8UKO

cAMP-dependent protein kinase A catalytic domain in complex with voltage gated calcium channel peptide ternary complex 2

External Resource: Annotation

Domain Annotation: SCOP2 Classification
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)
A [auth E]	SCOP2B Superfamily	Protein kinase-like (PK-like)	8040503	3000066	SCOP2B (2022-06-29)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth E]	PF00069	Protein kinase domain (Pkinase)	Protein kinase domain		Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth E]	cAMP-dependent protein kinase catalytic subunit alpha	cation binding manganese ion binding transition metal ion binding ion binding binding metal ion binding small molecule binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding purine nucleotide binding anion binding cation binding manganese ion binding transition metal ion binding ion binding binding metal ion binding small molecule binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding purine nucleotide binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding catalytic activity, acting on a protein kinase activity protein kinase activity transferase activity catalytic activity phosphotransferase activity, alcohol group as acceptor transferase activity, transferring phosphorus-containing groups ubiquitin protein ligase binding protein binding ubiquitin-like protein ligase binding enzyme binding protein domain specific binding protein serine/threonine/tyrosine kinase activity protein serine/threonine kinase activity cyclic nucleotide-dependent protein kinase activity cAMP-dependent protein kinase activity protein serine kinase activity magnesium ion binding kinase binding protein kinase binding protein kinase A binding protein kinase A regulatory subunit binding	developmental process spermatid development spermatid differentiation sexual reproduction cellular developmental process spermatogenesis reproductive process multicellular organismal reproductive process cell development cellular process involved in reproduction in multicellular organism developmental maturation developmental process involved in reproduction gamete generation male gamete generation sperm capacitation developmental process spermatid development spermatid differentiation sexual reproduction cellular developmental process spermatogenesis reproductive process multicellular organismal reproductive process cell development cellular process involved in reproduction in multicellular organism developmental maturation developmental process involved in reproduction gamete generation male gamete generation sperm capacitation anatomical structure maturation cell differentiation anatomical structure development germ cell development cellular process cell maturation protein localization cellular localization establishment of protein localization nitrogen compound transport nucleocytoplasmic transport transport nuclear transport intracellular transport protein export from nucleus establishment of localization localization protein transport establishment of localization in cell cellular macromolecule localization macromolecule localization nuclear export intracellular protein transport cellular response to stimulus cellular response to heat response to stimulus cellular response to stress response to stress response to heat response to abiotic stimulus response to temperature stimulus RNA metabolic process primary metabolic process gene expression nucleobase-containing compound biosynthetic process mRNA processing mRNA metabolic process macromolecule biosynthetic process nucleic acid metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process biosynthetic process metabolic process macromolecule metabolic process RNA processing multicellular organismal process embryonic epithelial tube formation chordate embryonic development tube formation embryo development multicellular organism development epithelial tube formation tube morphogenesis primary neural tube formation embryo development ending in birth or egg hatching epithelial tube morphogenesis system development morphogenesis of embryonic epithelium epithelium development neural tube development tube development embryonic morphogenesis morphogenesis of an epithelium nervous system development tissue development anatomical structure morphogenesis tissue morphogenesis neural tube closure neural tube formation anatomical structure formation involved in morphogenesis tube closure trans-synaptic signaling regulation of biological process regulation of signaling regulation of cellular process modulation of chemical synaptic transmission signaling biological regulation cell-cell signaling chemical synaptic transmission cell communication synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of cell communication postsynaptic modulation of chemical synaptic transmission protein phosphorylation phosphorylation peptidyl-serine modification peptidyl-serine phosphorylation macromolecule modification peptidyl-amino acid modification phosphate-containing compound metabolic process protein metabolic process protein modification process phosphorus metabolic process catabolic process proteolysis involved in protein catabolic process macromolecule catabolic process regulation of primary metabolic process regulation of proteolysis involved in protein catabolic process regulation of proteolysis proteolysis regulation of protein metabolic process proteasomal protein catabolic process regulation of macromolecule metabolic process protein catabolic process regulation of catabolic process regulation of proteasomal protein catabolic process regulation of metabolic process regulation of protein catabolic process negative regulation of biological process negative regulation of RNA