5AXI

Crystal structure of Cbl-b TKB domain in complex with Cblin

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Protein Modification Annotation

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PF02761	e5axiA1	A: alpha arrays	X: EF-hand	H: EF-hand-related	T: EF-hand	F: PF02761	ECOD (1.6)
A	PF02262	e5axiA3	A: alpha bundles	X: N-cbl like	H: N-terminal domain of cbl (N-cbl) (From Topology)	T: N-terminal domain of cbl (N-cbl)	F: PF02262	ECOD (1.6)
A	PF02762	e5axiA2	A: a+b two layers	X: SH2 (From Topology)	H: SH2 (From Topology)	T: SH2	F: PF02762	ECOD (1.6)
B	PF02761	e5axiB3	A: alpha arrays	X: EF-hand	H: EF-hand-related	T: EF-hand	F: PF02761	ECOD (1.6)
B	PF02262	e5axiB1	A: alpha bundles	X: N-cbl like	H: N-terminal domain of cbl (N-cbl) (From Topology)	T: N-terminal domain of cbl (N-cbl)	F: PF02262	ECOD (1.6)
B	PF02762	e5axiB2	A: a+b two layers	X: SH2 (From Topology)	H: SH2 (From Topology)	T: SH2	F: PF02762	ECOD (1.6)
C	PF02761	e5axiC1	A: alpha arrays	X: EF-hand	H: EF-hand-related	T: EF-hand	F: PF02761	ECOD (1.6)
C	PF02262	e5axiC2	A: alpha bundles	X: N-cbl like	H: N-terminal domain of cbl (N-cbl) (From Topology)	T: N-terminal domain of cbl (N-cbl)	F: PF02262	ECOD (1.6)
C	PF02762	e5axiC3	A: a+b two layers	X: SH2 (From Topology)	H: SH2 (From Topology)	T: SH2	F: PF02762	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.20.930.20	Mainly Alpha	Up-down Bundle	Transcription Elongation Factor S-II	Chain A	CATH (4.3.0)
A	1.10.238.10	Mainly Alpha	Orthogonal Bundle	Recoverin	domain 1	CATH (4.3.0)
A	3.30.505.10	Alpha Beta	2-Layer Sandwich	SHC Adaptor Protein	SH2 domain	CATH (4.3.0)
B	1.20.930.20	Mainly Alpha	Up-down Bundle	Transcription Elongation Factor S-II	Chain A	CATH (4.3.0)
B	1.10.238.10	Mainly Alpha	Orthogonal Bundle	Recoverin	domain 1	CATH (4.3.0)
B	3.30.505.10	Alpha Beta	2-Layer Sandwich	SHC Adaptor Protein	SH2 domain	CATH (4.3.0)
C	1.20.930.20	Mainly Alpha	Up-down Bundle	Transcription Elongation Factor S-II	Chain A	CATH (4.3.0)
C	1.10.238.10	Mainly Alpha	Orthogonal Bundle	Recoverin	domain 1	CATH (4.3.0)
C	3.30.505.10	Alpha Beta	2-Layer Sandwich	SHC Adaptor Protein	SH2 domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C	PF02262	CBL proto-oncogene N-terminal domain 1 (Cbl_N)	CBL proto-oncogene N-terminal domain 1	Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated ...	Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. Cbl_N is comprised of 3 structural domains of which this is the first - a four helix bundle.	Domain
A, B, C	PF02762	CBL proto-oncogene N-terminus, SH2-like domain (Cbl_N3)	CBL proto-oncogene N-terminus, SH2-like domain	Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated ...	Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. The so called N-terminal domain is actually 3 structural domains, of which this is the C-terminal SH2 domain.	Domain
A, B, C	PF02761	CBL proto-oncogene N-terminus, EF hand-like domain (Cbl_N2)	CBL proto-oncogene N-terminus, EF hand-like domain	Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated ...	Cbl is an adaptor protein that binds EGF receptors (or other tyrosine kinases) and SH3 domains, functioning as a negative regulator of many signaling pathways. The N-terminal domain is evolutionarily conserved, and is known to bind to phosphorylated tyrosine residues. The so called N-terminal domain is actually 3 structural domains, of which this is the central EF hand domain.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C	E3 ubiquitin-protein ligase CBL-B	cation binding ion binding binding calcium ion binding metal ion binding small molecule binding phosphoprotein binding phosphotyrosine residue binding protein binding protein phosphorylated amino acid binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity cation binding ion binding binding calcium ion binding metal ion binding small molecule binding phosphoprotein binding phosphotyrosine residue binding protein binding protein phosphorylated amino acid binding aminoacyltransferase activity ubiquitin-like protein transferase activity catalytic activity, acting on a protein acyltransferase activity ubiquitin-like protein ligase activity ubiquitin protein ligase activity transferase activity catalytic activity ubiquitin-protein transferase activity SH3 domain binding protein domain specific binding kinase binding enzyme binding protein kinase binding protein tyrosine kinase binding signaling receptor binding receptor tyrosine kinase binding	regulation of biological process cell adhesion regulation of cellular process regulation of cell adhesion biological regulation cellular process cellular response to stimulus immune response-regulating cell surface receptor signaling pathway response to stimulus signaling positive regulation of biological process cell communication positive regulation of response to stimulus immune response-activating signaling pathway regulation of biological process cell adhesion regulation of cellular process