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UniProtKB - Q96LW4 (PRIPO_HUMAN)

Entry version 133 (12 Aug 2020)
Sequence version 3 (28 Mar 2018)
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Protein

DNA-directed primase/polymerase protein

Gene

PRIMPOL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them (PubMed:24126761, PubMed:24207056, PubMed:24240614, PubMed:24267451, PubMed:25255211, PubMed:24682820, PubMed:25262353, PubMed:25746449, PubMed:25550423, PubMed:27989484, PubMed:29608762, PubMed:30889508, PubMed:28534480). Required to facilitate mitochondrial and nuclear replication fork progression by initiating de novo DNA synthesis using dNTPs and acting as an error-prone DNA polymerase able to bypass certain DNA lesions (PubMed:24126761, PubMed:24207056, PubMed:24240614, PubMed:24267451, PubMed:25255211, PubMed:24682820, PubMed:25262353, PubMed:25746449, PubMed:25550423, PubMed:27989484, PubMed:29608762, PubMed:30889508, PubMed:30633872, PubMed:28534480). Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (PubMed:24126761, PubMed:24207056, PubMed:24240614, PubMed:24267451, PubMed:25746449). Provides different translesion synthesis alternatives when DNA replication is stalled: able to synthesize DNA primers downstream of lesions, such as ultraviolet (UV) lesions, R-loops and G-quadruplexes, to allow DNA replication to continue (PubMed:24240614, PubMed:26626482, PubMed:28534480, PubMed:30478192). Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion (PubMed:25746449). Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase (PubMed:24207056, PubMed:25255211, PubMed:25746449). Also required for reinitiating stalled forks after UV damage during nuclear DNA replication (PubMed:24240614). Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides (PubMed:24207056). Prevents APOBEC family-mediated DNA mutagenesis by repriming downstream of abasic site to prohibit error-prone translesion synthesis (By similarity). Has non-overlapping function with POLH (PubMed:24240614). In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (PubMed:30715459).By similarity17 Publications
Involved in adaptive response to cisplatin, a chemotherapeutic that causes reversal of replication forks, in cancer cells: reinitiates DNA synthesis past DNA lesions in BRCA1-deficient cancer cells treated with cisplatin via its de novo priming activity (PubMed:31676232). Repriming rescues fork degradation while leading to accumulation of internal ssDNA gaps behind the forks (PubMed:31676232). ATR regulates adaptive response to cisplatin (PubMed:31676232).1 Publication

Caution

According to a report, the association between the variant Asp-89 and high myopia MYP22 is unclear as this variant is found in control populations (PubMed:25680975). The paper also questions the relevance of functional study on this variant (PubMed:25680975). Authors of the functional characterization study replied that their analysis clearly shows that Asp-89 variant affects the DNA polymerase and primase activities, regardless of its association with high myopia MYP22 (PubMed:25680976). Additional studies are therefore required to confirm the link between this variant and high myopia MYP22.Curated2 Publications

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mn2+1 Publication5 PublicationsNote: Can act both with Mn2+ and Mg2+ as cofactor in vitro, but Mn2+ is the preferred cofactor in vivo (PubMed:25255211, PubMed:25746449, PubMed:27989484, PubMed:30889508, PubMed:30633872). The polymerase activity incorporates correct dNTPs with much higher efficiency with Mn2+ than with Mg2+ (PubMed:25255211, PubMed:30889508). The fidelity is slightly more accurate when Mg2+ is the cofactor compared to Mn2+ (PubMed:25255211, PubMed:30889508). In the presence of Mn2+, a conformational transition step from non-productive to productive PRIMPOL:DNA complexes limits the enzymatic turnover, whereas in the presence of Mg2+, the chemical step becomes rate limiting (PubMed:30633872).5 Publications

