Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

DNA polymerase

Gene

43

Organism
Enterobacteria phage T4 (Bacteriophage T4)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Replicates the viral genomic DNA. This polymerase possesses two enzymatic activities: DNA synthesis (polymerase) and an exonucleolytic activity that degrades single-stranded DNA in the 3'- to 5'-direction for proofreading purpose.2 Publications

Catalytic activityi

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).1 Publication

Cofactori

Mg2+1 PublicationNote: Magnesium 1 and 2 form the active site of the 3'-5' exonuclease activity (PubMed:9665720). Magnesium 3 and 4 form the active site of the polymerase activity (By similarity). Magnesium 3 is responsible for bringing the 3' hydroxyl group at the primer-terminus closer to the alpha-phosphorus atom of the incoming dNTP enabling phosphodiester bond formation (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi112 – 1121Magnesium 1; catalytic1 Publication
Metal bindingi114 – 1141Magnesium 1; catalytic1 Publication
Metal bindingi219 – 2191Magnesium 2; catalytic1 Publication
Metal bindingi324 – 3241Magnesium 1 and 2; catalytic1 Publication
Metal bindingi408 – 4081Magnesium 3 and 4; catalyticBy similarity
Metal bindingi409 – 4091Magnesium 4; via carbonyl oxygen; catalyticBy similarity
Binding sitei479 – 4791SubstrateBy similarity
Binding sitei557 – 5571SubstrateBy similarity
Sitei618 – 6181Optimization of metal coordination by the polymerase active siteBy similarity
Metal bindingi620 – 6201Magnesium 3 and 4; catalyticBy similarity
Sitei703 – 7031Optimization of metal coordination by the polymerase active siteBy similarity
Sitei711 – 7111Essential for viral replicationBy similarity

GO - Molecular functioni

  • 3'-5' exonuclease activity Source: UniProtKB
  • DNA binding Source: UniProtKB-KW
  • DNA-directed DNA polymerase activity Source: UniProtKB
  • nucleotide binding Source: InterPro

GO - Biological processi

  • bidirectional double-stranded viral DNA replication Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

DNA-directed DNA polymerase, Exonuclease, Hydrolase, Nuclease, Nucleotidyltransferase, Transferase

Keywords - Biological processi

DNA replication, Viral DNA replication

Keywords - Ligandi

DNA-binding, Magnesium, Metal-binding

Enzyme and pathway databases

BRENDAi2.7.7.7. 9245.
SABIO-RKP04415.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA polymerase (EC:2.7.7.71 Publication, EC:3.1.11.-4 Publications)
Alternative name(s):
Gene product 43
Short name:
Gp43
Gene namesi
Name:43
OrganismiEnterobacteria phage T4 (Bacteriophage T4)
Taxonomic identifieri10665 [NCBI]
Taxonomic lineageiVirusesdsDNA viruses, no RNA stageCaudoviralesMyoviridaeTevenvirinaeT4likevirus
Virus hostiEscherichia coli [TaxID: 562]
Proteomesi
  • UP000009087 Componenti: Genome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi112 – 1121D → A: Almost complete loss of exonuclease activity. Decreased replication fidelity. 1 Publication
Mutagenesisi114 – 1141E → A: Almost complete loss of exonuclease activity. Decreased replication fidelity. 1 Publication
Mutagenesisi219 – 2191D → A: Almost complete loss of exonuclease activity. Decreased replication fidelity. 2 Publications
Mutagenesisi324 – 3241D → A: Almost complete loss of exonuclease activity. Decreased replication fidelity. 1 Publication

Chemistry

ChEMBLiCHEMBL5946.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 898898DNA polymerasePRO_0000046546Add
BLAST

Interactioni

Subunit structurei

Part of the replicase complex that includes the DNA polymerase, the polymerase clamp, the clamp loader complex, the single-stranded DNA binding protein, the primase, the helicase and the helicase assembly factor (PubMed:16800624). Interacts with the polymerase clamp; this interaction constitutes the polymerase holoenzyme (PubMed:8475061, PubMed:8917503).3 Publications

Chemistry

BindingDBiP04415.

