DNA primase large subunit
Also known as: PRIM2, PRIM2A
Function
Regulatory subunit of the DNA primase complex and component of the DNA polymerase alpha complex (also known as the alpha DNA polymerase-primase complex) which play 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, an accessory subunit POLA2 and two primase subunits, the catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1 (By similarity). 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 (By similarity). In the primase complex, both subunits are necessary for the initial di-nucleotide formation, but the extension of the primer depends only on the catalytic subunit. Binds RNA:DNA duplex and coordinates the catalytic activities of PRIM1 and POLA2 during primase-to-polymerase switch.
Classification
- Family (Pfam)
- PF04104 DNA_primase_lrg, PF26466 DNA_primase_lrg_N
- InterPro
- DNA_primase_C, DNA_primase_lsu_euk, DNA_primase_lsu_euk/arc
- Functional cluster
- Aminoacyl-tRNA Synthetases
Experimental structures · PDB · 22
- 3L9Q X-ray 1.70A
- 3Q36 X-ray 2.50A
- 4BPU X-ray 2.70A
- 4BPW X-ray 3.00A
- 4BPX X-ray 3.40A
- 4RR2 X-ray 2.65A
- 5DQO X-ray 2.30A
- 5EXR X-ray 3.60A
- 5F0Q X-ray 2.21A
- 5F0S X-ray 3.00A
- 5I7M X-ray 1.93A
- 6DHW X-ray 2.01A
- … and 10 more
A predicted model is available from AlphaFold.
Gene Ontology · 8
Drugs targeting this protein · 6
- FLUDARABINE PHOSPHATE inhibitor
- GEMCITABINE HYDROCHLORIDE inhibitor
- CLOFARABINE inhibitor
- TROXACITABINE inhibitor
- ASPACYTARABINE inhibitor
- CYTARABINE inhibitor
Related proteins · sequence + function similarity
- DNA primase large subunit 0.98
- DNA primase large subunit 0.97
- DNA primase large subunit 0.84
- Probable DNA primase large subunit 0.81
- DNA primase large subunit 0.80
- DNA primase large subunit 0.78
- DNA primase large subunit 0.73
- DNA primase large subunit 0.73
- Probable DNA primase large subunit 0.71
- Cryptochrome DASH 0.51
- Cryptochrome DASH 0.49
- DNA primase large subunit PriL 0.46
Co-cited proteins · studied together in the literature
- DNA primase small subunit 6 shared papers
- DNA polymerase alpha subunit B 2 shared papers
- DNA polymerase alpha catalytic subunit 2 shared papers
- DNA primase large subunit 1 shared papers
- DNA primase small subunit 1 shared papers
- DNA polymerase alpha catalytic subunit 1 shared papers
Literature · 14 cited papers
- Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome. J. Biol. Chem. · 2016
- Crystal structure of the human primase. J. Biol. Chem. · 2015
- Structures of human primase reveal design of nucleotide elongation site and mode of Pol alpha tethering. Proc. Natl. Acad. Sci. U.S.A. · 2013
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal. Chem. · 2009
- Large-scale proteomics analysis of the human kinome. Mol. Cell. Proteomics · 2009
- An iron-sulfur cluster in the C-terminal domain of the p58 subunit of human DNA primase. J. Biol. Chem. · 2007
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
- The DNA sequence and analysis of human chromosome 6. Nature · 2003
- … and 2 more in the literature graph