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P33609 (DPOLA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA polymerase alpha catalytic subunit

EC=2.7.7.7
Alternative name(s):
DNA polymerase alpha catalytic subunit p180
Gene names
Name:Pola1
Synonyms:Pola
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1465 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).

Cofactor

Binds 1 4Fe-4S cluster By similarity.

Subunit structure

The DNA polymerase alpha complex is composed of four subunits: the catalytic subunit POLA1, the regulatory subunit POLA2, and the small and the large primase subunits PRIM1 and PRIM2 respectively. Interacts with PARP1; this interaction functions as part of the control of replication fork progression. Interacts with MCM10 and WDHD1; these interactions recruit the polymerase alpha complex to the pre-replicative complex bound to DNA. Interacts with RPA1; this interaction stabilizes the replicative complex and reduces the misincorporation rate of DNA polymerase alpha by acting as a fidelity clamp By similarity.

Subcellular location

Nucleus.

Domain

The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes By similarity.

Miscellaneous

In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.

Conserved regions II, IV, III and I are thought to be involved in substrate recognition, binding or PP(i) hydrolysis.

Sequence similarities

Belongs to the DNA polymerase type-B family.

Contains 1 CysA-type zinc finger.

Ontologies

Keywords
   Biological processDNA replication
   Cellular componentNucleus
   DomainZinc-finger
   Ligand4Fe-4S
DNA-binding
Iron
Iron-sulfur
Metal-binding
Zinc
   Molecular functionDNA-directed DNA polymerase
Nucleotidyltransferase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from sequence or structural similarity. Source: UniProtKB

DNA replication initiation

Inferred from sequence or structural similarity. Source: UniProtKB

DNA strand elongation involved in DNA replication

Inferred from sequence or structural similarity. Source: UniProtKB

cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

double-strand break repair via nonhomologous end joining

Inferred from sequence or structural similarity. Source: UniProtKB

lagging strand elongation

Inferred from sequence or structural similarity. Source: UniProtKB

leading strand elongation

Inferred from sequence or structural similarity. Source: UniProtKB

mitotic S phase

Inferred from sequence or structural similarity. Source: UniProtKB

nucleic acid phosphodiester bond hydrolysis

Inferred from Biological aspect of Ancestor. Source: GOC

translesion synthesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentalpha DNA polymerase:primase complex

Inferred from sequence or structural similarity. Source: UniProtKB

chromatin

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from electronic annotation. Source: Ensembl

nuclear envelope

Inferred from sequence or structural similarity. Source: UniProtKB

nuclear matrix

Inferred from sequence or structural similarity. Source: UniProtKB

nucleolus

Inferred from sequence or structural similarity. Source: UniProtKB

nucleoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_function3'-5' exonuclease activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

4 iron, 4 sulfur cluster binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

DNA primase activity

Inferred from electronic annotation. Source: Ensembl

DNA-directed DNA polymerase activity

Inferred from sequence or structural similarity. Source: UniProtKB

chromatin binding

Inferred from sequence or structural similarity. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

nucleoside binding

Inferred from electronic annotation. Source: InterPro

nucleotide binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction PubMed 10523676. Source: IntAct

protein heterodimerization activity

Inferred from physical interaction PubMed 9584195. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Pola2P336115EBI-688051,EBI-848759
Prim1P206644EBI-688051,EBI-848742

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14651465DNA polymerase alpha catalytic subunit
PRO_0000046429

Regions

Zinc finger1287 – 131731CysA-type
Region654 – 71966DNA-binding region Potential
Region1249 – 1380132DNA-binding region Potential
Motif1352 – 137827CysB motif

Sites

Metal binding12871Zinc By similarity
Metal binding12901Zinc By similarity
Metal binding13141Zinc By similarity
Metal binding13191Zinc By similarity
Metal binding13521Iron-sulfur (4Fe-4S) By similarity
Metal binding13571Iron-sulfur (4Fe-4S) By similarity
Metal binding13751Iron-sulfur (4Fe-4S) By similarity
Metal binding13781Iron-sulfur (4Fe-4S) By similarity

Amino acid modifications

Modified residue1801Phosphothreonine By similarity
Modified residue1921Phosphoserine By similarity
Modified residue2151Phosphoserine By similarity
Modified residue2301N6-acetyllysine Ref.3
Modified residue9741N6-succinyllysine Ref.3

Natural variations

Natural variant11801S → F in temperature-sensitive FT20 cell line; defective activity. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P33609 [UniParc].

Last modified June 1, 1994. Version 2.
Checksum: 46D1A9818A7944A3

FASTA1,465167,340
        10         20         30         40         50         60 
MAPMHEEDCK LEASAVSDSG SFAASRARRE KKSKKGRQEA LERLKKAKAG EKYKYEVEDL 

        70         80         90        100        110        120 
TSVYEEVDEE QYSKLVQARQ DDDWIVDDDG IGYVEDGREI FDDDLEDDAL DTCGKGSDGK 

       130        140        150        160        170        180 
AHRKDRKDVK KPSVTKPNNI KAMFIASAGK KTTDKAVDLS KDDLLGDILQ DLNTETAQIT 

       190        200        210        220        230        240 
PPPVLIPKKK RSTGALLNPF SVHTPKAIPS GKPASPVLRN EPLLTPIPLK RAELAGELAQ 

       250        260        270        280        290        300 
PECPEDEQEL GVMEFEDGDF DESMDTEKVD EKPVTAKTWD QETEPVERVE HEADPERGTT 

       310        320        330        340        350        360 
SYLENFLPDV SCWDIDQDDE SIPQEVQVDS SNLPLVKGAD DEQVFQFYWL DAYEDPYNQP 

       370        380        390        400        410        420 
GVVFLFGKVW IESVKTHVSC CVMVKNIERT LYFLPREMKF DLNTGKETAI PVTMKDVYEE 

       430        440        450        460        470        480 
FDSKISAKYK IMKFKSKIVE KNYAFEIPDV PEKSEYLEVR YSAEVPQLPQ NLKGETFSHV 

       490        500        510        520        530        540 
FGTNTSSLEL FLMNRKIKGP CWLEVKNPQL LNQPISWCKF EVMALKPDLV NVIKDVSPPP 

       550        560        570        580        590        600 
LVVMSFSMKT MQNVQNHQHE IIAMAALVHH SFALDKAPPE PPFQTHFCVV SKPKDCIFPC 

       610        620        630        640        650        660 
DFKEVISKKN MKVEIAATER TLIGFFLAKV HKIDPDILVG HNICSFELEV LLQRINECKV 

       670        680        690        700        710        720 
PYWSKIGRLR RSNMPKLGSR SGFGERNATC GRMICDVEIS AKELIHCKSY HLSELVQQIL 

       730        740        750        760        770        780 
KTERIVIPTE NIRNMYSESS YLLYLLEHIW KDARFILQIM CELNVLPLAL QITNIAGNIM 

       790        800        810        820        830        840 
SRTLMGGRSE RNEFLLLHAF YENNYIVPDK QIFRKPQQKL GDEDEEIDGD TNKYKKGRKK 

       850        860        870        880        890        900 
ATYAGGLVLD PKVGFYDKFI LLLDFNSLYP SIIQEFNICF TTVQRVTSEV QKATEDEEQE 

       910        920        930        940        950        960 
QIPELPDPNL EMGILPREIR KLVERRKQVK QLMKQQDLNP DLVLQYDIRQ KALKLTANSM 

       970        980        990       1000       1010       1020 
YGCLGFSYSR FYAKPLAALV TYKGREILMH TKDMVQKMNL EVIYGDTDSI MINTNSTNLE 

      1030       1040       1050       1060       1070       1080 
EVFKLGNKVK SEVNKLYKLL EIDIDAVFKS LLLLKKKKYA ALVVEPTSDG NYITKQELKG 

      1090       1100       1110       1120       1130       1140 
LDIVRRDWCD LAKDTGNFVI GQILSDQSRD TIVENIQKRL IEIGENVLNG SVPVSQFEIN 

      1150       1160       1170       1180       1190       1200 
KALTKDPQDY PDRKSLPHVH VALWINSQGG RKVKAGDTVS YVICQDGSNL TATQRAYAPE 

