HORDB

General Information

ID: hor006376
Uniprot ID: P01275
Protein name: Glucagon-like peptide 2
Gene name: GCG
Organism: Homo sapiens (Human)
Family: Glucagon family
Source: Human
Expression: [Glucagon]: Release is stimulated by hypoglycemia and inhibited by hyperglycemia, insulin, and somatostatin. |[Glucagon]: Secreted in the A cells of the islets of Langerhans. [Glucagon-like peptide 2]: Secreted from enteroendocrine cells throughout the ga
Disease: Diseases associated with GCG include Dumping Syndrome and Hyperglycemia.
Comments: NA
Taxonomy: Homo (genus), Homininae (subfamily), Hominidae (family), Hominoidea (superfamily), Catarrhini (parvorder), Simiiformes (infraorder), Haplorrhini (suborder), Primates (order), Euarchontoglires (superorder), Boreoeutheria, Eutheria, Theria, Mammalia (class), Amniota, Tetrapoda, Dipnotetrapodomorpha, Sarcopterygii (superclass), Euteleostomi, Teleostomi, Gnathostomata, Vertebrata, Craniata (subphylum), Chordata (phylum), Deuterostomia, Bilateria, Eumetazoa, Metazoa (kingdom), Opisthokonta, Eukaryota (superkingdom), cellular organisms
GO MF: GO:0005102 signaling receptor binding; GO:0005179 hormone activity; GO:0005515 protein binding; GO:0031769 glucagon receptor binding; GO:0042802 identical protein binding; GO:0048018 receptor ligand activity
GO BP: GO:0006094 gluconeogenesis; GO:0007186 G protein-coupled receptor signaling pathway; GO:0007188 adenylate cyclase-modulating G protein-coupled receptor signaling pathway; GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway; GO:0007631 feeding behavior; GO:0010737 protein kinase A signaling; GO:0010800 positive regulation of peptidyl-threonine phosphorylation; GO:0014823 response to activity; GO:0033138 positive regulation of peptidyl-serine phosphorylation; GO:0035774 positive regulation of insulin secretion involved in cellular response to glucose stimulus; GO:0042593 glucose homeostasis; GO:0043066 negative regulation of apoptotic process; GO:0045722 positive regulation of gluconeogenesis; GO:0050796 regulation of insulin secretion; GO:0050896 response to stimulus; GO:0051571 obsolete positive regulation of histone H3-K4 methylation; GO:0070374 positive regulation of ERK1 and ERK2 cascade; GO:0071377 cellular response to glucagon stimulus; GO:0090280 positive regulation of calcium ion import; GO:1900118 negative regulation of execution phase of apoptosis
GO CC: GO:0005576 extracellular region; GO:0005615 extracellular space; GO:0005737 cytoplasm; GO:0005788 endoplasmic reticulum lumen; GO:0005886 plasma membrane; GO:0034774 secretory granule lumen

Sequence Information

Sequence: HADGSFSDEMNTILDNLAARDFINWLIQTKITD
Length: 33
Propeptide: MKSIYFVAGLFVMLVQGSWQRSLQDTEEKSRSFSASQADPLSDPDQMNEDKRHSQGTFTSDYSKYLDSRRAQDFVQWLMNTKRNRNNIAKRHDEFERHAEGTFTSDVSSYLEGQAAKEFIAWLVKGRGRRDFPEEVAIVEELGRRHADGSFSDEMNTILDNLAARDFINWLIQTKITDRK
Signal peptide: MKSIYFVAGLFVMLVQGSWQ
Modification: T5 Phosphoserine;T7 Phosphoserine
Glycosylation: NA
Mutagenesis: NA

Activity

Function: [Glucagon]: Plays a key role in glucose metabolism and homeostasis. Regulates blood glucose by increasing gluconeogenesis and decreasing glycolysis. A counterregulatory hormone of insulin, raises plasma glucose levels in response to insulin-induced hypoglycemia. Plays an important role in initiating and maintaining hyperglycemic conditions in diabetes.
Mechanism: In the glucagon antagonist, His-53 and Phe-58 are missing. This antagonist has been successfully utilized to reduce glucose concentration in vivo.
Cross BBB: NA
Target: GCGR, GLP1R
Target Unid: P47871, P43220
IC50: NA
EC50: NA
ED50: NA
kd: NA
Half life: 6.8±0.8 minutes; /408 seconds ( PubMed ID: 17107718 )

Structure

Disulfide bond: NA
Structure ID: AF-P01275-F1(AlphaFold_DB_ID)

Structure: (PDB_ID-from https://www.rcsb.org/; AlphaFold_DB_ID-from https://alphafold.ebi.ac.uk/; hordbxxxxxx_AF2.pdb was predicted structure by AlphaFold2; hordbxxxxxx_ESM.pdb was predicted structure by ESMFold)

hor006376_AF2.pdb

hor006376_ESM.pdb

Physical Information

Mass:	433715	Formula:	C165H254N44O55S
Absent amino acids:	CPVY	Common amino acids:	D
pI:	4.01	Basic residues:	3
Polar residues:	9	Hydrophobic residues:	13
Hydrophobicity:	-28.18	Boman Index:	-6406
Half-Life:	3.5 hour	Half-Life Yeast:	10 min
Half-Life E.Coli:	>10 hour	Aliphatic Index	91.82
Instability Index:	612.73	Extinction Coefficient cystines:	5500
Absorbance 280nm:	171.88

Literature

PubMed ID: 2901414
Title: Glucagon gene expression in vertebrate brain.
PubMed ID: 3725587
Title: Structure of the human glucagon gene.
PubMed ID: 6877358
Title: Exon duplication and divergence in the human preproglucagon gene.
PubMed ID: 15815621
Title: Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
PubMed ID: 15489334
Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
PubMed ID: 11946536
Title: The amino acid sequence of human glucagon.
PubMed ID: 2753890
Title: Complete sequences of glucagon-like peptide-1 from human and pig small intestine.
PubMed ID: 8482423
Title: Biological effects and metabolic rates of glucagonlike peptide-1 7-36 amide and glucagonlike peptide-1 7-37 in healthy subjects are indistinguishable.
PubMed ID: 14557443
Title: Oxyntomodulin suppresses appetite and reduces food intake in humans.
PubMed ID: 14632334
Title: Postnatal and postprandial changes in plasma concentrations of glicentin in term and preterm infants.
PubMed ID: 9287128
Title: Role of the prohormone convertase PC2 in the processing of proglucagon to glucagon.
PubMed ID: 12651102
Title: Expression, purification, and PC1-mediated processing of human proglucagon, glicentin, and major proglucagon fragment.
PubMed ID: 10605628
Title: The glucagon-like peptides.
PubMed ID: 10322410
Title: Glucagon-like Peptide 2.
PubMed ID: 12626323
Title: Glucagon and regulation of glucose metabolism.
PubMed ID: 14719035
Title: Direct and indirect mechanisms regulating secretion of glucagon-like peptide-1 and glucagon-like peptide-2.
PubMed ID: 12554744
Title: Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis.
PubMed ID: 22037645
Title: Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells.
PubMed ID: 9667960
Title: Structure-function studies on positions 17, 18, and 21 replacement analogues of glucagon: the importance of charged residues and salt bridges in glucagon biological activity.
PubMed ID: 11943215
Title: NMR studies of the aggregation of glucagon-like peptide-1: formation of a symmetric helical dimer.
PubMed ID: 12627948
Title: NMR solution structure of the glucagon antagonist [desHis1, desPhe6, Glu9]glucagon amide in the presence of perdeuterated dodecylphosphocholine micelles.
PubMed ID: 17107718
Title: