PRIPO_DANRE
ID PRIPO_DANRE Reviewed; 523 AA.
AC Q32PL8; F1R2H2;
DT 06-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-JAN-2014, sequence version 2.
DT 03-AUG-2022, entry version 80.
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};
GN ORFNames=zgc:123274 {ECO:0000303|Ref.2};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (OCT-2005) 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 (By similarity). Shows a
CC high capacity to tolerate DNA damage lesions such as 8oxoG and abasic
CC sites in DNA (By similarity). Provides different translesion synthesis
CC alternatives when DNA replication is stalled: able to synthesize DNA
CC primers downstream of lesions, such as UV lesions, R-loops and G-
CC quadruplexes, to allow DNA replication to continue (By similarity). Can
CC also realign primers ahead of 'unreadable lesions' such as abasic sites
CC and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping
CC the lesion. Also able to incorporate nucleotides opposite DNA lesions
CC such as 8oxoG, like a regular translesion synthesis DNA polymerase.
CC Also required for reinitiating stalled forks after ultraviolet (UV)
CC damage during nuclear DNA replication. Required for mitochondrial DNA
CC (mtDNA) synthesis and replication, by reinitiating synthesis after UV
CC damage or in the presence of chain-terminating nucleotides. In addition
CC to its 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:A0A3Q2TTB3,
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.
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}.
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 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-119 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}.
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DR EMBL; BX284619; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC108066; AAI08067.1; -; mRNA.
DR RefSeq; NP_001032455.1; NM_001037378.1.
DR AlphaFoldDB; Q32PL8; -.
DR SMR; Q32PL8; -.
DR STRING; 7955.ENSDARP00000022890; -.
DR PaxDb; Q32PL8; -.
DR Ensembl; ENSDART00000006147; ENSDARP00000022890; ENSDARG00000033273.
DR GeneID; 556571; -.
DR KEGG; dre:556571; -.
DR CTD; 201973; -.
DR ZFIN; ZDB-GENE-051113-100; primpol.
DR eggNOG; ENOG502QS1Q; Eukaryota.
DR GeneTree; ENSGT00390000003901; -.
DR HOGENOM; CLU_027838_0_0_1; -.
DR InParanoid; Q32PL8; -.
DR OMA; ADWWMDA; -.
DR OrthoDB; 1373896at2759; -.
DR PhylomeDB; Q32PL8; -.
DR TreeFam; TF328961; -.
DR PRO; PR:Q32PL8; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 1.
DR Bgee; ENSDARG00000033273; Expressed in testis and 21 other tissues.
DR ExpressionAtlas; Q32PL8; 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; DNA damage; DNA repair; DNA-directed DNA polymerase;
KW DNA-directed RNA polymerase; Manganese; Metal-binding; Mitochondrion;
KW Nucleotidyltransferase; Nucleus; Reference proteome; Transcription;
KW Transferase; Zinc.
FT CHAIN 1..523
FT /note="DNA-directed primase/polymerase protein"
FT /id="PRO_0000279397"
FT REGION 203..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 467..523
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 390..423
FT /note="Zinc knuckle motif"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT COMPBIAS 209..230
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 498..514
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 78
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 117..119
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 117
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 119
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 168..172
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 258..261
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 267
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 390
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 397
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 417
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 422
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT CONFLICT 193
FT /note="H -> N (in Ref. 2; AAI08067)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="E -> Q (in Ref. 2; AAI08067)"
FT /evidence="ECO:0000305"
FT CONFLICT 340
FT /note="L -> Q (in Ref. 2; AAI08067)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="T -> A (in Ref. 2; AAI08067)"
FT /evidence="ECO:0000305"
FT CONFLICT 497
FT /note="Q -> H (in Ref. 2; AAI08067)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 523 AA; 60194 MW; 5BDF30811D95773D CRC64;
MTGGKWQDRV KSVEQRASSF QSSPLSCPYK PRLSQPWQPS SIWRLFPRQN AAIAFAQHIK
QDVHIFSLEK EGSDAGQRIF LVTSYSELWH YYSTHRHSLM HCYEVILEGA VCKLYFDLEF
HKASNKNLDG KMMVAKLIQY VCEKLEEVYG LHCSAKDVLD LDSSTSDKFS HHLIFMLPNA
AFKDNSHVGR FIHDILHPAL TNLKKSNPEA PGENRDDVEG TQAKRRKTEE NDLGFLTVKN
EKGQEQLFVD LGVYTKNRNF RLYKSSKLGK NAAFIVAEDN KFVPNPSKQI TKDERIFLAS
LITNVSFTGQ RILTYDMTQK STAGSECPTL ERESHSSDLL GDQKTSPFKE VDEFVLTLVC
KDGIQGSIRR WNYFACEQLL VYDIEKFRWC HNVKRFHKSN NIIIVVDLKE EVWYQKCHDP
ECRRQNYRSS SFPLPQEVCM SHLLMEDEED QAYLTDELGN IELAVTAPAE STSTTPSEDT
EGWGDWPDDP AYLRALQEVE EEEEDEDEEV PDELLLQAVN ECE
