UniProt:P09884 POLA1

chain
  • chain:1-1462
checksum DC40C3EDD6F4B495
comment
  • 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).CATALYTIC ACTIVITY DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphateACTIVITY REGULATION Autoinhibited in apo-primosome, where the zinc motif of POLA1 and oligonucleotide/olicosaccharide-binding domain of POLA2 are placed into the active site blocking RNA:DNA duplex entry.SUBUNIT Component of the alpha DNA polymerase complex (also known as the alpha DNA polymerase-primase complex) consisting of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the primase complex subunits PRIM1 and PRIM2 respectively (PubMed:26975377, PubMed:9705292). Interacts with PARP1; this interaction functions as part of the control of replication fork progression (PubMed:9518481). Interacts with MCM10 and WDHD1; these interactions recruit the polymerase alpha complex to the pre-replicative complex bound to DNA (PubMed:19608746). Interacts with RPA1; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp (PubMed:9214288).SUBUNIT (Microbial infection) Interacts with SV40 Large T antigen; this interaction allows viral DNA replication.SUBUNIT (Microbial infection) Interacts with herpes simplex virus 1/HHV-1 replication origin-binding protein UL9.INTERACTION In the cytosol, colocalizes with RNA:DNA hybrids with a speckled pattern.DOMAIN The CysA-type zinc finger is required for PCNA-binding.PTM A 165 kDa form is probably produced by proteolytic cleavage at Lys-124.DISEASE The disease is caused by variants affecting the gene represented in this entry. XLPDR is caused by a recurrent intronic mutation that results in missplicing and reduced POLA1 expression. This leads to a decrease in cytosolic RNA:DNA hybrids and constitutive activation of type I interferon responses, but has no effect on cell replication.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.SIMILARITY Belongs to the DNA polymerase type-B family.
crossReference
databaseName UniProt
dbId 89346
description
  • recommendedName: DNA polymerase alpha catalytic subunit ecNumber evidence="12 14"2.7.7.7 alternativeName: DNA polymerase alpha catalytic subunit p180
displayName UniProt:P09884 POLA1
geneName
  • POLA1
  • POLA
identifier P09884
isSequenceChanged false
keyword
  • 3D-structure
  • Acetylation
  • Cytoplasm
  • Direct protein sequencing
  • Disease variant
  • DNA replication
  • DNA-binding
  • DNA-directed DNA polymerase
  • Dwarfism
  • Host-virus interaction
  • Intellectual disability
  • Metal-binding
  • Nucleotidyltransferase
  • Nucleus
  • Phosphoprotein
  • Proteomics identification
  • Reference proteome
  • Transferase
  • Zinc
  • Zinc-finger
modified [InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType Protein
name
  • POLA1
otherIdentifier
  • 11726156_at
  • 17102230
  • 17102272
  • 204835_PM_at
  • 204835_at
  • 3745479
  • 3972092
  • 3972094
  • 3972095
  • 3972098
  • 3972099
  • 3972101
  • 3972102
  • 3972103
  • 3972104
  • 3972105
  • 3972106
  • 3972107
  • 3972108
  • 3972110
  • 3972111
  • 3972112
  • 3972113
  • 3972114
  • 3972115
  • 3972116
  • 3972117
  • 3972118
  • 3972119
  • 3972120
  • 3972121
  • 3972122
  • 3972123
  • 3972124
  • 3972126
  • 3972127
  • 3972128
  • 3972129
  • 3972130
  • 3972131
  • 3972138
  • 3972147
  • 3972149
  • 3972150
  • 3972152
  • 3972153
  • 3972155
  • 3972156
  • 3972158
  • 3972159
  • 3972160
  • 3972166
  • 3972174
  • 3972189
  • 3972190
  • 3972205
  • 3972207
  • 3972209
  • 5422
  • 786_at
  • 8166525
  • 8166563
  • A_14_P116005
  • A_21_P0000353
  • A_32_P1701
  • A_33_P3737979
  • GE62468
  • GO:0000166
  • GO:0000731
  • GO:0000785
  • GO:0003676
  • GO:0003677
  • GO:0003682
  • GO:0003688
  • GO:0003697
  • GO:0003824
  • GO:0003887
  • GO:0005515
  • GO:0005634
  • GO:0005635
  • GO:0005654
  • GO:0005658
  • GO:0005730
  • GO:0005737
  • GO:0005829
  • GO:0006260
  • GO:0006261
  • GO:0006269
  • GO:0006270
  • GO:0006271
  • GO:0006272
  • GO:0006273
  • GO:0006281
  • GO:0006303
  • GO:0008270
  • GO:0016363
  • GO:0016740
  • GO:0016779
  • GO:0019901
  • GO:0032479
  • GO:0034061
  • GO:0046872
  • GO:0140097
  • GO:1902975
  • HMNXSV003009756
  • HMNXSV003018604
  • HMNXSV003019039
  • ILMN_2191436
  • PH_hs_0013709
  • RNA33523|snoRNA_scaRNA_119_130
  • TC0X000120.hg
  • TC0X000121.hg
  • X06745_at
  • g8393994_3p_at
  • p25626
  • p27852
  • p27853
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • DPOLA_HUMAN
  • Q86UQ7
sequenceLength 1462
species [Species:48887] Homo sapiens
stId uniprot:P09884
url http://purl.uniprot.org/uniprot/P09884
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