Structurei

Secondary structure

1
898
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 118Combined sources
Beta strandi14 – 207Combined sources
Beta strandi26 – 327Combined sources
Beta strandi36 – 383Combined sources
Helixi40 – 434Combined sources
Turni49 – 524Combined sources
Helixi63 – 7614Combined sources
Helixi82 – 9413Combined sources
Helixi103 – 1053Combined sources
Beta strandi108 – 1158Combined sources
Turni123 – 1253Combined sources
Beta strandi130 – 1378Combined sources
Turni138 – 1414Combined sources
Beta strandi142 – 1487Combined sources
Beta strandi150 – 1534Combined sources
Helixi161 – 1655Combined sources
Helixi168 – 1703Combined sources
Helixi177 – 1804Combined sources
Beta strandi183 – 1897Combined sources
Helixi191 – 20414Combined sources
Beta strandi208 – 2114Combined sources
Turni215 – 2184Combined sources
Helixi219 – 23618Combined sources
Helixi237 – 2393Combined sources
Beta strandi245 – 2495Combined sources
Helixi252 – 2543Combined sources
Beta strandi258 – 2625Combined sources
Beta strandi265 – 2673Combined sources
Helixi270 – 2778Combined sources
Helixi287 – 2959Combined sources
Helixi306 – 3083Combined sources
Helixi309 – 33527Combined sources
Helixi337 – 34812Combined sources
Helixi352 – 3565Combined sources
Helixi358 – 36912Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NOYX-ray2.20A/B1-388[»]
1NOZX-ray2.20A/B1-388[»]
ProteinModelPortaliP04415.
SMRiP04415. Positions 1-897.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP04415.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni101 – 3372373'-5'exonuclease1 PublicationAdd
BLAST
Regioni245 – 26117Beta hairpin1 PublicationAdd
BLAST
Regioni377 – 898522Polymerase1 PublicationAdd
BLAST
Regioni702 – 7054Binding of DNA in B-conformationBy similarity
Regioni893 – 8986Interaction with the polymerase clamp1 Publication

Domaini

The N-terminus contains the 3'-5' exonuclease activity (PubMed:7592876). The C-terminus contains the polymerase activity and is involved in binding to the polymerase clamp protein (PubMed:7592876). A beta hairpin structure is necessary for the proofreading function of the polymerase (PubMed:25753811).2 Publications

