InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: POLG

Summary

InnateDB Protein

IDBP-29262.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

POLG

Protein Name

polymerase (DNA directed), gamma

Synonyms

MDP1; MIRAS; MTDPS4A; MTDPS4B; PEO; POLG1; POLGA; SANDO; SCAE;

Species

Homo sapiens

Ensembl Protein

ENSP00000268124

InnateDB Gene

IDBG-29260 (POLG)

Protein Structure

UniProt Annotation

Function

Involved in the replication of mitochondrial DNA. Associates with mitochondrial DNA.

Subcellular Localization

Mitochondrion {ECO:0000269PubMed:18063578}. Mitochondrion matrix, mitochondrion nucleoid {ECO:0000269PubMed:18063578}.

Disease Associations

Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant, 1 (PEOA1) [MIM:157640]: A disorder is characterized by progressive weakness of ocular muscles and levator muscle of the upper eyelid. In a minority of cases, it is associated with skeletal myopathy, which predominantly involves axial or proximal muscles and which causes abnormal fatigability and even permanent muscle weakness. Ragged- red fibers and atrophy are found on muscle biopsy. A large proportion of chronic ophthalmoplegias are associated with other symptoms, leading to a multisystemic pattern of this disease. Additional symptoms are variable, and may include cataracts, hearing loss, sensory axonal neuropathy, ataxia, depression, hypogonadism, and parkinsonism. {ECO:0000269PubMed:12210792, ECO:0000269PubMed:15351195, ECO:0000269PubMed:15534189, ECO:0000269PubMed:17420318, ECO:0000269PubMed:18575922}. Note=The disease is caused by mutations affecting the gene represented in this entry.Progressive external ophthalmoplegia with mitochondrial DNA deletions autosomal recessive (PEOB) [MIM:258450]: A severe form of progressive external ophthalmoplegia. It is clinically more heterogeneous than the autosomal dominant forms. {ECO:0000269PubMed:11431686, ECO:0000269PubMed:12565911, ECO:0000269PubMed:12707443, ECO:0000269PubMed:12872260, ECO:0000269PubMed:12975295, ECO:0000269PubMed:14635118, ECO:0000269PubMed:15349879, ECO:0000269PubMed:15351195, ECO:0000269PubMed:15477547, ECO:0000269PubMed:15917273, ECO:0000269PubMed:16401742, ECO:0000269PubMed:16621917, ECO:0000269PubMed:16634032, ECO:0000269PubMed:16639411}. Note=The disease is caused by mutations affecting the gene represented in this entry.Sensory ataxic neuropathy dysarthria and ophthalmoparesis (SANDO) [MIM:607459]: A systemic disorder resulting from mitochondrial dysfunction associated with mitochondrial depletion in skeletal muscle and peripheral nerve tissue. The clinical triad of symptoms consists of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis. However, the phenotype varies widely, even within the same family, and can also include myopathy, seizures, and hearing loss. An atypical form of the disease is characterized by headaches and/or seizures manifesting in childhood or adolescence, followed by development of cerebellar and sensory ataxia, dysarthria, progressive external ophthalmoplegia, and myoclonus in early adulthood. {ECO:0000269PubMed:12565911, ECO:0000269PubMed:14745080, ECO:0000269PubMed:15477547, ECO:0000269PubMed:15824347, ECO:0000269PubMed:15917273, ECO:0000269PubMed:16080118, ECO:0000269PubMed:16621917, ECO:0000269PubMed:16639411, ECO:0000269PubMed:16919951}. Note=The disease is caused by mutations affecting the gene represented in this entry.Mitochondrial DNA depletion syndrome 4A (MTDPS4A) [MIM:203700]: An autosomal recessive hepatocerebral syndrome due to mitochondrial dysfunction. The typical course of the disease includes severe developmental delay, intractable seizures, liver failure, and death in childhood. Refractory seizures, cortical blindness, progressive liver dysfunction, and acute liver failure after exposure to valproic acid are considered diagnostic features. The neuropathological hallmarks are neuronal loss, spongiform degeneration, and astrocytosis of the visual cortex. Liver biopsy results show steatosis, often progressing to cirrhosis. {ECO:0000269PubMed:15122711, ECO:0000269PubMed:15689359, ECO:0000269PubMed:15929042, ECO:0000269PubMed:16621917, ECO:0000269PubMed:16639411, ECO:0000269PubMed:18828154}. Note=The disease is caused by mutations affecting the gene represented in this entry.Mitochondrial DNA depletion syndrome 4B (MTDPS4B) [MIM:613662]: An autosomal recessive progressive multisystem disorder due to mitochondrial dysfunction. It is clinically characterized by chronic gastrointestinal dysmotility and pseudo- obstruction, cachexia, progressive external ophthalmoplegia, axonal sensory ataxic neuropathy, and muscle weakness. {ECO:0000269PubMed:12825077, ECO:0000269PubMed:19307547}. Note=The disease is caused by mutations affecting the gene represented in this entry.Leigh syndrome (LS) [MIM:256000]: An early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, and dysphagia. {ECO:0000269PubMed:18828154}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	6 [view]
Protein-Protein	6 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0002020	protease binding
GO:0003676	nucleic acid binding
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003887	DNA-directed DNA polymerase activity
GO:0004527	exonuclease activity
GO:0005515	protein binding

Biological Process

GO:0006259	DNA metabolic process
GO:0006260	DNA replication
GO:0006261	DNA-dependent DNA replication
GO:0006264	mitochondrial DNA replication
GO:0006287	base-excision repair, gap-filling
GO:0007568	aging
GO:0008219	cell death
GO:0090305	nucleic acid phosphodiester bond hydrolysis

Cellular Component

GO:0005739	mitochondrion
GO:0005743	mitochondrial inner membrane
GO:0005760	gamma DNA polymerase complex
GO:0042645	mitochondrial nucleoid
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR001098 DNA-directed DNA polymerase, family A, palm domain
IPR002297 DNA-directed DNA-polymerase, family A, mitochondria
IPR012337 Ribonuclease H-like domain
IPR016265 DNA-directed DNA polymerase, family A, mitochondria, subgroup

PFAM

PF00476

PRINTS

PR00867

PIRSF

PIRSF000797

SMART

SM00482

TIGRFAMs

Post-translational Modifications

Modification

Cross-References