UniProtKB - Q96LW4 (PRIPO_HUMAN)
DNA-directed primase/polymerase protein
PRIMPOL
Functioni
Caution
Cofactori
Kineticsi
- KM=14 µM for dTTP (in presence of 2 mM of Mn2+1 Publication
- KM=24 µM for dTTP (in presence of 50 µM of Mn2+1 Publication
- KM=430 µM for dTTP (in presence of 2 mM of Mg2+1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 76 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 114 | Manganese; catalyticCombined sources2 Publications | 1 | |
Metal bindingi | 116 | Manganese; catalyticCombined sources1 Publication | 1 | |
Binding sitei | 297 | SubstrateCombined sources1 Publication | 1 | |
Metal bindingi | 419 | Zinc1 Publication | 1 | |
Metal bindingi | 426 | Zinc1 Publication | 1 | |
Metal bindingi | 446 | Zinc1 Publication | 1 | |
Metal bindingi | 451 | Zinc1 Publication | 1 |
GO - Molecular functioni
- chromatin binding Source: UniProtKB
- DNA-directed DNA polymerase activity Source: UniProtKB
- DNA primase activity Source: UniProtKB
- manganese ion binding Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- error-prone translesion synthesis Source: UniProtKB
- mitochondrial DNA repair Source: UniProtKB
- mitochondrial DNA replication Source: UniProtKB
- replication fork processing Source: UniProtKB
- response to UV Source: UniProtKB
- R-loop disassembly Source: UniProtKB
- translesion synthesis Source: UniProtKB
Keywordsi
Molecular function | DNA-directed DNA polymerase, Nucleotidyltransferase, Transferase |
Biological process | DNA damage, DNA repair, Transcription |
Ligand | Manganese, Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q96LW4 |
Names & Taxonomyi
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 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000164306.10 |
HGNCi | HGNC:26575, PRIMPOL |
MIMi | 615421, gene |
neXtProti | NX_Q96LW4 |
Subcellular locationi
Mitochondrion
- Mitochondrion matrix 1 Publication
Nucleus
- Nucleus 2 Publications
Other locations
- Chromosome 1 Publication
Note: Present in the nucleus, but a larger fraction is localized inside mitochondria (PubMed:24207056). Associates with nuclear chromatin during the G1 and S phases of unperturbed cell cycles (PubMed:24207056). Recruited to stalled replication forks following interaction with RPA1 (PubMed:28534480).2 Publications
Mitochondrion
- mitochondrial matrix Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Other locations
- replication fork Source: UniProtKB
Keywords - Cellular componenti
Chromosome, DNA-directed RNA polymerase, Mitochondrion, NucleusPathology & Biotechi
Involvement in diseasei
Myopia 22, autosomal dominant (MYP22)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070120 | 89 | Y → 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 89 | Y → F: Does not affect DNA primase activity. 1 Publication | 1 | |
Mutagenesisi | 89 | Y → S: Reduced DNA primase activity. 1 Publication | 1 | |
Mutagenesisi | 114 – 116 | DLE → ALA in AxA; abolished DNA primase and polymerase activities. 7 Publications | 3 | |
Mutagenesisi | 114 | D → A: Abolishes DNA primase and polymerase activities. 1 Publication | 1 | |
Mutagenesisi | 169 | H → N: Abolishes DNA primase and polymerase activities. 1 Publication | 1 | |
Mutagenesisi | 280 | D → A: Abolished Mn(2+) DNA primase activity. 1 Publication | 1 | |
Mutagenesisi | 419 | C → A: Abolished zinc-binding, leading to altered translesion synthesis; when associated with A-426. 3 Publications | 1 | |
Mutagenesisi | 419 | C → G in mutant CH; abolished DNA primase activity and impaired ability to restart stalled forks; when associated with Y-426. 1 Publication | 1 | |
Mutagenesisi | 426 | H → A: Abolished zinc-binding, leading to altered translesion synthesis; when associated with A-419. 3 Publications | 1 | |