      1210       1220       1230       1240       1250       1260 
QLQKLDNLAI DTQYYLAQQI HPVVARICEP IDGIDAVLIA LWLGLDSTQF RVHQYHKDEE 

      1270       1280       1290       1300       1310       1320 
NDALLGGPAQ LTDEEKYKDC EKFKCLCPSC GTENIYDNVF EGSGLDMEPS LYRCSNVDCK 

      1330       1340       1350       1360       1370       1380 
VSPLTFMVQL SNKLIMDIRR CIKKYYDGWL ICEEPTCCSR LRRLPLHFSR NGPLCPVCMK 

      1390       1400       1410       1420       1430       1440 
AVLRPEYSDK SLYTQLCFYR YIFDADCALE KLTEHEKDKL KKQFFPLRVL QDYRKVKNIA 

      1450       1460 
EQFLSWSGYS EVNLSKLFAN YAGKS 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the cDNAs for the four subunits of mouse DNA polymerase alpha-primase complex and their gene expression during cell proliferation and the cell cycle."
Miyazawa H., Izumi M., Tada S., Takada R., Masutani M., Ui M., Hanaoka F.
J. Biol. Chem. 268:8111-8122(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 454-472 AND 1438-1455.
[2]"DNA replication in vitro by recombinant DNA-polymerase-alpha-primase."
Stadlbauer F., Brueckner A., Rehfuess C., Eckerskorn C., Lottspeich F., Foerster V., Tseng B.Y., Nasheuer H.-P.
Eur. J. Biochem. 222:781-793(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-230, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-974, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[4]"Identification of a point mutation in the cDNA of the catalytic subunit of DNA polymerase alpha from a temperature-sensitive mouse FM3A cell line."
Izumi M., Miyazawa H., Harakawa S., Yatagai F., Hanaoka F.
J. Biol. Chem. 269:7639-7644(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHE-1180.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D13543 mRNA. Translation: BAA40003.1.
D17384 mRNA. Translation: BAA04202.1.
CCDSCCDS30272.1.
PIRS45628.
RefSeqNP_032918.1. NM_008892.2.
UniGeneMm.1923.

3D structure databases

ProteinModelPortalP33609.
SMRP33609. Positions 345-1244, 1273-1426.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202287. 1 interaction.
IntActP33609. 4 interactions.
MINTMINT-1727003.

Chemistry

BindingDBP33609.

PTM databases

PhosphoSiteP33609.

Proteomic databases

MaxQBP33609.
PaxDbP33609.
PRIDEP33609.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000006856; ENSMUSP00000006856; ENSMUSG00000006678.
GeneID18968.
KEGGmmu:18968.
UCSCuc009tss.2. mouse.

Organism-specific databases

CTD5422.
MGIMGI:99660. Pola1.

Phylogenomic databases

eggNOGCOG0417.
GeneTreeENSGT00550000074891.
HOGENOMHOG000163524.
HOVERGENHBG080008.
InParanoidP33609.
KOK02320.
OMAEKYRDCE.
OrthoDBEOG7CNZDZ.
PhylomeDBP33609.
TreeFamTF103001.

Gene expression databases

ArrayExpressP33609.
BgeeP33609.
CleanExMM_POLA1.
GenevestigatorP33609.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
3.90.1600.10. 2 hits.
InterProIPR006172. 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.
[Graphical view]
PfamPF12254. DNA_pol_alpha_N. 1 hit.
PF00136. DNA_pol_B. 1 hit.
PF03104. DNA_pol_B_exo1. 1 hit.
PF08996. zf-DNA_Pol. 1 hit.
[Graphical view]
PRINTSPR00106. DNAPOLB.
SMARTSM00486. POLBc. 1 hit.
[Graphical view]
SUPFAMSSF53098. SSF53098. 1 hit.
TIGRFAMsTIGR00592. pol2. 1 hit.
PROSITEPS00116. DNA_POLYMERASE_B. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio295308.
PROP33609.
SOURCESearch...

Entry information

Entry nameDPOLA_MOUSE
AccessionPrimary (citable) accession number: P33609
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1994
Last sequence update: June 1, 1994
Last modified: July 9, 2014
This is version 123 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot