4O28

Structural Basis for Resistance to Diverse Classes of NAMPT Inhibitors

External Resource: Annotation

Domain Annotation: SCOP/SCOPe 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: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d4o28a2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	Nicotinate/Quinolinate PRTase C-terminal domain-like	Nicotinate phosphoribosyltransferase C-terminal domain-like	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d4o28a1	Alpha and beta proteins (a+b)	alpha/beta-Hammerhead	Nicotinate/Quinolinate PRTase N-terminal domain-like	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4o28b2	Alpha and beta proteins (a/b)	TIM beta/alpha-barrel	Nicotinate/Quinolinate PRTase C-terminal domain-like	Nicotinate phosphoribosyltransferase C-terminal domain-like	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4o28b1	Alpha and beta proteins (a+b)	alpha/beta-Hammerhead	Nicotinate/Quinolinate PRTase N-terminal domain-like	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PRK09198,NAPRTase	e4o28A1	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Nicotinate/Quinolinate PRTase N-terminal domain-like	F: PRK09198,NAPRTase	ECOD (1.6)
A	NAPRTase	e4o28A2	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: NAPRTase	ECOD (1.6)
A	EUF08675	e4o28A3	A: few secondary structure elements	X: Rubredoxin-like	H: Nicotinate phosphoribosyltransferase C-terminal domain-related (From Topology)	T: Nicotinate phosphoribosyltransferase C-terminal domain-related	F: EUF08675	ECOD (1.6)
B	PRK09198,NAPRTase	e4o28B1	A: a+b complex topology	X: alpha/beta-Hammerhead/Barrel-sandwich hybrid	H: alpha/beta-Hammerhead/Barrel-sandwich hybrid	T: Nicotinate/Quinolinate PRTase N-terminal domain-like	F: PRK09198,NAPRTase	ECOD (1.6)
B	NAPRTase	e4o28B3	A: a/b barrels	X: TIM beta/alpha-barrel	H: TIM barrels (From Topology)	T: TIM barrels	F: NAPRTase	ECOD (1.6)
B	EUF08675	e4o28B2	A: few secondary structure elements	X: Rubredoxin-like	H: Nicotinate phosphoribosyltransferase C-terminal domain-related (From Topology)	T: Nicotinate phosphoribosyltransferase C-terminal domain-related	F: EUF08675	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.20.20.70	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Aldolase class I	CATH (4.3.0)
B	3.20.20.70	Alpha Beta	Alpha-Beta Barrel	TIM Barrel	Aldolase class I	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF04095	Nicotinate phosphoribosyltransferase (NAPRTase) family (NAPRTase)	Nicotinate phosphoribosyltransferase (NAPRTase) family	-	Family
A, B	PF18127	Nicotinamide phosphoribosyltransferase, N-terminal domain (NAMPT_N)	Nicotinamide phosphoribosyltransferase, N-terminal domain	This is the N-terminal domain found in Nicotinamide phosphoribosyltransferase (NAMPT) present in Homo sapiens. NAMPT captures nicotinamide (NAM) and replenish the nicotinamide adenine dinucleotide (NAD+) pool during ADP-ribosylation and transferase r ...	This is the N-terminal domain found in Nicotinamide phosphoribosyltransferase (NAMPT) present in Homo sapiens. NAMPT captures nicotinamide (NAM) and replenish the nicotinamide adenine dinucleotide (NAD+) pool during ADP-ribosylation and transferase reactions [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Nicotinamide phosphoribosyltransferase	protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity cytokine activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity pentosyltransferase activity glycosyltransferase activity transferase activity nicotinamide phosphoribosyltransferase activity catalytic activity protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity cytokine activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity pentosyltransferase activity glycosyltransferase activity transferase activity nicotinamide phosphoribosyltransferase activity catalytic activity identical protein binding	regulation of cellular process cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process regulation of nitric-oxide synthase biosynthetic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process nitric-oxide synthase biosynthetic process positive regulation of cellular process regulation of biosynthetic process regulation of biological process cellular metabolic process regulation of cellular process cellular biosynthetic process positive regulation of biological process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process regulation of nitric-oxide synthase biosynthetic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process nitric-oxide synthase biosynthetic process positive regulation of cellular process regulation of biosynthetic process regulation of biological process cellular metabolic process biological regulation regulation of cellular metabolic process regulation of macromolecule metabolic process macromolecule biosynthetic process regulation of cellular biosynthetic process biosynthetic process regulation of macromolecule biosynthetic process metabolic process cellular process macromolecule metabolic process positive regulation of nitric-oxide synthase biosynthetic process regulation of metabolic process positive regulation of cellular biosynthetic process cell population proliferation positive regulation of cell population proliferation regulation of cell population proliferation nucleotide biosynthetic process NAD metabolic process NAD biosynthesis via nicotinamide riboside salvage pathway nucleobase-containing compound metabolic process purine nucleotide metabolic process nucleobase-containing small molecule metabolic process purine-containing compound biosynthetic process phosphate-containing compound metabolic process pyridine-containing compound metabolic process small molecule metabolic process phosphorus metabolic process pyridine nucleotide metabolic process NAD biosynthetic process pyridine nucleotide biosynthetic process nucleoside phosphate metabolic process nicotinamide nucleotide metabolic process pyridine-containing compound biosynthetic process primary metabolic process nucleotide metabolic process nucleobase-containing compound biosynthetic process purine-containing compound metabolic process nicotinamide nucleotide biosynthetic process organophosphate metabolic process organophosphate biosynthetic process nucleoside phosphate biosynthetic process purine nucleotide biosynthetic process signaling cell-cell signaling cell communication positive regulation of DNA-templated transcription RNA metabolic process regulation of primary metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II gene expression nucleic acid metabolic process positive regulation of RNA metabolic process regulation of gene expression positive regulation of RNA biosynthetic process regulation of DNA-templated transcription cellular response to stimulus response to stimulus signal transduction rhythmic process circadian regulation of gene expression circadian rhythm	cell junction cellular anatomical entity membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle nucleoplasm organelle lumen organelle cell junction cellular anatomical entity membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle cytoplasm cytosol

