4LF3

Inhibitory Mechanism of an Allosteric Antibody Targeting the Glucagon Receptor

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
IMGT Antibody Annotation
SAbDab Antibody Annotation
Thera-SAbDab Antibody Annotation
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	d4lf3a2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
A	d4lf3a1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
D	d4lf3d2	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	C1 set domains (antibody constant domain-like)	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
D	d4lf3d1	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	automated matches	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
E	d4lf3e_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	V set domains (antibody variable domain-like)	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)
B	d4lf3b_	All beta proteins	Immunoglobulin-like beta-sandwich	Immunoglobulin	V set domains (antibody variable domain-like)	automated matches	mouse (Mus musculus ) [TaxId: 10090 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
C	SCOP2B Superfamily	FnI-like domain	8091140	3000979	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	FnI-like domain	8091140	3000979	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)
A	C1-set_4	e4lf3A1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
A	V-set	e4lf3A2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)
D	C1-set_4	e4lf3D1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_4	ECOD (1.6)
D	V-set	e4lf3D2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set	ECOD (1.6)
E	V-set_8	e4lf3E2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
E	C1-set_1	e4lf3E1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
B	V-set_8	e4lf3B2	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: V-set_8	ECOD (1.6)
B	C1-set_1	e4lf3B1	A: beta sandwiches	X: Immunoglobulin-like beta-sandwich	H: Immunoglobulin-related	T: Immunoglobulin/Fibronectin type III/E set domains/PapD-like	F: C1-set_1	ECOD (1.6)
C	HRM	e4lf3C1	A: few secondary structure elements	X: Hormone receptor domain (HRM, Pfam 02793) (From Topology)	H: Hormone receptor domain (HRM, Pfam 02793) (From Topology)	T: Hormone receptor domain (HRM, Pfam 02793)	F: HRM	ECOD (1.6)
F	HRM	e4lf3F1	A: few secondary structure elements	X: Hormone receptor domain (HRM, Pfam 02793) (From Topology)	H: Hormone receptor domain (HRM, Pfam 02793) (From Topology)	T: Hormone receptor domain (HRM, Pfam 02793)	F: HRM	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
D	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
E	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
B	2.60.40.10	Mainly Beta	Sandwich	Immunoglobulin-like	Immunoglobulins	CATH (4.3.0)
C	4.10.1240.10	Few Secondary Structures	Irregular	Hormone receptor fold	GPCR, family 2, extracellular hormone receptor domain	CATH (4.3.0)
F	4.10.1240.10	Few Secondary Structures	Irregular	Hormone receptor fold	GPCR, family 2, extracellular hormone receptor domain	CATH (4.3.0)

IMGT Antibody Annotation IMGT Database Homepage

Chain	Protein Name	Description	Organism Name	Gene Allele Name(s)	Domain Name(s)	Receptor Type	Receptor Description	Provenance Source
A, D	FAB-GAMMA-1_KAPPA	L-KAPPA	Mus musculus (house mouse)	IGKV11-12501, IGKV12-9801, IGKJ101, IGKJ201, IGKC*03	V-DOMAIN V-KAPPA, C-DOMAIN C-KAPPA	IG	FAB-GAMMA-1_KAPPA	IMGT (202452-0)
B, E	FAB-GAMMA-1_KAPPA	VH-CH1	Mus musculus (house mouse)	IGHV5-1702, IGHJ301, IGHG1*02	V-DOMAIN VH, C-DOMAIN CH1	IG	FAB-GAMMA-1_KAPPA	IMGT (202452-0)

SAbDab Antibody Annotation SAbDab Database Homepage

Chain	Chain Class	Chain Subclass	Chain Type	Antigen Name(s)	Provenance Source
A, D	Light Chain	IGKV1	Kappa	glucagon receptor	SAbDab (2025-01-03)
B, E	Heavy Chain	IGHV3	-	glucagon receptor	SAbDab (2025-01-03)