Mutagenesisi | 426 | H → D: Abolishes DNA primase activity, while it increases DNA polymerase activity. 2 Publications | 1 | |
Mutagenesisi | 426 | H → Y in mutant CH; abolished DNA primase activity and impaired ability to restart stalled forks; when associated with G-419. 2 Publications | 1 | |
Mutagenesisi | 519 – 522 | DAYF → RAYA: Abolished interaction with RPA1, impairing recruitment to chromatin and reducing DNA primase activity; when associated with 551-R--A-554. 1 Publication | 4 | |
Mutagenesisi | 551 – 554 | DELI → RELA: Abolished interaction with RPA1, impairing recruitment to chromatin and reducing DNA primase activity; when associated with 519-R--A-522. 1 Publication | 4 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 201973 |
MalaCardsi | PRIMPOL |
MIMi | 615420, phenotype |
OpenTargetsi | ENSG00000164306 |
PharmGKBi | PA145008751 |
Miscellaneous databases
Pharosi | Q96LW4, Tbio |
Polymorphism and mutation databases
BioMutai | PRIMPOL |
DMDMi | 296434425 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000279395 | 1 – 560 | DNA-directed primase/polymerase proteinAdd BLAST | 560 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 255 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q96LW4 |
MassIVEi | Q96LW4 |
PaxDbi | Q96LW4 |
PeptideAtlasi | Q96LW4 |
PRIDEi | Q96LW4 |
ProteomicsDBi | 14139 77258 [Q96LW4-1] |
PTM databases
iPTMneti | Q96LW4 |
PhosphoSitePlusi | Q96LW4 |
Expressioni
Gene expression databases
Bgeei | ENSG00000164306, Expressed in zone of skin and 208 other tissues |
ExpressionAtlasi | Q96LW4, baseline and differential |
Genevisiblei | Q96LW4, HS |
Organism-specific databases
HPAi | ENSG00000164306, Low tissue specificity |
Interactioni
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 PublicationsBinary interactionsi
Hide detailsQ96LW4
Protein-protein interaction databases
BioGRIDi | 128410, 20 interactors |
IntActi | Q96LW4, 18 interactors |
MINTi | Q96LW4 |
STRINGi | 9606.ENSP00000313816 |
Miscellaneous databases
RNActi | Q96LW4, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q96LW4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 114 – 116 | Substrate bindingCombined sources1 Publication | 3 | |
Regioni | 165 – 169 | Substrate bindingCombined sources1 Publication | 5 | |
Regioni | 288 – 291 | Substrate bindingCombined sources1 Publication | 4 | |
Regioni | 481 – 560 | Interaction with RPA11 PublicationAdd BLAST | 80 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 1 – 22 | Sequence analysisAdd BLAST | 22 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 419 – 452 | Zinc knuckle motif1 PublicationAdd BLAST | 34 | |
Motifi | 513 – 527 | RPA1-binding motif 11 PublicationAdd BLAST | 15 | |
Motifi | 548 – 556 | RPA1-binding motif 21 Publication | 9 |
Domaini
Sequence similaritiesi
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | ENOG502QS1Q, Eukaryota |
GeneTreei | ENSGT00390000003901 |
InParanoidi | Q96LW4 |
OMAi | PEIDQFV |
OrthoDBi | 1373896at2759 |
PhylomeDBi | Q96LW4 |
TreeFami | TF328961 |
Family and domain databases
InterProi | View protein in InterPro IPR002755, DNA_primase_S |
Pfami | View protein in Pfam PF01896, DNA_primase_S, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A5S6SZ32 | A0A5S6SZ32_HUMAN | DNA-directed primase/polymerase pro... | PRIMPOL FLJ33167, hCG_1786938 | 431 | Annotation score: | ||
D6R971 | D6R971_HUMAN | DNA-directed primase/polymerase pro... | PRIMPOL | 93 | Annotation score: | ||
D6R908 | D6R908_HUMAN | DNA-directed primase/polymerase pro... | PRIMPOL | 112 | Annotation score: | ||
