Q6P1E7 · PRIPO_MOUSE
- ProteinDNA-directed primase/polymerase protein
- GenePrimpol
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids537 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them (PubMed:26926109, PubMed:29073063).
Required to facilitate mitochondrial and nuclear replication fork progression by initiating de novo DNA synthesis using dNTPs and acting as an error-prone DNA polymerase able to bypass certain DNA lesions (By similarity).
Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (By similarity).
Provides different translesion synthesis alternatives when DNA replication is stalled: able to synthesize DNA primers downstream of lesions, such as ultraviolet (UV) lesions, R-loops and G-quadruplexes, to allow DNA replication to continue (By similarity).
Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion. Repriming avoids fork degradation while leading to accumulation of internal ssDNA gaps behind the forks (By similarity).
Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase (By similarity).
Also required for reinitiating stalled forks after UV damage during nuclear DNA replication (By similarity).
Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides (PubMed:29073063).
Prevents APOBEC family-mediated DNA mutagenesis by repriming downstream of abasic site to prohibit error-prone translesion synthesis (PubMed:26926109).
Has non-overlapping function with POLH (By similarity).
In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (By similarity).
Required to facilitate mitochondrial and nuclear replication fork progression by initiating de novo DNA synthesis using dNTPs and acting as an error-prone DNA polymerase able to bypass certain DNA lesions (By similarity).
Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (By similarity).
Provides different translesion synthesis alternatives when DNA replication is stalled: able to synthesize DNA primers downstream of lesions, such as ultraviolet (UV) lesions, R-loops and G-quadruplexes, to allow DNA replication to continue (By similarity).
Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion. Repriming avoids fork degradation while leading to accumulation of internal ssDNA gaps behind the forks (By similarity).
Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase (By similarity).
Also required for reinitiating stalled forks after UV damage during nuclear DNA replication (By similarity).
Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides (PubMed:29073063).
Prevents APOBEC family-mediated DNA mutagenesis by repriming downstream of abasic site to prohibit error-prone translesion synthesis (PubMed:26926109).
Has non-overlapping function with POLH (By similarity).
In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (By similarity).
Catalytic activity
- a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1)This reaction proceeds in the forward direction.
Cofactor
Note: Can act both with Mn2+ and Mg2+ as cofactor in vitro, but Mn2+ is the preferred cofactor in vivo. The polymerase activity incorporates correct dNTPs with much higher efficiency with Mn2+ than with Mg2+. The fidelity is slightly more accurate when Mg2+ is the cofactor compared to Mn2+. In the presence of Mn2+, a conformational transition step from non-productive to productive PRIMPOL:DNA complexes limits the enzymatic turnover, whereas in the presence of Mg2+, the chemical step becomes rate limiting.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 76 | substrate | ||||
Sequence: R | ||||||
Binding site | 114 | Mn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: D | ||||||
Binding site | 114-116 | substrate | ||||
Sequence: DLE | ||||||
Binding site | 116 | Mn2+ (UniProtKB | ChEBI); catalytic | ||||
Sequence: E | ||||||
Binding site | 165-169 | substrate | ||||
Sequence: KFSRH | ||||||
Binding site | 270-273 | substrate | ||||
Sequence: RNFR | ||||||
Binding site | 279 | substrate | ||||
Sequence: K | ||||||
Binding site | 401 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 408 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 428 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 433 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | DNA-directed RNA polymerase complex | |
Cellular Component | mitochondrial matrix | |
Cellular Component | nucleus | |
Cellular Component | replication fork | |
Molecular Function | chromatin binding | |
Molecular Function | DNA primase activity | |
Molecular Function | DNA-directed DNA polymerase activity | |
Molecular Function | manganese ion binding | |
Molecular Function | zinc ion binding | |
Biological Process | error-prone translesion synthesis | |
Biological Process | mitochondrial DNA repair | |
Biological Process | mitochondrial DNA replication | |
Biological Process | R-loop processing | |
Biological Process | replication fork processing | |
Biological Process | response to UV | |
Biological Process | translesion synthesis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDNA-directed primase/polymerase protein
- EC number
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ6P1E7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Present in the nucleus, but a larger fraction is localized inside mitochondria. Associates with nuclear chromatin during the G1 and S phases of unperturbed cell cycles. Recruited to stalled replication forks following interaction with RPA1.
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Mice are viable but show defects in mitochondrial DNA synthesis.
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 32 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000279396 | 1-537 | DNA-directed primase/polymerase protein | |||
Sequence: MLRKWEARVKQIEERASHYERKPLSSVYRPRLAKPEEPSSIWKLFHRQNQAFNFVKSCKESVHVFALECKRGNGQRIYLVTSYAQLWFYYKTRKTLLHCYEVIPENAVCKLYFDLEFNKLANPGADGKMMVALLIQHVCKALEEFYNVQCSAEDVFNLDSSTEEKFSRHLIFQLHNVAFKDNRHAGNFVRKILQPALHLIAEDDEAKVPEAVGQDASGFSVTPLKQEISEAREKVGLPKQCDPDLSFLVVKNHMGEKCLFVDLGVYTKNRNFRLYQSSKIGKCVSLEVAEDNRFIPKQSKDISEENQYFLSSLVSNVRFSDTLRVLTCHPSQTKRKRAECFNSTGTSVESIEGFQGSPYPEVDQFVLSLVNKHDIKGGIRRWNYFFPEELLVYDICKYRWCENIGRAHKSNNIMILVDLKNEVWYQKCHDPVCKAQNFKSTCSPLPTEVSLLFLLKDEDFTSGETDDTSTSLTKDSQTPPSCNLSAGGLSAAAWDDEDDALFLEATEDAEFADAADKSLGSMDDIPDELIIEALQNS |
Proteomic databases
PTM databases
Expression
Gene expression databases
Structure
Family & Domains
Features
Showing features for coiled coil, motif, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Coiled coil | 1-22 | |||||
Sequence: MLRKWEARVKQIEERASHYERK | ||||||
Motif | 401-434 | Zinc knuckle motif | ||||
Sequence: CENIGRAHKSNNIMILVDLKNEVWYQKCHDPVCK | ||||||
Region | 462-481 | Disordered | ||||
Sequence: SGETDDTSTSLTKDSQTPPS | ||||||
Region | 462-536 | Interaction with RPA1 | ||||
Sequence: SGETDDTSTSLTKDSQTPPSCNLSAGGLSAAAWDDEDDALFLEATEDAEFADAADKSLGSMDDIPDELIIEALQN | ||||||
Compositional bias | 465-481 | Polar residues | ||||
Sequence: TDDTSTSLTKDSQTPPS | ||||||
Motif | 494-507 | RPA1-binding motif 1 | ||||
Sequence: WDDEDDALFLEATE | ||||||
Motif | 524-532 | RPA1-binding motif 2 | ||||
Sequence: DIPDELIIE |
Domain
The zinc knuckle motif binds zinc and is required for the DNA primase activity. It facilitates the binding and selection of the 5'-nucleotide of the newly synthesized primer and the recognition of preferred initiation sites.
The RPA1-binding motifs (RBM) mediate interaction with RPA1 and are essential for recruitment to chromatin. The interaction is primarily mediated by RPA1-binding motif 1, which binds to the basic cleft of RPA1, with motif 2 plays a supporting role in RPA1-binding.
The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn2+ ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis. Glu-116 is required to stabilize the incoming nucleotide at the 3'-site.
Sequence similarities
Belongs to the eukaryotic-type primase small subunit family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q6P1E7-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length537
- Mass (Da)61,330
- Last updated2004-07-05 v1
- ChecksumF44F0A18155AFB3F
Q6P1E7-2
- Name2
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
D3YXL5 | D3YXL5_MOUSE | Primpol | 114 | ||
A0A1B0GT20 | A0A1B0GT20_MOUSE | Primpol | 30 | ||
A0A1B0GRW0 | A0A1B0GRW0_MOUSE | Primpol | 38 | ||
A0A1B0GRB9 | A0A1B0GRB9_MOUSE | Primpol | 265 |
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 110 | in Ref. 1; BAC27128 | ||||
Sequence: K → R | ||||||
Sequence conflict | 299 | in Ref. 1; BAC27128 | ||||
Sequence: S → T | ||||||
Alternative sequence | VSP_023420 | 314-328 | in isoform 2 | |||
Sequence: VSNVRFSDTLRVLTC → ILRYSASSHMPPISD | ||||||
Alternative sequence | VSP_023421 | 329-537 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 465-481 | Polar residues | ||||
Sequence: TDDTSTSLTKDSQTPPS |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AK030772 EMBL· GenBank· DDBJ | BAC27128.1 EMBL· GenBank· DDBJ | mRNA | ||
BC065112 EMBL· GenBank· DDBJ | AAH65112.1 EMBL· GenBank· DDBJ | mRNA |