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

Kcat is 0.05 sec(-1) for dTTP (in presence of 2 mM of Mn2+. Kcat is 0.02 sec(-1) for dTTP (in presence of 50 µM of Mn2+. Kcat is 0.01 sec(-1) for dTTP (in presence of 2 mM of Mg2+.
  1. KM=14 µM for dTTP (in presence of 2 mM of Mn2+1 Publication
  2. KM=24 µM for dTTP (in presence of 50 µM of Mn2+1 Publication
  3. KM=430 µM for dTTP (in presence of 2 mM of Mg2+1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei76SubstrateCombined sources1 Publication1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi114Manganese; catalyticCombined sources2 Publications1
    Metal bindingi116Manganese; catalyticCombined sources1 Publication1
    Binding sitei297SubstrateCombined sources1 Publication1
    Metal bindingi419Zinc1 Publication1
    Metal bindingi426Zinc1 Publication1
    Metal bindingi446Zinc1 Publication1
    Metal bindingi451Zinc1 Publication1

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    Complete GO annotation on QuickGO ...

    GO - Biological processi

    Complete GO annotation on QuickGO ...

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionDNA-directed DNA polymerase, Nucleotidyltransferase, Transferase
    Biological processDNA damage, DNA repair, Transcription
    LigandManganese, Metal-binding, Zinc

    Enzyme and pathway databases

    Pathway Commons web resource for biological pathway data

    More...    PathwayCommonsi    		Q96LW4

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    DNA-directed primase/polymerase protein1 Publication (EC:2.7.7.-6 Publications)
    Short name:
    hPrimpol11 Publication
    Alternative name(s):
    Coiled-coil domain-containing protein 1111 Publication
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    Name:PRIMPOL1 PublicationImported
    Synonyms:CCDC1111 Publication
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
    • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 4

    Organism-specific databases

    Eukaryotic Pathogen Database Resources

    More...    EuPathDBi    		HostDB:ENSG00000164306.10

    Human Gene Nomenclature Database

    More...    HGNCi    		HGNC:26575, PRIMPOL

    Online Mendelian Inheritance in Man (OMIM)

    More...    MIMi    		615421, gene

    neXtProt; the human protein knowledge platform

    More...    neXtProti    		NX_Q96LW4

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>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 & Seán O’Donoghue; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Chromosome, DNA-directed RNA polymerase, Mitochondrion, Nucleus

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

    <p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

    Myopia 22, autosomal dominant (MYP22)2 Publications
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far.
    Related information in OMIM
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_07012089Y → D in MYP22; unknown pathological significance; reduced DNA polymerase and DNA primase activities; reduced DNA-binding. 2 PublicationsCorresponds to variant dbSNP:rs200857997EnsemblClinVar.1

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi89Y → F: Does not affect DNA primase activity. 1 Publication1
    Mutagenesisi89Y → S: Reduced DNA primase activity. 1 Publication1
    Mutagenesisi114 – 116DLE → ALA in AxA; abolished DNA primase and polymerase activities. 7 Publications3
    Mutagenesisi114D → A: Abolishes DNA primase and polymerase activities. 1 Publication1
    Mutagenesisi169H → N: Abolishes DNA primase and polymerase activities. 1 Publication1
    Mutagenesisi280D → A: Abolished Mn(2+) DNA primase activity. 1 Publication1
    Mutagenesisi419C → A: Abolished zinc-binding, leading to altered translesion synthesis; when associated with A-426. 3 Publications1
    Mutagenesisi419C → G in mutant CH; abolished DNA primase activity and impaired ability to restart stalled forks; when associated with Y-426. 1 Publication1
    Mutagenesisi426H → A: Abolished zinc-binding, leading to altered translesion synthesis; when associated with A-419. 3 Publications1
    Mutagenesisi426H → D: Abolishes DNA primase activity, while it increases DNA polymerase activity. 2 Publications1
    Mutagenesisi426H → Y in mutant CH; abolished DNA primase activity and impaired ability to restart stalled forks; when associated with G-419. 2 Publications1
    Mutagenesisi519 – 522DAYF → RAYA: Abolished interaction with RPA1, impairing recruitment to chromatin and reducing DNA primase activity; when associated with 551-R--A-554. 1 Publication4
    Mutagenesisi551 – 554DELI → RELA: Abolished interaction with RPA1, impairing recruitment to chromatin and reducing DNA primase activity; when associated with 519-R--A-522. 1 Publication4

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    DisGeNET

    More...    DisGeNETi    		201973

    MalaCards human disease database

    More...    MalaCardsi    		PRIMPOL
    MIMi615420, phenotype

    Open Targets

    More...    OpenTargetsi    		ENSG00000164306

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...    PharmGKBi    		PA145008751

    Miscellaneous databases

    Pharos NIH Druggable Genome Knowledgebase

    More...    Pharosi    		Q96LW4, Tbio

    Polymorphism and mutation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...    BioMutai    		PRIMPOL

    Domain mapping of disease mutations (DMDM)

    More...    DMDMi    		296434425

    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002793951 – 560DNA-directed primase/polymerase proteinAdd BLAST560

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei255PhosphoserineCombined sources1

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    jPOST - Japan Proteome Standard Repository/Database

    More...    jPOSTi    		Q96LW4

    MassIVE - Mass Spectrometry Interactive Virtual Environment

    More...    MassIVEi    		Q96LW4

    PaxDb, a database of protein abundance averages across all three domains of life

    More...    PaxDbi    		Q96LW4

    PeptideAtlas

    More...    PeptideAtlasi    		Q96LW4

    PRoteomics IDEntifications database

    More...    PRIDEi    		Q96LW4

    ProteomicsDB: a multi-organism proteome resource

    More...    ProteomicsDBi    		14139
    77258 [Q96LW4-1]

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...    iPTMneti    		Q96LW4

    Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

    More...    PhosphoSitePlusi    		Q96LW4

    <p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...    Bgeei    		ENSG00000164306, Expressed in zone of skin and 208 other tissues

    ExpressionAtlas, Differential and Baseline Expression

    More...    ExpressionAtlasi    		Q96LW4, baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...    Genevisiblei    		Q96LW4, HS

    Organism-specific databases

    Human Protein Atlas

    More...    HPAi    		ENSG00000164306, Low tissue specificity

    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Interacts with RPA1; leading to recruitment to chromatin and stimulate DNA primase activity (PubMed:24126761, PubMed:25550423, PubMed:28396594, PubMed:28534480).

    Interacts with SSBP1 (PubMed:25550423).

    Interacts with POLDIP2; leading to enhance DNA polymerase activity (PubMed:26984527).

    5 Publications

    <p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

    Hide details

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGRID)

    More...    BioGRIDi    		128410, 15 interactors

    Protein interaction database and analysis system

    More...    IntActi    		Q96LW4, 18 interactors

    Molecular INTeraction database

    More...    MINTi    		Q96LW4

    STRING: functional protein association networks

    More...    STRINGi    		9606.ENSP00000313816

    Miscellaneous databases

    RNAct, Protein-RNA interaction predictions for model organisms.

    More...    RNActi    		Q96LW4, protein

    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    Secondary structure

    1560
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    SWISS-MODEL Repository - a database of annotated 3D protein structure models

    More...    SMRi    		Q96LW4

    Database of comparative protein structure models

    More...    ModBasei    		Search...

    Protein Data Bank in Europe - Knowledge Base

    More...    PDBe-KBi    		Search...

    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni114 – 116Substrate bindingCombined sources1 Publication3
    Regioni165 – 169Substrate bindingCombined sources1 Publication5
    Regioni288 – 291Substrate bindingCombined sources1 Publication4
    Regioni481 – 560Interaction with RPA11 PublicationAdd BLAST80

    Coiled coil

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and domains' section denotes the positions of regions of coiled coil within the protein.<p><a href='/help/coiled' target='_top'>More...</a></p>Coiled coili1 – 22Sequence analysisAdd BLAST22

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi419 – 452Zinc knuckle motif1 PublicationAdd BLAST34
    Motifi513 – 527RPA1-binding motif 11 PublicationAdd BLAST15
    Motifi548 – 556RPA1-binding motif 21 Publication9

    <p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

    The zinc knuckle motif binds zinc and is required for the DNA primase activity (PubMed:24682820, PubMed:29608762). It facilitates the binding and selection of the 5'-nucleotide of the newly synthesized primer and the recognition of preferred initiation sites (PubMed:29608762).2 Publications
    The RPA1-binding motifs (RBM) mediate interaction with RPA1 and are essential for recruitment to chromatin (PubMed:28534480). The interaction is primarily mediated by RPA1-binding motif 1, which binds to the basic cleft of RPA1, with motif 2 plays a supporting role in RPA1-binding (PubMed:28534480).1 Publication
    The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn2+ ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis (PubMed:30889508). Glu-116 is required to stabilize the incoming nucleotide at the 3'-site (PubMed:30889508).1 Publication

    <p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Belongs to the eukaryotic-type primase small subunit family.Curated

    Keywords - Domaini

    Coiled coil

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...    eggNOGi    		ENOG502QS1Q, Eukaryota

    Ensembl GeneTree

    More...    GeneTreei    		ENSGT00390000003901

    InParanoid: Eukaryotic Ortholog Groups

    More...    InParanoidi    		Q96LW4

    KEGG Orthology (KO)

    More...    KOi    		K22761

    Identification of Orthologs from Complete Genome Data

    More...    OMAi    		PEIDQFV

    Database of Orthologous Groups

    More...    OrthoDBi    		1373896at2759

    Database for complete collections of gene phylogenies

    More...    PhylomeDBi    		Q96LW4

    TreeFam database of animal gene trees

    More...    TreeFami    		TF328961

    Family and domain databases

    Integrated resource of protein families, domains and functional sites

    More...    InterProi    		View protein in InterPro
    IPR002755, DNA_primase_S

    Pfam protein domain database

    More...    Pfami    		View protein in Pfam
    PF01896, DNA_primase_S, 1 hit

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

    This entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

    Isoform 1 (identifier: Q96LW4-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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    MNRKWEAKLK QIEERASHYE RKPLSSVYRP RLSKPEEPPS IWRLFHRQAQ 
            60         70         80         90        100
    AFNFVKSCKE DVHVFALECK VGDGQRIYLV TTYAEFWFYY KSRKNLLHCY 
           110        120        130        140        150
    EVIPENAVCK LYFDLEFNKP ANPGADGKKM VALLIEYVCK ALQELYGVNC 
           160        170        180        190        200
    SAEDVLNLDS STDEKFSRHL IFQLHDVAFK DNIHVGNFLR KILQPALDLL 
           210        220        230        240        250
    GSEDDDSAPE TTGHGFPHFS EAPARQGFSF NKMFTEKATE ESWTSNSKKL 
           260        270        280        290        300
    ERLGSAEQSS PDLSFLVVKN NMGEKHLFVD LGVYTRNRNF RLYKSSKIGK 
           310        320        330        340        350
    RVALEVTEDN KFFPIQSKDV SDEYQYFLSS LVSNVRFSDT LRILTCEPSQ 
           360        370        380        390        400
    NKQKGVGYFN SIGTSVETIE GFQCSPYPEV DHFVLSLVNK DGIKGGIRRW 
           410        420        430        440        450
    NYFFPEELLV YDICKYRWCE NIGRAHKSNN IMILVDLKNE VWYQKCHDPV 
           460        470        480        490        500
    CKAENFKSDC FPLPAEVCLL FLFKEEEEFT TDEADETRSN ETQNPHKPSP 
           510        520        530        540        550
    SRLSTGASAD AVWDNGIDDA YFLEATEDAE LAEAAENSLL SYNSEVDEIP 
           560
    DELIIEVLQE
    Length:560
    Mass (Da):64,412
    Last modified:March 28, 2018 - v3
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i2B58D2B57F51DD4E
    GO
    Isoform 2 (identifier: Q96LW4-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         366-366: Missing.

    Show »
    Length:559
    Mass (Da):64,312
    Checksum:iB5544871BEBB0508
    GO

    <p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

    There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
    EntryEntry nameProtein names
    		Gene namesLengthAnnotation
    A0A5S6SZ32A0A5S6SZ32_HUMAN
    DNA-directed primase/polymerase pro...
    PRIMPOL FLJ33167, hCG_1786938
    		431Annotation score:

    Annotation score:1 out of 5

    <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
    D6R971D6R971_HUMAN
    DNA-directed primase/polymerase pro...
    PRIMPOL
    		93Annotation score:

    Annotation score:1 out of 5

    <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
    D6R908D6R908_HUMAN
    DNA-directed primase/polymerase pro...
    PRIMPOL
    		112Annotation score:

    Annotation score:1 out of 5

    <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
    H0Y9N8H0Y9N8_HUMAN
    DNA-directed primase/polymerase pro...
    PRIMPOL
    		172Annotation score:

    Annotation score:1 out of 5

    <p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti322D → G in CAI46079 (PubMed:17974005).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_07012089Y → D in MYP22; unknown pathological significance; reduced DNA polymerase and DNA primase activities; reduced DNA-binding. 2 PublicationsCorresponds to variant dbSNP:rs200857997EnsemblClinVar.1
    Natural variantiVAR_030878168R → Q. Corresponds to variant dbSNP:rs2463447Ensembl.1
    Natural variantiVAR_030879505T → K. Corresponds to variant dbSNP:rs14969Ensembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_053600366Missing in isoform 2. 1 Publication1

    Sequence databases

    Select the link destinations:

    EMBL nucleotide sequence database

    More...    EMBLi

    GenBank nucleotide sequence database

    More...    GenBanki

    DNA Data Bank of Japan; a nucleotide sequence database

    More...    DDBJi
    Links Updated
    		AK057729 mRNA Translation: BAB71553.1
    BX647575 mRNA Translation: CAI46079.1
    AC079257 Genomic DNA No translation available.
    KF459591 Genomic DNA No translation available.
    CH471056 Genomic DNA Translation: EAX04667.1
    CH471056 Genomic DNA Translation: EAX04669.1
    CH471056 Genomic DNA Translation: EAX04670.1
    BC064600 mRNA Translation: AAH64600.1

    The Consensus CDS (CCDS) project

    More...    CCDSi    		CCDS3837.1 [Q96LW4-1]
    CCDS75211.1 [Q96LW4-2]

    NCBI Reference Sequences

    More...    RefSeqi    		NP_001287696.1, NM_001300767.1
    NP_001287697.1, NM_001300768.1 [Q96LW4-2]
    NP_001332824.1, NM_001345895.1 [Q96LW4-1]
    NP_001332825.1, NM_001345896.1 [Q96LW4-2]
    NP_689896.1, NM_152683.3 [Q96LW4-1]

    Genome annotation databases

    Ensembl eukaryotic genome annotation project

    More...    Ensembli    		ENST00000314970; ENSP00000313816; ENSG00000164306 [Q96LW4-1]
    ENST00000503752; ENSP00000420860; ENSG00000164306 [Q96LW4-1]
    ENST00000512834; ENSP00000425316; ENSG00000164306 [Q96LW4-2]

    Database of genes from NCBI RefSeq genomes

    More...    GeneIDi    		201973

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...    KEGGi    		hsa:201973

    UCSC genome browser

    More...    UCSCi    		uc003iwj.3, human
    uc003iwk.3, human [Q96LW4-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    <p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

    <p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    		AK057729 mRNA Translation: BAB71553.1
    BX647575 mRNA Translation: CAI46079.1
    AC079257 Genomic DNA No translation available.
    KF459591 Genomic DNA No translation available.
    CH471056 Genomic DNA Translation: EAX04667.1
    CH471056 Genomic DNA Translation: EAX04669.1
    CH471056 Genomic DNA Translation: EAX04670.1
    BC064600 mRNA Translation: AAH64600.1
    CCDSiCCDS3837.1 [Q96LW4-1]
    CCDS75211.1 [Q96LW4-2]
    RefSeqiNP_001287696.1, NM_001300767.1
    NP_001287697.1, NM_001300768.1 [Q96LW4-2]
    NP_001332824.1, NM_001345895.1 [Q96LW4-1]
    NP_001332825.1, NM_001345896.1 [Q96LW4-2]
    NP_689896.1, NM_152683.3 [Q96LW4-1]

    3D structure databases

    Select the link destinations:

    Protein Data Bank Europe

    More...    PDBei

    Protein Data Bank RCSB

    More...    RCSB PDBi

    Protein Data Bank Japan

    More...    PDBji
    Links Updated
    		PDB entryMethodResolution (Å)ChainPositionsPDBsum
    5L2XX-ray2.20A/B1-353[»]
    5N85X-ray2.00B514-528[»]
    5N8AX-ray1.28X480-560[»]
    SMRiQ96LW4
    ModBaseiSearch...
    PDBe-KBiSearch...

