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POLA1 Gene(Protein Coding)

Polymerase (DNA) Alpha 1, Catalytic Subunit

GCID:
GC0XP024712
GIFtS:
63
Genes Participants
UDN Logo

Aliases for POLA1 Gene

Aliases for POLA1 Gene

  • Polymerase (DNA) Alpha 1, Catalytic Subunit 2 3
  • Polymerase (DNA Directed), Alpha 1, Catalytic Subunit 2 3 5
  • DNA Polymerase Alpha Catalytic Subunit P180 3 4
  • EC 2.7.7.7 4 63
  • POLA 3 4
  • N Syndrome (Mental Retardation, Malformations, Chromosome Breakage) 2
  • DNA Polymerase Alpha 1 Catalytic Subunit 3
  • Polymerase (DNA-Directed), Alpha (70kD) 3
  • Polymerase (DNA Directed), Alpha 1 2
  • DNA Polymerase Alpha P180 Subunit 3
  • Polymerase (DNA Directed), Alpha 2
  • P180 3
  • NSX 3

External Ids for POLA1 Gene

Previous HGNC Symbols for POLA1 Gene

  • POLA
  • NSX

Previous GeneCards Identifiers for POLA1 Gene

  • GC0XP024622
  • GC0XP022457

Summaries for POLA1 Gene

Entrez Gene Summary for POLA1 Gene

  • This gene encodes the catalytic subunit of DNA polymerase, which together with a regulatory and two primase subunits, forms the DNA polymerase alpha complex. The catalytic subunit plays an essential role in the initiation of DNA replication. [provided by RefSeq, Mar 2010]

GeneCards Summary for POLA1 Gene

POLA1 (Polymerase (DNA) Alpha 1, Catalytic Subunit) is a Protein Coding gene. Diseases associated with POLA1 include X-Linked Reticulate Pigmentary Disorder With Systemic Manifestations and Microvascular Complications Of Diabetes 1. Among its related pathways are CDK-mediated phosphorylation and removal of Cdc6 and RB in Cancer. GO annotations related to this gene include nucleic acid binding and nucleotide binding.

UniProtKB/Swiss-Prot for POLA1 Gene

  • 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.

Gene Wiki entry for POLA1 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for POLA1 Gene

Genomics for POLA1 Gene

Products:

  1. Regulatory Element

Regulatory Elements for POLA1 Gene

Enhancers for POLA1 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around POLA1 on UCSC Golden Path with GeneCards custom track

Promoters for POLA1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around POLA1 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the POLA1 gene promoter:

Genomic Location for POLA1 Gene

Chromosome:
X
Start:
24,693,874 bp from pter
End:
24,996,986 bp from pter
Size:
303,113 bases
Orientation:
Plus strand

Genomic View for POLA1 Gene

Genes around POLA1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
POLA1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for POLA1 Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for POLA1 Gene

Proteins for POLA1 Gene

Products:

  1. Antibody
  2. Protein
  3. Assay

  • Protein details for POLA1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P09884-DPOLA_HUMAN
    Recommended name:
    DNA polymerase alpha catalytic subunit
    Protein Accession:
    P09884
    Secondary Accessions:
    • Q86UQ7

    Protein attributes for POLA1 Gene

    Size:
    1462 amino acids
    Molecular mass:
    165913 Da
    Cofactor:
    Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
    Quaternary 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. Interacts with SV40 Large T antigen; this interaction allows viral DNA replication. Interacts with herpes simplex virus 1 (HHV-1) replication origin-binding protein UL9.
    Miscellaneous:
    • In eukaryotes there are five DNA polymerases: alpha, beta, gamma, delta, and epsilon which are responsible for different reactions of DNA synthesis.