biosynthetic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of cellular process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II negative regulation of metabolic process regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process formation of primary germ layer mesoderm morphogenesis gastrulation mesoderm formation mesoderm development regulation of osteoblast differentiation regulation of developmental process regulation of cell differentiation osteoblast differentiation ossification monosaccharide metabolic process positive regulation of biological process gluconeogenesis positive regulation of metabolic process regulation of small molecule metabolic process positive regulation of biosynthetic process small molecule metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process positive regulation of cellular process positive regulation of gluconeogenesis carbohydrate metabolic process small molecule biosynthetic process carbohydrate biosynthetic process hexose metabolic process monosaccharide biosynthetic process hexose biosynthetic process positive regulation of glucose metabolic process regulation of gluconeogenesis positive regulation of carbohydrate metabolic process regulation of carbohydrate biosynthetic process positive regulation of small molecule metabolic process glucose metabolic process homeostatic process response to oxygen-containing compound cellular response to glucose stimulus intracellular glucose homeostasis cellular response to oxygen-containing compound response to hexose cellular response to carbohydrate stimulus cellular response to chemical stimulus cellular homeostasis response to monosaccharide response to carbohydrate chemical homeostasis response to glucose response to chemical glucose homeostasis carbohydrate homeostasis cellular response to hexose stimulus intracellular chemical homeostasis cellular response to monosaccharide stimulus cellular response to nitrogen compound response to endogenous stimulus response to peptide hormone cellular response to peptide hormone stimulus response to nitrogen compound response to glucagon cellular response to glucagon stimulus cellular response to endogenous stimulus response to hormone cellular response to hormone stimulus regulation of steroid biosynthetic process regulation of cholesterol biosynthetic process regulation of cholesterol metabolic process steroid metabolic process regulation of lipid metabolic process sterol metabolic process cholesterol metabolic process lipid biosynthetic process alcohol metabolic process positive regulation of lipid metabolic process steroid biosynthetic process secondary alcohol biosynthetic process regulation of alcohol biosynthetic process regulation of steroid metabolic process cholesterol biosynthetic process positive regulation of cholesterol biosynthetic process secondary alcohol metabolic process positive regulation of steroid biosynthetic process sterol biosynthetic process positive regulation of lipid biosynthetic process regulation of sterol biosynthetic process alcohol biosynthetic process positive regulation of cholesterol metabolic process positive regulation of steroid metabolic process regulation of lipid biosynthetic process positive regulation of alcohol biosynthetic process positive regulation of sterol biosynthetic process lipid metabolic process bicellular tight junction assembly regulation of bicellular tight junction assembly regulation of cellular component organization tight junction organization apical junction assembly regulation of cellular component biogenesis cellular component organization cellular component biogenesis regulation of cell junction assembly cell junction organization cellular component assembly cell junction assembly tight junction assembly cellular component organization or biogenesis cell-cell junction assembly cell-cell junction organization negative regulation of signaling regulation of signal transduction negative regulation of cell communication negative regulation of smoothened signaling pathway signal transduction regulation of smoothened signaling pathway cell surface receptor signaling pathway negative regulation of response to stimulus negative regulation of signal transduction smoothened signaling pathway regulation of response to stimulus regulation of protein maturation protein maturation regulation of protein processing protein processing adenylate cyclase-activating G protein-coupled receptor signaling pathway adenylate cyclase-modulating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway regulation of localization regulation of protein localization positive regulation of nucleocytoplasmic transport positive regulation of establishment of protein localization positive regulation of protein transport positive regulation of intracellular transport regulation of protein export from nucleus regulation of intracellular transport regulation of transport regulation of establishment of protein localization regulation of nucleocytoplasmic transport regulation of protein transport positive regulation of protein export from nucleus positive regulation of transport regulation of cellular localization positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport protein localization to organelle protein localization to lipid droplet intracellular signal transduction cAMP/PKA signal transduction intracellular signaling cassette adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway cellular response to parathyroid hormone stimulus response to parathyroid hormone ribonucleotide catabolic process pyridine nucleotide catabolic process negative regulation of small molecule metabolic process negative regulation of glycolytic process oxoacid metabolic process carbohydrate catabolic process