4GPL

Structure of Cbl(TKB) bound to a phosphorylated pentapeptide

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
Protein Modification Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d4gplb2	All alpha proteins	EF Hand-like	EF-hand	EF-hand modules in multidomain proteins	Cbl	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4gplb1	All alpha proteins	N-cbl like	N-terminal domain of cbl (N-cbl)	N-terminal domain of cbl (N-cbl)	N-terminal domain of cbl (N-cbl)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d4gplb3	Alpha and beta proteins (a+b)	SH2-like	SH2 domain	SH2 domain	Cbl	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)
B	SCOP2B Superfamily	EF-hand	8039549	3001983	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	N-terminal domain of cbl (N-cbl)	8039550	3000373	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	SH2 domain	8039553	3000197	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
B	PF02761	e4gplB1	A: alpha arrays	X: EF-hand	H: EF-hand-related	T: EF-hand	F: PF02761	ECOD (1.6)
B	PF02262	e4gplB2	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	e4gplB3	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)
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)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
B	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
B	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
B	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	ACE-PTR-THR-PRO-GLU-PRO, PEPTIDE INHIBITOR	-	-	-
B	E3 ubiquitin-protein ligase CBL	phosphoprotein binding phosphotyrosine residue binding protein binding 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 phosphoprotein binding phosphotyrosine residue binding protein binding 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 cell adhesion molecule binding cadherin binding signaling receptor binding ephrin receptor binding protein tyrosine kinase binding kinase binding receptor tyrosine kinase binding enzyme binding protein kinase binding cation binding ion binding calcium ion binding metal ion binding small molecule binding phosphatidylinositol 3-kinase binding phosphatidylinositol 3-kinase regulatory subunit binding	cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction cellular response to stimulus cellular response to stress response to stimulus DNA damage response response to stress cellular process developmental process multicellular organismal process gonad development reproductive system development reproductive process sex differentiation animal organ development developmental process involved in reproduction male gonad development male sex differentiation multicellular organism development development of primary male sexual characteristics development of primary sexual characteristics anatomical structure development reproductive structure development system development biological process involved in interspecies interaction between organisms entry of bacterium into host cell symbiont entry into host biological process involved in interaction with host biological process involved in symbiotic interaction response to organic substance regulation of biological process regulation of cellular process 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 organic substance signal transduction response to ketone response to lipid response to oxygen-containing compound response to testosterone response to organic cyclic compound response to decreased oxygen levels cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus organonitrogen compound metabolic process protein autoubiquitination primary metabolic process organic substance metabolic process protein ubiquitination macromolecule modification metabolic process protein metabolic process macromolecule metabolic process post-translational protein modification protein modification process protein modification by small protein conjugation protein modification by small protein conjugation or removal negative regulation of signaling negative regulation of ERBB signaling pathway negative regulation of biological process regulation of signal transduction cell surface receptor protein tyrosine kinase signaling pathway negative regulation of cell communication regulation of epidermal growth factor receptor signaling pathway negative regulation of cellular process epidermal growth factor receptor signaling pathway enzyme-linked receptor protein signaling pathway regulation of signaling regulation of ERBB signaling pathway negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus negative regulation of epidermal growth factor receptor signaling pathway ERBB signaling pathway regulation of cell communication positive regulation of cell communication positive regulation of signal transduction positive regulation of biological process positive regulation of response to stimulus positive regulation of ERBB signaling pathway positive regulation of cellular process positive regulation of epidermal growth factor receptor signaling pathway positive regulation of signaling cellular response to endogenous stimulus cellular response to growth factor stimulus response to endogenous stimulus cellular response to nerve growth factor stimulus response to nerve growth factor response to growth factor organonitrogen compound catabolic process catabolic process proteolysis involved in protein catabolic process protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process organic substance catabolic process protein polyubiquitination regulation of localization import into cell positive regulation of cellular component organization regulation of cellular component organization transport vesicle-mediated transport cellular component organization localization positive regulation of endocytosis cellular component organization or biogenesis positive regulation of receptor-mediated endocytosis regulation of endocytosis regulation of transport regulation of receptor-mediated endocytosis regulation of vesicle-mediated transport establishment of localization positive regulation of transport endocytosis receptor-mediated endocytosis platelet-derived growth factor receptor-alpha signaling pathway platelet-derived growth factor receptor signaling pathway regulation of platelet-derived growth factor receptor signaling pathway regulation of platelet-derived growth factor receptor-alpha signaling pathway protein monoubiquitination response to nutrient levels response to starvation cellular response to platelet-derived growth factor stimulus response to platelet-derived growth factor negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death response to activity small GTPase-mediated signal transduction regulation of small GTPase mediated signal transduction regulation of Rap protein signal transduction intracellular signal transduction regulation of intracellular signal transduction intracellular signaling cassette Rap protein signal transduction regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction positive regulation of intracellular signal transduction positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction phosphatidylinositol 3-kinase/protein kinase B signal transduction protein localization ubiquitin-dependent endocytosis establishment of protein localization cellular localization nitrogen compound transport organic substance transport establishment of protein localization to organelle protein transport cellular macromolecule localization macromolecule localization protein localization to organelle response to alcohol response to ethanol establishment of organelle localization regulated exocytosis cell activation involved in immune response leukocyte degranulation myeloid leukocyte activation myeloid leukocyte mediated immunity leukocyte activation secretion by cell organelle localization leukocyte activation involved in immune response establishment of localization in cell mast cell activation leukocyte mediated immunity mast cell mediated immunity immune response secretion cell activation vacuolar localization export from cell mast cell degranulation myeloid cell activation involved in immune response immune effector process mast cell activation involved in immune response exocytosis immune system process lysosome localization response to ionizing radiation response to radiation response to gamma radiation	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane raft protein-containing complex plasma membrane protein complex plasma membrane raft membrane plasma membrane membrane protein complex caveola membrane microdomain cell periphery intracellular anatomical structure cytoplasm cellular anatomical entity cytosol membrane raft protein-containing complex plasma membrane protein complex plasma membrane raft membrane plasma membrane membrane protein complex caveola membrane microdomain cell periphery flotillin complex plasma membrane region membrane-bounded organelle intracellular organelle Golgi apparatus organelle intracellular membrane-bounded organelle endomembrane system perinuclear region of cytoplasm cell projection cilium plasma membrane bounded cell projection anchoring junction cell junction focal adhesion cell-substrate junction growth cone axon distal axon neuron projection site of polarized growth

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
B	IPR024162	Adaptor protein Cbl	Family
B	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
B	IPR009060	UBA-like superfamily	Homologous Superfamily
B	IPR001841	Zinc finger, RING-type	Domain
B	IPR036860	SH2 domain superfamily	Homologous Superfamily
B	IPR024159	Adaptor protein Cbl, PTB domain	Domain
B	IPR003153	Adaptor protein Cbl, N-terminal helical	Domain
B	IPR011992	EF-hand domain pair	Homologous Superfamily
B	IPR015940	Ubiquitin-associated domain	Domain
B	IPR018957	Zinc finger, C3HC4 RING-type	Domain
B	IPR017907	Zinc finger, RING-type, conserved site	Conserved Site
B	IPR014741	Adaptor protein Cbl, EF hand-like	Domain
B	IPR014742	Adaptor protein Cbl, SH2-like domain	Domain
B	IPR036537	Adaptor protein Cbl, N-terminal domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
B	Pharos: P22681	juvenile myelomonocytic leukemia CBL-related disorder vasculitis male infertility cryptorchidism intellectual disability myelodysplastic syndrome ovarian cancer Abdominal Cryptorchidism primitive neuroectodermal tumor developmental disability glioblastoma hydrops fetalis pancreatic intraductal papillary-mucinous neoplasm acute myeloid leukemia juvenile myelomonocytic leukemia CBL-related disorder vasculitis male infertility cryptorchidism intellectual disability myelodysplastic syndrome ovarian cancer Abdominal Cryptorchidism primitive neuroectodermal tumor developmental disability glioblastoma hydrops fetalis pancreatic intraductal papillary-mucinous neoplasm acute myeloid leukemia rheumatoid arthritis cancer ulcerative colitis large cell medulloblastoma malignant glioma osteosarcoma Pick disease atypical teratoid rhabdoid tumor Sjogren syndrome congenital anemia genetic endocrine growth disease hematopoietic and lymphoid system neoplasm

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
A	ACE	RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359
A	NH2	RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 , AA0081 , AA0083 , AA0084 , AA0086 , AA0087 , AA0088 , AA0090 , AA0091 , AA0092 , AA0093 , AA0095 , AA0096 , AA0097 , AA0098 , AA0099 , AA0100 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359 , L-alanine amide MOD:00090 , L-asparagine amide MOD:00092 , L-aspartic acid 1-amide MOD:00093 , L-glutamine amide MOD:00095 , L-glutamic acid 1-amide MOD:00096 , glycine amide MOD:00097 , L-isoleucine amide MOD:00099 , L-leucine amide MOD:00100 , L-lysine amide MOD:00101 , L-methionine amide MOD:00102 , L-proline amide MOD:00104 , L-serine amide MOD:00105 , L-threonine amide MOD:00106 , L-tryptophan amide MOD:00107 , L-tyrosine amide MOD:00108 , L-valine amide MOD:00109
A	PTR	Parent Component: TYR RESID: AA0041 , AA0042 , AA0043 , AA0044 , AA0045 , AA0046 , AA0049 , AA0050 , AA0051 , AA0052 , AA0053 , AA0054 , AA0354 , AA0081 , AA0083 , AA0084 , AA0086 , AA0087 , AA0088 , AA0090 , AA0091 , AA0092 , AA0093 , AA0095 , AA0096 , AA0097 , AA0098 , AA0099 , AA0100 , AA0039 PSI-MOD : N-acetyl-L-alanine MOD:00050 , N-acetyl-L-aspartic acid MOD:00051 , N-acetyl-L-cysteine MOD:00052 , N-acetyl-S-archeol-cysteine MOD:00897 , N-acetyl-L-glutamic acid MOD:00053 , N-acetyl-L-glutamine MOD:00054 , N-acetylglycine MOD:00055 , N-acetyl-L-methionine MOD:00058 , N-acetyl-L-proline MOD:00059 , N-acetyl-L-serine MOD:00060 , N,O-diacetylated L-serine MOD:00648 , N-acetyl-L-threonine MOD:00061 , N-acetyl-L-tyrosine MOD:00062 , N-acetyl-L-valine MOD:00063 , N2-acetyl-L-arginine MOD:00359 , L-alanine amide MOD:00090 , L-asparagine amide MOD:00092 , L-aspartic acid 1-amide MOD:00093 , L-glutamine amide MOD:00095 , L-glutamic acid 1-amide MOD:00096 , glycine amide MOD:00097 , L-isoleucine amide MOD:00099 , L-leucine amide MOD:00100 , L-lysine amide MOD:00101 , L-methionine amide MOD:00102 , L-proline amide MOD:00104 , L-serine amide MOD:00105 , L-threonine amide MOD:00106 , L-tryptophan amide MOD:00107 , L-tyrosine amide MOD:00108 , L-valine amide MOD:00109 , 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.