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR016471	Nicotinamide phosphoribosyl transferase	Family
A, B	IPR041525	Nicotinate/nicotinamide phosphoribosyltransferase	Domain
A, B	IPR013785	Aldolase-type TIM barrel	Homologous Superfamily
A, B	IPR041529	Nicotinamide phosphoribosyltransferase, N-terminal domain	Domain
A, B	IPR036068	Nicotinate phosphoribosyltransferase-like, C-terminal	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P43490	obesity disorder colitis colorectal cancer allergic contact dermatitis interstitial lung disease malignant ependymoma Malignant neoplasm of mouth acute myeloid leukemia astrocytic tumor pancreatic ductal adenocarcinoma pituitary cancer rheumatoid arthritis gastric carcinoma head and neck squamous cell carcinoma type 2 diabetes mellitus obesity disorder colitis colorectal cancer allergic contact dermatitis interstitial lung disease malignant ependymoma Malignant neoplasm of mouth acute myeloid leukemia astrocytic tumor pancreatic ductal adenocarcinoma pituitary cancer rheumatoid arthritis gastric carcinoma head and neck squamous cell carcinoma type 2 diabetes mellitus inborn carbohydrate metabolic disorder large cell medulloblastoma malignant glioma malignant pancreatic neoplasm myopathy adrenal cortex carcinoma oral cavity neoplasm atrial fibrillation pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia progressive supranuclear palsy Sjogren syndrome glioblastoma transitional cell carcinoma hepatocellular carcinoma ulcerative colitis interstitial cystitis lung cancer malignant mesothelioma medulloblastoma non-small cell lung carcinoma ovarian cancer B-cell chronic lymphocytic leukemia Pick disease colorectal carcinoma psoriasis gastric cancer spondyloarthropathy head and neck cancer tuberculosis IgA glomerulonephritis

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), 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 R01GM157729.