DNA polymerase alpha catalytic subunit

Details

Name
DNA polymerase alpha catalytic subunit
Synonyms
  • 2.7.7.7
  • DNA polymerase alpha catalytic subunit p180
  • POLA
Gene Name
POLA1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0016127|DNA polymerase alpha catalytic subunit
MAPVHGDDSLSDSGSFVSSRARREKKSKKGRQEALERLKKAKAGEKYKYEVEDFTGVYEE
VDEEQYSKLVQARQDDDWIVDDDGIGYVEDGREIFDDDLEDDALDADEKGKDGKARNKDK
RNVKKLAVTKPNNIKSMFIACAGKKTADKAVDLSKDGLLGDILQDLNTETPQITPPPVMI
LKKKRSIGASPNPFSVHTATAVPSGKIASPVSRKEPPLTPVPLKRAEFAGDDVQVESTEE
EQESGAMEFEDGDFDEPMEVEEVDLEPMAAKAWDKESEPAEEVKQEADSGKGTVSYLGSF
LPDVSCWDIDQEGDSSFSVQEVQVDSSHLPLVKGADEEQVFHFYWLDAYEDQYNQPGVVF
LFGKVWIESAETHVSCCVMVKNIERTLYFLPREMKIDLNTGKETGTPISMKDVYEEFDEK
IATKYKIMKFKSKPVEKNYAFEIPDVPEKSEYLEVKYSAEMPQLPQDLKGETFSHVFGTN
TSSLELFLMNRKIKGPCWLEVKSPQLLNQPVSWCKVEAMALKPDLVNVIKDVSPPPLVVM
AFSMKTMQNAKNHQNEIIAMAALVHHSFALDKAAPKPPFQSHFCVVSKPKDCIFPYAFKE
VIEKKNVKVEVAATERTLLGFFLAKVHKIDPDIIVGHNIYGFELEVLLQRINVCKAPHWS
KIGRLKRSNMPKLGGRSGFGERNATCGRMICDVEISAKELIRCKSYHLSELVQQILKTER
VVIPMENIQNMYSESSQLLYLLEHTWKDAKFILQIMCELNVLPLALQITNIAGNIMSRTL
MGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKLGDEDEEIDGDTNKYKKGRKKAAYA
GGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVASEAQKVTEDGEQEQIPE
LPDPSLEMGILPREIRKLVERRKQVKQLMKQQDLNPDLILQYDIRQKALKLTANSMYGCL
GFSYSRFYAKPLAALVTYKGREILMHTKEMVQKMNLEVIYGDTDSIMINTNSTNLEEVFK
LGNKVKSEVNKLYKLLEIDIDGVFKSLLLLKKKKYAALVVEPTSDGNYVTKQELKGLDIV
RRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQFEINKALT
KDPQDYPDKKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLTASQRAYAPEQLQK
QDNLTIDTQYYLAQQIHPVVARICEPIDGIDAVLIATWLGLDPTQFRVHHYHKDEENDAL
LGGPAQLTDEEKYRDCERFKCPCPTCGTENIYDNVFDGSGTDMEPSLYRCSNIDCKASPL
TFTVQLSNKLIMDIRRFIKKYYDGWLICEEPTCRNRTRHLPLQFSRTGPLCPACMKATLQ
PEYSDKSLYTQLCFYRYIFDAECALEKLTTDHEKDKLKKQFFTPKVLQDYRKLKNTAEQF
LSRSGYSEVNLSKLFAGCAVKS
Number of residues
1462
Molecular Weight
165911.405
Theoretical pI
5.59
GO Classification
Functions
3'-5' exonuclease activity / 4 iron, 4 sulfur cluster binding / chromatin binding / DNA binding / DNA-directed DNA polymerase activity / metal ion binding / nucleoside binding / nucleotide binding / protein kinase binding
Processes
cell proliferation / DNA biosynthetic process / DNA replication / DNA replication initiation / DNA replication, synthesis of RNA primer / DNA strand elongation involved in DNA replication / double-strand break repair via nonhomologous end joining / G1/S transition of mitotic cell cycle / lagging strand elongation / leading strand elongation / mitotic cell cycle / regulation of transcription involved in G1/S transition of mitotic cell cycle / telomere maintenance / telomere maintenance via recombination / telomere maintenance via semi-conservative replication / viral process
