4ZGM

Crystal structure of Semaglutide peptide backbone in complex with the GLP-1 receptor extracellular domain

External Resource: Annotation

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: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	FnI-like domain	8086309	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	HRM	e4zgmA1	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	4.10.1240.10	Few Secondary Structures	Irregular	Hormone receptor fold	GPCR, family 2, extracellular hormone receptor domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	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	Glucagon-like peptide 1 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 glucagon-like peptide 1 receptor activity	positive regulation of cytosolic calcium ion concentration biological regulation regulation of biological quality heart process multicellular organismal process system process regulation of biological process regulation of heart contraction regulation of system process circulatory system process regulation of blood circulation regulation of multicellular organismal process heart contraction blood circulation positive regulation of cytosolic calcium ion concentration biological regulation regulation of biological quality heart process multicellular organismal process system process regulation of biological process regulation of heart contraction regulation of system process circulatory system process regulation of blood circulation regulation of multicellular organismal process heart contraction blood circulation regulation of blood pressure positive regulation of blood pressure cellular response to stimulus regulation of cellular process response to stimulus signaling adenylate cyclase-activating G protein-coupled receptor signaling pathway cell communication adenylate cyclase-modulating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway cellular process signal transduction response to stress response to psychosocial stress cell surface receptor signaling pathway behavior learning or memory nervous system process cognition transport secretion regulation of hormone levels cell-cell signaling export from cell hormone secretion establishment of localization localization secretion by cell signal release hormone transport positive regulation of adenylate cyclase activity positive regulation of cyclase activity regulation of catalytic activity positive regulation of catalytic activity positive regulation of molecular function regulation of molecular function regulation of lyase activity activation of adenylate cyclase activity regulation of adenylate cyclase activity regulation of cyclase activity positive regulation of lyase activity intracellular signal transduction cAMP-mediated signaling intracellular signaling cassette protein localization establishment of protein localization cellular localization nitrogen compound transport protein targeting protein transmembrane transport cellular macromolecule localization establishment of localization in cell post-translational protein targeting to membrane, translocation establishment of protein localization to endoplasmic reticulum protein localization to endoplasmic reticulum establishment of protein localization to membrane intracellular protein transmembrane transport intracellular transport post-translational protein targeting to endoplasmic reticulum membrane localization within membrane protein localization to membrane protein targeting to membrane transmembrane transport establishment of protein localization to organelle protein transport macromolecule localization protein localization to organelle intracellular protein transport protein targeting to ER negative regulation of blood pressure	cellular anatomical structure membrane cell periphery plasma membrane
B	Semaglutide peptide backbone; 8Aib,34R-GLP-1(7-37)-OH	protein binding binding signaling receptor binding molecular function activator activity molecular function regulator activity signaling receptor regulator activity receptor ligand activity signaling receptor activator activity G protein-coupled receptor binding glucagon receptor binding hormone activity identical protein binding	monosaccharide metabolic process regulation of cellular process positive regulation of biological process gluconeogenesis regulation of primary metabolic process positive regulation of metabolic process regulation of small molecule metabolic process positive regulation of biosynthetic process small molecule metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process positive regulation of cellular process positive regulation of gluconeogenesis regulation of biosynthetic process monosaccharide metabolic process regulation of cellular process positive regulation of biological process gluconeogenesis regulation of primary metabolic process positive regulation of metabolic process regulation of small molecule metabolic process positive regulation of biosynthetic process small molecule metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process positive regulation of cellular process positive regulation of gluconeogenesis regulation of biosynthetic process carbohydrate metabolic process regulation of biological process small molecule biosynthetic process carbohydrate biosynthetic process biological regulation hexose metabolic process primary metabolic process monosaccharide biosynthetic process hexose biosynthetic process positive regulation of glucose metabolic process biosynthetic process regulation of gluconeogenesis metabolic process cellular process positive regulation of carbohydrate metabolic process regulation of carbohydrate biosynthetic process positive regulation of small molecule metabolic process regulation of metabolic process glucose metabolic process 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 positive regulation of ERK1 and ERK2 cascade regulation of intracellular signal transduction intracellular signaling cassette signal transduction regulation of signaling positive regulation of MAPK cascade positive regulation of intracellular signal transduction regulation of MAPK cascade regulation of response to stimulus MAPK cascade regulation of cell communication ERK1 and ERK2 cascade regulation of ERK1 and ERK2 cascade positive regulation of signaling 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 positive regulation of phosphorylation regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process regulation of peptidyl-threonine phosphorylation positive regulation of phosphate metabolic process positive regulation of protein modification process regulation of phosphate metabolic process phosphate-containing compound metabolic process peptidyl-amino acid modification positive regulation of macromolecule metabolic process protein metabolic process peptidyl-threonine modification positive regulation of protein phosphorylation phosphorus metabolic process protein modification process protein phosphorylation positive regulation of phosphorus metabolic process positive regulation of peptidyl-threonine phosphorylation phosphorylation regulation of protein metabolic process regulation of macromolecule metabolic process macromolecule modification regulation of phosphorus metabolic process regulation of phosphorylation macromolecule metabolic process peptidyl-threonine phosphorylation cellular response to nitrogen compound response to endogenous stimulus 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 cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone response to chemical cellular response to hormone stimulus response to activity adenylate cyclase-modulating G protein-coupled receptor signaling pathway G protein-coupled receptor signaling pathway regulation of peptidyl-serine phosphorylation peptidyl-serine modification peptidyl-serine phosphorylation positive regulation of peptidyl-serine phosphorylation protein kinase A signaling negative regulation of execution phase of apoptosis regulation of execution phase of apoptosis execution phase of apoptosis behavior multicellular organismal process feeding behavior adenylate cyclase-activating G protein-coupled receptor signaling pathway protein localization regulation of localization establishment of protein localization nitrogen compound transport localization cellular macromolecule localization regulation of biological quality regulation of peptide hormone secretion regulation of hormone levels establishment of protein localization to extracellular region protein secretion establishment of localization regulation of protein secretion regulation of secretion cellular localization regulation of hormone secretion regulation of protein localization regulation of peptide secretion transport hormone secretion protein localization to extracellular region peptide secretion secretion by cell regulation of secretion by cell amide transport signal release secretion regulation of transport regulation of peptide transport regulation of establishment of protein localization cell-cell signaling export from cell regulation of protein transport peptide transport protein transport regulation of cellular localization regulation of insulin secretion peptide hormone secretion macromolecule localization hormone transport insulin secretion positive regulation of establishment of protein localization carbohydrate homeostasis establishment of localization in cell positive regulation of insulin secretion involved in cellular response to glucose stimulus positive regulation of insulin secretion positive regulation of peptide hormone secretion intracellular glucose homeostasis cellular response to carbohydrate stimulus chemical homeostasis response to glucose glucose homeostasis positive regulation of protein localization insulin secretion involved in cellular response to glucose stimulus homeostatic process positive regulation of secretion by cell positive regulation of protein transport positive regulation of hormone secretion response to monosaccharide response to carbohydrate positive regulation of secretion cellular response to hexose stimulus intracellular chemical homeostasis cellular response to monosaccharide stimulus positive regulation of peptide secretion cellular response to glucose stimulus positive regulation of protein secretion response to hexose cellular homeostasis positive regulation of transport regulation of insulin secretion involved in cellular response to glucose stimulus regulation of calcium ion import regulation of calcium ion transport positive regulation of calcium ion transport positive regulation of calcium ion import regulation of monoatomic ion transport calcium ion transport metal ion transport positive regulation of monoatomic ion transport monoatomic ion transport calcium ion import monoatomic cation transport regulation of metal ion transport	cell periphery cellular anatomical structure plasma membrane membrane membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen organelle cell periphery cellular anatomical structure plasma membrane membrane membrane-bounded organelle intracellular anatomical structure membrane-enclosed lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen endoplasmic reticulum lumen intracellular organelle organelle lumen organelle endoplasmic reticulum cytoplasm extracellular region vesicle lumen intracellular vesicle cytoplasmic vesicle lumen secretory granule lumen cytoplasmic vesicle secretory granule secretory vesicle vesicle extracellular space

