Protein: DNA polymerase alpha catalytic subunit (EC 2.7.7.7) (DNA polymerase alpha catalytic subunit p180) (O89042)
Organism: Rattus norvegicus (Rat)
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 (By similarity).
Subcellular location: Nucleus {ECO:0000250|UniProtKB:P09884}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:P09884}. Note=In the cytosol, colocalizes with RNA:DNA hybrids with a speckled pattern. {ECO:0000250|UniProtKB:P09884}.
Sequence: MAPVHGDDCKLETSAVSDSGSFVASRARREKKSKKGRQEALERLKKAKAGEKYKYEVEDLTSVYEEVDEEQYSKLVQARQDDDWIVDDDGIGYVEDGREIFDDDLEDDALDTCGEGSDGKAHRKDRKDVKKPSVTKPNNIKAMFIASAGKKTTDKTVDLSKDDLLGDILQDLNTETPQIAPPPVLIPKKKRSTGASPNPFSVHTATAVPSGKIASPVSRKEPPLTPVPLKRAEFAGDLAQPECPEDEQESGVIEFEDGDFDEPMDTEEVDEEEPVTAKIWDQESEPVEGVKHEADPETGTTSFLDSFLPDVSCWDIDQKDENSFLLQEVQVDSNHLPLVKGADDEQVFQFYWLDAYEDPYNQPGVVFLFGKVWVESAKTHVSCCVMVKNIERTLYFLPREMKIDLNTGKETATPITMKDVYEEFDSKISAKYKIMKFKSKIVEKNYAFEIPDVPEKSEYLEVRYSAEVPQLPQNLKGETFSHVFGTNTSSLELFLMNRKIKGPCWLEVKNPQLLNQPISWCKFEAMALKPDLVNVIKDVSPPPLVVMSFSMKTMQNVQNHQHEIIAMAALVHHNFPLDKAPPKPPFQTHFCVVSKPKDCIFPCAFKEVIKKKNMEVEVAATERTLLGFFLAKVHKLDPDILVGHNICGFELEVLLQRINECKVPFWSKIGRLRRSNMPKLGSRSGFGERNATCGRMICDVEISVKELIHCKSYHLSELVQQILKTERIVIPTENIRNMYSEPSHLLYLLEHIWKDARFILQIMCELNVLPLALQITNIAGNIMSRTLMGGRSERNEFLLLHAFYENNYIVPDKQIFRKPQQKPGDEDEEIDGDTNKYKKGRKKAAYAGGLVLDPKVGFYDKFILLLDFNSLYPSIIQEFNICFTTVQRVASETLKATEDEEQEQIPELPDPNLDMGILPREIRKLVERRKQVKQLMKQQDLNPDLVLQYDIRQKALKLTANSMYGCLGFSYSRFYAKPLAALVTYKGREILMHTKEMVQKMNLEVIYGDTDSIMINTNSTNLEEVFKLGNKVKNEVNKLYKLLEIDIDGVFKSLLLLKKKKYAALVVEPTSDGNYITKQELKGLDIVRRDWCDLAKDTGNFVIGQILSDQSRDTIVENIQKRLIEIGENVLNGSVPVSQFEINKALTKDPQDYPDKKSLPHVHVALWINSQGGRKVKAGDTVSYVICQDGSNLPATQRAYAPEQLQKQDNLAIDTQYYLAQQIHPVVARICEPIDGIDAVLIALWLGLDSTQFRVHQYHKDEENDALLGGPAQLTDEEKYKDCEKFKCLCPSCGTENIYDNVFEGSGMDMEPSLNRCSNIDCKASPATFMVQLSNKLIMDIRRCIKKYYDGWLICEEPTCRNRIRRLPLHFSRNGPLCPACMKAVLRPEYSDKSLYTQLCFYRYIFDADCALEKLPEHEKDKLKKQFFTPRVLQDYRKVKNIAEHFLSWSG
InterPro domains: - IPR042087: DNA polymerase family B, thumb domain (homologous_superfamily) [1084-1264]
- IPR043502: DNA/RNA polymerase superfamily (homologous_superfamily) [806-1246]
- IPR023211: DNA polymerase, palm domain superfamily (homologous_superfamily) [838-1069]
- IPR017964: DNA-directed DNA polymerase, family B, conserved site (conserved_site) [1007-1015]
- IPR006133: DNA-directed DNA polymerase, family B, exonuclease domain (domain) [482-717]
- IPR015088: Zinc finger, DNA-directed DNA polymerase, family B, alpha (domain) [1273-1451]
- IPR012337: Ribonuclease H-like superfamily (homologous_superfamily) [432-805]
- IPR036397: Ribonuclease H superfamily (homologous_superfamily) [542-837]
- IPR024647: DNA polymerase alpha catalytic subunit, N-terminal domain (domain) [41-102]
- IPR006172: DNA-directed DNA polymerase, family B (family) [542-1019]
- IPR006134: DNA-directed DNA polymerase, family B, multifunctional domain (domain) [782-1234]
- IPR045846: DNA polymerase alpha catalytic subunit, catalytic domain (domain) [839-1249]
- IPR038256: DNA polymerase alpha, zinc finger domain superfamily (homologous_superfamily) [1272-1449]
Interaction partners: - DNA primase large subunit
- DNA primase
- DNA polymerase alpha subunit B
- WD repeat and HMG-box DNA-binding protein 1
- DNA polymerase delta subunit 2
- DNA polymerase epsilon subunit
- DNA polymerase epsilon catalytic subunit
- DNA polymerase delta catalytic subunit
- DNA replication licensing factor MCM4
- DNA replication licensing factor MCM2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0003824 (catalytic activity), GO:0044877 (protein-containing complex binding), GO:0016740 (transferase activity), GO:0005515 (protein binding), GO:0019899 (enzyme binding), GO:0016772 (transferase activity, transferring phosphorus-containing groups), GO:0097747 (RNA polymerase activity), GO:0016779 (nucleotidyltransferase activity), GO:0003887 (DNA-directed DNA polymerase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009059 (macromolecule biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0090304 (nucleic acid metabolic process), GO:0019438 (aromatic compound biosynthetic process), GO:0018130 (heterocycle biosynthetic process), GO:0006259 (DNA metabolic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0006260 (DNA replication), GO:0016070 (RNA metabolic process), GO:0006270 (DNA replication initiation), GO:0032774 (RNA biosynthetic process), GO:0006269 (DNA replication, synthesis of RNA primer), GO:0006261 (DNA-templated DNA replication)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0032993 (protein-DNA complex), GO:0000785 (chromatin), GO:0031974 (membrane-enclosed lumen), GO:0005657 (replication fork), GO:0140535 (intracellular protein-containing complex), GO:0031975 (envelope), GO:1902494 (catalytic complex), GO:0140513 (nuclear protein-containing complex), GO:0012505 (endomembrane system), GO:0005654 (nucleoplasm), GO:0030880 (RNA polymerase complex), GO:0031967 (organelle envelope), GO:1990234 (transferase complex), GO:0030894 (replisome), GO:0043229 (intracellular organelle), GO:0042575 (DNA polymerase complex), GO:0043596 (nuclear replication fork), GO:0043228 (non-membrane-bounded organelle), GO:0043233 (organelle lumen), GO:0055029 (nuclear DNA-directed RNA polymerase complex), GO:0005635 (nuclear envelope), GO:0043601 (nuclear replisome), GO:0043227 (membrane-bounded organelle), GO:0000428 (DNA-directed RNA polymerase complex), GO:0005658 (alpha DNA polymerase:primase complex), GO:0043231 (intracellular membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0061695 (transferase complex, transferring phosphorus-containing groups), GO:0070013 (intracellular organelle lumen), GO:0005634 (nucleus), GO:0031981 (nuclear lumen), GO:0005694 (chromosome), GO:0000228 (nuclear chromosome)