2BEC

Crystal structure of CHP2 in complex with its binding region in NHE1 and insights into the mechanism of pH regulation

External Resource: Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d2beca_	All alpha proteins	EF Hand-like	EF-hand	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	Calmodulin-like	8062940	4000924	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	EF-hand	8062941	3001983	SCOP2 (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	EF-hand_7_2	e2becA1	A: alpha arrays	X: EF-hand	H: EF-hand-related	T: EF-hand	F: EF-hand_7_2	ECOD (1.6)
A	EF-hand_7_10	e2becA2	A: alpha arrays	X: EF-hand	H: EF-hand-related	T: EF-hand	F: EF-hand_7_10	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.238.10	Mainly Alpha	Orthogonal Bundle	Recoverin	domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF13202	EF hand (EF-hand_5)	EF hand	-	Domain
A	PF00036	EF hand (EF-hand_1)	EF hand	The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typica ...	The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Calcineurin B homologous protein 2	cation binding ion binding binding calcium ion binding metal ion binding small molecule binding	regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process regulation of phosphatase activity regulation of catalytic activity positive regulation of cellular metabolic process positive regulation of phosphate metabolic process positive regulation of molecular function regulation of biological process cell population proliferation regulation of cellular process positive regulation of cell population proliferation regulation of cell population proliferation biological regulation positive regulation of biological process cellular process positive regulation of cellular process regulation of phosphatase activity regulation of catalytic activity positive regulation of cellular metabolic process positive regulation of phosphate metabolic process positive regulation of molecular function positive regulation of metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process positive regulation of phosphatase activity phosphorus metabolic process positive regulation of phosphorus metabolic process positive regulation of dephosphorylation regulation of dephosphorylation cellular metabolic process dephosphorylation positive regulation of catalytic activity regulation of cellular metabolic process regulation of molecular function positive regulation of hydrolase activity regulation of hydrolase activity regulation of phosphorus metabolic process metabolic process regulation of metabolic process protein localization establishment of protein localization cellular localization nitrogen compound transport transport organic substance transport establishment of localization localization protein transport cellular macromolecule localization macromolecule localization calcineurin-NFAT signaling cascade cellular response to stimulus positive regulation of cell communication positive regulation of signal transduction response to stimulus signaling regulation of signal transduction intracellular signal transduction cell communication positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette regulation of calcineurin-mediated signaling positive regulation of calcineurin-NFAT signaling cascade regulation of calcium-mediated signaling signal transduction positive regulation of calcium-mediated signaling regulation of calcineurin-NFAT signaling cascade regulation of signaling positive regulation of calcineurin-mediated signaling positive regulation of intracellular signal transduction calcium-mediated signaling regulation of response to stimulus regulation of cell communication calcineurin-mediated signaling positive regulation of signaling positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process primary metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process positive regulation of biosynthetic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process regulation of localization nucleocytoplasmic transport nuclear transport positive regulation of establishment of protein localization import into nucleus establishment of localization in cell regulation of intracellular transport positive regulation of protein localization to nucleus positive regulation of protein import into nucleus intracellular transport regulation of nucleocytoplasmic transport protein localization to nucleus establishment of protein localization to organelle positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport intracellular protein transport regulation of protein localization positive regulation of nucleocytoplasmic transport regulation of protein localization to nucleus positive regulation of protein transport regulation of protein import into nucleus protein import into nucleus positive regulation of intracellular transport regulation of transport regulation of establishment of protein localization regulation of protein transport positive regulation of transport regulation of cellular localization protein localization to organelle cellular response to inorganic substance cellular response to metal ion response to inorganic substance cellular response to chemical stimulus response to metal ion response to chemical cellular response to calcium ion response to calcium ion	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 cytoplasm cytosol cell periphery plasma membrane membrane nucleoplasm
B	Sodium/hydrogen exchanger 1	ion binding binding small molecule binding phospholipid binding lipid binding protein-macromolecule adaptor activity molecular adaptor activity monoatomic cation transmembrane transporter activity metal cation:monoatomic cation antiporter activity proton transmembrane transporter activity sodium:proton antiporter activity sodium ion transmembrane transporter activity secondary active transmembrane transporter activity antiporter activity ion binding binding small molecule binding phospholipid binding lipid binding protein-macromolecule adaptor activity molecular adaptor activity monoatomic cation transmembrane transporter activity metal cation:monoatomic cation antiporter activity proton transmembrane transporter activity sodium:proton antiporter activity sodium ion transmembrane transporter activity secondary active transmembrane transporter activity antiporter activity active monoatomic ion transmembrane transporter activity metal cation:proton antiporter activity active transmembrane transporter activity inorganic molecular entity transmembrane transporter activity inorganic cation transmembrane transporter activity monoatomic ion transmembrane transporter activity transporter activity metal ion transmembrane transporter activity transmembrane transporter