H0Y9N8 | H0Y9N8_HUMAN | DNA-directed primase/polymerase pro... | PRIMPOL | 172 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 322 | D → G in CAI46079 (PubMed:17974005).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_070120 | 89 | Y → 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_030878 | 168 | R → Q. Corresponds to variant dbSNP:rs2463447Ensembl. | 1 | |
Natural variantiVAR_030879 | 505 | T → K. Corresponds to variant dbSNP:rs14969Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_053600 | 366 | Missing in isoform 2. 1 Publication | 1 |
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 |
CCDSi | CCDS3837.1 [Q96LW4-1] CCDS75211.1 [Q96LW4-2] |
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
Ensembli | ENST00000314970; ENSP00000313816; ENSG00000164306 [Q96LW4-1] ENST00000503752; ENSP00000420860; ENSG00000164306 [Q96LW4-1] ENST00000512834; ENSP00000425316; ENSG00000164306 [Q96LW4-2] |
GeneIDi | 201973 |
KEGGi | hsa:201973 |
UCSCi | uc003iwj.3, human uc003iwk.3, human [Q96LW4-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS3837.1 [Q96LW4-1] CCDS75211.1 [Q96LW4-2] |
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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5L2X | X-ray | 2.20 | A/B | 1-353 | [»] | |
5N85 | X-ray | 2.00 | B | 514-528 | [»] | |
5N8A | X-ray | 1.28 | X | 480-560 | [»] | |
SMRi | Q96LW4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 128410, 20 interactors |
IntActi | Q96LW4, 18 interactors |
MINTi | Q96LW4 |
STRINGi | 9606.ENSP00000313816 |
PTM databases
iPTMneti | Q96LW4 |
PhosphoSitePlusi | Q96LW4 |
Polymorphism and mutation databases
BioMutai | PRIMPOL |
DMDMi | 296434425 |
Proteomic databases
jPOSTi | Q96LW4 |
MassIVEi | Q96LW4 |
PaxDbi | Q96LW4 |
PeptideAtlasi | Q96LW4 |
PRIDEi | Q96LW4 |
ProteomicsDBi | 14139 77258 [Q96LW4-1] |
Protocols and materials databases
Antibodypediai | 66503, 30 antibodies |
Genome annotation databases
Ensembli | ENST00000314970; ENSP00000313816; ENSG00000164306 [Q96LW4-1] ENST00000503752; ENSP00000420860; ENSG00000164306 [Q96LW4-1] ENST00000512834; ENSP00000425316; ENSG00000164306 [Q96LW4-2] |
GeneIDi | 201973 |
KEGGi | hsa:201973 |
UCSCi | uc003iwj.3, human uc003iwk.3, human [Q96LW4-1] |
Organism-specific databases
CTDi | 201973 |
DisGeNETi | 201973 |
EuPathDBi | HostDB:ENSG00000164306.10 |
GeneCardsi | PRIMPOL |
HGNCi | HGNC:26575, PRIMPOL |
HPAi | ENSG00000164306, Low tissue specificity |
MalaCardsi | PRIMPOL |
MIMi | 615420, phenotype 615421, gene |
neXtProti | NX_Q96LW4 |
OpenTargetsi | ENSG00000164306 |
PharmGKBi | PA145008751 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502QS1Q, Eukaryota |
GeneTreei | ENSGT00390000003901 |
InParanoidi | Q96LW4 |
OMAi | PEIDQFV |
OrthoDBi | 1373896at2759 |
PhylomeDBi | Q96LW4 |
TreeFami | TF328961 |
Enzyme and pathway databases
PathwayCommonsi | Q96LW4 |
Miscellaneous databases
BioGRID-ORCSi | 201973, 1 hit in 831 CRISPR screens |
ChiTaRSi | PRIMPOL, human |
GenomeRNAii | 201973 |
Pharosi | Q96LW4, Tbio |
PROi | PR:Q96LW4 |
RNActi | Q96LW4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164306, Expressed in zone of skin and 208 other tissues |
ExpressionAtlasi | Q96LW4, baseline and differential |
Genevisiblei | Q96LW4, HS |
Family and domain databases
InterProi | View protein in InterPro IPR002755, DNA_primase_S |
Pfami | View protein in Pfam PF01896, DNA_primase_S, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | PRIPO_HUMAN | |
Accessioni | Q96LW4Primary (citable) accession number: Q96LW4 Secondary accession number(s): A0A0A0MTC0 Q5HYJ9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 6, 2007 |
Last sequence update: | March 28, 2018 | |
Last modified: | December 2, 2020 | |
This is version 135 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations