PRI2_HUMAN
ID PRI2_HUMAN Reviewed; 509 AA.
AC P49643; Q53FJ8; Q6P1Q7; Q8WVL2; Q9H413;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 2.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=DNA primase large subunit;
DE AltName: Full=DNA primase 58 kDa subunit;
DE Short=p58;
GN Name=PRIM2; Synonyms=PRIM2A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8026492; DOI=10.1111/j.1432-1033.1994.tb18925.x;
RA Stadlbauer F., Brueckner A., Rehfuess C., Eckerskorn C., Lottspeich F.,
RA Foerster V., Tseng B.Y., Nasheuer H.-P.;
RT "DNA replication in vitro by recombinant DNA-polymerase-alpha-primase.";
RL Eur. J. Biochem. 222:781-793(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, AND INTERACTION WITH PRIM1; POLA2 AND POLA1.
RX PubMed=9705292; DOI=10.1074/jbc.273.34.21608;
RA Schneider A., Smith R.W., Kautz A.R., Weisshart K., Grosse F.,
RA Nasheuer H.P.;
RT "Primase activity of human DNA polymerase alpha-primase. Divalent cations
RT stabilize the enzyme activity of the p48 subunit.";
RL J. Biol. Chem. 273:21608-21615(1998).
RN [5]
RP FUNCTION, IRON-SULFUR CLUSTER, COFACTOR, INTERACTION WITH PRIM1, AND
RP IDENTIFICATION IN THE DNA PRIMASE COMPLEX.
RX PubMed=17893144; DOI=10.1074/jbc.m705826200;
RA Weiner B.E., Huang H., Dattilo B.M., Nilges M.J., Fanning E., Chazin W.J.;
RT "An iron-sulfur cluster in the C-terminal domain of the p58 subunit of
RT human DNA primase.";
RL J. Biol. Chem. 282:33444-33451(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-470, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-253, INTERACTION WITH POLA1,
RP AND MUTAGENESIS OF ARG-97; PHE-104; ARG-107 AND LEU-108.
RX PubMed=24043831; DOI=10.1073/pnas.1311185110;
RA Kilkenny M.L., Longo M.A., Perera R.L., Pellegrini L.;
RT "Structures of human primase reveal design of nucleotide elongation site
RT and mode of Pol alpha tethering.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:15961-15966(2013).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) IN COMPLEX WITH IRON-SULFUR
RP (4FE-4S), FUNCTION, COFACTOR, DOMAIN, AND MUTAGENESIS OF 256-SER--LYS-270.
RX PubMed=25550159; DOI=10.1074/jbc.m114.624742;
RA Baranovskiy A.G., Zhang Y., Suwa Y., Babayeva N.D., Gu J., Pavlov Y.I.,
RA Tahirov T.H.;
RT "Crystal structure of the human primase.";
RL J. Biol. Chem. 290:5635-5646(2015).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 266-456 IN COMPLEX WITH
RP IRON-SULFUR (4FE-4S), FUNCTION, SUBUNIT, AND DOMAIN.
RX PubMed=26975377; DOI=10.1074/jbc.m116.717405;
RA Baranovskiy A.G., Babayeva N.D., Zhang Y., Gu J., Suwa Y., Pavlov Y.I.,
RA Tahirov T.H.;
RT "Mechanism of Concerted RNA-DNA Primer Synthesis by the Human Primosome.";
RL J. Biol. Chem. 291:10006-10020(2016).
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] SER-465, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
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:9705292, PubMed:17893144,
CC PubMed:25550159, PubMed:26975377). During the S phase of the cell
CC cycle, the DNA polymerase alpha complex (composed of a catalytic
CC subunit POLA1, an accessory subunit POLA2 and two primase subunits, the
CC catalytic subunit PRIM1 and the regulatory subunit PRIM2) is recruited
CC to DNA at the replicative forks via direct interactions with MCM10 and
CC WDHD1 (By similarity). The primase subunit of the polymerase alpha
CC complex initiates DNA synthesis by oligomerising short RNA primers on
CC both leading and lagging strands (PubMed:17893144). These primers are
CC initially extended by the polymerase alpha catalytic subunit and
CC subsequently transferred to polymerase delta and polymerase epsilon for
CC processive synthesis on the lagging and leading strand, respectively
CC (By similarity). In the primase complex, both subunits are necessary
CC for the initial di-nucleotide formation, but the extension of the
CC primer depends only on the catalytic subunit (PubMed:17893144,
CC PubMed:25550159). Binds RNA:DNA duplex and coordinates the catalytic
CC activities of PRIM1 and POLA2 during primase-to-polymerase switch.
