POLD3
DNA polymerase delta subunit 3
Also known as: DPOD3_HUMAN, KIAA0039, P66, P68, PPP1R128
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- Q15054
- Gene
- POLD3
- Ensembl
- ENSG00000077514
- Chromosome
- 11
- Canonical length
- 466 aa
- Protein class
- Metabolic proteins, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm
OverviewNCBI Gene
This gene encodes the 66-kDa subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. The encoded protein plays a role in regulating the activity of DNA polymerase delta through interactions with other subunits and the processivity cofactor proliferating cell nuclear antigen (PCNA). Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Mar 2012]
Canonical amino-acid sequenceUniProt
466 residues, UniProt reviewed canonical sequence.
>Q15054|POLD3
1 MADQLYLENI DEFVTDQNKI VTYKWLSYTL GVHVNQAKQM LYDYVERKRK ENSGAQLHVT
61 YLVSGSLIQN GHSCHKVAVV REDKLEAVKS KLAVTASIHV YSIQKAMLKD SGPLFNTDYD
121 ILKSNLQNCS KFSAIQCAAA VPRAPAESSS SSKKFEQSHL HMSSETQANN ELTTNGHGPP
181 ASKQVSQQPK GIMGMFASKA AAKTQETNKE TKTEAKEVTN ASAAGNKAPG KGNMMSNFFG
241 KAAMNKFKVN LDSEQAVKEE KIVEQPTVSV TEPKLATPAG LKKSSKKAEP VKVLQKEKKR
301 GKRVALSDDE TKETENMRKK RRRIKLPESD SSEDEVFPDS PGAYEAESPS PPPPPSPPLE
361 PVPKTEPEPP SVKSSSGENK RKRKRVLKSK TYLDGEGCIV TEKVYESESC TDSEEELNMK
421 TSSVHRPPAM TVKKEPREER KGPKKGTAAL GKANRQVSIT GFFQRKLocalizationUniProt · AlphaFold · HPA
Whether an antibody against POLD3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.58
- Highest tissue expression
- 40 nTPM
Expression across tissuesHPA
Tissue
- kidney: 40 nTPM
- testis: 18 nTPM
- rectum: 16 nTPM
- colon: 15 nTPM
- endometrium: 15 nTPM
- duodenum: 14 nTPM
Single-cell type
- proximal tubule cells: 99 nCPM
- respiratory ciliated cells: 90 nCPM
- ependymal cells: 86 nCPM
- monocyte progenitors: 85 nCPM
- gastric progenitor cells: 85 nCPM
- late primary spermatocytes: 82 nCPM
Immune cell
- classical monocyte: 23 nTPM
- neutrophil: 20 nTPM
- non-classical monocyte: 19 nTPM
- intermediate monocyte: 19 nTPM
- myeloid DC: 18 nTPM
- eosinophil: 16 nTPM
Brain region
- choroid plexus: 22 nTPM
- white matter: 20 nTPM
- cerebral cortex: 18 nTPM
- cerebellum: 17 nTPM
- hypothalamus: 17 nTPM
- basal ganglia: 17 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about POLD3.
Disease | AllUniProt
Conditions POLD3 is implicated in, by any mechanism.
- Immunodeficiency 122 (IMD122) MIM:620869
Disease | GeneticClinVar
1 pathogenic / likely-pathogenic of 67 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
ReferencesPubMed · IEDB
Publications for POLD3 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.
Reference: AutoantibodyPubMed
5 publications
- Autoantibodies in rheumatoid arthritis and their clinical significance.
2002 · Arthritis Res · RCR 2.6 · 120 citations - Epitope mapping with a recombinant human 68-kDa (U1) ribonucleoprotein antigen reveals heterogeneous autoantibody profiles in human autoimmune sera.
1988 · J Immunol · RCR 2.3 · 89 citations - Human anti-p68 autoantibodies recognize a common epitope of U1 RNA containing small nuclear ribonucleoprotein and influenza B virus.
1990 · J Exp Med · RCR 1.7 · 63 citations - Repetitive P68-autoantigen specific epitopes recognized by human anti-(U1) small nuclear ribonucleoprotein autoantibodies.
1991 · J Autoimmun · RCR 0.6 · 20 citations - The p68 autoantigen characteristic of rheumatoid arthritis is reactive with carbohydrate epitope specific autoantibodies.
1998 · Ann Rheum Dis · RCR 0.5 · 21 citations
Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.24
- gnomAD pLI
- 1
- gnomAD missense Z
- 0.09
- DepMap mean gene effect
- -1.58
- DepMap dependency class
- pan
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- DNA biosynthetic process
- DNA strand elongation involved in DNA replication
- DNA synthesis involved in DNA repair
- DNA synthesis involved in UV-damage excision repair
- DNA-templated DNA replication
- error-prone translesion synthesis
- mismatch repair
- nucleotide-excision repair, DNA gap filling
Molecular functions
Cellular components
Protein domainsUniProt · Pfam · InterPro
- DNA polymerase delta subunit 3
- DNA polymerase delta subunit 3 superfamily
- DNA polymerase subunit Cdc27
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of POLD3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads POLD3 as an antibody target. Whether an autoantibody or antibody against POLD3 could matter depends on whether native POLD3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
POLD3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label POLD3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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