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR017983	GPCR, family 2, secretin-like, conserved site	Conserved Site
A	IPR050332	G-protein coupled receptor 2	Family
A	IPR003290	GPCR, family 2, glucagon-like peptide-1/glucagon receptor	Family
A	IPR036445	GPCR family 2, extracellular hormone receptor domain superfamily	Homologous Superfamily
A	IPR000832	GPCR, family 2, secretin-like	Family
A	IPR047033	Glucagon-like peptide-1 receptor, 7TM	Domain
A	IPR017981	GPCR, family 2-like, 7TM	Domain
A	IPR001879	GPCR, family 2, extracellular hormone receptor domain	Domain
A	IPR003292	GPCR, family 2, glucagon-like peptide-1 receptor	Family
B	IPR000532	Glucagon/GIP/secretin/VIP	Domain
B	IPR015550	Glucagon	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P43220	type 2 diabetes mellitus hypertensive disorder cancer hyperplasia benign neoplasm heart disease Neoplasms osteosarcoma hyperglycemia hypoglycemia nephrolithiasis psoriasis myocardial infarction obesity disorder
B	Pharos: P01275	obesity disorder hyperglycemia hyperinsulinism type 2 diabetes mellitus malignant colon neoplasm hypertensive disorder Aberrant Crypt Foci colitis congestive heart failure vascular disease poisoning heart disease stomach disease pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia prediabetes syndrome obesity disorder hyperglycemia hyperinsulinism type 2 diabetes mellitus malignant colon neoplasm hypertensive disorder Aberrant Crypt Foci colitis congestive heart failure vascular disease poisoning heart disease stomach disease pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia prediabetes syndrome heart failure hyperlipidemia kidney disease coronary artery disease pancreatic insulinoma pancreatitis hypotensive disorder Crohn disease maturity-onset diabetes of the young non-alcoholic fatty liver disease pancreatic intraductal papillary-mucinous carcinoma familial hyperlipidemia short bowel syndrome hyperinsulinemic hypoglycemia benign colon neoplasm hypoglycemia colonic neoplasm inherited lipid metabolism disorder constipation disorder metabolic acidosis

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.