2DSQ

Structural Basis for the Inhibition of Insulin-like Growth Factors by IGF Binding Proteins

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)
C [auth A]	d2dsqa_	Small proteins	Knottins (small inhibitors, toxins, lectins)	Growth factor receptor domain	Growth factor receptor domain	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A [auth B]	d2dsqb_	Small proteins	Knottins (small inhibitors, toxins, lectins)	Growth factor receptor domain	Growth factor receptor domain	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D [auth C]	d2dsqc_	Small proteins	Insulin-like	Insulin-like	Insulin-like	Insulin-like growth factor	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B [auth I]	d2dsqi_	Small proteins	Insulin-like	Insulin-like	Insulin-like	Insulin-like growth factor	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
E [auth G]	d2dsqg1	Small proteins	Thyroglobulin type-1 domain	Thyroglobulin type-1 domain	Thyroglobulin type-1 domain	Insulin-like growth factor-binding protein 1, IGFBP1	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
F [auth H]	d2dsqh_	Small proteins	Thyroglobulin type-1 domain	Thyroglobulin type-1 domain	Thyroglobulin type-1 domain	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)
C [auth A]	SCOP2B Superfamily	Growth factor receptor domain-like	8032824	3000398	SCOP2B (2022-06-29)
A [auth B]	SCOP2B Superfamily	Growth factor receptor domain-like	8032824	3000398	SCOP2B (2022-06-29)
E [auth G]	SCOP2 Family	Thyroglobulin type-1 domain	8020448	4003524	SCOP2 (2022-06-29)
E [auth G]	SCOP2 Superfamily	Thyroglobulin type-1 domain	8032828	3000991	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)
C [auth A]	PF00219	e2dsqA1	A: few secondary structure elements	X: EGF-like	H: Growth factor receptor domain (From Topology)	T: Growth factor receptor domain	F: PF00219	ECOD (1.6)
A [auth B]	PF00219	e2dsqB1	A: few secondary structure elements	X: EGF-like	H: Growth factor receptor domain (From Topology)	T: Growth factor receptor domain	F: PF00219	ECOD (1.6)
D [auth C]	PF00049	e2dsqC1	A: few secondary structure elements	X: Insulin-like (From Topology)	H: Insulin-like (From Topology)	T: Insulin-like	F: PF00049	ECOD (1.6)
B [auth I]	PF00049	e2dsqI1	A: few secondary structure elements	X: Insulin-like (From Topology)	H: Insulin-like (From Topology)	T: Insulin-like	F: PF00049	ECOD (1.6)
E [auth G]	PF00086	e2dsqG1	A: few secondary structure elements	X: Thyroglobulin type-1 domain (From Topology)	H: Thyroglobulin type-1 domain (From Topology)	T: Thyroglobulin type-1 domain	F: PF00086	ECOD (1.6)
F [auth H]	PF00086	e2dsqH2	A: few secondary structure elements	X: Thyroglobulin type-1 domain (From Topology)	H: Thyroglobulin type-1 domain (From Topology)	T: Thyroglobulin type-1 domain	F: PF00086	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
C [auth A]	4.10.40.20	Few Secondary Structures	Irregular	Omega-AgatoxinV		CATH (4.3.0)
A [auth B]	4.10.40.20	Few Secondary Structures	Irregular	Omega-AgatoxinV		CATH (4.3.0)
D [auth C]	1.10.100.10	Mainly Alpha	Orthogonal Bundle	Insulin-like, subunit E	Insulin-like	CATH (4.3.0)
B [auth I]	1.10.100.10	Mainly Alpha	Orthogonal Bundle	Insulin-like, subunit E	Insulin-like	CATH (4.3.0)
E [auth G]	4.10.800.10	Few Secondary Structures	Irregular	Invariant Chain	Chain I	CATH (4.3.0)
F [auth H]	4.10.800.10	Few Secondary Structures	Irregular	Invariant Chain	Chain I	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A [auth B], C [auth A]	PF00219	Insulin-like growth factor binding protein (IGFBP)	Insulin-like growth factor binding protein	-	Domain
B [auth I], D [auth C]	PF00049	Insulin/IGF/Relaxin family (Insulin)	Insulin/IGF/Relaxin family	Superfamily includes insulins; relaxins; insulin-like growth factor; and bombyxin. All are secreted regulatory hormones. Disulfide rich, all-alpha fold. Alignment includes B chain, linker (which is processed out of the final product), and A chain.	Domain
