2W3O

Crystal structure of the human PNKP FHA domain in complex with an XRCC1-derived phosphopeptide

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
Protein Modification Annotation

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	SMAD/FHA domain-like	8058041	3000137	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	SMAD/FHA domain-like	8058041	3000137	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)
B	PF17913	e2w3oB1	A: beta sandwiches	X: SMAD/FHA domain (From Topology)	H: SMAD/FHA domain (From Topology)	T: SMAD/FHA domain	F: PF17913	ECOD (1.6)
A	PF17913	e2w3oA1	A: beta sandwiches	X: SMAD/FHA domain (From Topology)	H: SMAD/FHA domain (From Topology)	T: SMAD/FHA domain	F: PF17913	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	2.60.200.20	Mainly Beta	Sandwich	Tumour Suppressor Smad4		CATH (4.3.0)
A	2.60.200.20	Mainly Beta	Sandwich	Tumour Suppressor Smad4		CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF17913	FHA domain (FHA_2)	FHA domain	This entry represents a divergent FHA domain which in PNK binds to phosphorylated segment of XRCC1 [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	BIFUNCTIONAL POLYNUCLEOTIDE PHOSPHATASE/KINASE	DNA binding binding organic cyclic compound binding damaged DNA binding nucleic acid binding nucleobase-containing compound kinase activity polynucleotide 5'-hydroxyl-kinase activity kinase activity ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity transferase activity ATP-dependent polynucleotide 5'-hydroxyl-kinase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups DNA binding binding organic cyclic compound binding damaged DNA binding nucleic acid binding nucleobase-containing compound kinase activity polynucleotide 5'-hydroxyl-kinase activity kinase activity ATP-dependent polydeoxyribonucleotide 5'-hydroxyl-kinase activity transferase activity ATP-dependent polynucleotide 5'-hydroxyl-kinase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding double-stranded DNA binding phosphoric ester hydrolase activity hydrolase activity, acting on ester bonds phosphatase activity hydrolase activity polynucleotide 3'-phosphatase activity endonuclease activity nuclease activity	regulation of molecular function regulation of catalytic activity negative regulation of transferase activity biological regulation negative regulation of molecular function negative regulation of catalytic activity regulation of transferase activity negative regulation of protein ADP-ribosylation regulation of protein ADP-ribosylation cellular response to stimulus regulation of cellular process regulation of double-strand break repair response to stimulus regulation of cellular response to stress regulation of molecular function regulation of catalytic activity negative regulation of transferase activity biological regulation negative regulation of molecular function negative regulation of catalytic activity regulation of transferase activity negative regulation of protein ADP-ribosylation regulation of protein ADP-ribosylation cellular response to stimulus regulation of cellular process regulation of double-strand break repair response to stimulus regulation of cellular response to stress positive regulation of biological process regulation of primary metabolic process nucleobase-containing compound metabolic process positive regulation of response to stimulus positive regulation of metabolic process organic substance metabolic process positive regulation of DNA repair cellular response to stress response to stress regulation of response to stress positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process positive regulation of cellular process regulation of double-strand break repair via nonhomologous end joining DNA repair double-strand break repair regulation of biological process positive regulation of nucleobase-containing compound metabolic process positive regulation of double-strand break repair via nonhomologous end joining double-strand break repair via nonhomologous end joining primary metabolic process DNA metabolic process regulation of macromolecule metabolic process nucleic acid metabolic process positive regulation of double-strand break repair regulation of DNA repair organic cyclic compound metabolic process positive regulation of DNA metabolic process DNA damage response regulation of response to stimulus metabolic process cellular process macromolecule metabolic process regulation of metabolic process regulation of DNA metabolic process DNA-templated DNA replication DNA replication DNA ligation involved in DNA repair DNA ligation response to radiation response to abiotic stimulus regulation of DNA biosynthetic process positive regulation of macromolecule biosynthetic process organic substance biosynthetic process cellular metabolic process regulation of cellular metabolic process biosynthetic process organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process DNA biosynthetic process regulation of telomerase activity cellular biosynthetic process positive regulation of cellular metabolic process nucleic acid biosynthetic process positive regulation of molecular function positive regulation of biosynthetic process regulation of biosynthetic process positive regulation of telomerase activity positive regulation of transferase activity positive regulation of catalytic activity positive regulation of DNA biosynthetic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process regulation of cellular biosynthetic process positive regulation of cellular biosynthetic process positive regulation of organelle organization telomere organization RNA-templated DNA biosynthetic process telomere maintenance via telomere lengthening positive regulation of telomere maintenance via telomere lengthening positive regulation of telomere maintenance regulation of chromosome organization regulation of telomere maintenance via telomere lengthening regulation of organelle organization positive regulation of chromosome organization telomere maintenance positive regulation of telomere maintenance via telomerase regulation of telomere maintenance regulation of cellular component organization positive regulation of cellular component organization cellular component organization cellular component organization or biogenesis telomere maintenance via telomerase chromosome organization regulation of telomere maintenance via telomerase organelle organization nucleotide-excision repair phosphorylation phosphate-containing compound metabolic process phosphorus metabolic process base-excision repair, gap-filling base-excision repair response to oxidative stress positive regulation of telomere capping telomere capping regulation of telomere capping	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle cellular anatomical entity nucleolus intracellular organelle lumen intracellular organelle organelle lumen organelle intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle cellular anatomical entity nucleolus intracellular organelle lumen intracellular organelle organelle lumen organelle intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle membrane nucleoplasm site of double-strand break site of DNA damage chromosome
