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Molecule Details

General Information of the Molecule
Name
Herpes simplex virus DNA polymerase UL30 (HSV UL30)
Synonyms
HSV DNA polymerase catalytic subunit
Gene Name
HSV UL30
Gene ID
2703462
Sequence
MFSGGGGPLSPGGKSAARAASGFFAPAGPRGASRGPPPCLRQNFYNPYLAPVGTQQKPTG
PTQRHTYYSECDEFRFIAPRVLDEDAPPEKRAGVHDGHLKRAPKVYCGGDERDVLRVGSG
GFWPRRSRLWGGVDHAPAGFNPTVTVFHVYDILENVEHAYGMRAAQFHARFMDAITPTGT
VITLLGLTPEGHRVAVHVYGTRQYFYMNKEEVDRHLQCRAPRDLCERMAAALRESPGASF
RGISADHFEAEVVERTDVYYYETRPALFYRVYVRSGRVLSYLCDNFCPAIKKYEGGVDAT
TRFILDNPGFVTFGWYRLKPGRNNTLAQPAAPMAFGTSSDVEFNCTADNLAIEGGMSDLP
AYKLMCFDIECKAGGEDELAFPVAGHPEDLVIQISCLLYDLSTTALEHVLLFSLGSCDLP
ESHLNELAARGLPTPVVLEFDSEFEMLLAFMTLVKQYGPEFVTGYNIINFDWPFLLAKLT
DIYKVPLDGYGRMNGRGVFRVWDIGQSHFQKRSKIKVNGMVNIDMYGIITDKIKLSSYKL
NAVAEAVLKDKKKDLSYRDIPAYYAAGPAQRGVIGEYCIQDSLLVGQLFFKFLPHLELSA
VARLAGINITRTIYDGQQIRVFTCLLRLADQKGFILPDTQGRFRGAGGEAPKRPAAARED
EERPEEEGEDEDEREEGGGEREPEGARETAGRHVGYQGARVLDPTSGFHVNPVVVFDFAS
LYPSIIQAHNLCFSTLSLRADAVAHLEAGKDYLEIEVGGRRLFFVKAHVRESLLSILLRD
WLAMRKQIRSRIPQSSPEEAVLLDKQQAAIKVVCNSVYGFTGVQHGLLPCLHVAATVTTI
GREMLLATREYVHARWAAFEQLLADFPEAADMRAPGPYSMRIIYGDTDSIFVLCRGLTAA
GLTAVGDKMASHISRALFLPPIKLECEKTFTKLLLIAKKKYIGVIYGGKMLIKGVDLVRK
NNCAFINRTSRALVDLLFYDDTVSGAAAALAERPAEEWLARPLPEGLQAFGAVLVDAHRR
ITDPERDIQDFVLTAELSRHPRAYTNKRLAHLTVYYKLMARRAQVPSIKDRIPYVIVAQT
REVEETVARLAALRELDAAAPGDEPAPPAALPSPAKRPRETPSPADPPGGASKPRKLLVS
ELAEDPAYAIAHGVALNTDYYFSHLLGAACVTFKALFGNNAKITESLLKRFIPEVWHPPD
DVAARLRTAGFGAVGAGATAEETRRMLHRAFDTLA
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Function
Replicates viral genomic DNA. The replication complex is composed of six viral proteins: the DNA polymerase, processivity factor, primase, primase-associated factor, helicase, and ssDNA-binding protein. Additionally, the polymerase contains an intrinsic ribonuclease H (RNase H) activity that specifically degrades RNA/DNA heteroduplexes or duplex DNA substrates in the 5' to 3' direction. Therefore, it can catalyze the excision of the RNA primers that initiate the synthesis of Okazaki fragments at a replication fork during viral DNA replication.
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Uniprot ID
DPOL_HHV11
EC Number
EC: 2.7.7.7 ; EC: 3.1.26.4
TC Number
TC: 2.7.7.7; TC: 3.1.26.4
Pfam
PF00136 ; PF03104 ; PF11590
TTD ID
T37847
Natural Product(s) of This Target
1 Betulinic Acid  NP Info  Phase 1 Rubus alceifolius
2 Cidofovir  NP Info  Approved Homo sapiens
3 Oleanolic acid  NP Info  Investigative Olea europaea
4 Penciclovir  NP Info  Approved Homo sapiens
5 Ursolic acid  NP Info  Investigative Potentilla indica
Drug(s) of This Target
1 Acyclovir  Drug Info  Approved Virus infection
2 Cytarabine  Drug Info  Approved Mantle cell lymphoma
3 Ganciclovir  Drug Info  Approved Virus infection
4 Thymidine kinase/ganciclovir  Drug Info  Approved Cytomegaloviral disease
References
Reference 1 DNA polymerase beta inhibitors from Tetracera boiviniana. J Nat Prod. 1999 Dec;62(12):1660-3.
Reference 2 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
Reference 3 DNA polymerase beta inhibitors from Baeckea gunniana. J Nat Prod. 1999 Dec;62(12):1624-6.
Reference 4 Antimicrobial strategies: inhibition of viral polymerases by 3'-hydroxyl nucleosides. Drugs. 2009;69(2):151-66.
Reference 5 Chromatin-associated proteins HMGB1/2 and PDIA3 trigger cellular response to chemotherapy-induced DNA damage. Mol Cancer Ther. 2009 Apr;8(4):864-72.
Reference 6 Application of real time polymerase chain reaction to the diagnosis and treatment of cytomegalovirus infection after allogeneic hematopoietic stem cell transplantation. Zhonghua Xue Ye Xue Za Zhi. 2009 Feb;30(2):77-81.
Reference 7 Ganciclovir. Profiles Drug Subst Excip Relat Methodol. 2018;43:1-208.
Cite NPCDR
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Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China