Components
alpha DNA polymerase / cytoplasm / nuclear envelope / nuclear matrix / nucleolus / nucleoplasm / nucleus
General Function
Protein kinase binding
Specific Function
Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0016128|DNA polymerase alpha catalytic subunit (POLA1)
ATGGCACCTGTGCACGGCGACGACTCTCTGTCAGATTCAGGGAGTTTTGTATCTTCTCGA
GCCCGGCGAGAAAAAAAATCAAAGAAGGGGCGCCAAGAAGCCCTAGAAAGACTGAAAAAG
GCTAAAGCTGGTGAGAAGTATAAATATGAAGTCGAGGACTTCACAGGTGTTTATGAAGAA
GTTGATGAAGAACAGTATTCGAAGCTGGTTCAGGCACGCCAGGATGATGACTGGATTGTG
GATGATGATGGTATTGGCTATGTGGAAGATGGCCGAGAGATTTTTGATGATGACCTTGAA
GATGATGCCCTTGATGCTGATGAGAAAGGAAAAGATGGTAAAGCACGCAATAAAGACAAG
AGGAATGTAAAGAAGCTCGCAGTGACAAAACCGAACAACATTAAGTCAATGTTCATTGCT
TGTGCTGGAAAGAAAACTGCAGATAAAGCTGTAGACTTGTCCAAGGATGGTCTGCTAGGT
GACATTCTACAGGATCTTAACACTGAGACACCTCAAATAACTCCACCACCTGTAATGATA
CTGAAGAAGAAAAGATCCATTGGAGCTTCACCGAATCCTTTCTCTGTGCACACCGCCACG
GCAGTTCCTTCAGGAAAAATTGCTTCCCCTGTCTCCAGAAAGGAGCCTCCATTAACTCCT
GTTCCTCTTAAACGTGCTGAATTTGCTGGCGATGATGTACAGGTCGAGAGTACAGAAGAA
GAGCAGGAGTCAGGGGCAATGGAGTTTGAAGATGGTGACTTTGATGAGCCCATGGAAGTT
GAAGAGGTGGACCTGGAGCCTATGGCTGCCAAGGCTTGGGACAAAGAGAGTGAGCCAGCA
GAGGAAGTGAAACAAGAGGCGGATTCTGGGAAAGGGACCGTGTCCTACTTAGGAAGTTTT
CTCCCGGATGTCTCTTGTTGGGACATTGATCAAGAAGGTGATAGCAGTTTCTCAGTGCAA
GAAGTTCAAGTGGATTCCAGTCACCTCCCATTGGTAAAAGGGGCAGATGAGGAACAAGTA
TTCCACTTTTATTGGTTGGATGCTTATGAGGATCAGTACAACCAACCAGGTGTGGTATTT
CTGTTTGGGAAAGTTTGGATTGAATCAGCCGAGACCCATGTGAGCTGTTGTGTCATGGTG
AAAAATATCGAGCGAACGCTTTACTTCCTTCCCCGTGAAATGAAAATTGATCTAAATACG
GGGAAAGAAACAGGAACTCCAATTTCAATGAAGGATGTTTATGAGGAATTTGATGAGAAA
ATAGCAACAAAATATAAAATTATGAAGTTCAAGTCTAAGCCAGTGGAAAAGAACTATGCT
TTTGAGATACCTGATGTTCCAGAAAAATCTGAGTACTTGGAAGTTAAATACTCGGCTGAA
ATGCCACAGCTTCCTCAAGATTTGAAAGGAGAAACTTTTTCTCATGTATTTGGGACCAAC
ACATCTAGCCTGGAACTGTTCTTGATGAACAGAAAGATCAAAGGACCTTGTTGGCTTGAA
GTAAAAAGTCCACAGCTCTTGAATCAGCCAGTCAGTTGGTGTAAAGTTGAGGCAATGGCT
TTGAAACCAGACCTGGTGAATGTAATTAAGGATGTCAGTCCACCACCGCTTGTCGTGATG
GCTTTCAGCATGAAGACAATGCAGAATGCAAAGAACCATCAAAATGAGATTATTGCTATG
GCAGCTTTGGTCCATCACAGTTTTGCATTGGATAAAGCAGCCCCAAAGCCTCCCTTTCAG
TCACACTTCTGTGTTGTGTCTAAACCAAAGGACTGTATTTTTCCATATGCTTTCAAAGAA
GTCATTGAGAAAAAGAATGTGAAGGTTGAGGTTGCTGCAACAGAAAGAACACTGCTAGGT
TTTTTCCTTGCAAAAGTTCACAAAATTGATCCTGATATCATTGTGGGTCATAATATTTAT
GGGTTTGAACTGGAAGTACTACTGCAGAGAATTAATGTGTGCAAAGCTCCTCACTGGTCC
AAGATAGGTCGACTGAAGCGATCCAACATGCCAAAGCTTGGGGGCCGGAGTGGATTTGGT
GAAAGAAATGCTACCTGTGGTCGAATGATCTGTGATGTGGAAATTTCAGCAAAGGAATTG