C, D	DNA REPAIR PROTEIN XRCC1	DNA binding oxidized DNA binding binding organic cyclic compound binding damaged DNA binding nucleic acid binding endonuclease activity catalytic activity, acting on a nucleic acid hydrolase activity 3' overhang single-stranded DNA endodeoxyribonuclease activity single-stranded DNA endodeoxyribonuclease activity DNA nuclease activity DNA endonuclease activity catalytic activity, acting on DNA DNA binding oxidized DNA binding binding organic cyclic compound binding damaged DNA binding nucleic acid binding endonuclease activity catalytic activity, acting on a nucleic acid hydrolase activity 3' overhang single-stranded DNA endodeoxyribonuclease activity single-stranded DNA endodeoxyribonuclease activity DNA nuclease activity DNA endonuclease activity catalytic activity, acting on DNA nuclease activity hydrolase activity, acting on ester bonds catalytic activity ADP-D-ribose modification-dependent protein binding protein binding modification-dependent protein binding poly-ADP-D-ribose binding carbohydrate derivative binding enzyme binding	response to stimulus response to chemical response to xenobiotic stimulus regulation of molecular function regulation of catalytic activity negative regulation of transferase activity biological regulation negative regulation of molecular function negative regulation of catalytic activity regulation of transferase activity negative regulation of protein ADP-ribosylation regulation of protein ADP-ribosylation cellular response to stimulus double-strand break repair response to stimulus response to chemical response to xenobiotic stimulus regulation of molecular function regulation of catalytic activity negative regulation of transferase activity biological regulation negative regulation of molecular function negative regulation of catalytic activity regulation of transferase activity negative regulation of protein ADP-ribosylation regulation of protein ADP-ribosylation cellular response to stimulus double-strand break repair DNA recombination primary metabolic process DNA metabolic process nucleic acid metabolic process nucleobase-containing compound metabolic process organic cyclic compound metabolic process organic substance metabolic process replication-born double-strand break repair via sister chromatid exchange cellular response to stress DNA damage response response to stress recombinational repair metabolic process cellular process macromolecule metabolic process double-strand break repair via homologous recombination DNA repair developmental process multicellular organismal process head development forebrain development animal organ development brain development nervous system development pallium development multicellular organism development central nervous system development anatomical structure development telencephalon development hippocampus development limbic system development system development response to organic substance voluntary musculoskeletal movement multicellular organismal movement musculoskeletal movement system process nervous system process neuromuscular process cerebellum morphogenesis hindbrain morphogenesis anatomical structure morphogenesis cerebellum development metencephalon development hindbrain development telomere maintenance in response to DNA damage negative regulation of telomere maintenance regulation of cellular process regulation of cellular response to stress negative regulation of biological process telomere organization regulation of primary metabolic process negative regulation of chromosome organization negative regulation of nucleobase-containing compound metabolic process negative regulation of telomere maintenance in response to DNA damage regulation of nucleobase-containing compound metabolic process regulation of biological process negative regulation of cellular component organization negative regulation of metabolic process regulation of chromosome organization regulation of organelle organization telomere maintenance telomere capping regulation of response to stimulus regulation of metabolic process regulation of DNA metabolic process regulation of telomere maintenance regulation of cellular component organization regulation of protection from non-homologous end joining at telomere cellular component organization regulation of response to stress negative regulation of cellular process cellular component organization or biogenesis negative regulation of macromolecule metabolic process regulation of telomere maintenance in response to DNA damage negative regulation of response to stimulus protection from non-homologous end joining at telomere chromosome organization regulation of macromolecule metabolic process negative regulation of protection from non-homologous end joining at telomere organelle organization negative regulation of organelle organization negative regulation of telomere capping negative regulation of DNA metabolic process regulation of telomere capping single strand break repair positive regulation of biological process positive regulation of single strand break repair positive regulation of response to stimulus positive regulation of metabolic process positive regulation of DNA repair positive regulation of macromolecule metabolic process positive regulation of cellular process positive regulation of nucleobase-containing compound metabolic process regulation of single strand break repair regulation of DNA repair positive regulation of DNA metabolic process mitotic recombination telomeric DNA-containing double minutes formation telomere maintenance via recombination base-excision repair response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus response to oxidative stress response to oxygen-containing compound response to hydroperoxide DNA ligation positive regulation of molecular function regulation of ligase activity regulation of DNA ligation positive regulation of DNA ligation regulation of DNA ligase activity positive regulation of catalytic activity positive regulation of DNA ligase activity positive regulation of ligase activity double-strand break repair via nonhomologous end joining	membrane-bounded organelle protein-containing complex intracellular anatomical structure nucleus nuclear protein-containing complex intracellular membrane-bounded organelle cellular anatomical entity intracellular organelle organelle nucleotide-excision repair complex ERCC4-ERCC1 complex membrane-enclosed lumen nucleolus intracellular organelle lumen membrane-bounded organelle protein-containing complex intracellular anatomical structure nucleus nuclear protein-containing complex intracellular membrane-bounded organelle cellular anatomical entity intracellular organelle organelle nucleotide-excision repair complex ERCC4-ERCC1 complex membrane-enclosed lumen nucleolus intracellular organelle lumen organelle lumen intracellular non-membrane-bounded organelle nuclear lumen non-membrane-bounded organelle nucleoplasm protein-DNA complex chromatin chromosome chromosome, telomeric region chromosomal region site of DNA damage