regulation of cell adhesion biological regulation cellular process cellular response to stimulus immune response-regulating cell surface receptor signaling pathway response to stimulus signaling positive regulation of biological process cell communication positive regulation of response to stimulus immune response-activating signaling pathway immune response-regulating signaling pathway positive regulation of immune response regulation of immune system process signal transduction positive regulation of immune system process cell surface receptor signaling pathway immune response-activating cell surface receptor signaling pathway immune response T cell receptor signaling pathway regulation of response to stimulus immune system process regulation of immune response antigen receptor-mediated signaling pathway activation of immune response negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death cell death negative regulation of apoptotic process negative regulation of cellular process apoptotic process programmed cell death regulation of antigen receptor-mediated signaling pathway regulation of signal transduction regulation of signaling regulation of T cell receptor signaling pathway regulation of cell communication organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process primary metabolic process protein catabolic process macromolecule catabolic process organic substance metabolic process metabolic process protein metabolic process macromolecule metabolic process organic substance catabolic process regulation of protein modification process positive regulation of protein metabolic process regulation of protein ubiquitination positive regulation of post-translational protein modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process protein ubiquitination positive regulation of macromolecule metabolic process regulation of protein modification by small protein conjugation or removal protein modification process positive regulation of protein modification by small protein conjugation or removal positive regulation of protein ubiquitination regulation of post-translational protein modification regulation of protein metabolic process regulation of macromolecule metabolic process macromolecule modification post-translational protein modification regulation of metabolic process protein modification by small protein conjugation protein modification by small protein conjugation or removal regulation of catabolic process positive regulation of protein catabolic process positive regulation of catabolic process regulation of protein catabolic process immune system development multicellular organismal process regulation of T cell anergy lymphocyte anergy regulation of lymphocyte anergy positive regulation of lymphocyte anergy positive regulation of T cell tolerance induction multicellular organism development positive regulation of T cell anergy anatomical structure development regulation of multicellular organismal process regulation of T cell tolerance induction T cell anergy system development developmental process T cell tolerance induction positive regulation of multicellular organismal process regulation of tolerance induction positive regulation of tolerance induction tolerance induction T cell activation cell activation lymphocyte activation leukocyte activation negative regulation of signaling negative regulation of antigen receptor-mediated signaling pathway negative regulation of cell communication negative regulation of response to stimulus negative regulation of signal transduction negative regulation of T cell receptor signaling pathway negative regulation of immune system process platelet-derived growth factor receptor-alpha signaling pathway platelet-derived growth factor receptor signaling pathway regulation of platelet-derived growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway regulation of platelet-derived growth factor receptor-alpha signaling pathway enzyme-linked receptor protein signaling pathway negative regulation of lymphocyte proliferation regulation of alpha-beta T cell activation regulation of leukocyte activation regulation of cell activation negative regulation of T cell proliferation negative regulation of cell adhesion negative regulation of leukocyte proliferation alpha-beta T cell proliferation lymphocyte proliferation alpha-beta T cell activation regulation of leukocyte proliferation cell population proliferation regulation of CD4-positive, alpha-beta T cell proliferation negative regulation of CD4-positive, alpha-beta T cell activation negative regulation of T cell activation negative regulation of leukocyte cell-cell adhesion mononuclear cell proliferation regulation of cell population proliferation negative regulation of cell-cell adhesion regulation of leukocyte cell-cell adhesion negative regulation of multicellular organismal process negative regulation of leukocyte activation negative regulation