ID   EXE1_HELSU              Reviewed;          38 AA.
AC   P04203;
DT   20-MAR-1987, integrated into UniProtKB/Swiss-Prot.
DT   20-MAR-1987, sequence version 1.
DT   25-MAY-2022, entry version 73.
DE   RecName: Full=Exendin-1;
DE   AltName: Full=Helospectin I;
DE   AltName: Full=Helospectin-1;
DE   AltName: Full=VIP-like 1;
DE   Contains:
DE     RecName: Full=Exendin-1b;
DE     AltName: Full=Helospectin II;
DE     AltName: Full=Helospectin-2;
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   PROTEIN SEQUENCE.
RC   TISSUE=Venom;
RX   PubMed=6207171; DOI=10.1016/s0021-9258(20)71275-5;
RA   Parker D.S., Raufman J.-P., O'Donohue T.L., Bledsoe M., Yoshida H.,
RA   Pisano J.J.;
RT   "Amino acid sequences of helospectins, new members of the glucagon
RT   superfamily, found in Gila monster venom.";
RL   J. Biol. Chem. 259:11751-11755(1984).
RN   [2]
RP   PROTEIN SEQUENCE, FUNCTION, GLYCOSYLATION AT SER-32, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RC   TISSUE=Venom;
RX   PubMed=10880980; DOI=10.1046/j.1432-1327.2000.01506.x;
RA   Vandermeers-Piret M.C., Vandermeers A., Gourlet P., Ali M.H.,
RA   Waelbroeck M., Robberecht P.;
RT   "Evidence that the lizard helospectin peptides are O-glycosylated.";
RL   Eur. J. Biochem. 267:4556-4560(2000).
RN   [3]
RP   FUNCTION.
RX   PubMed=9928018; DOI=10.1111/j.1749-6632.1998.tb11184.x;
RA   Gourlet P., Vandermeers A., Van Rampelbergh J., De Neef P., Cnudde J.,
RA   Waelbroeck M., Robberecht P.;
RT   "Analogues of VIP, helodermin, and PACAP discriminate between rat and human
RT   VIP1 and VIP2 receptors.";
RL   Ann. N. Y. Acad. Sci. 865:247-252(1998).
RN   [4]
RP   FUNCTION.
RX   PubMed=15003357; DOI=10.1016/j.peptides.2003.11.010;
RA   Tsueshita T., Onyukusel H., Sethi V., Gandhi S., Rubinstein I.;
RT   "Helospectin I and II evoke vasodilation in the intact peripheral
RT   microcirculation.";
RL   Peptides 25:65-69(2004).
RN   [5]
RP   SYNTHESIS, 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).
CC   -!- FUNCTION: O-linked and free exendin-1 and exendin-1b have vasoactive
CC       intestinal peptide(VIP)/secretin-like biological activities. They
CC       interact with rat and human VIP receptors 1 (VIPR1) and 2 (VIPR2), with
CC       the highest affinity for the human VIPR2. They induce hypotension that
CC       is mediated by relaxation of cardiac smooth muscle.
CC       {ECO:0000269|PubMed:10880980, ECO:0000269|PubMed:15003357,
CC       ECO:0000269|PubMed:19837656, ECO:0000269|PubMed:9928018}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC   -!- PTM: Thr-32 is glycosylated by N-acetylgalactosamine and a hexose,
CC       probably Glu-GalNAc-Thr, a mucin type O-glycosylation which may affect
CC       the biological stability of exendin-1 and exendin-1b.
CC       {ECO:0000269|PubMed:10880980}.
CC   -!- SIMILARITY: Belongs to the glucagon family. {ECO:0000305}.
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DR   AlphaFoldDB; P04203; -.
DR   SMR; P04203; -.
DR   iPTMnet; P04203; -.
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   Direct protein sequencing; G-protein coupled receptor impairing toxin;
KW   Glycoprotein; Hypotensive agent; Secreted; Toxin.
FT   CHAIN           1..38
FT                   /note="Exendin-1"
FT                   /id="PRO_0000011419"
FT   CHAIN           1..37
FT                   /note="Exendin-1b"
FT                   /id="PRO_0000011420"
FT   CARBOHYD        32
FT                   /note="O-linked (GalNAc...) serine; in Exendin-1 and
FT                   Exendin-1b"
FT                   /evidence="ECO:0000269|PubMed:10880980"
SQ   SEQUENCE   38 AA;  4096 MW;  54275BCFC368314A CRC64;
     HSDATFTAEY SKLLAKLALQ KYLESILGSS TSPRPPSS