    Three dimensional structures from OCA and Proteopedia for POLA1 Gene

neXtProt entry for POLA1 Gene

Proteomics data for POLA1 Gene at MOPED

Protein Expression for POLA1 Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for POLA1 Gene

P09884:

Post-translational modifications for POLA1 Gene

  • A 165 kDa form is probably produced by proteolytic cleavage at Lys-124.
  • Ubiquitination at Lys 970, Lys 1200, Lys 1316, and Lys 1376
  • Modification sites at PhosphoSitePlus

Other Protein References for POLA1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Domains & Families for POLA1 Gene

Gene Families for POLA1 Gene

HGNC:

Protein Domains for POLA1 Gene

InterPro:
Blocks:
ProtoNet:

Suggested Antigen Peptide Sequences for POLA1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P09884

UniProtKB/Swiss-Prot:

DPOLA_HUMAN :
  • The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.
  • Belongs to the DNA polymerase type-B family.
  • Contains 1 CysA-type zinc finger.
Domain:
  • The CysB motif binds 1 4Fe-4S cluster and is required for the formation of polymerase complexes.
Family:
  • Belongs to the DNA polymerase type-B family.
Similarity:
  • Contains 1 CysA-type zinc finger.
genes like me logo Genes that share domains with POLA1: view

Function for POLA1 Gene

Products:

  1. Animal Model
  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line
  7. Flow Cytometry

Molecular function for POLA1 Gene

UniProtKB/Swiss-Prot CatalyticActivity:
Deoxynucleoside triphosphate + DNA(n) = diphosphate + DNA(n+1).
UniProtKB/Swiss-Prot 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.

Enzyme Numbers (IUBMB) for POLA1 Gene

Gene Ontology (GO) - Molecular Function for POLA1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001882 nucleoside binding IEA --
GO:0003682 chromatin binding IDA 16762037
GO:0003887 DNA-directed DNA polymerase activity IEA,IMP 4084590
GO:0003896 contributes_to DNA primase activity IDA 2175912
GO:0005515 protein binding IEA,IPI 1311258
genes like me logo Genes that share ontologies with POLA1: view

Phenotypes for POLA1 Gene

MGI mutant phenotypes for POLA1:
inferred from 1 alleles
GenomeRNAi human phenotypes for POLA1:
genes like me logo Genes that share phenotypes with POLA1: view

Human Phenotype Ontology for POLA1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Model Products

miRNA for POLA1 Gene

miRTarBase miRNAs that target POLA1

Inhibitory RNA Products

Flow Cytometry Products

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for POLA1 Gene

Localization for POLA1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for POLA1 Gene

Nucleus.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for POLA1 Gene COMPARTMENTS Subcellular localization image for POLA1 gene
Compartment Confidence
nucleus 5
cytosol 3
mitochondrion 2
plasma membrane 1

Gene Ontology (GO) - Cellular Components for POLA1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005635 nuclear envelope IDA 9518481
GO:0005737 cytoplasm IDA --
genes like me logo Genes that share ontologies with POLA1: view

Pathways & Interactions for POLA1 Gene

genes like me logo Genes that share pathways with POLA1: view

Gene Ontology (GO) - Biological Process for POLA1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000278 mitotic cell cycle TAS --
GO:0006270 DNA replication initiation IEA,TAS --
GO:0006271 DNA strand elongation involved in DNA replication TAS --
GO:0006272 leading strand elongation IDA 2175912
GO:0006273 lagging strand elongation IDA 2175912
genes like me logo Genes that share ontologies with POLA1: view

No data available for SIGNOR curated interactions for POLA1 Gene

Drugs & Compounds for POLA1 Gene

Products:

  1. Drug

(14) Drugs for POLA1 Gene - From: DrugBank, ApexBio, DGIdb, FDA Approved Drugs, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Clofarabine Approved, Investigational Pharma inhibitor, binder, Target Antimetabolite,inhibit DNA polymerase and ribonucleotide reductase 154
Fludarabine Approved Pharma inhibitor, Target DNA synthsis inhibitor 1075
Nelarabine Approved, Investigational Pharma binder, Target, inhibitor Prodrug of ara-G for T-LBL/T-ALL 0
Cladribine Approved, Investigational Pharma Target, inhibitor Apoptosis inducer in CLL cells 68
Cytarabine Approved, Investigational Pharma 1054

(2) Additional Compounds for POLA1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
phosphoric acid
  • Acide phosphorique (FRENCH)
  • Acido fosforico [Italian]
  • Acidum phosphoricum
  • Diphosphate tetrasodium
  • Fosforzuuroplossingen [Dutch]
 7664-38-2
Thymidine 5'-triphosphate
  • 2'-Deoxythymidine 5'-triphosphate
  • 2'-Deoxythymidine triphosphate
  • 5'-TTP
  • 5-Methyl-dUTP
  • Deoxy-TTP
 365-08-2

(3) ApexBio Compounds for POLA1 Gene

Compound Action Cas Number
Cytarabine 147-94-4
Fludarabine Phosphate (Fludara) Inhibits STAT1 activation and DNA synthesis 75607-67-9
Vitamin D2 (Ergocalciferol) DNA Polymerase inhibitor 50-14-6
genes like me logo Genes that share compounds with POLA1: view

Drug Products

Transcripts for POLA1 Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone
  5. Flow Cytometry

mRNA/cDNA for POLA1 Gene

(5) REFSEQ mRNAs :
(2) Additional mRNA sequences :
(62) Selected AceView cDNA sequences:
(6) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for POLA1 Gene

Polymerase (DNA directed), alpha 1, catalytic subunit:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for POLA1 Gene

No ASD Table

Relevant External Links for POLA1 Gene

GeneLoc Exon Structure for
POLA1
ECgene alternative splicing isoforms for
POLA1

Expression for POLA1 Gene

Products:

  1. Primer

mRNA expression in normal human tissues for POLA1 Gene

mRNA expression in normal human tissues for POLA1 Gene
mRNA expression by BioGPS for POLA1 GenemRNA expression by GTEx for POLA1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for POLA1 Gene

This gene is overexpressed in Breast (29.5), Heart (22.3), and Plasma (6.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for POLA1 Gene



SOURCE GeneReport for Unigene cluster for POLA1 Gene Hs.567319

genes like me logo Genes that share expression patterns with POLA1: view

Primer Products

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Protein tissue co-expression partners for POLA1 Gene

Orthologs for POLA1 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for POLA1 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
 Mammalia POLA1 35
  • 90.99 (n)
  • 90.56 (a)
POLA1 36
  • 89 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia POLA1 35
  • 92.03 (n)
  • 91.64 (a)
POLA1 36
  • 91 (a)
 OneToOne
mouse
(Mus musculus)
 Mammalia Pola1 35
  • 89.06 (n)
  • 88.28 (a)
Pola1 16
Pola1 36
  • 88 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia POLA1 35
  • 98.79 (n)
  • 98.24 (a)
POLA1 36
  • 99 (a)
 OneToOne
rat
(Rattus norvegicus)
 Mammalia Pola1 35
  • 89.73 (n)
  • 89.94 (a)
oppossum
(Monodelphis domestica)
 Mammalia POLA1 36
  • 81 (a)
 OneToOne
chicken
(Gallus gallus)
 Aves POLA1 35
  • 75.63 (n)
  • 76.02 (a)
POLA1 36
  • 74 (a)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia POLA1 36
  • 73 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia pola1 35
  • 70.68 (n)
  • 73.49 (a)
Str.19655 35
African clawed frog
(Xenopus laevis)
 Amphibia LOC398200 35
zebrafish
(Danio rerio)
 Actinopterygii mpzf637-2-001461 35
pola1 35
  • 67.55 (n)
  • 70.56 (a)
pola1 36
  • 69 (a)
 OneToOne
African malaria mosquito
(Anopheles gambiae)
 Insecta AgaP_AGAP001929 35
  • 49.73 (n)
  • 44.8 (a)
fruit fly
(Drosophila melanogaster)
 Insecta DNApol-alpha180 35
  • 50.36 (n)
  • 43.28 (a)
DNApol-alpha180 36
  • 38 (a)
 OneToOne
worm
(Caenorhabditis elegans)
 Secernentea Y47D3A.29 35
  • 49.43 (n)
  • 41.3 (a)
Y47D3A.29 36
  • 36 (a)
 OneToOne
A. gosspyii yeast
(Ashbya gossypii)
 Saccharomycetes AGOS_AER381C 35
  • 48.17 (n)
  • 38.61 (a)
K. lactis yeast
(Kluyveromyces lactis)
 Saccharomycetes KLLA0C13255g 35
  • 46.72 (n)
  • 36.53 (a)
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes POL1 35
  • 49.12 (n)
  • 39.14 (a)
POL1 36
  • 31 (a)
 OneToOne
POL1 38
thale cress
(Arabidopsis thaliana)
 eudicotyledons ICU2 35
  • 50.94 (n)
  • 40.69 (a)
rice
(Oryza sativa)
 Liliopsida Os.47313 35
Os01g0868300 35
  • 51.71 (n)
  • 44.49 (a)
sea squirt
(Ciona intestinalis)
 Ascidiacea Cin.10716 35
bread mold
(Neurospora crassa)
 Ascomycetes NCU07870 35
  • 46.45 (n)
  • 36.82 (a)
fission yeast
(Schizosaccharomyces pombe)
 Schizosaccharomycetes pol1 35
  • 48.91 (n)
  • 38.22 (a)
sea squirt
(Ciona savignyi)
 Ascidiacea CSA.7288 36
  • 50 (a)
 OneToOne
Species with no ortholog for POLA1:
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for POLA1 Gene

