ID   EXE3_HELHO              Reviewed;          87 AA.
AC   P20394; Q7SZU6;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   09-JAN-2007, sequence version 2.
DT   25-MAY-2022, entry version 74.
DE   RecName: Full=Exendin-3;
DE   AltName: Full=Glucagon-like 3;
DE   Flags: Precursor;
OS   Heloderma horridum horridum (Mexican beaded lizard).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC   Anguimorpha; Neoanguimorpha; Helodermatidae; Heloderma.
OX   NCBI_TaxID=8552;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 48-86, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=16386282; DOI=10.1016/j.toxicon.2005.11.004;
RA   Chen T., Kwok H., Ivanyi C., Shaw C.;
RT   "Isolation and cloning of exendin precursor cDNAs from single samples of
RT   venom from the Mexican beaded lizard (Heloderma horridum) and the Gila
RT   monster (Heloderma suspectum).";
RL   Toxicon 47:288-295(2006).
RN   [2]
RP   PROTEIN SEQUENCE OF 48-86, AND AMIDATION AT SER-86.
RC   TISSUE=Venom;
RX   PubMed=1700785; DOI=10.1016/s0021-9258(17)30498-2;
RA   Eng J., Andrew P.C., Kleinman W.A., Singh L., Raufman J.-P.;
RT   "Purification and structure of exendin-3, a new pancreatic secretagogue
RT   isolated from Heloderma horridum venom.";
RL   J. Biol. Chem. 265:20259-20262(1990).
RN   [3]
RP   FUNCTION.
RX   PubMed=1704369; DOI=10.1016/s0021-9258(18)49932-2;
RA   Raufman J.P., Singh L., Eng J.;
RT   "Exendin-3, a novel peptide from Heloderma horridum venom, interacts with
RT   vasoactive intestinal peptide receptors and a newly described receptor on
RT   dispersed acini from guinea pig pancreas. Description of exendin-3(9-39)
RT   amide, a specific exendin receptor antagonist.";
RL   J. Biol. Chem. 266:2897-2902(1991).
RN   [4]
RP   SYNTHESIS OF 48-86, AND FUNCTION.
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   [5]
RP   BIOTECHNOLOGY.
RX   PubMed=20111963; DOI=10.1007/s00259-009-1363-y;
RA   Brom M., Oyen W.J., Joosten L., Gotthardt M., Boerman O.C.;
RT   "68Ga-labelled exendin-3, a new agent for the detection of insulinomas with
RT   PET.";
RL   Eur. J. Nucl. Med. Mol. Imaging 37:1345-1355(2010).
CC   -!- FUNCTION: Stimulates vasoactive intestinal peptide (VIP) receptors in
CC       high concentrations (>100 nM), resulting in both an increase in cAMP
CC       and amylase secretion from pancreatic acini, although at low
CC       concentrations (between 0.3 and 3 nM) it increases cAMP without
CC       stimulating amylase release. Stimulates the GLP-1 receptor (GLP1R).
CC       Induces hypotension that is mediated by relaxation of cardiac smooth
CC       muscle. {ECO:0000269|PubMed:1704369, ECO:0000269|PubMed:19837656}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- MASS SPECTROMETRY: Mass=4203.2; Method=MALDI;
CC       Evidence={ECO:0000269|PubMed:16386282};
CC   -!- BIOTECHNOLOGY: [Lys(40)((68)Ga-DOTA)]exendin-3 is a promising tracer to
CC       visualize insulinomas (neuroendocrine tumors derived from pancreatic
CC       beta-cells in which GLP1R is expressed at >90%) with PET imaging.
CC       {ECO:0000269|PubMed:20111963}.
CC   -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
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DR   EMBL; AJ580309; CAE30483.1; -; mRNA.
DR   PIR; A23674; HWGH3Z.
DR   AlphaFoldDB; P20394; -.
DR   SMR; P20394; -.
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   1: Evidence at protein level;
KW   Amidation; Cleavage on pair of basic residues; Direct protein sequencing;
KW   G-protein coupled receptor impairing toxin; Hypotensive agent; Secreted;
KW   Signal; Toxin.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   PROPEP          22..45
FT                   /id="PRO_0000271136"
FT   PEPTIDE         48..86
FT                   /note="Exendin-3"
FT                   /id="PRO_0000044748"
FT   MOD_RES         86
FT                   /note="Serine amide"
FT                   /evidence="ECO:0000269|PubMed:1700785"
SQ   SEQUENCE   87 AA;  9481 MW;  E66FA6F15AE5F127 CRC64;
     MKIILWLCVF GLFLATLFPV SWQMPVESGL SSEDSASSES FASKIKRHSD GTFTSDLSKQ
     MEEEAVRLFI EWLKNGGPSS GAPPPSG