3IKM

Crystal structure of human mitochondrial DNA polymerase holoenzyme

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	Class II aaRS ABD-related	8041652	3000465	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Class II aaRS and biotin synthetases	8041653	3000058	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Class II aaRS and biotin synthetases	8041653	3000058	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Class II aaRS ABD-related	8041652	3000465	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Class II aaRS and biotin synthetases	8041653	3000058	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Class II aaRS ABD-related	8041652	3000465	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Class II aaRS ABD-related	8041652	3000465	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Class II aaRS and biotin synthetases	8041653	3000058	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	F_UNCLASSIFIED	e3ikmA4	A: alpha arrays	X: helical bundle in Bacillus stearothermophilus-like DNA polymerase I (From Topology)	H: helical bundle in Bacillus stearothermophilus-like DNA polymerase I (From Topology)	T: helical bundle in Bacillus stearothermophilus-like DNA polymerase I	F: F_UNCLASSIFIED	ECOD (1.6)
A	F_UNCLASSIFIED	e3ikmA2	A: alpha bundles	X: fingers domain in bacteriophage RB69-like DNA polymerase I (From Topology)	H: fingers domain in bacteriophage RB69-like DNA polymerase I (From Topology)	T: fingers domain in bacteriophage RB69-like DNA polymerase I	F: F_UNCLASSIFIED	ECOD (1.6)
A	F_UNCLASSIFIED	e3ikmA3	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: F_UNCLASSIFIED	ECOD (1.6)
A	PF18136	e3ikmA1	A: mixed a+b and a/b	X: Ribonuclease H-like	H: Ribonuclease H-like (From Topology)	T: Ribonuclease H-like	F: PF18136	ECOD (1.6)
D	F_UNCLASSIFIED	e3ikmD6	A: alpha arrays	X: helical bundle in Bacillus stearothermophilus-like DNA polymerase I (From Topology)	H: helical bundle in Bacillus stearothermophilus-like DNA polymerase I (From Topology)	T: helical bundle in Bacillus stearothermophilus-like DNA polymerase I	F: F_UNCLASSIFIED	ECOD (1.6)
D	F_UNCLASSIFIED	e3ikmD5	A: alpha bundles	X: fingers domain in bacteriophage RB69-like DNA polymerase I (From Topology)	H: fingers domain in bacteriophage RB69-like DNA polymerase I (From Topology)	T: fingers domain in bacteriophage RB69-like DNA polymerase I	F: F_UNCLASSIFIED	ECOD (1.6)
D	F_UNCLASSIFIED	e3ikmD7	A: a+b two layers	X: Alpha-beta plaits	H: Adenylyl and guanylyl cyclase catalytic domain-like	T: Adenylyl and guanylyl cyclase catalytic domain-like	F: F_UNCLASSIFIED	ECOD (1.6)
D	PF18136	e3ikmD8	A: mixed a+b and a/b	X: Ribonuclease H-like	H: Ribonuclease H-like (From Topology)	T: Ribonuclease H-like	F: PF18136	ECOD (1.6)
B	F_UNCLASSIFIED	e3ikmB3	A: a+b three layers	X: Class II aaRS and biotin synthetases (From Topology)	H: Class II aaRS and biotin synthetases (From Topology)	T: Class II aaRS and biotin synthetases	F: F_UNCLASSIFIED	ECOD (1.6)
B	PF03129	e3ikmB2	A: a/b three-layered sandwiches	X: Anticodon-binding domain of Class II aaRS (From Topology)	H: Anticodon-binding domain of Class II aaRS (From Topology)	T: Anticodon-binding domain of Class II aaRS	F: PF03129	ECOD (1.6)
C	F_UNCLASSIFIED	e3ikmC5	A: a+b three layers	X: Class II aaRS and biotin synthetases (From Topology)	H: Class II aaRS and biotin synthetases (From Topology)	T: Class II aaRS and biotin synthetases	F: F_UNCLASSIFIED	ECOD (1.6)
C	PF03129	e3ikmC6	A: a/b three-layered sandwiches	X: Anticodon-binding domain of Class II aaRS (From Topology)	H: Anticodon-binding domain of Class II aaRS (From Topology)	T: Anticodon-binding domain of Class II aaRS	F: PF03129	ECOD (1.6)
E	F_UNCLASSIFIED	e3ikmE3	A: a+b three layers	X: Class II aaRS and biotin synthetases (From Topology)	H: Class II aaRS and biotin synthetases (From Topology)	T: Class II aaRS and biotin synthetases	F: F_UNCLASSIFIED	ECOD (1.6)
E	PF03129	e3ikmE2	A: a/b three-layered sandwiches	X: Anticodon-binding domain of Class II aaRS (From Topology)	H: Anticodon-binding domain of Class II aaRS (From Topology)	T: Anticodon-binding domain of Class II aaRS	F: PF03129	ECOD (1.6)
F	F_UNCLASSIFIED	e3ikmF5	A: a+b three layers	X: Class II aaRS and biotin synthetases (From Topology)	H: Class II aaRS and biotin synthetases (From Topology)	T: Class II aaRS and biotin synthetases	F: F_UNCLASSIFIED	ECOD (1.6)
