PRIPO_BOVIN
ID PRIPO_BOVIN Reviewed; 555 AA.
AC Q08DZ8;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=DNA-directed primase/polymerase protein {ECO:0000250|UniProtKB:Q96LW4};
DE EC=2.7.7.- {ECO:0000250|UniProtKB:Q96LW4};
GN Name=PRIMPOL {ECO:0000250|UniProtKB:Q96LW4};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Brain cortex;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: DNA primase and DNA polymerase required to tolerate
CC replication-stalling lesions by bypassing them. Required to facilitate
CC mitochondrial and nuclear replication fork progression by initiating de
CC novo DNA synthesis using dNTPs and acting as an error-prone DNA
CC polymerase able to bypass certain DNA lesions. Shows a high capacity to
CC tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA.
CC Provides different translesion synthesis alternatives when DNA
CC replication is stalled: able to synthesize DNA primers downstream of
CC lesions, such as ultraviolet (UV) lesions, R-loops and G-quadruplexes,
CC to allow DNA replication to continue. Can also realign primers ahead of
CC 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4
CC pyrimidine-pyrimidinone), thereby skipping the lesion. Also able to
CC incorporate nucleotides opposite DNA lesions such as 8oxoG, like a
CC regular translesion synthesis DNA polymerase. Also required for
CC reinitiating stalled forks after UV damage during nuclear DNA
CC replication. Required for mitochondrial DNA (mtDNA) synthesis and
CC replication, by reinitiating synthesis after UV damage or in the
CC presence of chain-terminating nucleotides (By similarity). Prevents
CC APOBEC family-mediated DNA mutagenesis by repriming downstream of
CC abasic site to prohibit error-prone translesion synthesis (By
CC similarity). Has non-overlapping function with POLH. In addition to its
CC role in DNA damage response, also required to maintain efficient
CC nuclear and mitochondrial DNA replication in unperturbed cells (By
CC similarity). {ECO:0000250|UniProtKB:Q6P1E7,
CC ECO:0000250|UniProtKB:Q96LW4}.
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q96LW4};
CC Note=Can act both with Mn(2+) and Mg(2+) as cofactor in vitro, but
CC Mn(2+) is the preferred cofactor in vivo. The polymerase activity
CC incorporates correct dNTPs with much higher efficiency with Mn(2+) than
CC with Mg(2+). The fidelity is slightly more accurate when Mg(2+) is the
CC cofactor compared to Mn(2+). In the presence of Mn(2+), a
CC conformational transition step from non-productive to productive
CC PRIMPOL:DNA complexes limits the enzymatic turnover, whereas in the
CC presence of Mg(2+), the chemical step becomes rate limiting.
CC {ECO:0000250|UniProtKB:Q96LW4};
CC -!- SUBUNIT: Interacts with RPA1; leading to recruitment to chromatin and
CC stimulate DNA primase activity. Interacts with SSBP1. Interacts with
CC POLDIP2; leading to enhance DNA polymerase activity.
CC {ECO:0000250|UniProtKB:Q96LW4}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q96LW4}.
CC Mitochondrion matrix {ECO:0000250|UniProtKB:Q96LW4}. Chromosome
CC {ECO:0000250|UniProtKB:Q96LW4}. Note=Present in the nucleus, but a
CC larger fraction is localized inside mitochondria. Associates with
CC nuclear chromatin during the G1 and S phases of unperturbed cell
CC cycles. Recruited to stalled replication forks following interaction
CC with RPA1. {ECO:0000250|UniProtKB:Q96LW4}.
CC -!- DOMAIN: The zinc knuckle motif binds zinc and is required for the DNA
CC primase activity. It facilitates the binding and selection of the 5'-
CC nucleotide of the newly synthesized primer and the recognition of
CC preferred initiation sites. {ECO:0000250|UniProtKB:Q96LW4}.
CC -!- DOMAIN: The RPA1-binding motifs (RBM) mediate interaction with RPA1 and
CC are essential for recruitment to chromatin. The interaction is
CC primarily mediated by RPA1-binding motif 1, which binds to the basic
CC cleft of RPA1, with motif 2 plays a supporting role in RPA1-binding.
CC {ECO:0000250|UniProtKB:Q96LW4}.
CC -!- DOMAIN: The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding
CC active site favors the use of Mn(2+) ions to achieve optimal incoming
CC nucleotide stabilization, especially required during primer synthesis.
CC Glu-116 is required to stabilize the incoming nucleotide at the 3'-
CC site. {ECO:0000250|UniProtKB:Q96LW4}.
CC -!- SIMILARITY: Belongs to the eukaryotic-type primase small subunit
CC family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC123492; AAI23493.1; -; mRNA.
DR RefSeq; NP_001068956.1; NM_001075488.1.