Thera-SAbDab Antibody Annotation Thera-SAbDab Database Homepage

Chain	Name	Target	Provenance Source
A, D	Volagidemab	GCCR/NR3C1	Therapeutic SAbDab (2025-01-03)
B, E	Volagidemab	GCCR/NR3C1	Therapeutic SAbDab (2025-01-03)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
C, F	PF02793	Hormone receptor domain (HRM)	Hormone receptor domain	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, D	Fab heavy chain	-	-	-
B, E	Fab light chain	-	-	-
C, F	Glucagon receptor	glucagon receptor activity peptide receptor activity molecular transducer activity G protein-coupled receptor activity G protein-coupled peptide receptor activity transmembrane signaling receptor activity signaling receptor activity amide binding binding peptide hormone binding hormone binding GTPase regulator activity enzyme regulator activity guanyl-nucleotide exchange factor activity glucagon receptor activity peptide receptor activity molecular transducer activity G protein-coupled receptor activity G protein-coupled peptide receptor activity transmembrane signaling receptor activity signaling receptor activity amide binding binding peptide hormone binding hormone binding GTPase regulator activity enzyme regulator activity guanyl-nucleotide exchange factor activity nucleoside-triphosphatase regulator activity molecular function regulator activity	multicellular organismal process system process circulatory system process regulation of blood pressure biological regulation regulation of biological quality blood circulation regulation of biosynthetic process regulation of biological process regulation of cellular process positive regulation of biological process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process multicellular organismal process system process circulatory system process regulation of blood pressure biological regulation regulation of biological quality blood circulation regulation of biosynthetic process regulation of biological process regulation of cellular process positive regulation of biological process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process positive regulation of macromolecule biosynthetic process regulation of gene expression positive regulation of metabolic process biosynthetic process positive regulation of gene expression positive regulation of biosynthetic process regulation of macromolecule biosynthetic process metabolic process cellular process positive regulation of macromolecule metabolic process macromolecule metabolic process regulation of metabolic process positive regulation of cellular process cellular response to stimulus response to stimulus signaling response to endogenous stimulus hormone-mediated signaling pathway cell communication cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone response to chemical signal transduction cellular response to hormone stimulus cellular response to nitrogen compound response to peptide hormone cellular response to peptide hormone stimulus response to oxygen-containing compound response to nitrogen compound response to glucagon cellular response to oxygen-containing compound cellular response to glucagon stimulus carbohydrate metabolic process energy derivation by oxidation of organic compounds glycogen metabolic process primary metabolic process regulation of generation of precursor metabolites and energy generation of precursor metabolites and energy regulation of polysaccharide metabolic process regulation of primary metabolic process glucan metabolic process polysaccharide metabolic process energy reserve metabolic process regulation of glycogen metabolic process regulation of carbohydrate metabolic process adenylate cyclase-modulating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway adenylate cyclase-activating G protein-coupled receptor signaling pathway cellular response to nutrient levels response to nutrient levels cellular response to stress response to stress response to starvation cellular response to starvation cell surface receptor signaling pathway response to nutrient localization secretion by cell exocytosis transport secretion export from cell establishment of localization vesicle-mediated transport chemical homeostasis homeostatic process glucose homeostasis carbohydrate homeostasis	cellular anatomical structure membrane cell periphery plasma membrane membrane-bounded organelle intracellular anatomical structure endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle organelle cytoplasm cellular anatomical structure membrane cell periphery plasma membrane membrane-bounded organelle intracellular anatomical structure endosome intracellular vesicle intracellular membrane-bounded organelle endomembrane system intracellular organelle cytoplasmic vesicle organelle cytoplasm vesicle

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
C, F	IPR017983	GPCR, family 2, secretin-like, conserved site	Conserved Site
C, F	IPR050332	G-protein coupled receptor 2	Family
C, F	IPR003290	GPCR, family 2, glucagon-like peptide-1/glucagon receptor	Family
C, F	IPR036445	GPCR family 2, extracellular hormone receptor domain superfamily	Homologous Superfamily
C, F	IPR000832	GPCR, family 2, secretin-like	Family
C, F	IPR017981	GPCR, family 2-like, 7TM	Domain
C, F	IPR001879	GPCR, family 2, extracellular hormone receptor domain	Domain
C, F	IPR003291	GPCR, family 2, glucagon receptor	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
C, F	Pharos: P47871	type 2 diabetes mellitus acquired metabolic disease diabetes mellitus hypoglycemia Severe hypoglycaemia in patients with diabetes ACTH-independent macronodular adrenal hyperplasia 1 Cushing syndrome due to macronodular adrenal hyperplasia maturity-onset diabetes of the young

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.