ENSEMBL:
Gene Tree for POLA1 (if available)
TreeFam:
Gene Tree for POLA1 (if available)

Paralogs for POLA1 Gene

No data available for Paralogs for POLA1 Gene

Variants for POLA1 Gene

Sequence variations from dbSNP and Humsavar for POLA1 Gene

SNP ID Clin Chr 0X pos Sequence Context AA Info Type
rs2230927 - 24,741,394(+) TGTTA(C/T)ACCTG reference, missense
rs747677647 -- 24,843,680(+) GATGT(A/G)AGTAT intron-variant
rs747677816 -- 24,741,575(+) TGTTA(C/T)ATGAT intron-variant
rs747694933 -- 24,869,211(+) TTACA(G/T)GCATG intron-variant
rs747721348 -- 24,962,524(+) ACAGT(-/A)AGGAT intron-variant

Structural Variations from Database of Genomic Variants (DGV) for POLA1 Gene

Variant ID Type Subtype PubMed ID
nsv517960 CNV Gain 19592680
esv2675627 CNV Deletion 23128226
esv2146318 CNV Deletion 18987734
esv2740014 CNV Deletion 23290073
esv2672026 CNV Deletion 23128226

Variation tolerance for POLA1 Gene

Residual Variation Intolerance Score: 16.4% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.60; 30.81% of all genes are more intolerant (likely to be disease-causing)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for POLA1 Gene

Disorders for POLA1 Gene

MalaCards: The human disease database

(7) MalaCards diseases for POLA1 Gene - From: OMIM, ClinVar, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
x-linked reticulate pigmentary disorder with systemic manifestations
  • familial cutaneous amyloidosis
microvascular complications of diabetes 1
  • diabetic nephropathy
n syndrome
  • nsx
macular degeneration, age-related, 1
  • macular degeneration, age-related, 2
latent syphilis
  • syphilis, latent
- elite association - COSMIC cancer census association via MalaCards
Search POLA1 in MalaCards View complete list of genes associated with diseases

Relevant External Links for POLA1

Genetic Association Database (GAD)
POLA1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
POLA1
genes like me logo Genes that share disorders with POLA1: view

No data available for UniProtKB/Swiss-Prot and Genatlas for POLA1 Gene

Publications for POLA1 Gene

  1. Physical interactions between Mcm10, DNA, and DNA polymerase alpha. (PMID: 19608746) Warren E.M. … Eichman B.F. (J. Biol. Chem. 2009) 3 4 67
  2. Use of clofarabine for acute childhood leukemia. (PMID: 20631817) Pession A. … Martoni A. (Biologics 2010) 25 26
  3. Current status of older and new purine nucleoside analogues in the treatment of lymphoproliferative diseases. (PMID: 19325518) Robak T. … Robak P. (Molecules 2009) 25 26
  4. Clofarabine as a novel nucleoside analogue approved to treat patients with haematological malignancies: mechanism of action and clinical activity. (PMID: 19519505) Lech-Maranda E. … Robak T. (Mini Rev Med Chem 2009) 25 26
  5. Mechanisms of anti-cancer action and pharmacology of clofarabine. (PMID: 19576186) Zhenchuk A. … Albertioni F. (Biochem. Pharmacol. 2009) 25 26

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Sources for POLA1 Gene

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