organophosphate catabolic process carbohydrate derivative metabolic process regulation of generation of precursor metabolites and energy nucleoside phosphate catabolic process organic acid metabolic process negative regulation of ATP metabolic process regulation of ATP metabolic process regulation of purine nucleotide catabolic process negative regulation of nucleotide metabolic process glycolytic process regulation of nucleotide metabolic process regulation of phosphate metabolic process pyridine-containing compound metabolic process purine ribonucleotide catabolic process pyridine nucleotide metabolic process negative regulation of carbohydrate metabolic process nucleoside phosphate metabolic process nicotinamide nucleotide metabolic process pyruvate metabolic process regulation of carbohydrate catabolic process negative regulation of purine nucleotide catabolic process purine nucleoside diphosphate metabolic process purine-containing compound catabolic process nucleotide metabolic process regulation of purine nucleotide metabolic process nucleobase-containing compound catabolic process nucleoside diphosphate metabolic process purine nucleoside diphosphate catabolic process nucleoside diphosphate catabolic process regulation of nucleotide catabolic process regulation of phosphorus metabolic process nucleoside triphosphate metabolic process monocarboxylic acid metabolic process purine ribonucleotide metabolic process pyridine-containing compound catabolic process ribose phosphate metabolic process ATP metabolic process negative regulation of purine nucleotide metabolic process negative regulation of phosphate metabolic process purine nucleotide metabolic process ribonucleotide metabolic process nucleobase-containing small molecule metabolic process purine ribonucleoside triphosphate metabolic process ribonucleoside diphosphate metabolic process ribonucleoside diphosphate catabolic process nucleotide catabolic process ribonucleoside triphosphate metabolic process negative regulation of nucleotide catabolic process negative regulation of catabolic process purine nucleoside triphosphate metabolic process purine nucleotide catabolic process carbohydrate derivative catabolic process regulation of glycolytic process through fructose-6-phosphate ADP catabolic process carboxylic acid metabolic process generation of precursor metabolites and energy regulation of glycolytic process purine-containing compound metabolic process ADP metabolic process organophosphate metabolic process negative regulation of phosphorus metabolic process purine ribonucleoside diphosphate metabolic process purine ribonucleoside diphosphate catabolic process negative regulation of glycolytic process through fructose-6-phosphate glycolytic process through fructose-6-phosphate negative regulation of intracellular signal transduction negative regulation of TORC1 signaling regulation of intracellular signal transduction negative regulation of TOR signaling regulation of TORC1 signaling TOR signaling regulation of TOR signaling TORC1 signaling cellular response to cold response to cold cell cycle regulation of cell cycle positive regulation of cell communication positive regulation of insulin secretion regulation of biological quality regulation of peptide hormone secretion regulation of hormone levels positive regulation of peptide hormone secretion establishment of protein localization to extracellular region protein secretion regulation of protein secretion regulation of secretion regulation of hormone secretion regulation of peptide secretion positive regulation of secretion by cell hormone secretion protein localization to extracellular region peptide secretion regulation of secretion by cell secretion by cell positive regulation of hormone secretion positive regulation of secretion amide transport signal release positive regulation of peptide secretion secretion regulation of peptide transport export from cell positive regulation of protein secretion peptide transport regulation of insulin secretion peptide hormone secretion hormone transport insulin secretion positive regulation of signaling	membrane-bounded organelle intracellular anatomical structure axoneme ciliary plasm cilium intracellular membraneless organelle cytoplasmic region plasma membrane bounded cell projection cytoplasm plasma membrane bounded cell projection intracellular organelle cell projection cellular anatomical structure cytoskeleton organelle membrane-bounded organelle intracellular anatomical structure axoneme ciliary plasm cilium intracellular membraneless organelle cytoplasmic region plasma membrane bounded cell projection cytoplasm plasma membrane bounded cell projection intracellular organelle cell projection cellular anatomical structure cytoskeleton organelle membraneless organelle cytoplasm nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body nucleoplasm organelle lumen nuclear lumen cytosol 9+2 motile cilium sperm flagellum motile cilium sperm midpiece synapse cell junction glutamatergic synapse neuromuscular junction perinuclear region of cytoplasm postsynapse acrosomal vesicle intracellular vesicle endomembrane system cytoplasmic vesicle secretory granule secretory vesicle vesicle mitochondrion centrosome microtubule organizing center microtubule cytoskeleton cell periphery plasma membrane membrane ciliary base protein kinase complex transferase complex, transferring phosphorus-containing groups protein-containing complex catalytic complex cAMP-dependent protein kinase complex serine/threonine protein kinase complex transferase complex intracellular protein-containing complex membrane microdomain membrane raft plasma membrane raft plasma membrane region