DR RefSeq; XP_010818555.1; XM_010820253.2.
DR RefSeq; XP_010818556.1; XM_010820254.2.
DR AlphaFoldDB; Q08DZ8; -.
DR SMR; Q08DZ8; -.
DR STRING; 9913.ENSBTAP00000025112; -.
DR PaxDb; Q08DZ8; -.
DR PRIDE; Q08DZ8; -.
DR Ensembl; ENSBTAT00000025112; ENSBTAP00000025112; ENSBTAG00000018863.
DR GeneID; 511080; -.
DR KEGG; bta:511080; -.
DR CTD; 201973; -.
DR VEuPathDB; HostDB:ENSBTAG00000018863; -.
DR VGNC; VGNC:33318; PRIMPOL.
DR eggNOG; ENOG502QS1Q; Eukaryota.
DR GeneTree; ENSGT00390000003901; -.
DR HOGENOM; CLU_027838_0_0_1; -.
DR InParanoid; Q08DZ8; -.
DR OMA; ADWWMDA; -.
DR OrthoDB; 1373896at2759; -.
DR TreeFam; TF328961; -.
DR Proteomes; UP000009136; Chromosome 27.
DR Bgee; ENSBTAG00000018863; Expressed in oocyte and 105 other tissues.
DR ExpressionAtlas; Q08DZ8; baseline and differential.
DR GO; GO:0000428; C:DNA-directed RNA polymerase complex; IEA:UniProtKB-KW.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005657; C:replication fork; ISS:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003896; F:DNA primase activity; ISS:UniProtKB.
DR GO; GO:0003887; F:DNA-directed DNA polymerase activity; ISS:UniProtKB.
DR GO; GO:0030145; F:manganese ion binding; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0042276; P:error-prone translesion synthesis; ISS:UniProtKB.
DR GO; GO:0043504; P:mitochondrial DNA repair; ISS:UniProtKB.
DR GO; GO:0006264; P:mitochondrial DNA replication; ISS:UniProtKB.
DR GO; GO:0062176; P:R-loop disassembly; ISS:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR GO; GO:0009411; P:response to UV; ISS:UniProtKB.
DR GO; GO:0019985; P:translesion synthesis; ISS:UniProtKB.
DR InterPro; IPR044917; PRIMPOL.
DR PANTHER; PTHR31399; PTHR31399; 1.
PE 2: Evidence at transcript level;
KW Chromosome; Coiled coil; DNA damage; DNA repair;
KW DNA-directed DNA polymerase; DNA-directed RNA polymerase; Manganese;
KW Metal-binding; Mitochondrion; Nucleotidyltransferase; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription; Transferase; Zinc.
FT CHAIN 1..555
FT /note="DNA-directed primase/polymerase protein"
FT /id="PRO_0000279394"
FT REGION 210..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 480..555
FT /note="Interaction with RPA1"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT REGION 480..503
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1..22
FT /evidence="ECO:0000255"
FT MOTIF 418..451
FT /note="Zinc knuckle motif"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT MOTIF 509..523
FT /note="RPA1-binding motif 1"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT MOTIF 543..551
FT /note="RPA1-binding motif 2"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT COMPBIAS 213..230
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 484..502
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 76
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 114..116
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 114
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 116
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 165..169
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 288..291
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 297
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 425
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 445
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 450
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
SQ SEQUENCE 555 AA; 63721 MW; 2B4DD6A8E1E95022 CRC64;
MKRKWEATLK QIEERASHYE RKPLSSVYRP RLSKPEEPPS IWKLFHRQTQ AFNFVKSCKQ
EVHVFALECK VGDGQRIYLV TTYTQLWFYY KSRRNLLHCY EVIPENAVCK LYFDLEFNKL
ANPGADGKKM VALLIEHVCK ALQEFYTVNC SAEDVLNLDS STEEKFSRHL IFQLHDVAFK
DNIHVGNFVR KILQPAFHLI ASEDEDMTPE TTGHEFTHFS ETPSEQGTCF SKMSTDIDVG
ESQTSNSEKL GRLGSAQQSS PDLSFLIVKN DMGEKRLFVD LGVYTRNRNF RLYKSSKIGK
YVALEVAEDN KFFPIQSKNI SKENQYFLSS LVSNVRFSDA LRILTCDVPQ SKQRVQCFSR
TGTSVEAIEG FQCSPYPEID QFVLSLVNKN GIKGGIRRWN YFFPEELLVY DICKYRWCEN
IGRAHRSNNI MILVDLKNEV WYQKCHDPVC KAENFKSDCF PLPAEVCLLS LLKEGEEFTT
DTTADTETKS PHGPSSSVLS KGAFSDADWD NGIDDTYILE ATEDAELAEA AENSLLAYNR
MDEIPDELLI EVLQE