CC {ECO:0000250|UniProtKB:P09884, ECO:0000250|UniProtKB:P33610,
CC ECO:0000269|PubMed:17893144, ECO:0000269|PubMed:25550159,
CC ECO:0000269|PubMed:26975377, ECO:0000269|PubMed:9705292}.
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:17893144, ECO:0000269|PubMed:25550159};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000269|PubMed:17893144,
CC ECO:0000269|PubMed:25550159};
CC -!- SUBUNIT: Heterodimer of a catalytic subunit PRIM1 and a regulatory
CC subunit PRIM2, also known as the DNA primase complex (PubMed:9705292,
CC PubMed:17893144). Interacts via (C-terminus) with PRIM1
CC (PubMed:17893144). 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:9705292, PubMed:26975377). Within the complex, POLA1 directly
CC interacts with PRIM2. {ECO:0000250|UniProtKB:P33610,
CC ECO:0000269|PubMed:17893144, ECO:0000269|PubMed:24043831,
CC ECO:0000269|PubMed:9705292}.
CC -!- INTERACTION:
CC P49643; P49642: PRIM1; NbExp=7; IntAct=EBI-850004, EBI-726050;
CC P49643; Q6P9E2: RECK; NbExp=3; IntAct=EBI-850004, EBI-10253121;
CC P49643; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-850004, EBI-5235340;
CC P49643-1; P15927: RPA2; NbExp=3; IntAct=EBI-15866483, EBI-621404;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49643-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49643-2; Sequence=VSP_015111, VSP_015112;
CC -!- DOMAIN: The RNA:DNA duplex-binding domain interacts with the template
CC phosphates at positions -2, -1, 1, and 2 positioning its bases -1, 1,
CC and 2 for duplex formation. Interacts only with the beta- and gamma-
CC phosphates of triphosphate moiety of initiating NTP of the primer. The
CC side chain of His-303 mimics a RNA base that would be paired with the
CC template nucleotide at position -1 via a hydrogen bond, thereby
CC facilitating the stacking of the initiating NTP. In the initiating
CC primosome a 'mini RNA:DNA' duplex is formed comprising three template
CC nucleotides at positions -1, 1, and 2 on one strand and His-303,
CC initiating NTP, and incoming NTP on the other strand.
CC {ECO:0000269|PubMed:26975377}.
CC -!- DOMAIN: The interdomain linker provides flexibility in movement
CC relative to primosome platform composed of PRIM1, the N-terminus of
CC PRIM2, the C-terminus of POLA1 and POLA2. Together with POLA1
CC interdomain linker, allows for large-scale conformational changes of
CC primosome and coordinated autoregulation of catalytic centers of PRIM1
CC and POLA1. It is proposed to move the C-terminus of PRIM2 close to
CC PRIM1 during initiation, then move it away with the 5'-end of the
CC nascent primer during elongation. The steric hindrance between the
CC N- and C-terminus of PRIM2 as the RNA primer is elongated limits its
CC length to 9 nucleotides. Ultimately a large rotation of the C-terminus
CC of PRIM2 transfers the primer to POLA1 active site for DNA synthesis.
CC {ECO:0000269|PubMed:25550159, ECO:0000269|PubMed:26975377}.
CC -!- SIMILARITY: Belongs to the eukaryotic-type primase large subunit
CC family. {ECO:0000305}.
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DR EMBL; X74331; CAA52378.1; -; mRNA.
DR EMBL; AL121975; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL162579; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017833; AAH17833.1; -; mRNA.
DR EMBL; BC064931; AAH64931.1; -; mRNA.
DR CCDS; CCDS75476.1; -. [P49643-1]
DR CCDS; CCDS75477.1; -. [P49643-2]
DR PIR; S45631; S45631.
DR RefSeq; NP_000938.2; NM_000947.4. [P49643-1]
DR RefSeq; NP_001269416.1; NM_001282487.1. [P49643-2]
DR RefSeq; NP_001269417.1; NM_001282488.1. [P49643-2]
DR PDB; 3L9Q; X-ray; 1.70 A; A/B=272-464.
DR PDB; 3Q36; X-ray; 2.50 A; A/B=266-457.
DR PDB; 4BPU; X-ray; 2.70 A; B/D=1-253.
DR PDB; 4BPW; X-ray; 3.00 A; B/D=1-253.
DR PDB; 4BPX; X-ray; 3.40 A; B/D=19-253.
DR PDB; 4RR2; X-ray; 2.65 A; B/D=1-509.
DR PDB; 5DQO; X-ray; 2.30 A; A/B/C/D=272-464.
DR PDB; 5EXR; X-ray; 3.60 A; B/F=1-509.
DR PDB; 5F0Q; X-ray; 2.21 A; A/B=266-456.
DR PDB; 5F0S; X-ray; 3.00 A; A/B=266-456.
DR PDB; 5I7M; X-ray; 1.93 A; A/B=272-457.
DR PDB; 6DHW; X-ray; 2.01 A; A/B=266-457.
DR PDB; 7OPL; EM; 4.12 A; D=1-509.
DR PDBsum; 3L9Q; -.
DR PDBsum; 3Q36; -.
DR PDBsum; 4BPU; -.
DR PDBsum; 4BPW; -.
DR PDBsum; 4BPX; -.
DR PDBsum; 4RR2; -.
DR PDBsum; 5DQO; -.
DR PDBsum; 5EXR; -.
DR PDBsum; 5F0Q; -.
DR PDBsum; 5F0S; -.
DR PDBsum; 5I7M; -.
DR PDBsum; 6DHW; -.
DR PDBsum; 7OPL; -.
DR AlphaFoldDB; P49643; -.
DR SMR; P49643; -.
DR BioGRID; 111548; 111.
DR ComplexPortal; CPX-2087; DNA polymerase alpha:primase complex.
DR CORUM; P49643; -.
DR DIP; DIP-36438N; -.
DR IntAct; P49643; 35.
DR MINT; P49643; -.
DR STRING; 9606.ENSP00000484105; -.
DR ChEMBL; CHEMBL2363042; -.
DR iPTMnet; P49643; -.
DR PhosphoSitePlus; P49643; -.
DR BioMuta; PRIM2; -.
DR DMDM; 51338777; -.
DR EPD; P49643; -.
DR jPOST; P49643; -.
DR MassIVE; P49643; -.
DR MaxQB; P49643; -.
DR PeptideAtlas; P49643; -.
DR PRIDE; P49643; -.
DR ProteomicsDB; 56041; -. [P49643-1]
DR ProteomicsDB; 56042; -. [P49643-2]
DR Antibodypedia; 31147; 164 antibodies from 26 providers.
DR DNASU; 5558; -.
DR Ensembl; ENST00000274891.10; ENSP00000485304.1; ENSG00000146143.19. [P49643-2]
DR Ensembl; ENST00000370687.6; ENSP00000483201.1; ENSG00000146143.19. [P49643-2]
DR Ensembl; ENST00000615550.5; ENSP00000484105.1; ENSG00000146143.19. [P49643-1]
DR GeneID; 5558; -.
DR KEGG; hsa:5558; -.
DR MANE-Select; ENST00000615550.5; ENSP00000484105.1; NM_000947.5; NP_000938.2.
DR UCSC; uc003pdv.3; human. [P49643-1]
DR CTD; 5558; -.
DR DisGeNET; 5558; -.
DR GeneCards; PRIM2; -.
DR HGNC; HGNC:9370; PRIM2.
DR HPA; ENSG00000146143; Tissue enhanced (prostate).
DR MIM; 176636; gene.
DR neXtProt; NX_P49643; -.
DR OpenTargets; ENSG00000146143; -.
DR PharmGKB; PA162400108; -.
DR VEuPathDB; HostDB:ENSG00000146143; -.
DR eggNOG; KOG2267; Eukaryota.
DR GeneTree; ENSGT00390000009790; -.
DR HOGENOM; CLU_118849_0_0_1; -.
DR InParanoid; P49643; -.
DR OMA; KTSMPLC; -.
DR OrthoDB; 479347at2759; -.
DR PhylomeDB; P49643; -.
DR BRENDA; 2.7.7.102; 2681.
DR PathwayCommons; P49643; -.
DR Reactome; R-HSA-113501; Inhibition of replication initiation of damaged DNA by RB1/E2F1.
DR Reactome; R-HSA-174411; Polymerase switching on the C-strand of the telomere.
DR Reactome; R-HSA-174430; Telomere C-strand synthesis initiation.
DR Reactome; R-HSA-68952; DNA replication initiation.
DR Reactome; R-HSA-68962; Activation of the pre-replicative complex.
DR Reactome; R-HSA-69091; Polymerase switching.
DR Reactome; R-HSA-69166; Removal of the Flap Intermediate.
DR Reactome; R-HSA-69183; Processive synthesis on the lagging strand.
DR Reactome; R-HSA-9710421; Defective pyroptosis.
DR SignaLink; P49643; -.
DR SIGNOR; P49643; -.
DR BioGRID-ORCS; 5558; 46 hits in 242 CRISPR screens.
DR ChiTaRS; PRIM2; human.
DR EvolutionaryTrace; P49643; -.
DR GeneWiki; PRIM2; -.
DR GenomeRNAi; 5558; -.
DR Pharos; P49643; Tbio.
DR PRO; PR:P49643; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P49643; protein.
DR Bgee; ENSG00000146143; Expressed in buccal mucosa cell and 106 other tissues.
DR ExpressionAtlas; P49643; baseline and differential.
DR Genevisible; P49643; HS.
DR GO; GO:0005658; C:alpha DNA polymerase:primase complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0071667; F:DNA/RNA hybrid binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006270; P:DNA replication initiation; IDA:ComplexPortal.
DR GO; GO:0006269; P:DNA replication, synthesis of RNA primer; IDA:UniProtKB.
DR GO; GO:1903934; P:positive regulation of DNA primase activity; 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 3D-structure; 4Fe-4S; Alternative splicing; DNA replication; DNA-binding;
KW Iron; Iron-sulfur; Metal-binding; Phosphoprotein; Primosome;
KW Reference proteome.
FT CHAIN 1..509
FT /note="DNA primase large subunit"
FT /id="PRO_0000046768"
FT REGION 253..270
FT /note="Interdomain linker"
FT /evidence="ECO:0000269|PubMed:25550159,
FT ECO:0000269|PubMed:26975377"
FT REGION 266..509
FT /note="Interacts with PRIM1"
FT /evidence="ECO:0000269|PubMed:17893144"
FT REGION 300..442
FT /note="RNA:DNA duplex-binding"
FT /evidence="ECO:0000269|PubMed:26975377"
FT REGION 461..486
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 287
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:17893144,
FT ECO:0000269|PubMed:25550159, ECO:0000269|PubMed:26975377"
FT BINDING 367
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:17893144,
FT ECO:0000269|PubMed:25550159, ECO:0000269|PubMed:26975377"
FT BINDING 384
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:17893144,
FT ECO:0000269|PubMed:25550159"
FT BINDING 424
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000269|PubMed:17893144,
FT ECO:0000269|PubMed:25550159, ECO:0000269|PubMed:26975377"
FT MOD_RES 470
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 154..158
FT /note="ISDEE -> VSIFL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015111"
FT VAR_SEQ 159..509
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015112"
FT VARIANT 181
FT /note="E -> K (in dbSNP:rs5011403)"
FT /id="VAR_059742"
FT VARIANT 204
FT /note="D -> G (in dbSNP:rs6913546)"
FT /id="VAR_059743"
FT VARIANT 259
FT /note="G -> S (in dbSNP:rs927192)"
FT /id="VAR_059744"
FT VARIANT 265
FT /note="Q -> L (in dbSNP:rs3763183)"
FT /id="VAR_051506"
FT VARIANT 287
FT /note="C -> Y (in dbSNP:rs9476080)"
FT /id="VAR_059745"
FT VARIANT 446
FT /note="Q -> H (in dbSNP:rs4294007)"
FT /id="VAR_059747"
FT VARIANT 465
FT /note="P -> S (in dbSNP:rs4294008)"
FT /evidence="ECO:0007744|PubMed:19369195"
FT /id="VAR_059748"
FT MUTAGEN 97
FT /note="R->A: Decreases primase affinity for POLA1 by 10-
FT fold."
FT /evidence="ECO:0000269|PubMed:24043831"
FT MUTAGEN 104
FT /note="F->A: Decreases primase affinity for POLA1 by 40-
FT fold."
FT /evidence="ECO:0000269|PubMed:24043831"
FT MUTAGEN 107
FT /note="R->A: Decreases primase affinity for POLA1 by 30-
FT fold."
FT /evidence="ECO:0000269|PubMed:24043831"
FT MUTAGEN 108
FT /note="L->A: Decreases primase affinity for POLA1 by 40-
FT fold."
FT /evidence="ECO:0000269|PubMed:24043831"
FT MUTAGEN 256..270
FT /note="Missing: Decreases RNA primer di-nucleotide
FT formation about 5-fold. Does not affect the ratio between
FT the di-nucleotide and its extension products."
FT /evidence="ECO:0000269|PubMed:25550159"
FT CONFLICT 8
FT /note="W -> R (in Ref. 1; CAA52378)"
FT /evidence="ECO:0000305"
FT CONFLICT 40
FT /note="I -> T (in Ref. 1; CAA52378)"
FT /evidence="ECO:0000305"
FT CONFLICT 88
FT /note="N -> K (in Ref. 1; CAA52378)"
FT /evidence="ECO:0000305"
FT HELIX 39..61
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 67..80
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:4BPX"
FT HELIX 96..110
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 114..134
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 137..145
FT /evidence="ECO:0007829|PDB:4RR2"
FT STRAND 146..148
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 156..169
FT /evidence="ECO:0007829|PDB:4RR2"
FT STRAND 170..172
FT /evidence="ECO:0007829|PDB:4RR2"
FT STRAND 179..181
FT /evidence="ECO:0007829|PDB:4BPW"
FT STRAND 183..187
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 188..191
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 192..195
FT /evidence="ECO:0007829|PDB:4RR2"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:4RR2"
FT STRAND 200..210
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 211..235
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 238..241
FT /evidence="ECO:0007829|PDB:4RR2"
FT TURN 245..250
FT /evidence="ECO:0007829|PDB:4RR2"
FT TURN 252..255
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 273..276
FT /evidence="ECO:0007829|PDB:3L9Q"
FT HELIX 277..283
FT /evidence="ECO:0007829|PDB:3L9Q"
FT HELIX 286..298
FT /evidence="ECO:0007829|PDB:3L9Q"
FT HELIX 303..316
FT /evidence="ECO:0007829|PDB:3L9Q"
FT STRAND 318..324
FT /evidence="ECO:0007829|PDB:3L9Q"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:5F0Q"
FT HELIX 338..343
FT /evidence="ECO:0007829|PDB:5F0Q"
FT STRAND 345..351
FT /evidence="ECO:0007829|PDB:3L9Q"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:4RR2"
FT HELIX 367..372
FT /evidence="ECO:0007829|PDB:3L9Q"
FT HELIX 385..388
FT /evidence="ECO:0007829|PDB:3L9Q"
FT HELIX 391..400
FT /evidence="ECO:0007829|PDB:3L9Q"
FT HELIX 405..416
FT /evidence="ECO:0007829|PDB:3L9Q"
FT HELIX 420..432
FT /evidence="ECO:0007829|PDB:3L9Q"
FT HELIX 444..455
FT /evidence="ECO:0007829|PDB:3L9Q"
SQ SEQUENCE 509 AA; 58806 MW; 80195D48103F87A7 CRC64;
MEFSGRKWRK LRLAGDQRNA SYPHCLQFYL QPPSENISLI EFENLAIDRV KLLKSVENLG
VSYVKGTEQY QSKLESELRK LKFSYRENLE DEYEPRRRDH ISHFILRLAY CQSEELRRWF
IQQEMDLLRF RFSILPKDKI QDFLKDSQLQ FEAISDEEKT LREQEIVASS PSLSGLKLGF
ESIYKIPFAD ALDLFRGRKV YLEDGFAYVP LKDIVAIILN EFRAKLSKAL ALTARSLPAV
QSDERLQPLL NHLSHSYTGQ DYSTQGNVGK ISLDQIDLLS TKSFPPCMRQ LHKALRENHH
LRHGGRMQYG LFLKGIGLTL EQALQFWKQE FIKGKMDPDK FDKGYSYNIR HSFGKEGKRT
DYTPFSCLKI ILSNPPSQGD YHGCPFRHSD PELLKQKLQS YKISPGGISQ ILDLVKGTHY
QVACQKYFEM IHNVDDCGFS LNHPNQFFCE SQRILNGGKD IKKEPIQPET PQPKPSVQKT
KDASSALASL NSSLEMDMEG LEDYFSEDS
