissue specificity

Expressed across a panel of tissues, with high levels of expression in heart and lung. Ref.9

Domain

The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes By similarity.

Involvement in disease

Colorectal cancer 10 (CRCS10) [MIM:612591]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.10

Mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL) [MIM:615381]: An autosomal dominant systemic disorder characterized by prominent loss of subcutaneous fat, metabolic abnormalities including insulin resistance and diabetes mellitus, sclerodermatous skin, and a facial appearance characterized by mandibular hypoplasia. Sensorineural deafness occurs late in the first or second decades of life.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

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 processDNA replication
   Cellular componentNucleus
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainZinc-finger
   Ligand4Fe-4S
DNA-binding
Iron
Iron-sulfur
Metal-binding
Zinc
   Molecular functionDNA-directed DNA polymerase
Exonuclease
Hydrolase
Nuclease
Nucleotidyltransferase
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Traceable author statement. Source: Reactome

DNA replication

Inferred from mutant phenotype PubMed 16762037. Source: UniProtKB

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 strand elongation involved in DNA replication

Traceable author statement. Source: Reactome

DNA synthesis involved in DNA repair

Inferred from direct assay PubMed 3335506. Source: UniProtKB

base-excision repair

Traceable author statement. Source: Reactome

base-excision repair, gap-filling

Inferred from direct assay PubMed 10559260PubMed 10559261. Source: UniProtKB

fatty acid homeostasis

Inferred from mutant phenotype Ref.9. Source: UniProtKB

mitotic cell cycle

Traceable author statement. Source: Reactome

nucleic acid phosphodiester bond hydrolysis

Inferred from Biological aspect of Ancestor. Source: GOC

nucleotide-excision repair

Traceable author statement. Source: Reactome

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

small molecule metabolic process

Traceable author statement. Source: Reactome

telomere maintenance

Traceable author statement. Source: Reactome

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_componentaggresome

Inferred from direct assay. Source: HPA

cytoplasm

Inferred from direct assay. Source: HPA

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

nucleus

Inferred from direct assay PubMed 16762037. Source: UniProtKB

   Molecular_function3'-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...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11071107DNA polymerase delta catalytic subunit
PRO_0000046442

Regions

Zinc finger1012 – 102918CysA-type
Motif4 – 1916Nuclear localization signal Potential
Motif1058 – 107619CysB motif

Sites

Metal binding10121Zinc By similarity
Metal binding10151Zinc By similarity
Metal binding10261Zinc By similarity
Metal binding10291Zinc By similarity
Metal binding10581Iron-sulfur (4Fe-4S) By similarity
Metal binding10611Iron-sulfur (4Fe-4S) By similarity
Metal binding10711Iron-sulfur (4Fe-4S) By similarity
Metal binding10761Iron-sulfur (4Fe-4S) By similarity

Natural variations

Natural variant51R → W.
Corresponds to variant rs9282830 [ dbSNP | Ensembl ].
VAR_048878
Natural variant191R → H. Ref.3
Corresponds to variant rs3218773 [ dbSNP | Ensembl ].
VAR_019340
Natural variant211G → C.
Corresponds to variant rs9282831 [ dbSNP | Ensembl ].
VAR_048879
Natural variant301R → W. Ref.1 Ref.3
Corresponds to variant rs3218772 [ dbSNP | Ensembl ].
VAR_016146
Natural variant1191R → H. Ref.2 Ref.3 Ref.4
Corresponds to variant rs1726801 [ dbSNP | Ensembl ].
VAR_019341
Natural variant1451A → D Found in a colorectal sample; somatic mutation. Ref.10
VAR_069333
Natural variant1731S → N. Ref.2 Ref.3
Corresponds to variant rs1726803 [ dbSNP | Ensembl ].
VAR_019342
Natural variant1771R → H. Ref.3
Corresponds to variant rs3218750 [ dbSNP | Ensembl ].
VAR_019343
Natural variant3471P → L.
Corresponds to variant rs2230243 [ dbSNP | Ensembl ].
VAR_048880
Natural variant4611Q → H Found in a colorectal sample; somatic mutation. Ref.10
VAR_069334
Natural variant4781S → N in CRCS10; associated with disease susceptibility. Ref.10
VAR_069335
Natural variant6051Missing in MDPL; the mutant enzyme lacks DNA polymerase ability; has decreased exonuclease activity; can bind DNA but is unable to interact with and incorporate dNTPs. Ref.9
VAR_070231
Natural variant7871P → L Found in a colorectal sample; somatic mutation. Ref.10
VAR_069336
Natural variant8081R → H Found in a colorectal sample; somatic mutation. Ref.10
VAR_069337
Natural variant8491R → H. Ref.3
Corresponds to variant rs3218775 [ dbSNP | Ensembl ].
VAR_019344
Natural variant8641A → T Found in a colorectal sample; somatic mutation. Ref.10
VAR_069338
Natural variant10861R → Q. Ref.3
Corresponds to variant rs3219457 [ dbSNP | Ensembl ].
VAR_019345

Experimental info

Sequence conflict4721Y → H in AAA58439. Ref.1
Sequence conflict7761R → G in AAA35768. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P28340 [UniParc].

