CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-006332
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA polymerase alpha catalytic subunit 
Protein Synonyms/Alias
 DNA polymerase alpha catalytic subunit p180 
Gene Name
 Pola1 
Gene Synonyms/Alias
 Pola 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
136VKKPSVTKPNNIKAMacetylation[1]
212PKAIPSGKPASPVLRacetylation[2]
230LLTPIPLKRAELAGEacetylation[1, 2, 3]
974SYSRFYAKPLAALVTacetylation[1, 2]
974SYSRFYAKPLAALVTsuccinylation[1]
Reference
 [1] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [2] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [3] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 
Functional Description
 Plays an essential role in the initiation of DNA replication. During the S phase of the cell cycle, the DNA polymerase alpha complex (composed of a catalytic subunit POLA1/p180, a regulatory subunit POLA2/p70 and two primase subunits PRIM1/p49 and PRIM2/p58) is recruited to DNA at the replicative forks via direct interactions with MCM10 and WDHD1. The primase subunit of the polymerase alpha complex initiates DNA synthesis by oligomerising short RNA primers on both leading and lagging strands. These primers are initially extended by the polymerase alpha catalytic subunit and subsequently transferred to polymerase delta and polymerase epsilon for processive synthesis on the lagging and leading strand, respectively. The reason this transfer occurs is because the polymerase alpha has limited processivity and lacks intrinsic 3' exonuclease activity for proofreading error, and therefore is not well suited for replicating long complexes (By similarity). 
Sequence Annotation
 ZN_FING 1287 1317 CysA-type.
 REGION 654 719 DNA-binding region (Potential).
 REGION 1249 1380 DNA-binding region (Potential).
 MOTIF 1352 1378 CysB motif.
 METAL 1287 1287 Zinc (By similarity).
 METAL 1290 1290 Zinc (By similarity).
 METAL 1314 1314 Zinc (By similarity).
 METAL 1319 1319 Zinc (By similarity).
 METAL 1352 1352 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 1357 1357 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 1375 1375 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 1378 1378 Iron-sulfur (4Fe-4S) (By similarity).
 MOD_RES 180 180 Phosphothreonine (By similarity).
 MOD_RES 192 192 Phosphoserine.
 MOD_RES 215 215 Phosphoserine.  
Keyword
 4Fe-4S; Complete proteome; Direct protein sequencing; DNA replication; DNA-binding; DNA-directed DNA polymerase; Iron; Iron-sulfur; Metal-binding; Nucleotidyltransferase; Nucleus; Phosphoprotein; Reference proteome; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1465 AA 
Protein Sequence
MAPMHEEDCK LEASAVSDSG SFAASRARRE KKSKKGRQEA LERLKKAKAG EKYKYEVEDL 60
TSVYEEVDEE QYSKLVQARQ DDDWIVDDDG IGYVEDGREI FDDDLEDDAL DTCGKGSDGK 120
AHRKDRKDVK KPSVTKPNNI KAMFIASAGK KTTDKAVDLS KDDLLGDILQ DLNTETAQIT 180
PPPVLIPKKK RSTGALLNPF SVHTPKAIPS GKPASPVLRN EPLLTPIPLK RAELAGELAQ 240
PECPEDEQEL GVMEFEDGDF DESMDTEKVD EKPVTAKTWD QETEPVERVE HEADPERGTT 300
SYLENFLPDV SCWDIDQDDE SIPQEVQVDS SNLPLVKGAD DEQVFQFYWL DAYEDPYNQP 360
GVVFLFGKVW IESVKTHVSC CVMVKNIERT LYFLPREMKF DLNTGKETAI PVTMKDVYEE 420
FDSKISAKYK IMKFKSKIVE KNYAFEIPDV PEKSEYLEVR YSAEVPQLPQ NLKGETFSHV 480
FGTNTSSLEL FLMNRKIKGP CWLEVKNPQL LNQPISWCKF EVMALKPDLV NVIKDVSPPP 540
LVVMSFSMKT MQNVQNHQHE IIAMAALVHH SFALDKAPPE PPFQTHFCVV SKPKDCIFPC 600
DFKEVISKKN MKVEIAATER TLIGFFLAKV HKIDPDILVG HNICSFELEV LLQRINECKV 660
PYWSKIGRLR RSNMPKLGSR SGFGERNATC GRMICDVEIS AKELIHCKSY HLSELVQQIL 720
KTERIVIPTE NIRNMYSESS YLLYLLEHIW KDARFILQIM CELNVLPLAL QITNIAGNIM 780
SRTLMGGRSE RNEFLLLHAF YENNYIVPDK QIFRKPQQKL GDEDEEIDGD TNKYKKGRKK 840
ATYAGGLVLD PKVGFYDKFI LLLDFNSLYP SIIQEFNICF TTVQRVTSEV QKATEDEEQE 900
QIPELPDPNL EMGILPREIR KLVERRKQVK QLMKQQDLNP DLVLQYDIRQ KALKLTANSM 960
YGCLGFSYSR FYAKPLAALV TYKGREILMH TKDMVQKMNL EVIYGDTDSI MINTNSTNLE 1020
EVFKLGNKVK SEVNKLYKLL EIDIDAVFKS LLLLKKKKYA ALVVEPTSDG NYITKQELKG 1080
LDIVRRDWCD LAKDTGNFVI GQILSDQSRD TIVENIQKRL IEIGENVLNG SVPVSQFEIN 1140
KALTKDPQDY PDRKSLPHVH VALWINSQGG RKVKAGDTVS YVICQDGSNL TATQRAYAPE 1200
QLQKLDNLAI DTQYYLAQQI HPVVARICEP IDGIDAVLIA LWLGLDSTQF RVHQYHKDEE 1260
NDALLGGPAQ LTDEEKYKDC EKFKCLCPSC GTENIYDNVF EGSGLDMEPS LYRCSNVDCK 1320
VSPLTFMVQL SNKLIMDIRR CIKKYYDGWL ICEEPTCCSR LRRLPLHFSR NGPLCPVCMK 1380
AVLRPEYSDK SLYTQLCFYR YIFDADCALE KLTEHEKDKL KKQFFPLRVL QDYRKVKNIA 1440
EQFLSWSGYS EVNLSKLFAN YAGKS 1465 
Gene Ontology
 GO:0005658; C:alpha DNA polymerase:primase complex; ISS:UniProtKB.
 GO:0000785; C:chromatin; IEA:Compara.
 GO:0005737; C:cytoplasm; IEA:Compara.
 GO:0005635; C:nuclear envelope; ISS:UniProtKB.
 GO:0016363; C:nuclear matrix; ISS:UniProtKB.
 GO:0005730; C:nucleolus; ISS:UniProtKB.
 GO:0005654; C:nucleoplasm; ISS:UniProtKB.
 GO:0008408; F:3'-5' exonuclease activity; IBA:RefGenome.
 GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
 GO:0003682; F:chromatin binding; ISS:UniProtKB.
 GO:0003677; F:DNA binding; ISS:UniProtKB.
 GO:0003896; F:DNA primase activity; IEA:Compara.
 GO:0003887; F:DNA-directed DNA polymerase activity; ISS:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0001882; F:nucleoside binding; IEA:InterPro.
 GO:0000166; F:nucleotide binding; ISS:UniProtKB.
 GO:0008283; P:cell proliferation; ISS:UniProtKB.
 GO:0006270; P:DNA replication initiation; ISS:UniProtKB.
 GO:0006303; P:double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
 GO:0006273; P:lagging strand elongation; ISS:UniProtKB.
 GO:0006272; P:leading strand elongation; ISS:UniProtKB.
 GO:0000084; P:S phase of mitotic cell cycle; ISS:UniProtKB.
 GO:0019985; P:translesion synthesis; IBA:RefGenome. 
Interpro
 IPR006172; DNA-dir_DNA_pol_B.
 IPR017964; DNA-dir_DNA_pol_B_CS.
 IPR006133; DNA-dir_DNA_pol_B_exonuc.
 IPR006134; DNA-dir_DNA_pol_B_multi_dom.
 IPR004578; DNA-dir_DNA_pol_B_pol2.
 IPR024647; DNA_pol_a_cat_su_N.
 IPR023211; DNA_pol_palm_dom.
 IPR012337; RNaseH-like_dom.
 IPR015088; Znf_DNA-dir_DNA_pol_B_alpha. 
Pfam
 PF12254; DNA_pol_alpha_N
 PF00136; DNA_pol_B
 PF03104; DNA_pol_B_exo1
 PF08996; zf-DNA_Pol 
SMART
 SM00486; POLBc 
PROSITE
 PS00116; DNA_POLYMERASE_B 
PRINTS
 PR00106; DNAPOLB.