activity protein binding calmodulin binding identical protein binding protein phosphatase binding phosphatase binding protein phosphatase 2B binding enzyme binding phosphatidylinositol-4,5-bisphosphate binding anion binding phosphatidylinositol bisphosphate binding phosphatidylinositol phosphate binding phosphatidylinositol binding sodium:proton antiporter activity involved in regulation of cardiac muscle cell membrane potential calcium-dependent protein binding potassium ion transmembrane transporter activity potassium:proton antiporter activity solute:potassium antiporter activity	cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein complex oligomerization protein-containing complex assembly cellular process cellular component organization or biogenesis transport proton transmembrane transport monoatomic ion transmembrane transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport cellular component organization cellular component biogenesis cellular component assembly protein-containing complex organization protein complex oligomerization protein-containing complex assembly cellular process cellular component organization or biogenesis transport proton transmembrane transport monoatomic ion transmembrane transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport transmembrane transport monoatomic cation transmembrane transport localization monoatomic ion transport monoatomic cation transport regulation of cellular process regulation of cellular component organization cell-substrate junction assembly cell adhesion cell junction assembly regulation of cell-substrate junction organization focal adhesion assembly regulation of biological process regulation of cell-substrate adhesion regulation of cell adhesion biological regulation cell-substrate adhesion regulation of cellular component biogenesis regulation of cell junction assembly cell junction organization cell-matrix adhesion regulation of cell-matrix adhesion cell-substrate junction organization regulation of focal adhesion assembly regulation of cell-substrate junction assembly membrane organization mitochondrial membrane organization organelle organization positive regulation of mitochondrial membrane permeability regulation of membrane permeability positive regulation of membrane permeability regulation of biological quality regulation of mitochondrial membrane permeability mitochondrial transport mitochondrion organization potassium ion transmembrane transport metal ion transport potassium ion transport heart process multicellular organismal process system process regulation of heart contraction regulation of system process circulatory system process regulation of blood circulation positive regulation of the force of heart contraction regulation of multicellular organismal process heart contraction regulation of the force of heart contraction blood circulation response to decreased oxygen levels cellular response to stimulus response to stimulus cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels cellular response to chemical stimulus cellular response to stress response to hypoxia response to stress response to chemical response to oxygen levels response to abiotic stimulus positive regulation of programmed cell death regulation of apoptotic process positive regulation of biological process regulation of programmed cell death cell death positive regulation of apoptotic process apoptotic process programmed cell death positive regulation of cellular process sodium ion export across plasma membrane export from cell sodium ion transmembrane transport export across plasma membrane sodium ion transport developmental process heart development cellular developmental process cardiac muscle tissue development cardiac muscle cell differentiation animal organ development muscle cell differentiation tissue development cardiocyte differentiation striated muscle tissue development circulatory system development muscle structure development multicellular organism development cell differentiation anatomical structure development striated muscle cell differentiation muscle tissue development system development cell migration cell motility regulation of calcium ion transmembrane transporter activity regulation of localization regulation of calcium ion transport positive regulation of cation transmembrane transport positive regulation of calcium ion transport regulation of sodium ion transport regulation of sodium ion transmembrane transport calcium ion transport positive regulation of sodium ion transport positive regulation of calcium:sodium antiporter activity positive regulation of monoatomic ion transport positive regulation of monoatomic ion transmembrane transport regulation of monoatomic ion transport regulation of molecular function regulation of calcium:sodium antiporter activity regulation of transmembrane transport positive regulation of sodium ion transmembrane transporter activity regulation of transmembrane transporter activity regulation of monoatomic ion transmembrane transport regulation of transporter activity regulation of calcium ion transmembrane transport regulation of sodium ion transmembrane transporter activity positive regulation of molecular function positive regulation of calcium ion transmembrane transporter activity positive regulation of calcium ion transmembrane transport positive regulation of transmembrane transport positive regulation of sodium ion transmembrane transport regulation of metal ion transport regulation of monoatomic ion transmembrane transporter activity regulation of transport positive regulation of transport positive regulation of transporter activity positive regulation of ion transmembrane transporter activity regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport cellular response to antibiotic response to antibiotic muscle hypertrophy regulation of muscle adaptation positive regulation of cardiac muscle hypertrophy striated muscle hypertrophy regulation of muscle system process muscle system process regulation of cardiac muscle hypertrophy regulation of muscle hypertrophy muscle adaptation regulation of response to stimulus positive regulation of muscle hypertrophy cardiac muscle hypertrophy positive regulation of multicellular organismal process homeostatic process regulation of intracellular pH cellular homeostasis chemical homeostasis intracellular monoatomic cation homeostasis regulation of pH monoatomic ion homeostasis intracellular chemical homeostasis monoatomic cation homeostasis regulation of cellular pH intracellular monoatomic ion homeostasis response to electrical stimulus cellular response to electrical stimulus cellular response to abiotic stimulus cellular