ID   EXE4_HELSC              Reviewed;          87 AA.
AC   C6EVG1;
DT   14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT   01-SEP-2009, sequence version 1.
DT   25-MAY-2022, entry version 33.
DE   RecName: Full=Exendin-4;
DE   Flags: Precursor;
OS   Heloderma suspectum cinctum (Banded Gila monster).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Anguimorpha; Neoanguimorpha; Helodermatidae; Heloderma.
OX   NCBI_TaxID=537493;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], SYNTHESIS OF 48-86, AND FUNCTION.
RC   TISSUE=Venom gland;
RX   PubMed=19837656; DOI=10.1093/molbev/msp251;
RA   Fry B.G., Roelants K., Winter K., Hodgson W.C., Griesman L., Kwok H.F.,
RA   Scanlon D., Karas J., Shaw C., Wong L., Norman J.A.;
RT   "Novel venom proteins produced by differential domain-expression strategies
RT   in beaded lizards and gila monsters (genus Heloderma).";
RL   Mol. Biol. Evol. 27:395-407(2010).
RN   [2]
RP   FUNCTION.
RX   PubMed=8405712; DOI=10.2337/diab.42.11.1678;
RA   Thorens B., Porret A., Buehler L., Deng S., Morel P., Widmann C.;
RT   "Cloning and functional expression of the human islet GLP-1 receptor.
RT   Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist
RT   of the receptor.";
RL   Diabetes 42:1678-1682(1993).
CC   -!- FUNCTION: Venom protein that mimics the incretin hormone glucagon-like
CC       peptide 1 (GLP-1). It stimulates insulin synthesis and secretion,
CC       protects against beta-cell apoptosis in response to different insults,
CC       and promotes beta-cell proliferation It also promotes satiety, reduces
CC       food intake, reduces fat deposition, reduces body weight and inhibits
CC       gastric emptying. Interacts with GLP-1 receptor (GLP1R). Induces
CC       hypotension that is mediated by relaxation of cardiac smooth muscle.
CC       {ECO:0000269|PubMed:19837656, ECO:0000269|PubMed:8405712}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; EU790959; ACE95061.1; -; mRNA.
DR   AlphaFoldDB; C6EVG1; -.
DR   SMR; C6EVG1; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005179; F:hormone activity; IEA:InterPro.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   GO; GO:0008217; P:regulation of blood pressure; IEA:UniProtKB-KW.
DR   InterPro; IPR000532; Glucagon_GIP_secretin_VIP.
DR   Pfam; PF00123; Hormone_2; 1.
DR   SMART; SM00070; GLUCA; 1.
DR   PROSITE; PS00260; GLUCAGON; 1.
PE   2: Evidence at transcript level;
KW   Amidation; Cleavage on pair of basic residues;
KW   G-protein coupled receptor impairing toxin; Hypotensive agent; Secreted;
KW   Signal; Toxin.
FT   SIGNAL          1..23
FT                   /evidence="ECO:0000255"
FT   PROPEP          24..45
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000414101"
FT   PEPTIDE         48..86
FT                   /note="Exendin-4"
FT                   /id="PRO_0000414102"
FT   MOD_RES         86
FT                   /note="Serine amide"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   87 AA;  9479 MW;  656BA6E3D87454A2 CRC64;
     MKIILWLCVF GLFLATLFPI SWQMPVESGL SSEDSASSES FASKIKRHGE GTFTSDLSKQ
     MEEEAVRLFI EWLKNGGPSS GAPPPSG