B [auth C]	ARG-GLY-PHE-LEU-ARG-SER-ALA-SER-LEU-GLY-ARG-ARG-ALA-SER-PHE-HIS-LEU	calcium channel activity monoatomic cation transmembrane transporter activity voltage-gated calcium channel activity gated channel activity monoatomic ion channel activity voltage-gated channel activity voltage-gated monoatomic ion channel activity voltage-gated monoatomic cation channel activity monoatomic cation channel activity passive transmembrane transporter activity calcium ion transmembrane transporter activity inorganic molecular entity transmembrane transporter activity channel activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity calcium channel activity monoatomic cation transmembrane transporter activity voltage-gated calcium channel activity gated channel activity monoatomic ion channel activity voltage-gated channel activity voltage-gated monoatomic ion channel activity voltage-gated monoatomic cation channel activity monoatomic cation channel activity passive transmembrane transporter activity calcium ion transmembrane transporter activity inorganic molecular entity transmembrane transporter activity channel activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity high voltage-gated calcium channel activity transporter activity metal ion transmembrane transporter activity transmembrane transporter activity cytoskeletal protein binding protein binding binding alpha-actinin binding actinin binding voltage-gated calcium channel activity involved in cardiac muscle cell action potential calmodulin binding voltage-gated calcium channel activity involved in AV node cell action potential cation binding ion binding metal ion binding small molecule binding	membrane depolarization during action potential membrane depolarization biological regulation membrane depolarization during cardiac muscle cell action potential action potential regulation of biological quality cardiac muscle cell action potential regulation of membrane potential heart process multicellular organismal process system process cardiac muscle cell action potential involved in contraction signaling atrial cardiac muscle cell to AV node cell signaling membrane depolarization during action potential membrane depolarization biological regulation membrane depolarization during cardiac muscle cell action potential action potential regulation of biological quality cardiac muscle cell action potential regulation of membrane potential heart process multicellular organismal process system process cardiac muscle cell action potential involved in contraction signaling atrial cardiac muscle cell to AV node cell signaling regulation of heart contraction regulation of system process cell-cell signaling involved in cardiac conduction cardiac muscle contraction striated muscle contraction cell communication circulatory system process actin filament-based process regulation of multicellular organismal process atrial cardiac muscle cell to AV node cell communication cell communication involved in cardiac conduction blood circulation cardiac muscle cell contraction regulation of biological process atrial cardiac muscle cell action potential cell-cell signaling actin filament-based movement muscle contraction muscle system process regulation of blood circulation membrane depolarization during atrial cardiac muscle cell action potential cardiac conduction cellular process actin-mediated cell contraction heart contraction positive regulation of cytosolic calcium ion concentration developmental process heart development multicellular organism development anatomical structure development animal organ development circulatory system development system development calcium ion transmembrane import into cytosol transport monoatomic ion transmembrane transport inorganic ion transmembrane transport establishment of localization calcium ion transport metal ion transport inorganic cation transmembrane transport transmembrane transport monoatomic cation transmembrane transport localization monoatomic ion transport monoatomic cation transport calcium ion transport into cytosol calcium ion transmembrane transport immune system development immune system process cell communication by electrical coupling involved in cardiac conduction cell communication by electrical coupling limb development appendage development embryonic forelimb morphogenesis embryonic limb morphogenesis embryonic morphogenesis embryonic appendage morphogenesis embryo development anatomical structure morphogenesis forelimb morphogenesis appendage morphogenesis limb morphogenesis AV node cell action potential membrane depolarization during AV node cell action potential AV node cell to bundle of His cell signaling AV node cell to bundle of His cell communication calcium ion transmembrane transport via high voltage-gated calcium channel sensory organ development eye development visual system development camera-type eye development sensory system development regulation of actin filament-based process regulation of cellular process regulation of ventricular cardiac muscle cell action potential regulation of cardiac muscle cell action potential regulation of action potential ventricular cardiac muscle cell action potential regulation of cardiac muscle contraction regulation of muscle system process regulation of striated muscle contraction regulation of actin filament-based movement regulation of muscle contraction regulation of cardiac muscle cell contraction positive regulation of adenylate cyclase activity positive regulation of molecular function regulation of molecular function positive regulation of cyclase activity regulation of adenylate cyclase activity regulation of catalytic activity positive regulation of catalytic activity positive regulation of lyase activity positive regulation of biological process