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
- UniProtKB Entry
- P09884Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- 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
- FunctionsDNA replication origin binding / single-stranded DNA binding / zinc ion bindingProcessesDNA repair / DNA replication, synthesis of primer / DNA synthesis involved in DNA repair / mitotic DNA replication initiation / regulation of type I interferon productionComponentschromatin / cytosol
- General Function
- Catalytic subunit of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which plays an essential role in the initiation of DNA synthesis. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1, a regulatory subunit POLA2 and two primase subunits PRIM1 and PRIM2) 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. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses (PubMed:27019227)
- Specific Function
- chromatin binding
- Pfam Domain Function
- Signal Regions
- Not Available
- 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
- Xp22.11-p21.3
- External Identifiers
Resource Link UniProtKB ID P09884 UniProtKB Entry Name DPOLA_HUMAN GenBank Protein ID 35568 GenBank Gene ID X06745 GeneCard ID POLA1 GenAtlas ID POLA1 HGNC ID HGNC:9173 PDB ID(s) 1K0P, 1K18, 1N5G, 4Q5V, 4QCL, 4Y97, 5EXR, 5IUD, 6AS7, 7N2M, 7OPL, 7U5C, 8B9D, 8D0B, 8D0K, 8D96, 8D9D, 8QJ7 KEGG ID hsa:5422 NCBI Gene ID 5422 - General References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
Associated Data
- Bio-Entities
Bio-Entity Type DNA polymerase alpha catalytic subunit (Humans) protein primary- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Clofarabine approved, investigational yes target inhibitor Details Fludarabine approved yes target inhibitor Details Cladribine approved, investigational yes target inhibitor Details Nelarabine approved, investigational yes target inhibitor Details