PRIPO_CHICK
ID PRIPO_CHICK Reviewed; 574 AA.
AC A0A3Q2TTB3; A0A3Q2UFR8; E1BS13;
DT 26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=DNA-directed primase/polymerase protein {ECO:0000303|PubMed:26694751};
DE EC=2.7.7.- {ECO:0000250|UniProtKB:Q96LW4};
GN Name=PRIMPOL {ECO:0000303|PubMed:26694751};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
RN [2]
RP FUNCTION.
RX PubMed=26694751; DOI=10.1080/15384101.2015.1128597;
RA Bailey L.J., Bianchi J., Hegarat N., Hochegger H., Doherty A.J.;
RT "PrimPol-deficient cells exhibit a pronounced G2 checkpoint response
RT following UV damage.";
RL Cell Cycle 15:908-918(2016).
RN [3]
RP FUNCTION.
RX PubMed=27230014; DOI=10.1080/15384101.2016.1191711;
RA Kobayashi K., Guilliam T.A., Tsuda M., Yamamoto J., Bailey L.J., Iwai S.,
RA Takeda S., Doherty A.J., Hirota K.;
RT "Repriming by PrimPol is critical for DNA replication restart downstream of
RT lesions and chain-terminating nucleosides.";
RL Cell Cycle 15:1997-2008(2016).
RN [4]
RP FUNCTION.
RX PubMed=26626482; DOI=10.1016/j.molcel.2015.10.038;
RA Schiavone D., Jozwiakowski S.K., Romanello M., Guilbaud G., Guilliam T.A.,
RA Bailey L.J., Sale J.E., Doherty A.J.;
RT "PrimPol is required for replicative tolerance of G quadruplexes in
RT vertebrate cells.";
RL Mol. Cell 61:161-169(2016).
CC -!- FUNCTION: DNA primase and DNA polymerase required to tolerate
CC replication-stalling lesions by bypassing them (PubMed:26626482).
CC Required to facilitate mitochondrial and nuclear replication fork
CC progression by initiating de novo DNA synthesis using dNTPs and acting
CC as an error-prone DNA polymerase able to bypass certain DNA lesions
CC (PubMed:26694751, PubMed:27230014). Shows a high capacity to tolerate
CC DNA damage lesions such as 8oxoG and abasic sites in DNA (By
CC similarity). Provides different translesion synthesis alternatives when
CC DNA replication is stalled: able to synthesize DNA primers downstream
CC of lesions, such as UV lesions, R-loops and G-quadruplexes, to allow
CC DNA replication to continue (PubMed:26694751, PubMed:27230014,
CC PubMed:26626482). Can also realign primers ahead of 'unreadable
CC lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-
CC pyrimidinone), thereby skipping the lesion (By similarity). Also able
CC to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a
CC regular translesion synthesis DNA polymerase (By similarity). Also
CC required for reinitiating stalled forks after ultraviolet (UV) damage
CC during nuclear DNA replication (By similarity). Required for
CC mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating
CC synthesis after UV damage or in the presence of chain-terminating
CC nucleotides (By similarity). In addition to its role in DNA damage
CC response, also required to maintain efficient nuclear and mitochondrial
CC DNA replication in unperturbed cells (By similarity).
CC {ECO:0000250|UniProtKB:Q96LW4, ECO:0000269|PubMed:26626482,
CC ECO:0000269|PubMed:26694751, ECO:0000269|PubMed:27230014}.
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=A0A3Q2TTB3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A0A3Q2TTB3-2; Sequence=VSP_060507;
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-118 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; AADN05000017; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_015131716.1; XM_015276230.1. [A0A3Q2TTB3-1]
DR AlphaFoldDB; A0A3Q2TTB3; -.
DR SMR; A0A3Q2TTB3; -.
DR STRING; 9031.ENSGALP00000037470; -.
DR Ensembl; ENSGALT00000095844; ENSGALP00000065409; ENSGALG00000010636. [A0A3Q2TTB3-1]
DR Ensembl; ENSGALT00000098402; ENSGALP00000072952; ENSGALG00000010636. [A0A3Q2TTB3-2]
DR GeneID; 422549; -.
DR CTD; 201973; -.
DR VEuPathDB; HostDB:geneid_422549; -.
DR eggNOG; ENOG502QS1Q; Eukaryota.
DR GeneTree; ENSGT00390000003901; -.
DR HOGENOM; CLU_027838_0_0_1; -.
DR OMA; ADWWMDA; -.
DR OrthoDB; 1373896at2759; -.
DR TreeFam; TF328961; -.
DR PRO; PR:A0A3Q2TTB3; -.
DR Proteomes; UP000000539; Chromosome 4.
DR Bgee; ENSGALG00000010636; Expressed in spermatid and 13 other tissues.
DR ExpressionAtlas; A0A3Q2TTB3; baseline and differential.
DR GO; GO:0000428; C:DNA-directed RNA polymerase complex; IEA:UniProtKB-KW.
DR GO; GO:0005759; C:mitochondrial matrix; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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; IMP: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; IBA:GO_Central.
DR GO; GO:0062176; P:R-loop disassembly; IMP:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; ISS:UniProtKB.
DR GO; GO:0009411; P:response to UV; IBA:GO_Central.
DR GO; GO:0019985; P:translesion synthesis; IBA:GO_Central.
DR InterPro; IPR044917; PRIMPOL.
DR PANTHER; PTHR31399; PTHR31399; 1.
PE 3: Inferred from homology;
KW Alternative splicing; Chromosome; Coiled coil; DNA damage; DNA repair;
KW DNA-directed DNA polymerase; DNA-directed RNA polymerase; Manganese;
KW Metal-binding; Mitochondrion; Nucleotidyltransferase; Nucleus;
KW Reference proteome; Transcription; Transferase; Zinc.
FT CHAIN 1..574
FT /note="DNA-directed primase/polymerase protein"
FT /id="PRO_0000449147"
FT COILED 2..22
FT /evidence="ECO:0000255"
FT MOTIF 424..457
FT /note="Zinc knuckle motif"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 76
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 116..118
FT /ligand="substrate"
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 118
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 167..171
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 291..294
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 300
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 424
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 431
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 451
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT BINDING 456
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q96LW4"
FT VAR_SEQ 371..400
FT /note="REPMEGYQESPYPEIDCFVRSLINKDGVQG -> R (in isoform 2)"
FT /id="VSP_060507"
SQ SEQUENCE 574 AA; 65865 MW; F9D55EEAF68C208D CRC64;
MKRKWEERVK KVEELASYYE RNPLPTVYKP RLSKPLQPSR VWKIFCRQAD AFRFVKTCKE
DVHVFALERN TQNGQRFYLV TTYQELWYYY TKGYKTSLMH CYEVIPEKDA CKLYFDLEFY
KAANPGADGK DMVAKLIELV SQKLKELYDV NCSARDVLNL DSSTDEKFSR HLIFLPCKTV
FKDNIHVGNF VRTILQPAIR LVGSNVAAPI AEGGAGYTSQ CSAPTVELDG PLTNLTAVED
ASKGWPAIAD QRKETETSHH GENSEFSFLI VNNKEGDKQL FVDLGVYTRN RNFRMYKSSK
AGKNVILTIA EDNKFVPNCE ENVSLEEAYF LSSLVCNVRF EDGTKILSSN FVEEEIKMSA
FLRSKTTRST REPMEGYQES PYPEIDCFVR SLINKDGVQG GIRQWNYFSG EEILVYDISG
YRWCENIGRA HRSNNIMILV DLKKEVWYQK CHDPVCREKN FKSQSLPLPS RICLSSLFIE
EEDHMVTDER ENTEVTSHSN PADLSESSAY LAINTSQDTQ WDNASDDAYL VETAEDVELA
EAADYSLGYD TEEIPDEVLL EMSWKQDTCS KDDS