    Protein-protein interaction databases

    BioGRIDi128410, 15 interactors
    IntActiQ96LW4, 18 interactors
    MINTiQ96LW4
    STRINGi9606.ENSP00000313816

    PTM databases

    iPTMnetiQ96LW4
    PhosphoSitePlusiQ96LW4

    Polymorphism and mutation databases

    BioMutaiPRIMPOL
    DMDMi296434425

    Proteomic databases

    jPOSTiQ96LW4
    MassIVEiQ96LW4
    PaxDbiQ96LW4
    PeptideAtlasiQ96LW4
    PRIDEiQ96LW4
    ProteomicsDBi14139
    77258 [Q96LW4-1]

    Protocols and materials databases

    Antibodypedia a portal for validated antibodies

    More...    Antibodypediai    		66503, 30 antibodies

    Genome annotation databases

    EnsembliENST00000314970; ENSP00000313816; ENSG00000164306 [Q96LW4-1]
    ENST00000503752; ENSP00000420860; ENSG00000164306 [Q96LW4-1]
    ENST00000512834; ENSP00000425316; ENSG00000164306 [Q96LW4-2]
    GeneIDi201973
    KEGGihsa:201973
    UCSCiuc003iwj.3, human
    uc003iwk.3, human [Q96LW4-1]

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...    CTDi    		201973
    DisGeNETi201973
    EuPathDBiHostDB:ENSG00000164306.10

    GeneCards: human genes, protein and diseases

    More...    GeneCardsi    		PRIMPOL
    HGNCiHGNC:26575, PRIMPOL
    HPAiENSG00000164306, Low tissue specificity
    MalaCardsiPRIMPOL
    MIMi615420, phenotype
    615421, gene
    neXtProtiNX_Q96LW4
    OpenTargetsiENSG00000164306
    PharmGKBiPA145008751

    GenAtlas: human gene database

    More...    GenAtlasi    		Search...

    Phylogenomic databases

    eggNOGiENOG502QS1Q, Eukaryota
    GeneTreeiENSGT00390000003901
    InParanoidiQ96LW4
    KOiK22761
    OMAiPEIDQFV
    OrthoDBi1373896at2759
    PhylomeDBiQ96LW4
    TreeFamiTF328961

    Enzyme and pathway databases

    PathwayCommonsiQ96LW4

    Miscellaneous databases

    BioGRID ORCS database of CRISPR phenotype screens

    More...    BioGRID-ORCSi    		201973, 1 hit in 859 CRISPR screens

    ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

    More...    ChiTaRSi    		PRIMPOL, human

    Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

    More...    GenomeRNAii    		201973
    PharosiQ96LW4, Tbio

    Protein Ontology

    More...    PROi    		PR:Q96LW4
    RNActiQ96LW4, protein

    The Stanford Online Universal Resource for Clones and ESTs

    More...    SOURCEi    		Search...

    Gene expression databases

    BgeeiENSG00000164306, Expressed in zone of skin and 208 other tissues
    ExpressionAtlasiQ96LW4, baseline and differential
    GenevisibleiQ96LW4, HS

    Family and domain databases

    InterProiView protein in InterPro
    IPR002755, DNA_primase_S
    PfamiView protein in Pfam
    PF01896, DNA_primase_S, 1 hit

    ProtoNet; Automatic hierarchical classification of proteins

    More...    ProtoNeti    		Search...

    MobiDB: a database of protein disorder and mobility annotations

    More...    MobiDBi    		Search...

    <p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

    <p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiPRIPO_HUMAN
    <p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q96LW4
    Secondary accession number(s): A0A0A0MTC0
    , D3DP55, D6RDM1, Q5HYJ9
    <p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 6, 2007
    Last sequence update: March 28, 2018
    Last modified: August 12, 2020
    This is version 133 of the entry and version 3 of the sequence. See complete history.
    <p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

    <p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

    Keywords - Technical termi

    3D-structure, Reference proteome

    Documents

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