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Identification
HMDB Protein ID HMDBP00951
Secondary Accession Numbers
  • 6239
Name DNA polymerase alpha catalytic subunit
Synonyms
  1. DNA polymerase alpha catalytic subunit p180
Gene Name POLA1
Protein Type Enzyme
Biological Properties
General Function Involved in nucleotide 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.
Pathways
  • DNA replication
  • Purine metabolism
  • Pyrimidine metabolism
Reactions
Deoxynucleoside triphosphate + DNA(n) → Pyrophosphate + DNA(n+1) details
Deoxyadenosine triphosphate + DNA → Pyrophosphate + DNA details
dGTP + DNA → Pyrophosphate + DNA details
dCTP + DNA → Pyrophosphate + DNA details
Thymidine 5'-triphosphate + DNA → Pyrophosphate + DNA details
GO Classification
Biological Process
telomere maintenance via recombination
telomere maintenance via semi-conservative replication
lagging strand elongation
double-strand break repair via nonhomologous end joining
cell proliferation
S phase of mitotic cell cycle
DNA replication initiation
M/G1 transition of mitotic cell cycle
virus-host interaction
DNA replication, synthesis of RNA primer
leading strand elongation
regulation of transcription involved in G1/S phase of mitotic cell cycle
translesion synthesis
Cellular Component
cytoplasm
nucleolus
nucleoplasm
nuclear matrix
alpha DNA polymerase:primase complex
nuclear envelope
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
binding
nucleotide binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
nucleoside binding
nucleotidyltransferase activity
dna polymerase activity
dna-directed dna polymerase activity
nucleic acid binding
dna binding
Molecular Function
nucleoside binding
metal ion binding
4 iron, 4 sulfur cluster binding
3'-5' exonuclease activity
DNA-directed DNA polymerase activity
double-stranded DNA binding
chromatin binding
purine nucleotide binding
pyrimidine nucleotide binding
DNA binding
nucleotide binding
Process
metabolic process
nitrogen compound metabolic process
cellular nitrogen compound metabolic process
nucleobase, nucleoside, nucleotide and nucleic acid metabolic process
macromolecule metabolic process
cellular macromolecule metabolic process
dna metabolic process
dna replication
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location X
Locus Xp22.1-p21.3
SNPs POLA1
Gene Sequence
>4389 bp
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
GTAAAAAAGTCCACAGCTCTTAATCAGCCAGTCAGTTGGTGTAAAGTTGAGGCAATGGCT
TTGAAACCAGACCTGGTGAATGTAATTAAGGATGTCAGTCCACCACCGCTTGTCGTGATG
GCTTTCAGCATGAAGACAATGCAGAATGCAAAGAACCATCAAAATGAGATTATTGCTATG
GCAGCTTTGGTCCATCACAGTTTTGCATTGGATAAAGCAGCCCCAAAGCCTCCCTTTCAG
TCACACTTCTGTGTTGTGTCTAAACCAAAGGACTGTATTTTTCCATATGCTTTCAAAGAA
GTCATTGAGAAAAAGAATGTGAAGGTTGAGGTTGCTGCAACAGAAAGAACACTGCTAGGT
TTTTTCCTTGCAAAAGTTCACAAAATTGATCCTGATATCATTGTGGGTCATAATATTTAT
GGGTTTGAACTGGAAGTACTACTGCAGAGAATTAATGTGTGCAAAGCTCCTCACTGGTCC
AAGATAGGTCGACTGAAGCGATCCAACATGCCAAAGCTTGGGGGCCGGAGTGGATTTGGT
GAAAGAAATGCTACCTGTGGTCGAATGATCTGTGATGTGGAAATTTCAGCAAAGGAATTG
ATTCGTTGTAAAAGCTACCATCTGTCTGAACTTGTTCAGCAGATTCTAAAAACTGAAAGG
GTTGTAATCCCAATGGAAAATATACAAAATATGTACAGTGAATCTTCTCAACTGTTATAC
CTGTTGGAACACACCTGGAAAGATGCCAAGTTCATTTTGCAGATCATGTGTGAGCTAAAT
GTTCTTCCATTAGCATTGCAGATCACTAACATCGCTGGGAACATTATGTCCAGGACGCTG
ATGGGTGGACGATCCGAGCGTAACGAGTTCTTGTTGCTTCATGCATTTTACGAAAACAAC
TATATTGTGCCTGACAAGCAGATTTTCAGAAAGCCTCAGCAAAAACTGGGAGATGAAGAT
GAAGAAATTGATGGAGATACCAATAAATACAAGAAAGGACGTAAGAAAGGAGCTTATGCT
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
Protein Properties
Number of Residues 1462
Molecular Weight 165911.405
Theoretical pI 5.848
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>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
GenBank ID Protein 35568
UniProtKB/Swiss-Prot ID P09884
UniProtKB/Swiss-Prot Entry Name DPOLA_HUMAN
PDB IDs
GenBank Gene ID X06745
GeneCard ID POLA1
GenAtlas ID POLA1
HGNC ID HGNC:9173
References
General References
  1. 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. [PubMed:18669648 ]
  2. 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. [PubMed:19690332 ]
  3. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  4. Wang B, Malik R, Nigg EA, Korner R: Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis. Anal Chem. 2008 Dec 15;80(24):9526-33. doi: 10.1021/ac801708p. [PubMed:19007248 ]
  5. 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. [PubMed:9518481 ]
  6. 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. [PubMed:3359994 ]
  7. 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. [PubMed:2005899 ]
  8. 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. [PubMed:2243771 ]
  9. 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. [PubMed:3025630 ]
  10. 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. [PubMed:7644508 ]
  11. 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. [PubMed:9214288 ]
  12. 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. [PubMed:19608746 ]
  13. 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. [PubMed:14499601 ]