F	PF03129	e3ikmF6	A: a/b three-layered sandwiches	X: Anticodon-binding domain of Class II aaRS (From Topology)	H: Anticodon-binding domain of Class II aaRS (From Topology)	T: Anticodon-binding domain of Class II aaRS	F: PF03129	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.420.390	Alpha Beta	2-Layer Sandwich	Nucleotidyltransferase	domain 5	CATH (4.3.0)
A	1.20.5.3960	Mainly Alpha	Up-down Bundle	Single alpha-helices involved in coiled-coils or other helix-helix interfaces		CATH (4.3.0)
D	3.30.420.390	Alpha Beta	2-Layer Sandwich	Nucleotidyltransferase	domain 5	CATH (4.3.0)
B	3.30.930.10	Alpha Beta	2-Layer Sandwich	BirA Bifunctional Protein	domain 2	CATH (4.3.0)
B	3.40.50.800	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Anticodon-binding domain	CATH (4.3.0)
C	3.30.930.10	Alpha Beta	2-Layer Sandwich	BirA Bifunctional Protein	domain 2	CATH (4.3.0)
C	3.40.50.800	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Anticodon-binding domain	CATH (4.3.0)
E	3.30.930.10	Alpha Beta	2-Layer Sandwich	BirA Bifunctional Protein	domain 2	CATH (4.3.0)
E	3.40.50.800	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Anticodon-binding domain	CATH (4.3.0)
F	3.30.930.10	Alpha Beta	2-Layer Sandwich	BirA Bifunctional Protein	domain 2	CATH (4.3.0)
F	3.40.50.800	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Anticodon-binding domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, D	PF18136	DNA mitochondrial polymerase exonuclease domain (DNApol_Exo)	DNA mitochondrial polymerase exonuclease domain	This domain belongs to human mitochondrial DNA polymerase (Pol-gamma). Pol-gamma has a catalytic subunit, Pol gamma-A, which possesses both polymerase and proofreading exonuclease activities and an accessory subunit, Pol gamma-B, which accelerates po ...	This domain belongs to human mitochondrial DNA polymerase (Pol-gamma). Pol-gamma has a catalytic subunit, Pol gamma-A, which possesses both polymerase and proofreading exonuclease activities and an accessory subunit, Pol gamma-B, which accelerates polymerization rate and suppresses exonuclease activity. This domain is the exonuclease domain of the catalytic subunit, Pol gamma-A [1].	Domain
B, C, E, F	PF03129	Anticodon binding domain (HGTP_anticodon)	Anticodon binding domain	This domain is found in histidyl, glycyl, threonyl and prolyl tRNA synthetases [1] it is probably the anticodon binding domain [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, D	DNA polymerase subunit gamma-1	catalytic activity, acting on DNA catalytic activity, acting on a nucleic acid 5'-deoxyribose-5-phosphate lyase activity lyase activity catalytic activity carbon-oxygen lyase activity DNA exonuclease activity 3'-5' exonuclease activity hydrolase activity DNA exonuclease activity, producing 5'-phosphomonoesters DNA nuclease activity exonuclease activity, active with either ribo- or deoxyribonucleic acids and producing 5'-phosphomonoesters single-stranded DNA exodeoxyribonuclease activity nuclease activity catalytic activity, acting on DNA catalytic activity, acting on a nucleic acid 5'-deoxyribose-5-phosphate lyase activity lyase activity catalytic activity carbon-oxygen lyase activity DNA exonuclease activity 3'-5' exonuclease activity hydrolase activity DNA exonuclease activity, producing 5'-phosphomonoesters DNA nuclease activity exonuclease activity, active with either ribo- or deoxyribonucleic acids and producing 5'-phosphomonoesters single-stranded DNA exodeoxyribonuclease activity nuclease activity hydrolase activity, acting on ester bonds 3'-5'-DNA exonuclease activity exonuclease activity single-stranded DNA 3'-5' DNA exonuclease activity protein-containing complex binding chromatin binding binding protein binding enzyme binding protease binding DNA-directed DNA polymerase activity DNA polymerase activity transferase activity nucleotidyltransferase activity transferase activity, transferring phosphorus-containing groups DNA binding organic cyclic compound binding nucleic acid binding	nucleobase-containing compound metabolic process organic cyclic compound metabolic process DNA-templated DNA replication DNA replication organic substance metabolic process metabolic process primary metabolic process DNA metabolic process macromolecule metabolic process nucleic acid metabolic process cellular response to stimulus response to stimulus DNA-templated DNA replication maintenance of fidelity DNA replication proofreading nucleobase-containing compound metabolic process organic cyclic compound metabolic process DNA-templated DNA replication DNA replication organic substance metabolic process metabolic process primary metabolic process DNA metabolic process macromolecule metabolic process nucleic acid metabolic process cellular response to stimulus response to stimulus DNA-templated DNA replication maintenance of fidelity DNA replication proofreading cellular response to stress DNA damage response response to stress cellular process DNA repair mitochondrial genome maintenance mitochondrial DNA metabolic process cellular component organization organelle organization mitochondrial DNA replication cellular component organization or biogenesis mitochondrion organization base-excision repair, gap-filling base-excision repair	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex mitochondrial protein-containing complex catalytic complex membrane-enclosed lumen transferase complex mitochondrial matrix membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle protein-containing complex mitochondrial protein-containing complex catalytic complex membrane-enclosed lumen transferase complex mitochondrial matrix DNA polymerase complex intracellular organelle lumen transferase complex, transferring phosphorus-containing groups organelle lumen gamma DNA polymerase complex intracellular protein-containing complex nucleoid intracellular non-membrane-bounded organelle mitochondrial nucleoid non-membrane-bounded organelle
B, C, E, F	DNA polymerase subunit gamma-2	catalytic activity, acting on DNA DNA-directed DNA polymerase activity DNA polymerase activity catalytic activity, acting on a nucleic acid transferase activity nucleotidyltransferase activity catalytic activity transferase activity, transferring phosphorus-containing groups DNA binding double-stranded DNA binding binding organic cyclic compound binding nucleic acid binding enzyme regulator activity catalytic activity, acting on DNA DNA-directed DNA polymerase activity DNA polymerase activity catalytic activity, acting on a nucleic acid transferase activity nucleotidyltransferase activity catalytic activity transferase activity, transferring phosphorus-containing groups DNA binding double-stranded DNA binding binding organic cyclic compound binding nucleic acid binding enzyme regulator activity DNA polymerase processivity factor activity enzyme activator activity molecular function activator activity molecular function regulator activity protein binding DNA polymerase binding enzyme binding identical protein binding	regulation of cellular process regulation of catalytic activity regulation of transferase activity regulation of DNA biosynthetic process positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process positive regulation of metabolic process organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of biological process positive regulation of nucleobase-containing compound metabolic process cellular metabolic process regulation of cellular process regulation of catalytic activity regulation of transferase activity regulation of DNA biosynthetic process positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process positive regulation of metabolic process organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of biological process positive regulation of nucleobase-containing compound metabolic process cellular metabolic process regulation of cellular metabolic process primary metabolic process DNA metabolic process organic cyclic compound metabolic process regulation of molecular function regulation of DNA-directed DNA polymerase activity DNA replication biosynthetic process positive regulation of DNA metabolic process organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process regulation of metabolic process DNA biosynthetic process positive regulation of DNA-directed DNA polymerase activity regulation of DNA metabolic process regulation of DNA replication cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process nucleic acid biosynthetic process positive regulation of molecular function organic substance metabolic process positive regulation of biosynthetic process positive regulation of cellular process regulation of biosynthetic process DNA-templated DNA replication positive regulation of transferase activity biological regulation positive regulation of catalytic activity positive regulation of DNA biosynthetic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process regulation of DNA-templated DNA replication cellular process positive regulation of cellular biosynthetic process mitochondrial genome maintenance