CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002832
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
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
599CIFPYAFKEVIEKKNacetylation[1]
970SYSRFYAKPLAALVTubiquitination[2]
1200YAPEQLQKQDNLTIDubiquitination[3]
Reference
 [1] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
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. 
Sequence Annotation
 ZN_FING 1283 1315 CysA-type.
 REGION 650 715 DNA-binding region (Potential).
 REGION 1245 1376 DNA-binding region (Potential).
 MOTIF 1348 1374 CysB motif.
 METAL 1283 1283 Zinc (By similarity).
 METAL 1286 1286 Zinc (By similarity).
 METAL 1310 1310 Zinc (By similarity).
 METAL 1315 1315 Zinc (By similarity).
 METAL 1348 1348 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 1353 1353 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 1371 1371 Iron-sulfur (4Fe-4S) (By similarity).
 METAL 1374 1374 Iron-sulfur (4Fe-4S) (By similarity).
 MOD_RES 174 174 Phosphothreonine.
 MOD_RES 186 186 Phosphoserine.
 MOD_RES 190 190 Phosphoserine.
 MOD_RES 209 209 Phosphoserine.  
Keyword
 3D-structure; 4Fe-4S; Complete proteome; Direct protein sequencing; DNA replication; DNA-binding; DNA-directed DNA polymerase; Host-virus interaction; Iron; Iron-sulfur; Metal-binding; Nucleotidyltransferase; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1462 AA 
Protein Sequence
MAPVHGDDSL SDSGSFVSSR ARREKKSKKG RQEALERLKK AKAGEKYKYE VEDFTGVYEE 60
VDEEQYSKLV QARQDDDWIV DDDGIGYVED GREIFDDDLE DDALDADEKG KDGKARNKDK 120
RNVKKLAVTK PNNIKSMFIA CAGKKTADKA VDLSKDGLLG DILQDLNTET PQITPPPVMI 180
LKKKRSIGAS PNPFSVHTAT AVPSGKIASP VSRKEPPLTP VPLKRAEFAG DDVQVESTEE 240
EQESGAMEFE DGDFDEPMEV EEVDLEPMAA KAWDKESEPA EEVKQEADSG KGTVSYLGSF 300
LPDVSCWDID QEGDSSFSVQ EVQVDSSHLP LVKGADEEQV FHFYWLDAYE DQYNQPGVVF 360
LFGKVWIESA ETHVSCCVMV KNIERTLYFL PREMKIDLNT GKETGTPISM KDVYEEFDEK 420
IATKYKIMKF KSKPVEKNYA FEIPDVPEKS EYLEVKYSAE MPQLPQDLKG ETFSHVFGTN 480
TSSLELFLMN RKIKGPCWLE VKSPQLLNQP VSWCKVEAMA LKPDLVNVIK DVSPPPLVVM 540
AFSMKTMQNA KNHQNEIIAM AALVHHSFAL DKAAPKPPFQ SHFCVVSKPK DCIFPYAFKE 600
VIEKKNVKVE VAATERTLLG FFLAKVHKID PDIIVGHNIY GFELEVLLQR INVCKAPHWS 660
KIGRLKRSNM PKLGGRSGFG ERNATCGRMI CDVEISAKEL IRCKSYHLSE LVQQILKTER 720
VVIPMENIQN MYSESSQLLY LLEHTWKDAK FILQIMCELN VLPLALQITN IAGNIMSRTL 780
MGGRSERNEF LLLHAFYENN YIVPDKQIFR KPQQKLGDED EEIDGDTNKY KKGRKKAAYA 840
GGLVLDPKVG FYDKFILLLD FNSLYPSIIQ EFNICFTTVQ RVASEAQKVT EDGEQEQIPE 900
LPDPSLEMGI LPREIRKLVE RRKQVKQLMK QQDLNPDLIL QYDIRQKALK LTANSMYGCL 960
GFSYSRFYAK PLAALVTYKG REILMHTKEM VQKMNLEVIY GDTDSIMINT NSTNLEEVFK 1020
LGNKVKSEVN KLYKLLEIDI DGVFKSLLLL KKKKYAALVV EPTSDGNYVT KQELKGLDIV 1080
RRDWCDLAKD TGNFVIGQIL SDQSRDTIVE NIQKRLIEIG ENVLNGSVPV SQFEINKALT 1140
KDPQDYPDKK SLPHVHVALW INSQGGRKVK AGDTVSYVIC QDGSNLTASQ RAYAPEQLQK 1200
QDNLTIDTQY YLAQQIHPVV ARICEPIDGI DAVLIATWLG LDPTQFRVHH YHKDEENDAL 1260
LGGPAQLTDE EKYRDCERFK CPCPTCGTEN IYDNVFDGSG TDMEPSLYRC SNIDCKASPL 1320
TFTVQLSNKL IMDIRRFIKK YYDGWLICEE PTCRNRTRHL PLQFSRTGPL CPACMKATLQ 1380
PEYSDKSLYT QLCFYRYIFD AECALEKLTT DHEKDKLKKQ FFTPKVLQDY RKLKNTAEQF 1440
LSRSGYSEVN LSKLFAGCAV KS 1462 
Gene Ontology
 GO:0005658; C:alpha DNA polymerase:primase complex; IDA:UniProtKB.
 GO:0005737; C:cytoplasm; IDA:HPA.
 GO:0005635; C:nuclear envelope; IDA:UniProtKB.
 GO:0016363; C:nuclear matrix; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; IDA: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; IDA:UniProtKB.
 GO:0003677; F:DNA binding; IDA:UniProtKB.
 GO:0003887; F:DNA-directed DNA polymerase activity; IDA:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0001882; F:nucleoside binding; IEA:InterPro.
 GO:0000166; F:nucleotide binding; IDA:UniProtKB.
 GO:0008283; P:cell proliferation; IDA:UniProtKB.
 GO:0006270; P:DNA replication initiation; IDA:UniProtKB.
 GO:0006269; P:DNA replication, synthesis of RNA primer; IDA:GOC.
 GO:0006303; P:double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
 GO:0006273; P:lagging strand elongation; IDA:UniProtKB.
 GO:0006272; P:leading strand elongation; IDA:UniProtKB.
 GO:0000083; P:regulation of transcription involved in G1/S phase of mitotic cell cycle; TAS:Reactome.
 GO:0000084; P:S phase of mitotic cell cycle; IDA:UniProtKB.
 GO:0000722; P:telomere maintenance via recombination; TAS:Reactome.
 GO:0032201; P:telomere maintenance via semi-conservative replication; TAS:Reactome.
 GO:0019985; P:translesion synthesis; IBA:RefGenome.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
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.