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Protein

Glucagon

Gene

Gcg

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity).By similarity
GLP-1 is a potent stimulator of glucose-dependent insulin release. Play important roles on gastric motility and the suppression of plasma glucagon levels. May be involved in the suppression of satiety and stimulation of glucose disposal in peripheral tissues, independent of the actions of insulin. Have growth-promoting activities on intestinal epithelium. May also regulate the hypothalamic pituitary axis (HPA) via effects on LH, TSH, CRH, oxytocin, and vasopressin secretion. Increases islet mass through stimulation of islet neogenesis and pancreatic beta cell proliferation (By similarity).By similarity
GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. The gastrointestinal tract, from the stomach to the colon is the principal target for GLP-2 action. Plays a key role in nutrient homeostasis, enhancing nutrient assimilation through enhanced gastrointestinal function, as well as increasing nutrient disposal. Stimulates intestinal glucose transport and decreases mucosal permeability (By similarity).By similarity
Oxyntomodulin significantly reduces food intake.By similarity
Glicentin may modulate gastric acid secretion and gastro-pyloro-duodenal activity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei52 – 532Cleavage; by PCSK2
Sitei83 – 842Cleavage; by PCSK1 and PCSK2
Sitei91 – 922Cleavage; by PCSK1
Sitei97 – 982Cleavage; by PCSK1
Sitei130 – 1312Cleavage; by PCSK1
Sitei145 – 1462Cleavage; by PCSK1

GO - Molecular functioni

  1. glucagon receptor binding Source: GO_Central
  2. hormone activity Source: GO_Central

GO - Biological processi

  1. adenylate cyclase-modulating G-protein coupled receptor signaling pathway Source: GO_Central
  2. negative regulation of apoptotic process Source: UniProtKB
  3. negative regulation of execution phase of apoptosis Source: MGI
  4. negative regulation of intrinsic apoptotic signaling pathway Source: UniProtKB
  5. positive regulation of calcium ion import Source: UniProtKB
  6. positive regulation of cAMP biosynthetic process Source: UniProtKB
  7. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  8. positive regulation of gluconeogenesis by positive regulation of transcription from RNA polymerase II promoter Source: MGI
  9. positive regulation of histone H3-K4 methylation Source: MGI
  10. positive regulation of insulin secretion involved in cellular response to glucose stimulus Source: UniProtKB
  11. positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
  12. positive regulation of peptidyl-threonine phosphorylation Source: UniProtKB
  13. positive regulation of protein binding Source: UniProtKB
  14. positive regulation of protein kinase activity Source: UniProtKB
  15. protein kinase A signaling Source: UniProtKB
  16. regulation of insulin secretion Source: MGI
  17. response to starvation Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Hormone

Enzyme and pathway databases

ReactomeiREACT_207651. G alpha (q) signalling events.
REACT_210399. Glucagon signaling in metabolic regulation.
REACT_231304. Glucagon-type ligand receptors.
REACT_233293. Synthesis, secretion, and deacylation of Ghrelin.
REACT_242871. G alpha (s) signalling events.
REACT_248547. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
REACT_259776. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).

Names & Taxonomyi

Protein namesi
Recommended name:
Glucagon
Cleaved into the following 8 chains:
Oxyntomodulin
Short name:
OXM
Short name:
OXY
Glucagon-like peptide 1
Short name:
GLP-1
Glucagon-like peptide 1(7-37)
Short name:
GLP-1(7-37)
Glucagon-like peptide 1(7-36)
Short name:
GLP-1(7-36)
Glucagon-like peptide 2
Short name:
GLP-2
Gene namesi
Name:Gcg
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:95674. Gcg.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. extracellular space Source: MGI
  3. secretory granule lumen Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020By similarityAdd
BLAST
Peptidei21 – 8969GlicentinBy similarityPRO_0000011273Add
BLAST
Peptidei21 – 5030Glicentin-related polypeptideBy similarityPRO_0000011274Add
BLAST
Peptidei53 – 8937OxyntomodulinBy similarityPRO_0000011275Add
BLAST
Peptidei53 – 8129GlucagonBy similarityPRO_0000011276Add
BLAST
Propeptidei84 – 896By similarityPRO_0000011277
Peptidei92 – 12837Glucagon-like peptide 1By similarityPRO_0000011278Add
BLAST
Peptidei98 – 12831Glucagon-like peptide 1(7-37)By similarityPRO_0000011279Add
BLAST
Peptidei98 – 12730Glucagon-like peptide 1(7-36)By similarityPRO_0000011280Add
BLAST
Propeptidei131 – 14515By similarityPRO_0000011281Add
BLAST
Peptidei146 – 17833Glucagon-like peptide 2By similarityPRO_0000011282Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei127 – 1271Arginine amideBy similarity