of lymphocyte activation leukocyte proliferation leukocyte cell-cell adhesion negative regulation of mononuclear cell proliferation regulation of alpha-beta T cell proliferation cell-cell adhesion CD4-positive, alpha-beta T cell activation regulation of cell-cell adhesion T cell proliferation regulation of lymphocyte proliferation CD4-positive, alpha-beta T cell proliferation negative regulation of cell population proliferation regulation of T cell activation negative regulation of cell activation regulation of T cell proliferation negative regulation of alpha-beta T cell proliferation regulation of CD4-positive, alpha-beta T cell activation negative regulation of CD4-positive, alpha-beta T cell proliferation regulation of mononuclear cell proliferation negative regulation of alpha-beta T cell activation regulation of lymphocyte activation intracellular signal transduction	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cell periphery plasma membrane membrane membrane microdomain membrane raft membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cell periphery plasma membrane membrane membrane microdomain membrane raft membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle nucleoplasm organelle lumen organelle nuclear lumen
D [auth E]	Cblin	protein binding binding signaling receptor binding insulin receptor binding phosphatidylinositol 3-kinase binding phosphoprotein binding phosphotyrosine residue binding protein phosphorylated amino acid binding protein-macromolecule adaptor activity molecular adaptor activity protein-containing complex binding phosphatidylinositol 3-kinase activator activity enzyme regulator activity molecular function regulator activity protein binding binding signaling receptor binding insulin receptor binding phosphatidylinositol 3-kinase binding phosphoprotein binding phosphotyrosine residue binding protein phosphorylated amino acid binding protein-macromolecule adaptor activity molecular adaptor activity protein-containing complex binding phosphatidylinositol 3-kinase activator activity enzyme regulator activity molecular function regulator activity phosphatidylinositol 3-kinase regulator activity kinase regulator activity insulin-like growth factor receptor binding transmembrane receptor protein tyrosine kinase adaptor activity protein tyrosine kinase binding receptor tyrosine kinase binding enzyme binding protein kinase binding signaling adaptor activity signaling receptor complex adaptor activity kinase binding protein domain specific binding SH2 domain binding protein kinase C binding	cellular response to stimulus response to organic substance regulation of biological process regulation of cellular process response to stimulus cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication cellular response to chemical stimulus response to chemical cellular response to cytokine stimulus cellular response to stimulus response to organic substance regulation of biological process regulation of cellular process response to stimulus cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication cellular response to chemical stimulus response to chemical cellular response to cytokine stimulus cellular process cellular response to organic substance signal transduction oxoacid metabolic process regulation of lipid metabolic process organic acid catabolic process organic acid metabolic process cellular lipid catabolic process regulation of primary metabolic process cellular catabolic process regulation of fatty acid oxidation positive regulation of metabolic process positive regulation of fatty acid beta-oxidation monocarboxylic acid catabolic process cellular ketone metabolic process regulation of small molecule metabolic process carboxylic acid catabolic process positive regulation of lipid metabolic process small molecule metabolic process regulation of cellular ketone metabolic process cellular metabolic process regulation of fatty acid beta-oxidation primary metabolic process regulation of cellular metabolic process regulation of lipid catabolic process positive regulation of fatty acid oxidation cellular lipid metabolic process regulation of fatty acid metabolic process metabolic process monocarboxylic acid metabolic process small molecule catabolic process regulation of metabolic process catabolic process positive regulation of biological process positive regulation of cellular metabolic process organic substance metabolic process fatty acid oxidation positive regulation of lipid catabolic process fatty acid beta-oxidation lipid oxidation positive regulation of cellular process positive regulation of fatty acid metabolic process fatty acid metabolic process lipid catabolic process carboxylic acid metabolic process lipid modification regulation of catabolic process fatty acid catabolic process positive regulation of catabolic process regulation of cellular catabolic process positive regulation of cellular catabolic