GLUC_HELSU
ID GLUC_HELSU Reviewed; 204 AA.
AC O12956; O12955;
DT 15-NOV-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Pro-glucagon;
DE Contains:
DE RecName: Full=Glicentin-related polypeptide;
DE Short=GRPP;
DE Contains:
DE RecName: Full=Glucagon;
DE Contains:
DE RecName: Full=Glucagon-like peptide 1;
DE Short=GLP-1;
DE Contains:
DE RecName: Full=Glucagon-like peptide 1(7-37);
DE Short=GLP-1(7-37);
DE Contains:
DE RecName: Full=Glucagon-like peptide 1(7-36);
DE Short=GLP-1(7-36);
DE Contains:
DE RecName: Full=Glucagon-like peptide 2;
DE Short=GLP-2;
DE Flags: Precursor;
GN Name=GCG;
OS Heloderma suspectum (Gila monster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Anguimorpha; Neoanguimorpha; Helodermatidae; Heloderma.
OX NCBI_TaxID=8554;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LPI AND LPII), AND TISSUE SPECIFICITY.
RC TISSUE=Intestine, and Pancreas;
RX PubMed=9020121; DOI=10.1074/jbc.272.7.4108;
RA Chen Y.E., Drucker D.J.;
RT "Tissue-specific expression of unique mRNAs that encode proglucagon-derived
RT peptides or exendin 4 in the lizard.";
RL J. Biol. Chem. 272:4108-4115(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 65-81 AND 110-132.
RC TISSUE=Lung;
RX PubMed=9545315; DOI=10.1074/jbc.273.16.9778;
RA Pohl M., Wank S.A.;
RT "Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard.
RT Relationship to vasoactive intestinal polypeptide/pituitary adenylate
RT cyclase activating polypeptide and glucagon-like peptide 1 and evidence
RT against the existence of mammalian homologues.";
RL J. Biol. Chem. 273:9778-9784(1998).
RN [3]
RP REVIEW.
RX PubMed=12554744; DOI=10.1210/me.2002-0306;
RA Drucker D.J.;
RT "Glucagon-like peptides: regulators of cell proliferation, differentiation,
RT and apoptosis.";
RL Mol. Endocrinol. 17:161-171(2003).
RN [4]
RP REVIEW.
RX PubMed=12626323; DOI=10.1152/ajpendo.00492.2002;
RA Jiang G., Zhang B.B.;
RT "Glucagon and regulation of glucose metabolism.";
RL Am. J. Physiol. 284:E671-E678(2003).
RN [5]
RP REVIEW.
RX PubMed=10322410; DOI=10.1016/s1043-2760(98)00136-2;
RA Drucker D.J.;
RT "Glucagon-like peptide 2.";
RL Trends Endocrinol. Metab. 10:153-156(1999).
RN [6]
RP REVIEW.
RX PubMed=10605628; DOI=10.1210/edrv.20.6.0385;
RA Kieffer T.J., Habener J.F.;
RT "The glucagon-like peptides.";
RL Endocr. Rev. 20:876-913(1999).
CC -!- FUNCTION: [Glucagon]: Plays a key role in glucose metabolism and
CC homeostasis. Regulates blood glucose by increasing gluconeogenesis and
CC decreasing glycolysis. {ECO:0000250|UniProtKB:P01275}.
CC -!- FUNCTION: [Glucagon-like peptide 1]: Potent stimulator of glucose-
CC dependent insulin release. Plays important roles on gastric motility
CC and the suppression of plasma glucagon levels.
CC {ECO:0000250|UniProtKB:P01275}.
CC -!- FUNCTION: [Glucagon-like peptide 2]: Stimulates intestinal growth and
CC up-regulates villus height in the small intestine, concomitant with
CC increased crypt cell proliferation and decreased enterocyte apoptosis.