Sequence similaritiesi

Belongs to the DNA polymerase type-B family.Curated

Phylogenomic databases

KOiK18942.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
3.90.1600.10. 3 hits.
InterProiIPR006172. 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.
IPR023211. DNA_pol_palm_dom.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF00136. DNA_pol_B. 1 hit.
PF03104. DNA_pol_B_exo1. 1 hit.
[Graphical view]
PRINTSiPR00106. DNAPOLB.
SMARTiSM00486. POLBc. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
PROSITEiPS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P04415-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKEFYISIET VGNNIVERYI DENGKERTRE VEYLPTMFRH CKEESKYKDI
60 70 80 90 100
YGKNCAPQKF PSMKDARDWM KRMEDIGLEA LGMNDFKLAY ISDTYGSEIV
110 120 130 140 150
YDRKFVRVAN CDIEVTGDKF PDPMKAEYEI DAITHYDSID DRFYVFDLLN
160 170 180 190 200
SMYGSVSKWD AKLAAKLDCE GGDEVPQEIL DRVIYMPFDN ERDMLMEYIN
210 220 230 240 250
LWEQKRPAIF TGWNIEGFDV PYIMNRVKMI LGERSMKRFS PIGRVKSKLI
260 270 280 290 300
QNMYGSKEIY SIDGVSILDY LDLYKKFAFT NLPSFSLESV AQHETKKGKL
310 320 330 340 350
PYDGPINKLR ETNHQRYISY NIIDVESVQA IDKIRGFIDL VLSMSYYAKM
360 370 380 390 400
PFSGVMSPIK TWDAIIFNSL KGEHKVIPQQ GSHVKQSFPG AFVFEPKPIA
410 420 430 440 450
RRYIMSFDLT SLYPSIIRQV NISPETIRGQ FKVHPIHEYI AGTAPKPSDE
460 470 480 490 500
YSCSPNGWMY DKHQEGIIPK EIAKVFFQRK DWKKKMFAEE MNAEAIKKII
510 520 530 540 550
MKGAGSCSTK PEVERYVKFS DDFLNELSNY TESVLNSLIE ECEKAATLAN
560 570 580 590 600
TNQLNRKILI NSLYGALGNI HFRYYDLRNA TAITIFGQVG IQWIARKINE
610 620 630 640 650
YLNKVCGTND EDFIAAGDTD SVYVCVDKVI EKVGLDRFKE QNDLVEFMNQ
660 670 680 690 700
FGKKKMEPMI DVAYRELCDY MNNREHLMHM DREAISCPPL GSKGVGGFWK
710 720 730 740 750
AKKRYALNVY DMEDKRFAEP HLKIMGMETQ QSSTPKAVQE ALEESIRRIL
760 770 780 790 800
QEGEESVQEY YKNFEKEYRQ LDYKVIAEVK TANDIAKYDD KGWPGFKCPF
810 820 830 840 850
HIRGVLTYRR AVSGLGVAPI LDGNKVMVLP LREGNPFGDK CIAWPSGTEL
860 870 880 890
PKEIRSDVLS WIDHSTLFQK SFVKPLAGMC ESAGMDYEEK ASLDFLFG
Length:898
Mass (Da):103,610
Last modified:January 1, 1988 - v1
Checksum:i925300C4CA5C7A24
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti89 – 891A → V in CAA25344 (PubMed:3054876).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M10160 Genomic DNA. Translation: AAC05397.1.
X00769 Genomic DNA. Translation: CAA25344.1.
AF158101 Genomic DNA. Translation: AAD42468.1.
M37159 Genomic DNA. Translation: AAA21706.1.
PIRiJS0791. DJBPT4.
RefSeqiNP_049662.1. NC_000866.4.

Genome annotation databases

GeneIDi1258685.
KEGGivg:1258685.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M10160 Genomic DNA. Translation: AAC05397.1.
X00769 Genomic DNA. Translation: CAA25344.1.
AF158101 Genomic DNA. Translation: AAD42468.1.
M37159 Genomic DNA. Translation: AAA21706.1.
PIRiJS0791. DJBPT4.
RefSeqiNP_049662.1. NC_000866.4.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NOYX-ray2.20A/B1-388[»]
1NOZX-ray2.20A/B1-388[»]
ProteinModelPortaliP04415.
SMRiP04415. Positions 1-897.
ModBaseiSearch...
MobiDBiSearch...

Chemistry

BindingDBiP04415.
ChEMBLiCHEMBL5946.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi1258685.
KEGGivg:1258685.

Phylogenomic databases

KOiK18942.

Enzyme and pathway databases

BRENDAi2.7.7.7. 9245.
SABIO-RKP04415.