Post-translational modificationi

Proglucagon is post-translationally processed in a tissue-specific manner in pancreatic A cells and intestinal L cells. In pancreatic A cells, the major bioactive hormone is glucagon cleaved by PCSK2/PC2. In the intestinal L cells PCSK1/PC1 liberates GLP-1, GLP-2, glicentin and oxyntomodulin. GLP-1 is further N-terminally truncated by post-translational processing in the intestinal L cells resulting in GLP-1(7-37) GLP-1-(7-36)amide. The C-terminal amidation is neither important for the metabolism of GLP-1 nor for its effects on the endocrine pancreas (By similarity).By similarity

Keywords - PTMi

Amidation, Cleavage on pair of basic residues

Proteomic databases

MaxQBiP55095.
PaxDbiP55095.
PRIDEiP55095.

PTM databases

PhosphoSiteiP55095.

Miscellaneous databases

PMAP-CutDBP55095.

Expressioni

Tissue specificityi

Glucagon is secreted in the A cells of the islets of Langerhans. GLP-1, GLP-2, oxyntomodulin and glicentin are secreted from enteroendocrine cells throughout the gastrointestinal tract. GLP-1 and GLP-2 are also secreted in selected neurons in the brain.

Inductioni

Glucagon release is stimulated by hypoglycemia and inhibited by hyperglycemia, insulin, and somatostatin. GLP-1 and GLP-2 are induced in response to nutrient ingestion (By similarity).By similarity

Gene expression databases

BgeeiP55095.
CleanExiMM_GCG.
ExpressionAtlasiP55095. baseline and differential.
GenevestigatoriP55095.

Structurei

3D structure databases

ProteinModelPortaliP55095.
SMRiP55095. Positions 53-81, 98-127, 146-178.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glucagon family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG42743.
GeneTreeiENSGT00390000005372.
HOGENOMiHOG000231876.
HOVERGENiHBG003010.
InParanoidiP55095.
KOiK05259.
OMAiKMKSIYF.
OrthoDBiEOG7WMCM1.
PhylomeDBiP55095.
TreeFamiTF332333.

Family and domain databases

InterProiIPR015550. Glucagon-like.
IPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PANTHERiPTHR11418. PTHR11418. 1 hit.
PfamiPF00123. Hormone_2. 3 hits.
[Graphical view]
PRINTSiPR00275. GLUCAGON.
SMARTiSM00070. GLUCA. 3 hits.
[Graphical view]
PROSITEiPS00260. GLUCAGON. 4 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P55095-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MKTIYFVAGL LIMLVQGSWQ HALQDTEENP RSFPASQTEA HEDPDEMNED
60 70 80 90 100
KRHSQGTFTS DYSKYLDSRR AQDFVQWLMN TKRNRNNIAK RHDEFERHAE
110 120 130 140 150
GTFTSDVSSY LEGQAAKEFI AWLVKGRGRR DFPEEVAIAE ELGRRHADGS
160 170 180
FSDEMSTILD NLATRDFINW LIQTKITDKK
Length:180
Mass (Da):20,906
Last modified:October 1, 1996 - v1
Checksum:i595AA6DD9A589950
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46845 mRNA. Translation: CAA86902.1.
AF276754 mRNA. Translation: AAK96898.1.
AK007911 mRNA. Translation: BAB25344.1.
AK148544 mRNA. Translation: BAE28612.1.
BC012975 mRNA. Translation: AAH12975.1.
CCDSiCCDS16066.1.
PIRiA57294.
RefSeqiNP_032126.1. NM_008100.3.
UniGeneiMm.45494.

Genome annotation databases

EnsembliENSMUST00000102733; ENSMUSP00000099794; ENSMUSG00000000394.
GeneIDi14526.
KEGGimmu:14526.
UCSCiuc008jvj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46845 mRNA. Translation: CAA86902.1.
AF276754 mRNA. Translation: AAK96898.1.
AK007911 mRNA. Translation: BAB25344.1.
AK148544 mRNA. Translation: BAE28612.1.
BC012975 mRNA. Translation: AAH12975.1.
CCDSiCCDS16066.1.
PIRiA57294.
RefSeqiNP_032126.1. NM_008100.3.
UniGeneiMm.45494.