CC {ECO:0000250|UniProtKB:P01275}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=LPII;
CC IsoId=O12956-1; Sequence=Displayed;
CC Name=LPI;
CC IsoId=O12956-2; Sequence=VSP_001756, VSP_001757;
CC -!- TISSUE SPECIFICITY: Isoform LPII is expressed in both pancreas and
CC intestine. Expression of isoform LPI is restricted to the pancreas.
CC Neither isoform is detected in salivary glands.
CC {ECO:0000269|PubMed:9020121}.
CC -!- INDUCTION: Produced in the A cells of the islets of Langerhans in
CC response to a drop in blood sugar concentration.
CC -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
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DR EMBL; U77612; AAB51129.1; -; mRNA.
DR EMBL; U77611; AAB51128.1; -; mRNA.
DR AlphaFoldDB; O12956; -.
DR SMR; O12956; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005179; F:hormone activity; IEA:UniProtKB-KW.
DR InterPro; IPR015550; Glucagon.
DR InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR PANTHER; PTHR11418; PTHR11418; 1.
DR Pfam; PF00123; Hormone_2; 3.
DR PRINTS; PR00275; GLUCAGON.
DR SMART; SM00070; GLUCA; 3.
DR PROSITE; PS00260; GLUCAGON; 2.
PE 2: Evidence at transcript level;
KW Alternative splicing; Amidation; Cleavage on pair of basic residues;
KW Hormone; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PEPTIDE 21..50
FT /note="Glicentin-related polypeptide"
FT /evidence="ECO:0000250|UniProtKB:P09686"
FT /id="PRO_0000011410"
FT PEPTIDE 53..81
FT /note="Glucagon"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011411"
FT PROPEP 84..109
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011412"
FT PEPTIDE 110..146
FT /note="Glucagon-like peptide 1"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011413"
FT PEPTIDE 116..146
FT /note="Glucagon-like peptide 1(7-37)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011414"
FT PEPTIDE 116..145
FT /note="Glucagon-like peptide 1(7-36)"
FT /evidence="ECO:0000250|UniProtKB:P01275"
FT /id="PRO_0000011415"
FT PROPEP 149..161
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011416"
FT PEPTIDE 164..196
FT /note="Glucagon-like peptide 2"
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011417"
FT PROPEP 197..204
FT /evidence="ECO:0000250|UniProtKB:P15438"
FT /id="PRO_0000011418"
FT SITE 52..53
FT /note="Cleavage; by PCSK2"
FT /evidence="ECO:0000250"
FT SITE 83..84
FT /note="Cleavage; by PCSK1 and PCSK2"
FT /evidence="ECO:0000250"
FT SITE 115..116
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT SITE 148..149
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT SITE 163..164
FT /note="Cleavage; by PCSK1"
FT /evidence="ECO:0000250"
FT MOD_RES 145
FT /note="Arginine amide"
FT /evidence="ECO:0000250"
FT VAR_SEQ 149
FT /note="D -> E (in isoform LPI)"
FT /evidence="ECO:0000303|PubMed:9020121"
FT /id="VSP_001756"
FT VAR_SEQ 150..204
FT /note="Missing (in isoform LPI)"
FT /evidence="ECO:0000303|PubMed:9020121"
FT /id="VSP_001757"
FT CONFLICT 120
FT /note="R -> T (in Ref. 2; no nucleotide entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 204 AA; 23553 MW; B132E3FE46873E72 CRC64;
MTSMYFVAGL LLMIVQGSWQ SPLQETEEKS RSFKASQAEP LDDSRQLNEV KRHSQGTFTS
DYSKYLDTRR AQDFVQWLMN TKRSGQQGVE EREKENLLDQ LSSNGLARHH AEYERHADGR
YTSDISSYLE GQAAKEFIAW LVNGRGRRDF LEEAGTADDI GRRHADGTFT SDYNQLLDDI
ATQEFLKWLI NQKVTQRDLL GEYQ
