| Identification |
|---|
| HMDB Protein ID
| HMDBP00951 |
| Secondary Accession Numbers
| |
| Name
| DNA polymerase alpha catalytic subunit |
| Synonyms
|
- 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
|
- 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
|
| External Links |
|---|
| 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
| - 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
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