ATTCGTTGTAAAAGCTACCATCTGTCTGAACTTGTTCAGCAGATTCTAAAAACTGAAAGG
GTTGTAATCCCAATGGAAAATATACAAAATATGTACAGTGAATCTTCTCAACTGTTATAC
CTGTTGGAACACACCTGGAAAGATGCCAAGTTCATTTTGCAGATCATGTGTGAGCTAAAT
GTTCTTCCATTAGCATTGCAGATCACTAACATCGCTGGGAACATTATGTCCAGGACGCTG
ATGGGTGGACGATCCGAGCGTAACGAGTTCTTGTTGCTTCATGCATTTTACGAAAACAAC
TATATTGTGCCTGACAAGCAGATTTTCAGAAAGCCTCAGCAAAAACTGGGAGATGAAGAT
GAAGAAATTGATGGAGATACCAATAAATACAAGAAAGGACGTAAGAAAGCAGCTTATGCT
GGAGGCTTGGTTTTGGACCCCAAAGTTGGTTTTTATGATAAGTTCATTTTGCTTCTGGAC
TTCAACAGTCTATATCCTTCCATCATTCAGGAATTTAACATTTGTTTTACAACAGTACAA
AGAGTTGCTTCAGAGGCACAGAAAGTTACAGAGGATGGAGAACAAGAACAGATCCCTGAG
TTGCCAGATCCAAGCTTAGAAATGGGCATTTTGCCCAGAGAGATCCGGAAACTGGTAGAA
CGGAGAAAACAAGTCAAACAGCTAATGAAACAGCAAGACTTAAATCCAGACCTTATTCTT
CAGTATGACATTCGACAGAAGGCTTTGAAGCTCACAGCGAACAGTATGTATGGTTGCCTG
GGATTTTCCTATAGCAGATTTTACGCCAAACCACTGGCTGCCTTGGTGACATACAAAGGA
AGGGAGATTTTGATGCATACGAAAGAGATGGTACAAAAGATGAATCTTGAAGTTATTTAT
GGAGATACAGATTCAATTATGATAAACACCAATAGCACCAATCTGGAAGAAGTATTTAAG
TTGGGAAACAAGGTAAAAAGTGAAGTGAATAAGTTGTACAAACTGCTTGAAATAGACATT
GATGGGGTTTTCAAGTCTCTGCTACTGCTGAAAAAAAAGAAGTACGCTGCTCTGGTTGTT
GAGCCAACGTCGGATGGGAATTATGTCACCAAACAGGAGCTCAAAGGATTAGATATAGTT
AGAAGAGATTGGTGTGATCTTGCTAAAGACACTGGAAACTTTGTGATTGGCCAGATTCTT
TCTGATCAAAGCCGGGACACTATAGTGGAAAACATTCAGAAGAGGCTGATAGAAATTGGA
GAAAATGTGCTAAATGGCAGTGTCCCAGTGAGCCAGTTTGAAATTAACAAGGCATTGACA
AAGGATCCCCAGGATTACCCTGATAAAAAAAGCCTACCTCATGTACATGTTGCCCTCTGG
ATAAATTCTCAAGGAGGCAGAAAGGTGAAAGCTGGAGATACTGTGTCATATGTCATCTGT
CAGGATGGATCAAACCTCACTGCAAGTCAGAGGGCCTATGCGCCTGAGCAGCTGCAGAAA
CAGGATAATCTAACCATTGACACCCAGTACTACCTGGCCCAGCAGATCCACCCAGTCGTG
GCTCGGATCTGTGAACCAATAGACGGAATTGATGCTGTCCTCATTGCAACGTGGTTGGGA
CTTGACCCCACCCAATTTAGAGTTCATCATTATCATAAAGATGAAGAGAATGATGCTCTA
CTTGGTGGCCCAGCACAGCTCACTGATGAAGAGAAATACAGGGACTGTGAAAGATTCAAA
TGTCCATGCCCTACATGTGGAACTGAGAATATTTATGATAATGTCTTTGATGGTTCGGGA
ACAGATATGGAGCCCAGCTTGTATCGTTGCAGTAACATCGATTGTAAGGCTTCACCTCTG
ACCTTTACAGTACAACTGAGCAACAAATTGATCATGGACATTAGACGTTTCATTAAAAAG
TACTATGATGGCTGGTTGATATGTGAAGAGCCAACCTGTCGCAATCGAACTCGTCACCTT
CCCCTTCAATTCTCCCGAACTGGGCCTCTTTGCCCAGCCTGCATGAAAGCTACACTTCAA
CCAGAGTATTCTGACAAGTCCCTGTACACCCAGCTGTGCTTTTACCGGTACATTTTTGAT
GCGGAGTGTGCACTGGAGAAACTTACTACCGATCATGAGAAAGATAAATTGAAGAAGCAA
TTTTTTACCCCCAAAGTTCTGCAGGACTACAGAAAACTCAAGAACACAGCAGAGCAATTC
TTGTCCCGAAGTGGCTACTCCGAAGTGAATCTGAGCAAACTCTTCGCTGGTTGTGCCGTG
AAATCCTAA
Chromosome Location
X
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP09884
UniProtKB Entry NameDPOLA_HUMAN
GenBank Protein ID35568
GenBank Gene IDX06745
GenAtlas IDPOLA1
HGNC IDHGNC:9173
General References