response to environmental stimulus response to pH response to acidic pH positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process positive regulation of metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II organic substance biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process cellular metabolic process primary metabolic process regulation of cellular metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process positive regulation of DNA-templated transcription cellular biosynthetic process RNA metabolic process positive regulation of cellular metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process positive regulation of biosynthetic process regulation of RNA biosynthetic process regulation of biosynthetic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process signaling cardiac muscle contraction intracellular signal transduction cell communication striated muscle contraction intracellular signaling cassette signal transduction regulation of cardiac muscle contraction by calcium ion signaling regulation of cardiac muscle contraction muscle contraction regulation of striated muscle contraction calcium-mediated signaling regulation of muscle contraction sodium ion homeostasis inorganic ion homeostasis intracellular sodium ion homeostasis regulation of growth growth positive regulation of cell growth regulation of cell growth cell growth positive regulation of growth regulation of cytoskeleton organization regulation of actin filament-based process regulation of actin filament bundle assembly actin filament bundle organization actin filament-based process stress fiber assembly regulation of actin filament organization actin cytoskeleton organization actomyosin structure organization actin filament organization regulation of organelle organization regulation of stress fiber assembly contractile actin filament bundle assembly regulation of actomyosin structure organization actin filament bundle assembly regulation of actin cytoskeleton organization regulation of supramolecular fiber organization supramolecular fiber organization cytoskeleton organization negative regulation of programmed cell death negative regulation of biological process negative regulation of apoptotic process negative regulation of cellular process cellular response to pH cellular response to acidic pH calcineurin-NFAT signaling cascade positive regulation of cell communication positive regulation of signal transduction regulation of signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction regulation of calcineurin-mediated signaling positive regulation of calcineurin-NFAT signaling cascade regulation of calcium-mediated signaling positive regulation of calcium-mediated signaling regulation of calcineurin-NFAT signaling cascade regulation of signaling positive regulation of calcineurin-mediated signaling positive regulation of intracellular signal transduction regulation of cell communication calcineurin-mediated signaling positive regulation of signaling regulation of the force of heart contraction by cardiac conduction cardiac conduction response to epinephrine cellular response to epinephrine stimulus regulation of action potential positive regulation of action potential action potential regulation of membrane potential import into cell import across plasma membrane sodium ion import across plasma membrane inorganic cation import across plasma membrane inorganic ion import across plasma membrane regulation of cardiac muscle cell membrane potential response to mechanical stimulus response to external stimulus cellular response to mechanical stimulus cellular response to external stimulus maintenance of cell polarity establishment or maintenance of cell polarity cardiac muscle cell contraction actin filament-based movement actin-mediated cell contraction cellular response to cold response to cold response to temperature stimulus cellular response to nitrogen compound response to organic substance response to endogenous stimulus response to organonitrogen compound response to peptide hormone response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound cellular response to endogenous stimulus cellular response to organonitrogen compound response to hormone response to insulin cellular response to organic substance cellular response to insulin stimulus cellular response to hormone stimulus stem cell differentiation response to muscle stretch	cell projection cell leading edge cellular anatomical entity plasma membrane bounded cell projection lamellipodium cell periphery sarcolemma plasma membrane membrane T-tubule extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle cell projection cell leading edge cellular anatomical entity plasma membrane bounded cell projection lamellipodium cell periphery sarcolemma plasma membrane membrane T-tubule extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle basal part of cell basal plasma membrane plasma membrane region basolateral plasma membrane intracellular anatomical structure cytoplasm perinuclear region of cytoplasm cell-cell junction intercalated disc anchoring junction cell junction cell-cell contact zone intracellular organelle mitochondrion intracellular membrane-bounded organelle focal adhesion cell-substrate junction apical part of cell apical plasma membrane cell surface ATPase dependent transmembrane transport complex cation-transporting ATPase complex protein-containing complex transmembrane transporter complex membrane protein complex transporter complex membrane microdomain membrane raft nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR018247	EF-Hand 1, calcium-binding site	Binding Site
A	IPR002048	EF-hand domain	Domain
A	IPR011992	EF-hand domain pair	Homologous Superfamily
B	IPR001970	Sodium/hydrogen exchanger 1-like	Family
B	IPR006153	Cation/H+ exchanger	Domain
B	IPR018422	Cation/H+ exchanger, CPA1 family	Family
B	IPR032103	Sodium/hydrogen exchanger, regulatory region	Domain
B	IPR004709	Na+/H+ exchanger	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: O43745	ulcerative colitis atopic eczema cutaneous lupus erythematosus interstitial cystitis psoriasis chronic obstructive pulmonary disease head and neck cancer malignant colon neoplasm Crohn disease inflammatory bowel disease osteosarcoma
B	Pharos: P19634	Lichtenstein-Knorr syndrome Barrett esophagus hypertrophic cardiomyopathy Diabetes Mellitus, Experimental congestive heart failure pancreatic intraductal papillary-mucinous neoplasm heart failure ischemia reperfusion injury pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia neurodegenerative disease pancreatic intraductal papillary-mucinous carcinoma

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.