Last modified July 19, 2004. Version 2.
Checksum: 9D04D34AB4AEE810

FASTA1,107123,631
        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 

« Hide

References

« Hide '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]"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].
[9]"An in-frame deletion at the polymerase active site of POLD1 causes a multisystem disorder with lipodystrophy."
Weedon M.N., Ellard S., Prindle M.J., Caswell R., Allen H.L., Oram R., Godbole K., Yajnik C.S., Sbraccia P., Novelli G., Turnpenny P., McCann E., Goh K.J., Wang Y., Fulford J., McCulloch L.J., Savage D.B., O'Rahilly S. expand/collapse author list , Kos K., Loeb L.A., Semple R.K., Hattersley A.T.
Nat. Genet. 45:947-950(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, VARIANT MDPL SER-605 DEL.
[10]"Germline mutations affecting the proofreading domains of POLE and POLD1 predispose to colorectal adenomas and carcinomas."
CORGI Consortium, WGS500 Consortium
Palles C., Cazier J.B., Howarth K.M., Domingo E., Jones A.M., Broderick P., Kemp Z., Spain S.L., Guarino Almeida E., Salguero I., Sherborne A., Chubb D., Carvajal-Carmona L.G., Ma Y., Kaur K., Dobbins S., Barclay E., Gorman M. expand/collapse author list , Martin L., Kovac M.B., Humphray S., Lucassen A., Holmes C.C., Bentley D., Donnelly P., Taylor J., Petridis C., Roylance R., Sawyer E.J., Kerr D.J., Clark S., Grimes J., Kearsey S.E., Thomas H.J., McVean G., Houlston R.S., Tomlinson I.
Nat. Genet. 45:136-144(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CRCS10 ASN-478, VARIANTS ASP-145; HIS-461; LEU-787; HIS-808 AND THR-864.
+Additional computationally mapped references.

Web resources

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.
PIRA41618.
RefSeqNP_001243778.1. NM_001256849.1.
NP_002682.2. NM_002691.3.
UniGeneHs.279413.

3D structure databases

ProteinModelPortalP28340.
SMRP28340. Positions 77-983.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111420. 47 interactions.
IntActP28340. 17 interactions.
MINTMINT-1414678.
STRING9606.ENSP00000262266.

Chemistry

BindingDBP28340.
ChEMBLCHEMBL2363042.

PTM databases

PhosphoSiteP28340.

Polymorphism databases

DMDM50403732.

Proteomic databases

PaxDbP28340.
PRIDEP28340.

Protocols and materials databases

DNASU5424.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000440232; ENSP00000406046; ENSG00000062822.
ENST00000599857; ENSP00000473052; ENSG00000062822.
GeneID5424.
KEGGhsa:5424.
UCSCuc002psb.5. human.

Organism-specific databases

CTD5424.
GeneCardsGC19P050889.
H-InvDBHIX0202825.
HGNCHGNC:9175. POLD1.
HPACAB004375.
HPA046524.
MIM174761. gene.
612591. phenotype.
615381. phenotype.
neXtProtNX_P28340.
Orphanet363649. Mandibular hypoplasia-deafness-progeroid syndrome.
PharmGKBPA33496.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0417.
HOGENOMHOG000036616.
HOVERGENHBG051395.
KOK02327.
PhylomeDBP28340.
TreeFamTF352785.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
REACT_115566. Cell Cycle.
REACT_216. DNA Repair.
REACT_383. DNA Replication.

Gene expression databases

ArrayExpressP28340.
BgeeP28340.
CleanExHS_POLD1.
GenevestigatorP28340.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
3.90.1600.10. 2 hits.
InterProIPR006172. 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]
PfamPF00136. DNA_pol_B. 1 hit.
PF03104. DNA_pol_B_exo1. 1 hit.
PF14260. zf-C4pol. 1 hit.
[Graphical view]
PRINTSPR00106. DNAPOLB.
SMARTSM00486. POLBc. 1 hit.
[Graphical view]
SUPFAMSSF53098. SSF53098. 1 hit.
TIGRFAMsTIGR00592. pol2. 1 hit.
PROSITEPS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiPOLD1.
GenomeRNAi5424.
NextBio20985.
PMAP-CutDBP28340.
PROP28340.
SOURCESearch...

Entry information

Entry nameDPOD1_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 144 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM