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Protein

DNA polymerase alpha catalytic subunit

Gene

POLA1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. In the cytosol, responsible for a substantial proportion of the physiological concentration of cytosolic RNA:DNA hybrids, which are necessary to prevent spontaneous activation of type I interferon responses (PubMed:27019227).2 Publications

Miscellaneous

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

Catalytic activityi

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

Cofactori

[4Fe-4S] clusterBy similarityNote: Binds 1 [4Fe-4S] cluster.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi1283ZincBy similarity1
Metal bindingi1286ZincBy similarity1
Metal bindingi1310ZincBy similarity1
Metal bindingi1315ZincBy similarity1
Metal bindingi1348Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1353Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1371Iron-sulfur (4Fe-4S)By similarity1
Metal bindingi1374Iron-sulfur (4Fe-4S)By similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1283 – 1315CysA-typeAdd BLAST33

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, DNA-directed DNA polymerase, Nucleotidyltransferase, Transferase
Biological processDNA replication, Host-virus interaction
Ligand4Fe-4S, Iron, Iron-sulfur, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-174411 Polymerase switching on the C-strand of the telomere
R-HSA-174430 Telomere C-strand synthesis initiation
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-68952 DNA replication initiation
R-HSA-68962 Activation of the pre-replicative complex
R-HSA-69091 Polymerase switching
R-HSA-69166 Removal of the Flap Intermediate
R-HSA-69183 Processive synthesis on the lagging strand

Names & Taxonomyi

Protein namesi
Recommended name:
DNA polymerase alpha catalytic subunit (EC:2.7.7.7)
Alternative name(s):
DNA polymerase alpha catalytic subunit p180
Gene namesi
Name:POLA1
Synonyms:POLA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000101868.10
HGNCiHGNC:9173 POLA1
MIMi312040 gene
neXtProtiNX_P09884

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Pigmentary disorder, reticulate, with systemic manifestations, X-linked (PDR)1 Publication
The disease is caused by mutations affecting the gene represented in this entry. XLPDR is caused by a recurrent intronic mutation that results in missplicing and reduced POLA1 expression. This leads to a decrease in cytosolic RNA:DNA hybrids and constitutive activation of type I interferon responses, but has no effect on cell replication.1 Publication
Disease descriptionA X-linked recessive disorder characterized by recurrent infections and sterile inflammation in various organs. Diffuse skin hyperpigmentation with a distinctive reticulate pattern is universally evident by early childhood. This is later followed in many patients by hypohidrosis, corneal inflammation and scarring, enterocolitis that resembles inflammatory bowel disease, and recurrent urethral strictures. Melanin and amyloid deposition is present in the dermis. Affected males also have a characteristic facies with frontally upswept hair and flared eyebrows. Female carriers have only restricted pigmentary changes along Blaschko's lines.
See also OMIM:301220

Organism-specific databases

DisGeNETi5422
MalaCardsiPOLA1
MIMi301220 phenotype
OpenTargetsiENSG00000101868
PharmGKBiPA162399856

Chemistry databases

ChEMBLiCHEMBL1828
DrugBankiDB00242 Cladribine
DB00631 Clofarabine
DB01073 Fludarabine
DB01280 Nelarabine

Polymorphism and mutation databases

BioMutaiPOLA1
DMDMi60392197

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000464281 – 1462DNA polymerase alpha catalytic subunitAdd BLAST1462

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei174PhosphothreonineCombined sources1
Modified residuei186PhosphoserineCombined sources1
Modified residuei190PhosphoserineCombined sources1
Modified residuei209PhosphoserineCombined sources1
Modified residuei224N6-acetyllysineBy similarity1
Modified residuei406PhosphothreonineCombined sources1
Modified residuei970N6-succinyllysineBy similarity1

Post-translational modificationi

A 165 kDa form is probably produced by proteolytic cleavage at Lys-124.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei124 – 125Cleavage2

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP09884
MaxQBiP09884
PaxDbiP09884
PeptideAtlasiP09884
PRIDEiP09884
ProteomicsDBi52272