E [auth G], F [auth H]	PF00086	Thyroglobulin type-1 repeat (Thyroglobulin_1)	Thyroglobulin type-1 repeat	Thyroglobulin type 1 repeats are thought to be involved in the control of proteolytic degradation [2]. The domain usually contains six conserved cysteines. These form three disulphide bridges. Cysteines 1 pairs with 2, 3 with 4 and 5 with 6.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A [auth B], C [auth A]	Insulin-like growth factor-binding protein 4	protein binding binding signaling receptor binding insulin-like growth factor binding insulin-like growth factor II binding growth factor binding insulin-like growth factor I binding	cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction cell surface receptor protein tyrosine kinase signaling pathway cell communication positive regulation of response to stimulus positive regulation of insulin-like growth factor receptor signaling pathway regulation of insulin-like growth factor receptor signaling pathway signal transduction cellular response to stimulus positive regulation of cell communication regulation of cellular process positive regulation of signal transduction response to stimulus signaling positive regulation of biological process regulation of signal transduction cell surface receptor protein tyrosine kinase signaling pathway cell communication positive regulation of response to stimulus positive regulation of insulin-like growth factor receptor signaling pathway regulation of insulin-like growth factor receptor signaling pathway signal transduction enzyme-linked receptor protein signaling pathway positive regulation of cellular process regulation of biological process regulation of signaling cell surface receptor signaling pathway biological regulation insulin-like growth factor receptor signaling pathway regulation of response to stimulus regulation of cell communication cellular process positive regulation of signaling intracellular signal transduction regulation of intracellular signal transduction intracellular signaling cassette positive regulation of MAPK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade MAPK cascade cell population proliferation type B pancreatic cell proliferation epithelial cell proliferation negative regulation of signaling regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway negative regulation of biological process negative regulation of cell communication negative regulation of Wnt signaling pathway negative regulation of cellular process Wnt signaling pathway regulation of Wnt signaling pathway negative regulation of response to stimulus negative regulation of signal transduction negative regulation of canonical Wnt signaling pathway regulation of growth regulation of cellular component organization growth regulation of cell growth cell growth cellular component organization cellular component organization or biogenesis response to organic substance response to chemical response to organic cyclic compound monosaccharide metabolic process carbohydrate metabolic process primary metabolic process hexose metabolic process regulation of primary metabolic process organic substance metabolic process regulation of small molecule metabolic process metabolic process small molecule metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process regulation of metabolic process glucose metabolic process	membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen organelle endoplasmic reticulum cytoplasm extracellular region membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen cellular anatomical entity intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen organelle endoplasmic reticulum cytoplasm extracellular region extracellular space
B [auth I], D [auth C]	Insulin-like growth factor IB	hormone activity protein binding binding molecular function activator activity signaling receptor binding molecular function regulator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity growth factor activity	developmental process anatomical structure development regulation of signaling regulation of biological process negative regulation of signaling signaling biological regulation negative regulation of biological process protein localization regulation of localization establishment of protein localization cellular localization nitrogen compound transport regulation of cellular process developmental process anatomical structure development regulation of signaling regulation of biological process negative regulation of signaling signaling biological regulation negative regulation of biological process protein localization regulation of localization establishment of protein localization cellular localization nitrogen compound transport regulation of cellular process regulation of protein localization transport positive regulation of biological process positive regulation of establishment of protein localization positive regulation of secretion by cell protein localization to extracellular region positive regulation of protein transport localization regulation of secretion by cell secretion by cell positive regulation of secretion cellular macromolecule localization positive regulation of cellular process regulation of transport secretion organic substance transport regulation