3D structure databases

ProteinModelPortaliP55095.
SMRiP55095. Positions 53-81, 98-127, 146-178.
ModBaseiSearch...
MobiDBiSearch...

PTM databases

PhosphoSiteiP55095.

Proteomic databases

MaxQBiP55095.
PaxDbiP55095.
PRIDEiP55095.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000102733; ENSMUSP00000099794; ENSMUSG00000000394.
GeneIDi14526.
KEGGimmu:14526.
UCSCiuc008jvj.1. mouse.

Organism-specific databases

CTDi2641.
MGIiMGI:95674. Gcg.

Phylogenomic databases

eggNOGiNOG42743.
GeneTreeiENSGT00390000005372.
HOGENOMiHOG000231876.
HOVERGENiHBG003010.
InParanoidiP55095.
KOiK05259.
OMAiKMKSIYF.
OrthoDBiEOG7WMCM1.
PhylomeDBiP55095.
TreeFamiTF332333.

Enzyme and pathway databases

ReactomeiREACT_207651. G alpha (q) signalling events.
REACT_210399. Glucagon signaling in metabolic regulation.
REACT_231304. Glucagon-type ligand receptors.
REACT_233293. Synthesis, secretion, and deacylation of Ghrelin.
REACT_242871. G alpha (s) signalling events.
REACT_248547. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
REACT_259776. Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).

Miscellaneous databases

ChiTaRSiGcg. mouse.
NextBioi286168.
PMAP-CutDBP55095.
PROiP55095.
SOURCEiSearch...

Gene expression databases

BgeeiP55095.
CleanExiMM_GCG.
ExpressionAtlasiP55095. baseline and differential.
GenevestigatoriP55095.

Family and domain databases

InterProiIPR015550. Glucagon-like.
IPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PANTHERiPTHR11418. PTHR11418. 1 hit.
PfamiPF00123. Hormone_2. 3 hits.
[Graphical view]
PRINTSiPR00275. GLUCAGON.
SMARTiSM00070. GLUCA. 3 hits.
[Graphical view]
PROSITEiPS00260. GLUCAGON. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Processing of mouse proglucagon by recombinant prohormone convertase 1 and immunopurified prohormone convertase 2 in vitro."
    Rothenberg M.E., Eilertson C.D., Klein K., Zhou Y., Linberg I., McDonald J.K., Mackin R.B., Noe B.D.
    J. Biol. Chem. 270:10136-10146(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Pancreatic islet.
  2. "Mouse glucagon full length cDNA."
    Shamsadin R., Knepel W.
    Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Pancreas.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Colon.
  5. "GLP-1 and GLP-1(7-36) amide: influences on basal and stimulated insulin and glucagon secretion in the mouse."
    Fridolf T., Bottcher G., Sundler F., Ahren B.
    Pancreas 6:208-215(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION OF GLP-1 AND GLP-1(7-36) AMIDE.
  6. "Role of the prohormone convertase PC3 in the processing of proglucagon to glucagon-like peptide 1."
    Rouille Y., Kantengwa S., Irminger J.C., Halban P.A.
    J. Biol. Chem. 272:32810-32816(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING BY PCSK1.
  7. "Severe defect in proglucagon processing in islet A-cells of prohormone convertase 2 null mice."
    Furuta M., Zhou A., Webb G., Carroll R., Ravazzola M., Orci L., Steiner D.F.
    J. Biol. Chem. 276:27197-27202(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEOLYTIC PROCESSING BY PCSK2.
  8. "Glucagon-like peptides: regulators of cell proliferation, differentiation, and apoptosis."
    Drucker D.J.
    Mol. Endocrinol. 17:161-171(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  9. "Glucagon and regulation of glucose metabolism."
    Jiang G., Zhang B.B.
    Am. J. Physiol. 284:E671-E678(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  10. Cited for: REVIEW.
  11. Cited for: REVIEW.

Entry informationi

Entry nameiGLUC_MOUSE
AccessioniPrimary (citable) accession number: P55095
Secondary accession number(s): Q3UFE9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: February 4, 2015
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.