PTM databases

CarbonylDBiP09884
iPTMnetiP09884
PhosphoSitePlusiP09884

Expressioni

Gene expression databases

BgeeiENSG00000101868 Expressed in 174 organ(s), highest expression level in intestine
CleanExiHS_POLA1
ExpressionAtlasiP09884 baseline and differential
GenevisibleiP09884 HS

Organism-specific databases

HPAiCAB012274
HPA002947

Interactioni

Subunit structurei

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.3 Publications
(Microbial infection) Interacts with SV40 Large T antigen; this interaction allows viral DNA replication.1 Publication
(Microbial infection) Interacts with herpes simplex virus 1/HHV-1 replication origin-binding protein UL9.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111418, 58 interactors
ComplexPortaliCPX-2087 DNA polymerase alpha:primase complex
CORUMiP09884
IntActiP09884, 14 interactors
MINTiP09884
STRINGi9606.ENSP00000368349

Chemistry databases

BindingDBiP09884

Structurei

Secondary structure

11462
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP09884
SMRiP09884
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09884

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni650 – 715DNA-binding regionSequence analysisAdd BLAST66
Regioni1245 – 1376DNA-binding regionSequence analysisAdd BLAST132

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1348 – 1374CysB motifAdd BLAST27

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi75 – 112Asp-richAdd BLAST38
Compositional biasi1047 – 1050Poly-Leu4
Compositional biasi1051 – 1054Poly-Lys4

Domaini

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

Sequence similaritiesi

Belongs to the DNA polymerase type-B family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1283 – 1315CysA-typeAdd BLAST33

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0970 Eukaryota
COG0417 LUCA
GeneTreeiENSGT00550000074891
HOGENOMiHOG000163524
HOVERGENiHBG080008
InParanoidiP09884
KOiK02320
PhylomeDBiP09884
TreeFamiTF103001