of establishment of protein localization establishment of protein localization to extracellular region export from cell regulation of protein transport protein secretion establishment of localization positive regulation of protein secretion regulation of protein secretion regulation of secretion positive regulation of transport protein transport regulation of cellular localization macromolecule localization positive regulation of protein localization cellular process regulation of protein stability regulation of biological quality protein stabilization carbohydrate derivative biosynthetic process proteoglycan biosynthetic process organonitrogen compound metabolic process cellular biosynthetic process cellular metabolic process organonitrogen compound biosynthetic process glycoprotein biosynthetic process carbohydrate derivative metabolic process primary metabolic process glycoprotein metabolic process macromolecule biosynthetic process organic substance metabolic process biosynthetic process organic substance biosynthetic process metabolic process protein metabolic process macromolecule metabolic process proteoglycan metabolic process positive regulation of glycoprotein metabolic process positive regulation of protein metabolic process positive regulation of cellular metabolic process positive regulation of macromolecule biosynthetic process regulation of primary metabolic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process regulation of glycoprotein biosynthetic process positive regulation of glycoprotein biosynthetic process regulation of biosynthetic process regulation of protein metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process regulation of glycoprotein metabolic process regulation of cellular biosynthetic process regulation of macromolecule biosynthetic process regulation of metabolic process positive regulation of cellular biosynthetic process negative regulation of cellular process regulation of cell communication negative regulation of cell communication cell communication	extracellular region extracellular space cellular anatomical entity
E [auth G], F [auth H]	Insulin-like growth factor-binding protein 1	insulin-like growth factor binding protein binding binding growth factor binding signaling receptor binding insulin-like growth factor II binding insulin-like growth factor I binding	regulation of biological process regulation of growth regulation of cellular process regulation of cellular component organization positive regulation of biological process biological regulation growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular process cellular component organization or biogenesis regulation of biological process regulation of growth regulation of cellular process regulation of cellular component organization positive regulation of biological process biological regulation growth positive regulation of cell growth regulation of cell growth cell growth cellular component organization positive regulation of growth cellular process cellular component organization or biogenesis positive regulation of cellular process cellular response to stimulus cellular response to nitrogen compound response to organic substance response to stimulus signaling response to peptide hormone insulin receptor signaling pathway cell surface receptor protein tyrosine kinase signaling pathway cell communication cellular response to endogenous stimulus response to hormone cellular response to organic substance signal transduction enzyme-linked receptor protein signaling pathway cellular response to hormone stimulus cell surface receptor signaling pathway response to endogenous stimulus response to organonitrogen compound response to oxygen-containing compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound cellular response to chemical stimulus cellular response to organonitrogen compound response to chemical response to insulin cellular response to insulin stimulus regulation of signaling regulation of signal transduction insulin-like growth factor receptor signaling pathway regulation of response to stimulus regulation of insulin-like growth factor receptor signaling pathway regulation of cell communication negative regulation of signaling regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway negative regulation of biological process negative regulation of cell communication negative regulation of Wnt signaling pathway negative regulation of cellular process Wnt signaling pathway regulation of Wnt signaling pathway negative regulation of response to stimulus negative regulation of signal