Miscellaneous databases

EvolutionaryTraceiP04415.
PROiP04415.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
3.90.1600.10. 3 hits.
InterProiIPR006172. 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.
IPR023211. DNA_pol_palm_dom.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF00136. DNA_pol_B. 1 hit.
PF03104. DNA_pol_B_exo1. 1 hit.
[Graphical view]
PRINTSiPR00106. DNAPOLB.
SMARTiSM00486. POLBc. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
PROSITEiPS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Primary structure of T4 DNA polymerase. Evolutionary relatedness to eucaryotic and other procaryotic DNA polymerases."
    Spicer E.K., Rush J., Fung C., Reha-Krantz L.J., Karam J.D., Konigsberg W.H.
    J. Biol. Chem. 263:7478-7486(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  2. "DNA polymerase of bacteriophage T4 is an autogenous translational repressor."
    Andrake M., Guild N., Hsu T., Gold L., Tuerk C., Karam J.
    Proc. Natl. Acad. Sci. U.S.A. 85:7942-7946(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "Deoxycytidylate hydroxymethylase gene of bacteriophage T4. Nucleotide sequence determination and over-expression of the gene."
    Lamm N., Wang Y., Mathews C.K., Rueger W.
    Eur. J. Biochem. 172:553-563(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 338-898.
  5. "Kinetic characterization of the polymerase and exonuclease activities of the gene 43 protein of bacteriophage T4."
    Capson T.L., Peliska J.A., Kaboord B.F., Frey M.W., Lively C., Dahlberg M., Benkovic S.J.
    Biochemistry 31:10984-10994(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY, FUNCTION.
  6. "Assembly of a functional replication complex without ATP hydrolysis: a direct interaction of bacteriophage T4 gp45 with T4 DNA polymerase."
    Reddy M.K., Weitzel S.E., von Hippel P.H.
    Proc. Natl. Acad. Sci. U.S.A. 90:3211-3215(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH THE POLYMERASE CLAMP.
  7. "Genetic and biochemical studies of bacteriophage T4 DNA polymerase 3'-->5'-exonuclease activity."
    Reha-Krantz L.J., Nonay R.L.
    J. Biol. Chem. 268:27100-27108(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: MUTAGENESIS OF ASP-112; GLU-114; ASP-219 AND ASP-324, CATALYTIC ACTIVITY.
  8. "Modular organization of T4 DNA polymerase. Evidence from phylogenetics."
    Wang C.C., Yeh L.-S., Karam J.D.
    J. Biol. Chem. 270:26558-26564(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN.
  9. "The carboxyl terminus of the bacteriophage T4 DNA polymerase is required for holoenzyme complex formation."
    Berdis A.J., Soumillion P., Benkovic S.J.
    Proc. Natl. Acad. Sci. U.S.A. 93:12822-12827(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH THE POLYMERASE CLAMP.
  10. "Exonuclease-polymerase active site partitioning of primer-template DNA strands and equilibrium Mg2+ binding properties of bacteriophage T4 DNA polymerase."
    Beechem J.M., Otto M.R., Bloom L.B., Eritja R., Reha-Krantz L.J., Goodman M.F.
    Biochemistry 37:10144-10155(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: COFACTOR.
  11. "Single-molecule investigation of the T4 bacteriophage DNA polymerase holoenzyme: multiple pathways of holoenzyme formation."
    Smiley R.D., Zhuang Z., Benkovic S.J., Hammes G.G.
    Biochemistry 45:7990-7997(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  12. "Mutational and pH studies of the 3' --> 5' exonuclease activity of bacteriophage T4 DNA polymerase."
    Elisseeva E., Mandal S.S., Reha-Krantz L.J.
    J. Biol. Chem. 274:25151-25158(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: CATALYTIC ACTIVITY.
  13. "Inactivation of the 3'-5' exonuclease of the replicative T4 DNA polymerase allows translesion DNA synthesis at an abasic site."
    Tanguy Le Gac N., Delagoutte E., Germain M., Villani G.
    J. Mol. Biol. 336:1023-1034(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ASP-219, CATALYTIC ACTIVITY.
  14. "Structural analysis of bacteriophage T4 DNA replication: a review in the Virology Journal series on bacteriophage T4 and its relatives."
    Mueser T.C., Hinerman J.M., Devos J.M., Boyer R.A., Williams K.J.
    Virol. J. 7:359-359(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  15. "DNA polymerase 3'->5' exonuclease activity: Different roles of the beta hairpin structure in family-B DNA polymerases."
    Darmawan H., Harrison M., Reha-Krantz L.J.
    DNA Repair 29:36-46(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: DOMAIN.
  16. "Coordinated DNA replication by the bacteriophage T4 replisome."
    Noble E., Spiering M.M., Benkovic S.J.
    Viruses 7:3186-3200(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW, SUBUNIT.
  17. "Crystal structures of an NH2-terminal fragment of T4 DNA polymerase and its complexes with single-stranded DNA and with divalent metal ions."
    Wang J., Yu P., Lin T.C., Konigsberg W.H., Steitz T.A.
    Biochemistry 35:8110-8119(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-388.

Entry informationi

Entry nameiDPOL_BPT4
AccessioniPrimary (citable) accession number: P04415
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 1, 1988
Last modified: July 6, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programViral Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.