process positive regulation of small molecule metabolic process organic substance catabolic process lipid metabolic process regulation of localization nitrogen compound transport negative regulation of biological process negative regulation of transport somatostatin secretion negative regulation of somatostatin secretion localization negative regulation of secretion negative regulation of hormone secretion negative regulation of secretion by cell regulation of biological quality regulation of peptide hormone secretion negative regulation of peptide hormone secretion regulation of hormone levels organic substance transport establishment of localization regulation of secretion regulation of somatostatin secretion regulation of hormone secretion regulation of peptide secretion transport negative regulation of signaling hormone secretion negative regulation of cell communication negative regulation of peptide secretion peptide secretion secretion by cell regulation of secretion by cell amide transport signal release negative regulation of cellular process regulation of signaling secretion regulation of transport regulation of peptide transport cell-cell signaling export from cell peptide transport peptide hormone secretion hormone transport regulation of cell communication regulation of biosynthetic process cellular biosynthetic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process organic substance biosynthetic process regulation of macromolecule biosynthetic process macromolecule metabolic process response to organonitrogen compound response to nitrogen compound response to purine-containing compound response to organic cyclic compound response to caffeine response to alkaloid developmental process mammary gland development gland development animal organ development anatomical structure development insulin-like growth factor receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway enzyme-linked receptor protein signaling pathway cell migration cell motility cellular response to nitrogen compound response to peptide hormone regulation of signal transduction insulin receptor signaling pathway regulation of cellular response to insulin stimulus cellular response to endogenous stimulus response to hormone cellular response to hormone stimulus negative regulation of response to stimulus response to endogenous stimulus regulation of insulin receptor signaling pathway response to oxygen-containing compound cellular response to peptide hormone stimulus negative regulation of signal transduction cellular response to oxygen-containing compound negative regulation of cellular response to insulin stimulus cellular response to organonitrogen compound regulation of response to stimulus negative regulation of insulin receptor signaling pathway response to insulin cellular response to insulin stimulus positive regulation of cell communication positive regulation of signal transduction positive regulation of response to stimulus positive regulation of cellular response to insulin stimulus positive regulation of insulin receptor signaling pathway positive regulation of signaling intracellular signal transduction intracellular signaling cassette phosphatidylinositol 3-kinase/protein kinase B signal transduction epithelium migration multicellular organismal process tissue migration ameboidal-type cell migration epithelial cell migration regulation of generation of precursor metabolites and energy positive regulation of macromolecule biosynthetic process positive regulation of glycogen metabolic process positive regulation of macromolecule metabolic process carbohydrate biosynthetic process hexose metabolic process positive regulation of glucose metabolic process positive regulation of glycogen biosynthetic process energy reserve metabolic process positive regulation of carbohydrate metabolic process regulation of glycogen metabolic process monosaccharide metabolic process regulation of glycogen biosynthetic process glucan biosynthetic process energy derivation by oxidation of organic compounds regulation of glucan biosynthetic process regulation of polysaccharide metabolic process polysaccharide metabolic process glucan metabolic process positive regulation of biosynthetic process regulation of carbohydrate metabolic process regulation of glucose metabolic process carbohydrate metabolic process polysaccharide biosynthetic process glycogen metabolic process generation of precursor metabolites and energy glycogen biosynthetic process regulation of polysaccharide biosynthetic process regulation of carbohydrate biosynthetic process positive regulation of cellular biosynthetic process glucose metabolic process positive regulation of mesenchymal cell proliferation cell population proliferation positive regulation of cell population proliferation regulation of mesenchymal cell proliferation regulation of cell population proliferation mesenchymal cell proliferation regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction regulation of intracellular signal transduction positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction protein localization negative regulation of protein transport establishment of protein localization cellular macromolecule localization establishment of protein localization to extracellular region negative regulation of establishment of protein localization protein secretion regulation of protein secretion negative regulation of protein secretion cellular localization regulation of protein localization protein localization to extracellular region negative regulation of protein localization regulation of establishment of protein localization regulation of protein transport negative regulation of insulin secretion protein transport regulation of cellular localization regulation of insulin secretion macromolecule localization insulin secretion positive regulation of phosphorylation positive regulation of phosphorus metabolic process phosphorylation positive regulation of phosphate metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process regulation of phosphorus metabolic process regulation of phosphorylation phosphorus metabolic process response to lipid response to fatty acid cellular response to fatty acid cellular response to lipid regulation of glucagon secretion positive regulation of glucagon secretion positive regulation of peptide hormone secretion glucagon secretion positive regulation of secretion by cell positive regulation of hormone secretion positive regulation of secretion positive regulation of peptide secretion positive regulation of transport hexose transmembrane transport glucose import carbohydrate transport positive regulation of transmembrane transport glucose transmembrane transport regulation of glucose import positive regulation of glucose transmembrane transport transmembrane transport regulation of glucose transmembrane transport regulation of transmembrane transport monosaccharide transmembrane transport positive regulation of glucose import carbohydrate transmembrane transport protein localization to organelle protein localization to nucleus positive regulation of locomotion regulation of cell motility positive regulation of cell migration positive regulation of epithelial cell migration positive regulation of cell motility regulation of cell migration regulation of multicellular organismal process regulation of epithelial cell migration locomotion regulation of locomotion	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle cilium plasma membrane bounded cell projection intracellular organelle ciliary basal body cell projection microtubule organizing center cytoskeleton organelle intracellular non-membrane-bounded organelle intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane-bounded organelle cilium plasma membrane bounded cell projection intracellular organelle ciliary basal body cell projection microtubule organizing center cytoskeleton organelle intracellular non-membrane-bounded organelle microtubule cytoskeleton non-membrane-bounded organelle membrane microdomain cell periphery membrane raft plasma membrane raft membrane plasma membrane plasma membrane region caveola nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen protein-containing complex catalytic complex plasma membrane protein complex membrane protein complex transferase complex receptor complex protein kinase complex transferase complex, transferring phosphorus-containing groups insulin receptor complex plasma membrane signaling receptor complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C	IPR036860	SH2 domain superfamily	Homologous Superfamily
A, B, C	IPR024159	Adaptor protein Cbl, PTB domain	Domain
A, B, C	IPR039520	E3 ubiquitin-protein ligase CBL-B, RING finger, HC subclass	Domain
A, B, C	IPR003153	Adaptor protein Cbl, N-terminal helical	Domain
A, B, C	IPR011992	EF-hand domain pair	Homologous Superfamily
A, B, C	IPR015940	Ubiquitin-associated domain	Domain
A, B, C	IPR018957	Zinc finger, C3HC4 RING-type	Domain
A, B, C	IPR017907	Zinc finger, RING-type, conserved site	Conserved Site
A, B, C	IPR024162	Adaptor protein Cbl	Family
A, B, C	IPR014741	Adaptor protein Cbl, EF hand-like	Domain
A, B, C	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
A, B, C	IPR014742	Adaptor protein Cbl, SH2-like domain	Domain
A, B, C	IPR036537	Adaptor protein Cbl, N-terminal domain superfamily	Homologous Superfamily
A, B, C	IPR001841	Zinc finger, RING-type	Domain
D [auth E]	IPR001849	Pleckstrin homology domain	Domain
D [auth E]	IPR002404	IRS-type PTB domain	Domain
D [auth E]	IPR039011	Insulin receptor substrate	Family
D [auth E]	IPR011993	PH-like domain superfamily	Homologous Superfamily

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
D [auth E]	PTR	Parent Component: TYR RESID: AA0039 PSI-MOD : O4'-phospho-L-tyrosine MOD:00048

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.