transduction negative regulation of canonical Wnt signaling pathway developmental process tissue regeneration developmental growth anatomical structure development regeneration response to organic cyclic compound	membrane-bounded organelle intracellular organelle intracellular anatomical structure Golgi apparatus organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle endomembrane system membrane-enclosed lumen intracellular organelle lumen endoplasmic reticulum lumen organelle lumen endoplasmic reticulum membrane-bounded organelle intracellular organelle intracellular anatomical structure Golgi apparatus organelle cytoplasm cellular anatomical entity intracellular membrane-bounded organelle endomembrane system membrane-enclosed lumen intracellular organelle lumen endoplasmic reticulum lumen organelle lumen endoplasmic reticulum extracellular region extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A [auth B], C [auth A]	IPR022321	Insulin-like growth factor-binding protein family 1-6, chordata	Family
A [auth B], C [auth A]	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily
A [auth B], C [auth A]	IPR036857	Thyroglobulin type-1 superfamily	Homologous Superfamily
A [auth B], C [auth A]	IPR022327	Insulin-like growth factor-binding protein 4	Family
A [auth B], C [auth A]	IPR017891	Insulin-like growth factor binding protein, N-terminal, Cys-rich conserved site	Conserved Site
A [auth B], C [auth A]	IPR000716	Thyroglobulin type-1	Domain
A [auth B], C [auth A]	IPR000867	Insulin-like growth factor-binding protein, IGFBP	Domain
B [auth I], D [auth C]	IPR022352	Insulin family	Family
B [auth I], D [auth C]	IPR016179	Insulin-like	Domain
B [auth I], D [auth C]	IPR022341	Insulin-like growth factor I	Family
B [auth I], D [auth C]	IPR022353	Insulin, conserved site	Conserved Site
B [auth I], D [auth C]	IPR022350	Insulin-like growth factor	Family
B [auth I], D [auth C]	IPR036438	Insulin-like superfamily	Homologous Superfamily
E [auth G], F [auth H]	IPR022321	Insulin-like growth factor-binding protein family 1-6, chordata	Family
E [auth G], F [auth H]	IPR009030	Growth factor receptor cysteine-rich domain superfamily	Homologous Superfamily
E [auth G], F [auth H]	IPR036857	Thyroglobulin type-1 superfamily	Homologous Superfamily
E [auth G], F [auth H]	IPR022322	Insulin-like growth factor-binding protein 1	Family
E [auth G], F [auth H]	IPR017891	Insulin-like growth factor binding protein, N-terminal, Cys-rich conserved site	Conserved Site
E [auth G], F [auth H]	IPR000716	Thyroglobulin type-1	Domain
E [auth G], F [auth H]	IPR000867	Insulin-like growth factor-binding protein, IGFBP	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A [auth B], C [auth A]	Pharos: P22692	malignant pancreatic neoplasm myopathy pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia primitive neuroectodermal tumor adrenal cortex carcinoma Becker muscular dystrophy diabetes mellitus gastric carcinoma interstitial lung disease limb-girdle muscular dystrophy malignant glioma MALT lymphoma ovarian cancer pilocytic astrocytoma psoriasis malignant pancreatic neoplasm myopathy pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia primitive neuroectodermal tumor adrenal cortex carcinoma Becker muscular dystrophy diabetes mellitus gastric carcinoma interstitial lung disease limb-girdle muscular dystrophy malignant glioma MALT lymphoma ovarian cancer pilocytic astrocytoma psoriasis atypical teratoid rhabdoid tumor Crohn disease Duchenne muscular dystrophy glioblastoma juvenile dermatomyositis lung carcinoma malignant mesothelioma medulloblastoma pancreatic ductal adenocarcinoma pituitary cancer B-cell chronic lymphocytic leukemia cystic fibrosis Emery-Dreifuss muscular dystrophy interstitial cystitis large cell medulloblastoma malignant ependymoma
E [auth G], F [auth H]	Pharos: P08833	primary biliary cholangitis Liver Cirrhosis, Experimental malignant colon neoplasm cirrhosis of liver endometriosis IgA glomerulonephritis malignant pancreatic neoplasm precancerous condition Silver-Russell syndrome benign colon neoplasm breast cancer inborn carbohydrate metabolic disorder myocardial infarction cystic fibrosis glioblastoma primary biliary cholangitis Liver Cirrhosis, Experimental malignant colon neoplasm cirrhosis of liver endometriosis IgA glomerulonephritis malignant pancreatic neoplasm precancerous condition Silver-Russell syndrome benign colon neoplasm breast cancer inborn carbohydrate metabolic disorder myocardial infarction cystic fibrosis glioblastoma malignant glioma ovarian cancer vascular disease acute kidney failure colonic neoplasm