positive regulation of muscle contraction positive regulation of multicellular organismal process import into cell import across plasma membrane inorganic cation import across plasma membrane calcium ion import across plasma membrane inorganic ion import across plasma membrane calcium ion import calcium ion import into cytosol cellular response to stimulus regulation of calcium ion transport regulation of localization intracellular calcium ion homeostasis response to stimulus negative regulation of biological process sarcoplasmic reticulum calcium ion transport release of sequestered calcium ion into cytosol by sarcoplasmic reticulum intracellular signal transduction intracellular signaling cassette signal transduction monoatomic cation homeostasis intracellular monoatomic ion homeostasis release of sequestered calcium ion into cytosol by endoplasmic reticulum regulation of release of sequestered calcium ion into cytosol regulation of monoatomic ion transport maintenance of location release of sequestered calcium ion into cytosol regulation of transmembrane transport chemical homeostasis calcium-mediated signaling cellular localization inorganic ion homeostasis homeostatic process calcium ion homeostasis regulation of monoatomic ion transmembrane transport negative regulation of sequestering of calcium ion regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion maintenance of location in cell regulation of calcium ion transmembrane transport intracellular monoatomic cation homeostasis monoatomic ion homeostasis negative regulation of cellular process intracellular chemical homeostasis regulation of metal ion transport regulation of sequestering of calcium ion regulation of cardiac muscle contraction by calcium ion signaling regulation of transport sequestering of calcium ion cellular homeostasis regulation of monoatomic cation transmembrane transport regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum regulation of heart rate by cardiac conduction regulation of heart rate	protein-containing complex plasma membrane protein complex sarcolemma voltage-gated calcium channel complex plasma membrane membrane membrane protein complex cation channel complex transporter complex cell periphery cellular anatomical structure transmembrane transporter complex T-tubule L-type voltage-gated calcium channel complex protein-containing complex plasma membrane protein complex sarcolemma voltage-gated calcium channel complex plasma membrane membrane membrane protein complex cation channel complex transporter complex cell periphery cellular anatomical structure transmembrane transporter complex T-tubule L-type voltage-gated calcium channel complex calcium channel complex monoatomic ion channel complex postsynaptic specialization membrane postsynaptic specialization synapse postsynaptic density membrane synaptic membrane postsynaptic density postsynapse neuron to neuron synapse organelle cell junction postsynaptic membrane asymmetric synapse plasma membrane region somatodendritic compartment cell body perikaryon neuronal cell body intracellular anatomical structure intracellular membraneless organelle Z disc sarcomere intracellular organelle I band membraneless organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer supramolecular complex cell projection dendrite dendritic tree neuron projection plasma membrane bounded cell projection

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth E]	IPR000719	Protein kinase domain	Domain
A [auth E]	IPR044109	cAMP-dependent protein kinase catalytic subunit	Family
A [auth E]	IPR017441	Protein kinase, ATP binding site	Binding Site
A [auth E]	IPR000961	AGC-kinase, C-terminal	Domain
A [auth E]	IPR011009	Protein kinase-like domain superfamily	Homologous Superfamily
A [auth E]	IPR008271	Serine/threonine-protein kinase, active site	Active Site
B [auth C]	IPR014873	Voltage-dependent calcium channel, alpha-1 subunit, IQ domain	Domain
B [auth C]	IPR002077	Voltage-dependent calcium channel, alpha-1 subunit	Family
B [auth C]	IPR031649	Voltage-dependent L-type calcium channel, IQ-associated domain	Domain
B [auth C]	IPR005451	Voltage-dependent calcium channel, L-type, alpha-1C subunit	Family
B [auth C]	IPR005821	Ion transport domain	Domain
B [auth C]	IPR005446	Voltage-dependent calcium channel, L-type, alpha-1 subunit	Family
B [auth C]	IPR050599	Voltage-dependent calcium channel alpha-1 subunit	Family
B [auth C]	IPR031688	Voltage-gated calcium channel subunit alpha, C-terminal	Domain
B [auth C]	IPR027359	Voltage-dependent channel domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B [auth C]	Pharos: Q13936	Timothy syndrome Brugada syndrome Brugada syndrome 3 hypertensive disorder long QT syndrome bipolar disorder primary immunodeficiency disease Limb Deformities, Congenital hypoglycemia schizophrenia depressive disorder heart disease intellectual disability major depressive disorder acute coronary syndrome Timothy syndrome Brugada syndrome Brugada syndrome 3 hypertensive disorder long QT syndrome bipolar disorder primary immunodeficiency disease Limb Deformities, Congenital hypoglycemia schizophrenia depressive disorder heart disease intellectual disability major depressive disorder acute coronary syndrome anorexia nervosa atrial fibrillation autism spectrum disorder short QT syndrome bipolar I disorder endogenous depression attention deficit hyperactivity disorder, inattentive type ventricular fibrillation, paroxysmal familial, type 1 cardiomyopathy autism Prinzmetal angina

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A [auth E]	SEP	Parent Component: SER RESID: AA0037 PSI-MOD : O-phospho-L-serine MOD:00046
A [auth E]	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 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.