mitochondrial DNA metabolic process cellular component organization organelle organization mitochondrial DNA replication cellular component organization or biogenesis mitochondrion organization developmental process multicellular organism development multicellular organismal process embryo development ending in birth or egg hatching chordate embryonic development anatomical structure development embryo development in utero embryonic development	membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle mitochondrial protein-containing complex protein-containing complex catalytic complex membrane-enclosed lumen transferase complex mitochondrial matrix membrane-bounded organelle intracellular organelle intracellular anatomical structure mitochondrion organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle mitochondrial protein-containing complex protein-containing complex catalytic complex membrane-enclosed lumen transferase complex mitochondrial matrix DNA polymerase complex intracellular organelle lumen transferase complex, transferring phosphorus-containing groups organelle lumen gamma DNA polymerase complex intracellular protein-containing complex nucleoid intracellular non-membrane-bounded organelle mitochondrial nucleoid non-membrane-bounded organelle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, D	IPR047580	DNA polymerase gamma, palm domain	Domain
A, D	IPR019760	DNA-directed DNA polymerase, family A, conserved site	Conserved Site
A, D	IPR012337	Ribonuclease H-like superfamily	Homologous Superfamily
A, D	IPR002297	DNA-directed DNA-polymerase, family A, mitochondria	Family
A, D	IPR043502	DNA/RNA polymerase superfamily	Homologous Superfamily
A, D	IPR001098	DNA-directed DNA polymerase, family A, palm domain	Domain
A, D	IPR041336	DNA mitochondrial polymerase, exonuclease domain	Domain
B, C, E, F	IPR045864	Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)	Homologous Superfamily
B, C, E, F	IPR004154	Anticodon-binding	Domain
B, C, E, F	IPR042064	POLG2, C-terminal	Domain
B, C, E, F	IPR036621	Anticodon-binding domain superfamily	Homologous Superfamily
B, C, E, F	IPR027031	Glycyl-tRNA synthetase/DNA polymerase subunit gamma-2	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, D	Pharos: P54098	mitochondrial DNA depletion syndrome 4a sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Leigh syndrome progressive external ophthalmoplegia mitochondrial DNA depletion syndrome 4b progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 mitochondrial DNA depletion syndrome 1 epilepsy progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 male infertility peripheral neuropathy adrenoleukodystrophy myopathy visual epilepsy Charcot-Marie-Tooth disease mitochondrial DNA depletion syndrome 4a sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Leigh syndrome progressive external ophthalmoplegia mitochondrial DNA depletion syndrome 4b progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 mitochondrial DNA depletion syndrome 1 epilepsy progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 1 male infertility peripheral neuropathy adrenoleukodystrophy myopathy visual epilepsy Charcot-Marie-Tooth disease spinocerebellar ataxia with epilepsy Balo concentric sclerosis Leigh Syndrome due to Mitochondrial Complex V Deficiency peripheral nervous system disease motor peripheral neuropathy neurodegenerative disease autosomal dominant progressive external ophthalmoplegia inborn mitochondrial metabolism disorder autosomal recessive progressive external ophthalmoplegia parkinsonian disorder bipolar disorder leukodystrophy rhabdomyolysis drug-induced liver injury muscle tissue disease osteosarcoma autosomal recessive juvenile Parkinson disease 2 intellectual disability pancreatic intraductal papillary-mucinous carcinoma Pelizaeus-Merzbacher disease cholestasis lung cancer Schilder disease muscular disease arthrogryposis attention deficit hyperactivity disorder, inattentive type inborn errors of metabolism ovarian cancer pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia
B, C, E, F	Pharos: Q9UHN1	progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 4 progressive external ophthalmoplegia progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1 large cell medulloblastoma Mitochondrial Diseases muscular disease rhabdomyolysis leukodystrophy mitochondrial DNA depletion syndrome 4a myopathy medulloblastoma muscle tissue disease osteosarcoma

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.