Family and domain databases

Gene3Di1.10.3200.20, 1 hit
3.30.420.10, 1 hit
3.90.1600.10, 1 hit
InterProiView protein in 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
IPR024647 DNA_pol_a_cat_su_N
IPR023211 DNA_pol_palm_dom_sf
IPR038256 Pol_alpha_znc_sf
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
IPR015088 Znf_DNA-dir_DNA_pol_B_alpha
PfamiView protein in Pfam
PF12254 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
PRINTSiPR00106 DNAPOLB
SMARTiView protein in SMART
SM00486 POLBc, 1 hit
SUPFAMiSSF53098 SSF53098, 1 hit
PROSITEiView protein in PROSITE
PS00116 DNA_POLYMERASE_B, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P09884-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAPVHGDDSL SDSGSFVSSR ARREKKSKKG RQEALERLKK AKAGEKYKYE
60 70 80 90 100
VEDFTGVYEE VDEEQYSKLV QARQDDDWIV DDDGIGYVED GREIFDDDLE
110 120 130 140 150
DDALDADEKG KDGKARNKDK RNVKKLAVTK PNNIKSMFIA CAGKKTADKA
160 170 180 190 200
VDLSKDGLLG DILQDLNTET PQITPPPVMI LKKKRSIGAS PNPFSVHTAT
210 220 230 240 250
AVPSGKIASP VSRKEPPLTP VPLKRAEFAG DDVQVESTEE EQESGAMEFE
260 270 280 290 300
DGDFDEPMEV EEVDLEPMAA KAWDKESEPA EEVKQEADSG KGTVSYLGSF
310 320 330 340 350
LPDVSCWDID QEGDSSFSVQ EVQVDSSHLP LVKGADEEQV FHFYWLDAYE
360 370 380 390 400
DQYNQPGVVF LFGKVWIESA ETHVSCCVMV KNIERTLYFL PREMKIDLNT
410 420 430 440 450
GKETGTPISM KDVYEEFDEK IATKYKIMKF KSKPVEKNYA FEIPDVPEKS
460 470 480 490 500
EYLEVKYSAE MPQLPQDLKG ETFSHVFGTN TSSLELFLMN RKIKGPCWLE
510 520 530 540 550
VKSPQLLNQP VSWCKVEAMA LKPDLVNVIK DVSPPPLVVM AFSMKTMQNA
560 570 580 590 600
KNHQNEIIAM AALVHHSFAL DKAAPKPPFQ SHFCVVSKPK DCIFPYAFKE
610 620 630 640 650
VIEKKNVKVE VAATERTLLG FFLAKVHKID PDIIVGHNIY GFELEVLLQR
660 670 680 690 700
INVCKAPHWS KIGRLKRSNM PKLGGRSGFG ERNATCGRMI CDVEISAKEL
710 720 730 740 750
IRCKSYHLSE LVQQILKTER VVIPMENIQN MYSESSQLLY LLEHTWKDAK
760 770 780 790 800
FILQIMCELN VLPLALQITN IAGNIMSRTL MGGRSERNEF LLLHAFYENN
810 820 830 840 850
YIVPDKQIFR KPQQKLGDED EEIDGDTNKY KKGRKKAAYA GGLVLDPKVG
860 870 880 890 900
FYDKFILLLD FNSLYPSIIQ EFNICFTTVQ RVASEAQKVT EDGEQEQIPE
910 920 930 940 950
LPDPSLEMGI LPREIRKLVE RRKQVKQLMK QQDLNPDLIL QYDIRQKALK
960 970 980 990 1000
LTANSMYGCL GFSYSRFYAK PLAALVTYKG REILMHTKEM VQKMNLEVIY
1010 1020 1030 1040 1050
GDTDSIMINT NSTNLEEVFK LGNKVKSEVN KLYKLLEIDI DGVFKSLLLL
1060 1070 1080 1090 1100
KKKKYAALVV EPTSDGNYVT KQELKGLDIV RRDWCDLAKD TGNFVIGQIL
1110 1120 1130 1140 1150
SDQSRDTIVE NIQKRLIEIG ENVLNGSVPV SQFEINKALT KDPQDYPDKK
1160 1170 1180 1190 1200
SLPHVHVALW INSQGGRKVK AGDTVSYVIC QDGSNLTASQ RAYAPEQLQK
1210 1220 1230 1240 1250
QDNLTIDTQY YLAQQIHPVV ARICEPIDGI DAVLIATWLG LDPTQFRVHH
1260 1270 1280 1290 1300
YHKDEENDAL LGGPAQLTDE EKYRDCERFK CPCPTCGTEN IYDNVFDGSG
1310 1320 1330 1340 1350
TDMEPSLYRC SNIDCKASPL TFTVQLSNKL IMDIRRFIKK YYDGWLICEE
1360 1370 1380 1390 1400
PTCRNRTRHL PLQFSRTGPL CPACMKATLQ PEYSDKSLYT QLCFYRYIFD
1410 1420 1430 1440 1450
AECALEKLTT DHEKDKLKKQ FFTPKVLQDY RKLKNTAEQF LSRSGYSEVN
1460
LSKLFAGCAV KS
Length:1,462
Mass (Da):165,913
Last modified:February 1, 2005 - v2
Checksum:iDC40C3EDD6F4B495
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A6NMQ1A6NMQ1_HUMAN
DNA polymerase
POLA1
1,468Annotation score:
A0A087WU64A0A087WU64_HUMAN
DNA polymerase
POLA1
1,461Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti503 – 506SPQL → KSTA in CAA29920 (PubMed:3359994).Curated4
Sequence conflicti837A → G in CAA29920 (PubMed:3359994).Curated1
Sequence conflicti1405L → C AA sequence (PubMed:2243771).Curated1
Sequence conflicti1426V → C AA sequence (PubMed:2243771).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048877740Y → H. Corresponds to variant dbSNP:rs2230927Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06745 mRNA Translation: CAA29920.1
AY275833 Genomic DNA Translation: AAP13534.1
M64481 Genomic DNA Translation: AAA52318.1
CCDSiCCDS14214.1
PIRiS00257 DJHUAC
RefSeqiNP_058633.2, NM_016937.3
UniGeneiHs.567319

Genome annotation databases

EnsembliENST00000379059; ENSP00000368349; ENSG00000101868
GeneIDi5422
KEGGihsa:5422
UCSCiuc004dbl.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X06745 mRNA Translation: CAA29920.1
AY275833 Genomic DNA Translation: AAP13534.1
M64481 Genomic DNA Translation: AAA52318.1
CCDSiCCDS14214.1
PIRiS00257 DJHUAC
RefSeqiNP_058633.2, NM_016937.3
UniGeneiHs.567319

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K0PNMR-A1347-1377[»]
1K18NMR-A1347-1377[»]
1N5GNMR-A1345-1382[»]
4Q5VX-ray2.52A/E336-1257[»]
4QCLX-ray2.20A336-1257[»]
4Y97X-ray2.51B/D/F/H1265-1444[»]
5EXRX-ray3.60C/G335-1462[»]
5IUDX-ray3.30A/D/G/J338-1255[»]
6AS7X-ray2.95A336-1257[»]
ProteinModelPortaliP09884
SMRiP09884
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111418, 58 interactors
ComplexPortaliCPX-2087 DNA polymerase alpha:primase complex
CORUMiP09884
IntActiP09884, 14 interactors
MINTiP09884
STRINGi9606.ENSP00000368349

Chemistry databases

BindingDBiP09884
ChEMBLiCHEMBL1828
DrugBankiDB00242 Cladribine
DB00631 Clofarabine
DB01073 Fludarabine
DB01280 Nelarabine

PTM databases

CarbonylDBiP09884
iPTMnetiP09884
PhosphoSitePlusiP09884

Polymorphism and mutation databases

BioMutaiPOLA1
DMDMi60392197

Proteomic databases

EPDiP09884
MaxQBiP09884
PaxDbiP09884
PeptideAtlasiP09884
PRIDEiP09884
ProteomicsDBi52272

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000379059; ENSP00000368349; ENSG00000101868
GeneIDi5422
KEGGihsa:5422
UCSCiuc004dbl.4 human

Organism-specific databases

CTDi5422
DisGeNETi5422
EuPathDBiHostDB:ENSG00000101868.10
GeneCardsiPOLA1
H-InvDBiHIX0028476
HGNCiHGNC:9173 POLA1
HPAiCAB012274
HPA002947
MalaCardsiPOLA1
MIMi301220 phenotype
312040 gene
neXtProtiNX_P09884
OpenTargetsiENSG00000101868
PharmGKBiPA162399856
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0970 Eukaryota
COG0417 LUCA
GeneTreeiENSGT00550000074891
HOGENOMiHOG000163524
HOVERGENiHBG080008
InParanoidiP09884
KOiK02320
PhylomeDBiP09884
TreeFamiTF103001

Enzyme and pathway databases

ReactomeiR-HSA-113501 Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-174411 Polymerase switching on the C-strand of the telomere
R-HSA-174430 Telomere C-strand synthesis initiation
R-HSA-539107 Activation of E2F1 target genes at G1/S
R-HSA-68952 DNA replication initiation
R-HSA-68962 Activation of the pre-replicative complex
R-HSA-69091 Polymerase switching
R-HSA-69166 Removal of the Flap Intermediate
R-HSA-69183 Processive synthesis on the lagging strand

Miscellaneous databases

ChiTaRSiPOLA1 human
EvolutionaryTraceiP09884
GeneWikiiPolymerase_(DNA_directed),_alpha_1
GenomeRNAii5422
PROiPR:P09884
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000101868 Expressed in 174 organ(s), highest expression level in intestine
CleanExiHS_POLA1
ExpressionAtlasiP09884 baseline and differential
GenevisibleiP09884 HS

Family and domain databases

Gene3Di1.10.3200.20, 1 hit
3.30.420.10, 1 hit
3.90.1600.10, 1 hit
InterProiView protein in 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
IPR024647 DNA_pol_a_cat_su_N
IPR023211 DNA_pol_palm_dom_sf
IPR038256 Pol_alpha_znc_sf
IPR012337 RNaseH-like_sf
IPR036397 RNaseH_sf
IPR015088 Znf_DNA-dir_DNA_pol_B_alpha
PfamiView protein in Pfam
PF12254 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
PRINTSiPR00106 DNAPOLB
SMARTiView protein in SMART
SM00486 POLBc, 1 hit
SUPFAMiSSF53098 SSF53098, 1 hit
PROSITEiView protein in PROSITE
PS00116 DNA_POLYMERASE_B, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDPOLA_HUMAN
AccessioniPrimary (citable) accession number: P09884
Secondary accession number(s): Q86UQ7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: February 1, 2005
Last modified: September 12, 2018
This is version 188 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  4. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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