PRI2_DROME
ID PRI2_DROME Reviewed; 533 AA.
AC Q9VPH2; Q9U9Q5;
DT 29-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=DNA primase large subunit {ECO:0000305};
DE AltName: Full=DNA polymerase subunit beta {ECO:0000303|PubMed:6409898};
DE AltName: Full=Suppressor of fat facets 240 {ECO:0000303|PubMed:11102374};
GN Name=Prim2 {ECO:0000312|FlyBase:FBgn0259676};
GN Synonyms=DNApol-alpha60 {ECO:0000312|FlyBase:FBgn0259676},
GN DNAprim {ECO:0000312|FlyBase:FBgn0259676},
GN S(faf)240 {ECO:0000303|PubMed:11102374};
GN ORFNames=CG5553 {ECO:0000312|FlyBase:FBgn0259676};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, MUTAGENESIS OF GLU-136, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=11102374; DOI=10.1093/genetics/156.4.1787;
RA Chen X., Li Q., Fischer J.A.;
RT "Genetic analysis of the Drosophila DNAprim gene. The function of the 60-kd
RT primase subunit of DNA polymerase opposes the fat facets signaling pathway
RT in the developing eye.";
RL Genetics 156:1787-1795(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Ovary;
RX PubMed=10731138; DOI=10.1126/science.287.5461.2222;
RA Rubin G.M., Hong L., Brokstein P., Evans-Holm M., Frise E., Stapleton M.,
RA Harvey D.A.;
RT "A Drosophila complementary DNA resource.";
RL Science 287:2222-2224(2000).
RN [5]
RP FUNCTION, IDENTIFICATION IN THE DNA POLYMERASE ALPHA COMPLEX, AND TISSUE
RP SPECIFICITY.
RX PubMed=6773966; DOI=10.1016/s0021-9258(19)70587-0;
RA Villani G., Sauer B., Lehman I.R.;
RT "DNA polymerase alpha from Drosophila melanogaster embryos. Subunit
RT structure.";
RL J. Biol. Chem. 255:9479-9483(1980).
RN [6]
RP FUNCTION.
RX PubMed=6812052; DOI=10.1073/pnas.79.15.4585;
RA Conaway R.C., Lehman I.R.;
RT "Synthesis by the DNA primase of Drosophila melanogaster of a primer with a
RT unique chain length.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:4585-4588(1982).
RN [7]
RP FUNCTION, IDENTIFICATION IN ALPHA DNA POLYMERASE COMPLEX, IDENTIFICATION IN
RP DNA PRIMASE COMPLEX, AND TISSUE SPECIFICITY.
RX PubMed=6403945; DOI=10.1073/pnas.80.8.2221;
RA Kaguni L.S., Rossignol J.M., Conaway R.C., Lehman I.R.;
RT "Isolation of an intact DNA polymerase-primase from embryos of Drosophila
RT melanogaster.";
RL Proc. Natl. Acad. Sci. U.S.A. 80:2221-2225(1983).
RN [8]
RP FUNCTION, IDENTIFICATION IN ALPHA DNA POLYMERASE COMPLEX, IDENTIFICATION IN
RP DNA PRIMASE COMPLEX, AND TISSUE SPECIFICITY.
RX PubMed=6409898; DOI=10.1016/s0021-9258(17)44626-6;
RA Kaguni L.S., Rossignol J.M., Conaway R.C., Banks G.R., Lehman I.R.;
RT "Association of DNA primase with the beta/gamma subunits of DNA polymerase
RT alpha from Drosophila melanogaster embryos.";
RL J. Biol. Chem. 258:9037-9039(1983).
RN [9]
RP DEVELOPMENTAL STAGE.
RX PubMed=10366721; DOI=10.1016/s0167-4781(99)00063-9;
RA Huikeshoven H., Cotterill S.;
RT "Cloning and characterisation of the gene for the large subunit of the DNA
RT primase from Drosophila melanogaster.";
RL Biochim. Biophys. Acta 1445:359-362(1999).
CC -!- FUNCTION: Regulatory subunit of the DNA primase complex and component
CC of the DNA polymerase alpha complex (also known as the alpha DNA
CC polymerase-primase complex) which play an essential role in the
CC initiation of DNA synthesis (PubMed:6773966, PubMed:6409898,
CC PubMed:6403945). During the S phase of the cell cycle, the DNA
CC polymerase alpha complex (composed of a catalytic subunit PolA1, an
CC accessory subunit PolA2 and two primase subunits, the catalytic subunit
CC Prim1 and the regulatory subunit Prim2) is recruited to DNA at the
CC replicative forks (By similarity). The primase subunit of the
CC polymerase alpha complex initiates DNA synthesis by oligomerising short
CC RNA primers on both leading and lagging strands (PubMed:6812052). These
CC primers are initially extended by the polymerase alpha catalytic
CC subunit and subsequently transferred to polymerase delta and polymerase
CC epsilon for processive synthesis on the lagging and leading strand,
CC respectively (By similarity). In the primase complex, both subunits are
CC necessary for the initial di-nucleotide formation, but the extension of
CC the primer depends only on the catalytic subunit (PubMed:6812052).
CC Stabilizes and modulates the activity of the catalytic subunit (By
CC similarity). {ECO:0000250|UniProtKB:P09884,
CC ECO:0000250|UniProtKB:P33610, ECO:0000269|PubMed:6403945,
CC ECO:0000269|PubMed:6409898, ECO:0000269|PubMed:6773966,
CC ECO:0000269|PubMed:6812052}.
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:P49643};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250|UniProtKB:P49643};
CC -!- SUBUNIT: Heterodimer of a catalytic subunit Prim1 and a regulatory
CC subunit Prim2, also known as the DNA primase complex (PubMed:6403945,
CC PubMed:6409898). Component of the alpha DNA polymerase complex (also
CC known as the alpha DNA polymerase-primase complex) consisting of four
CC subunits: the catalytic subunit PolA1, the regulatory subunit PolA2,
CC and the primase complex subunits Prim1 and Prim2 respectively
CC (PubMed:6773966, PubMed:6403945, PubMed:6409898). PolA1 associates with
CC the DNA primase complex before association with PolA2 (PubMed:6409898).
CC {ECO:0000269|PubMed:6403945, ECO:0000269|PubMed:6409898,
CC ECO:0000269|PubMed:6773966}.
CC -!- TISSUE SPECIFICITY: Expressed in embryos (at protein level).
CC {ECO:0000269|PubMed:6403945, ECO:0000269|PubMed:6409898,
CC ECO:0000269|PubMed:6773966}.
CC -!- DEVELOPMENTAL STAGE: Expressed at high levels in early embryos
CC (particularly at the 0-4 h stage), then low throughout the larval and
CC pupal stages and in adult males (PubMed:10366721). Shows elevated
CC levels in adult females (PubMed:10366721).
CC {ECO:0000269|PubMed:10366721}.
CC -!- DISRUPTION PHENOTYPE: Mutants exhibit eye defects and a delay in the
CC S- phase of the cell cycle. {ECO:0000269|PubMed:11102374}.
CC -!- SIMILARITY: Belongs to the eukaryotic-type primase large subunit
CC family. {ECO:0000305}.
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DR EMBL; AF291873; AAG01548.1; -; Genomic_DNA.
DR EMBL; AE014296; AAF51580.2; -; Genomic_DNA.
DR EMBL; AF160895; AAD46835.1; -; mRNA.
DR RefSeq; NP_652001.2; NM_143744.4.
DR AlphaFoldDB; Q9VPH2; -.
DR SMR; Q9VPH2; -.
DR BioGRID; 69380; 13.
DR ComplexPortal; CPX-2090; DNA polymerase alpha:primase complex.
DR IntAct; Q9VPH2; 9.
DR STRING; 7227.FBpp0077899; -.
DR PaxDb; Q9VPH2; -.
DR PRIDE; Q9VPH2; -.
DR DNASU; 44915; -.
DR EnsemblMetazoa; FBtr0078241; FBpp0077899; FBgn0259676.
DR GeneID; 44915; -.
DR KEGG; dme:Dmel_CG5553; -.
DR CTD; 44915; -.
DR FlyBase; FBgn0259676; Prim2.
DR VEuPathDB; VectorBase:FBgn0259676; -.
DR eggNOG; KOG2267; Eukaryota.
DR GeneTree; ENSGT00390000009790; -.
DR HOGENOM; CLU_026253_2_0_1; -.
DR InParanoid; Q9VPH2; -.
DR OMA; KTSMPLC; -.
DR OrthoDB; 479347at2759; -.
DR PhylomeDB; Q9VPH2; -.
DR Reactome; R-DME-113501; Inhibition of replication initiation of damaged DNA by RB1/E2F1.
DR Reactome; R-DME-68952; DNA replication initiation.
DR Reactome; R-DME-68962; Activation of the pre-replicative complex.
DR Reactome; R-DME-69091; Polymerase switching.
DR Reactome; R-DME-69166; Removal of the Flap Intermediate.
DR Reactome; R-DME-69183; Processive synthesis on the lagging strand.
DR BioGRID-ORCS; 44915; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 44915; -.
DR PRO; PR:Q9VPH2; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0259676; Expressed in secondary oocyte and 14 other tissues.
DR ExpressionAtlas; Q9VPH2; baseline and differential.
DR Genevisible; Q9VPH2; DM.
DR GO; GO:0005658; C:alpha DNA polymerase:primase complex; IDA:FlyBase.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0001745; P:compound eye morphogenesis; IMP:UniProtKB.
DR GO; GO:0006260; P:DNA replication; IMP:UniProtKB.
DR GO; GO:0006270; P:DNA replication initiation; IDA:ComplexPortal.
DR GO; GO:0006269; P:DNA replication, synthesis of RNA primer; IDA:FlyBase.
DR GO; GO:0006261; P:DNA-templated DNA replication; IDA:FlyBase.
DR GO; GO:0000278; P:mitotic cell cycle; IMP:UniProtKB.
DR CDD; cd07322; PriL_PriS_Eukaryotic; 1.
DR InterPro; IPR016558; DNA_primase_lsu_euk.
DR InterPro; IPR007238; DNA_primase_lsu_euk/arc.
DR PANTHER; PTHR10537; PTHR10537; 1.
DR Pfam; PF04104; DNA_primase_lrg; 1.
DR PIRSF; PIRSF009449; DNA_primase_large_subunit; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; DNA replication; DNA-binding; Iron; Iron-sulfur; Metal-binding;
KW Primosome; Reference proteome.
FT CHAIN 1..533
FT /note="DNA primase large subunit"
FT /id="PRO_0000046772"
FT REGION 466..492
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 298
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P49643"
FT BINDING 377
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P49643"
FT BINDING 393
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P49643"
FT BINDING 433
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250|UniProtKB:P49643"
FT MUTAGEN 136
FT /note="E->K: In DNApol-alpha60-T2; pupal lethal."
FT /evidence="ECO:0000269|PubMed:11102374"
FT CONFLICT 142
FT /note="Y -> F (in Ref. 4; AAD46835)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="S -> G (in Ref. 4; AAD46835)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 533 AA; 61436 MW; 92CE6049AA8685E5 CRC64;
MEFGLKKRAR HEVKVEVASL ETKYPHNVML YHYPPTEDVH IDEFEELALE RLRLLRVLDR
ASTRNLRVLS DEWKEIVSAD LTREGLRSYL RLCSTGGSAK HEADIQTRRR DYLSHFILRL
AYCRSEDLAR WFVAREMELF RYKFAALSSF EVKQFLEANG FEIHPLTEAQ KDEVKDGLYE
STVGQSVAKI ELLDFYKVPF TQVLDLVRGR RCFLKAGYAY VNTHDLVSLV GTKQQDEIEQ
GLQAAKTMVE DVEADERISR TLKALHNSYT GRDYTVCRDA AVPIESLDQL SKTSMPLCMR
MCHEHIRANH HIKHSGRMQY GLFLKGIGVA LEDSLRFWRE EFTKKMDADK FTRSYEYNIY
HNYGKKGSMV NYTPYSCAKI IKDVAGPGDC HGCPYKNMDQ GSLKTKLSSY GLSASAIDEV
MFFVSRGHYQ IGCGKYFQLT HNSPVEPSIN HPNNYFEESQ IAMGNRQKRA NGSAPPKARI
RPDIKGHGDR SMLMGDDDDE LWRIAETQER IMQSQKDISE AFNDDLDLTQ IDY