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR006551	Polynucleotide 3'-phosphatase	Domain
A, B	IPR041388	PNK, FHA domain	Domain
A, B	IPR006550	Bifunctional polynucleotide phosphatase/kinase PNKP	Family
A, B	IPR027417	P-loop containing nucleoside triphosphate hydrolase	Homologous Superfamily
A, B	IPR006549	HAD-superfamily hydrolase,subfamily IIIA	Domain
A, B	IPR023214	HAD superfamily	Homologous Superfamily
A, B	IPR008984	SMAD/FHA domain superfamily	Homologous Superfamily
A, B	IPR013954	Polynucleotide kinase 3 phosphatase	Family
A, B	IPR036412	HAD-like superfamily	Homologous Superfamily
C, D	IPR008979	Galactose-binding-like domain superfamily	Homologous Superfamily
C, D	IPR045080	XRCC1, first (central) BRCT domain	Domain
C, D	IPR001357	BRCT domain	Domain
C, D	IPR002706	DNA-repair protein Xrcc1, N-terminal	Domain
C, D	IPR036420	BRCT domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q96T60	microcephaly, seizures, and developmental delay microcephaly ataxia - oculomotor apraxia type 4 intellectual disability visual epilepsy Epileptic Seizures ovarian cancer developmental disability neurodegenerative disease developmental and epileptic encephalopathy DNA repair disease microlissencephaly osteosarcoma psoriasis spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 microcephaly, seizures, and developmental delay microcephaly ataxia - oculomotor apraxia type 4 intellectual disability visual epilepsy Epileptic Seizures ovarian cancer developmental disability neurodegenerative disease developmental and epileptic encephalopathy DNA repair disease microlissencephaly osteosarcoma psoriasis spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1 tuberculosis epilepsy
C, D	Pharos: P18887	esophageal squamous cell carcinoma mixed glioma prostate cancer spinocerebellar ataxia, autosomal recessive 26 Erythema stomatitis malignant glioma osteosarcoma cancer gastric neoplasm malignant mesothelioma mesothelioma neurodegenerative disease benign mesothelioma childhood acute lymphoblastic leukemia esophageal squamous cell carcinoma mixed glioma prostate cancer spinocerebellar ataxia, autosomal recessive 26 Erythema stomatitis malignant glioma osteosarcoma cancer gastric neoplasm malignant mesothelioma mesothelioma neurodegenerative disease benign mesothelioma childhood acute lymphoblastic leukemia glioma lung carcinoma schizophrenia xeroderma pigmentosum colorectal cancer gastric cancer hereditary diffuse gastric adenocarcinoma medulloblastoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
C, D	SEP	Parent Component: SER RESID: AA0037 PSI-MOD : O-phospho-L-serine MOD:00046
C, D	TPO	Parent Component: THR RESID: AA0037 , AA0038 PSI-MOD : O-phospho-L-serine MOD:00046 , O-phospho-L-threonine MOD:00047

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.