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 27-MAR-2024, entry version 193. 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}. 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; 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 PDB; 7U5C; EM; 4.60 A; B=1-509. DR PDB; 8B9D; EM; 3.40 A; P=1-509. DR PDB; 8D0B; EM; 3.43 A; E=16-256. DR PDB; 8D0K; EM; 4.27 A; E=2-509. DR PDB; 8D96; EM; 3.35 A; B=1-509. DR PDB; 8D9D; EM; 3.59 A; B=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 PDBsum; 7U5C; -. DR PDBsum; 8B9D; -. DR PDBsum; 8D0B; -. DR PDBsum; 8D0K; -. DR PDBsum; 8D96; -. DR PDBsum; 8D9D; -. DR AlphaFoldDB; P49643; -. DR EMDB; EMD-13020; -. DR EMDB; EMD-26346; -. DR EMDB; EMD-26347; -. DR EMDB; EMD-27104; -. DR EMDB; EMD-27107; -. DR EMDB; EMD-27256; -. DR EMDB; EMD-27258; -. DR EMDB; EMD-42033; -. DR EMDB; EMD-42034; -. DR EMDB; EMD-42035; -. DR EMDB; EMD-42036; -. DR EMDB; EMD-42037; -. DR SASBDB; P49643; -. DR SMR; P49643; -. DR BioGRID; 111548; 138. 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 GlyGen; P49643; 1 site, 1 O-linked glycan (1 site). 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 PaxDb; 9606-ENSP00000484105; -. DR PeptideAtlas; P49643; -. DR ProteomicsDB; 56041; -. [P49643-1] DR ProteomicsDB; 56042; -. [P49643-2] DR Pumba; P49643; -. DR Antibodypedia; 31147; 177 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 AGR; HGNC:9370; -. 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; RINYKPW; -. DR OrthoDB; 3184472at2759; -. 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; 53 hits in 302 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 108 other cell types or tissues. DR ExpressionAtlas; P49643; baseline and differential. 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 Gene3D; 1.20.930.80; -; 1. DR InterPro; IPR016558; DNA_primase_lsu_euk. DR InterPro; IPR007238; DNA_primase_lsu_euk/arc. DR PANTHER; PTHR10537; DNA PRIMASE LARGE SUBUNIT; 1. DR PANTHER; PTHR10537:SF3; DNA PRIMASE LARGE SUBUNIT; 1. DR Pfam; PF04104; DNA_primase_lrg; 1. DR PIRSF; PIRSF009449; DNA_primase_large_subunit; 1. DR SUPFAM; SSF140914; PriB N-terminal domain-like; 1. DR Genevisible; P49643; HS. 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:rs1419333837)" FT /evidence="ECO:0007744|PubMed:19369195" FT /id="VAR_059748" FT MUTAGEN 97 FT /note="R->A: Decreases primase affinity for POLA1 by FT 10-fold." FT /evidence="ECO:0000269|PubMed:24043831" FT MUTAGEN 104 FT /note="F->A: Decreases primase affinity for POLA1 by FT 40-fold." FT /evidence="ECO:0000269|PubMed:24043831" FT MUTAGEN 107 FT /note="R->A: Decreases primase affinity for POLA1 by FT 30-fold." FT /evidence="ECO:0000269|PubMed:24043831" FT MUTAGEN 108 FT /note="L->A: Decreases primase affinity for POLA1 by FT 40-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 17..21 FT /evidence="ECO:0007829|PDB:8D0B" FT STRAND 35..37 FT /evidence="ECO:0007829|PDB:8D0B" 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 //