  1. Wong SW, Wahl AF, Yuan PM, Arai N, Pearson BE, Arai K, Korn D, Hunkapiller MW, Wang TS: Human DNA polymerase alpha gene expression is cell proliferation dependent and its primary structure is similar to both prokaryotic and eukaryotic replicative DNA polymerases. EMBO J. 1988 Jan;7(1):37-47. [Article]
  2. Pearson BE, Nasheuer HP, Wang TS: Human DNA polymerase alpha gene: sequences controlling expression in cycling and serum-stimulated cells. Mol Cell Biol. 1991 Apr;11(4):2081-95. [Article]
  3. Hsi KL, Copeland WC, Wang TS: Human DNA polymerase alpha catalytic polypeptide binds ConA and RCA and contains a specific labile site in the N-terminus. Nucleic Acids Res. 1990 Nov 11;18(21):6231-7. [Article]
  4. Smale ST, Tjian R: T-antigen-DNA polymerase alpha complex implicated in simian virus 40 DNA replication. Mol Cell Biol. 1986 Nov;6(11):4077-87. [Article]
  5. Lee SS, Dong Q, Wang TS, Lehman IR: Interaction of herpes simplex virus 1 origin-binding protein with DNA polymerase alpha. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7882-6. [Article]
  6. Braun KA, Lao Y, He Z, Ingles CJ, Wold MS: Role of protein-protein interactions in the function of replication protein A (RPA): RPA modulates the activity of DNA polymerase alpha by multiple mechanisms. Biochemistry. 1997 Jul 15;36(28):8443-54. [Article]
  7. Dantzer F, Nasheuer HP, Vonesch JL, de Murcia G, Menissier-de Murcia J: Functional association of poly(ADP-ribose) polymerase with DNA polymerase alpha-primase complex: a link between DNA strand break detection and DNA replication. Nucleic Acids Res. 1998 Apr 15;26(8):1891-8. [Article]
  8. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [Article]
  9. Warren EM, Huang H, Fanning E, Chazin WJ, Eichman BF: Physical interactions between Mcm10, DNA, and DNA polymerase alpha. J Biol Chem. 2009 Sep 4;284(36):24662-72. doi: 10.1074/jbc.M109.020438. Epub 2009 Jul 16. [Article]
  10. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [Article]
  11. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [Article]
  12. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  13. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [Article]
  14. Evanics F, Maurmann L, Yang WW, Bose RN: Nuclear magnetic resonance structures of the zinc finger domain of human DNA polymerase-alpha. Biochim Biophys Acta. 2003 Sep 23;1651(1-2):163-71. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00631Clofarabineapproved, investigationalyesinhibitorDetails
DB01073FludarabineapprovedyesinhibitorDetails
DB00242Cladribineapproved, investigationalyesinhibitorDetails
DB01280Nelarabineapproved, investigationalyesinhibitorDetails