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Protein

Exendin-4

Gene
N/A
Organism
Heloderma suspectum (Gila monster)
Status
Reviewed-Annotation score: Annotation score: 3 out of 5-Experimental evidence at protein leveli

Functioni

Venom protein that mimics the incretin hormone glucagon-like peptide 1 (GLP-1). It stimulates insulin synthesis and secretion, protects against beta-cell apoptosis in response to different insults, and promotes beta-cell proliferation. It also promotes satiety, reduces food intake, reduces fat deposition, reduces body weight and inhibits gastric emptying. Interacts with GLP-1 receptor (GLP1R). Induces hypotension that is mediated by relaxation of cardiac smooth muscle.2 Publications

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor impairing toxin, Hypotensive agent, Toxin

Names & Taxonomyi

Protein namesi
Recommended name:
Exendin-4
Alternative name(s):
INN: Exenatide
OrganismiHeloderma suspectum (Gila monster)
Taxonomic identifieri8554 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiLepidosauriaSquamataBifurcataUnidentataEpisquamataToxicoferaAnguimorphaNeoanguimorphaHelodermatidaeHeloderma

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

Available under the name Byetta and Bydureon (extended-release exenatide) (Amylin Pharmaceuticals). Used for the treatment of type 2 diabetes. Enhances insulin secretion in response to elevated plasma glucose levels.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2323Sequence analysisAdd
BLAST
Propeptidei24 – 4522PRO_0000011421Add
BLAST
Peptidei48 – 8639Exendin-4PRO_0000011422Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei86 – 861Serine amide

Keywords - PTMi

Amidation, Cleavage on pair of basic residues

Expressioni

Tissue specificityi

Expressed by the venom gland.

Structurei

Secondary structure

1
87
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi57 – 7418Combined sources
Helixi77 – 793Combined sources
Beta strandi80 – 823Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JRJNMR-A48-86[»]
2MJ9NMR-A48-86[»]
2NAVNMR-A48-56[»]
2NAWNMR-A48-77[»]
3C59X-ray2.30B56-86[»]
3C5TX-ray2.10B56-86[»]
ProteinModelPortaliP26349.
SMRiP26349. Positions 48-86.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26349.

Family & Domainsi

Sequence similaritiesi

Belongs to the glucagon family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

HOVERGENiHBG081487.

Family and domain databases

InterProiIPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PfamiPF00123. Hormone_2. 1 hit.
[Graphical view]
SMARTiSM00070. GLUCA. 1 hit.
[Graphical view]
PROSITEiPS00260. GLUCAGON. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P26349-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKIILWLCVF GLFLATLFPI SWQMPVESGL SSEDSASSES FASKIKRHGE
60 70 80
GTFTSDLSKQ MEEEAVRLFI EWLKNGGPSS GAPPPSG
Length:87
Mass (Da):9,479
Last modified:July 15, 1998 - v2
Checksum:i656BA6E3D87454A2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti13 – 131F → G no nucleotide entry (PubMed:9545315).Curated

Mass spectrometryi

Molecular mass is 4186.02 Da from positions 48 - 86. Determined by MALDI. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77613 mRNA. Translation: AAB51130.1.
PIRiA42486. HWGH4G.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77613 mRNA. Translation: AAB51130.1.
PIRiA42486. HWGH4G.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JRJNMR-A48-86[»]
2MJ9NMR-A48-86[»]
2NAVNMR-A48-56[»]
2NAWNMR-A48-77[»]
3C59X-ray2.30B56-86[»]
3C5TX-ray2.10B56-86[»]
ProteinModelPortaliP26349.
SMRiP26349. Positions 48-86.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

HOVERGENiHBG081487.

Miscellaneous databases

EvolutionaryTraceiP26349.

Family and domain databases

InterProiIPR000532. Glucagon_GIP_secretin_VIP.
[Graphical view]
PfamiPF00123. Hormone_2. 1 hit.
[Graphical view]
SMARTiSM00070. GLUCA. 1 hit.
[Graphical view]
PROSITEiPS00260. GLUCAGON. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard."
    Chen Y.E., Drucker D.J.
    J. Biol. Chem. 272:4108-4115(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Molecular cloning of the helodermin and exendin-4 cDNAs in the lizard. Relationship to vasoactive intestinal polypeptide/pituitary adenylate cyclase activating polypeptide and glucagon-like peptide 1 and evidence against the existence of mammalian homologues."
    Pohl M., Wank S.A.
    J. Biol. Chem. 273:9778-9784(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Isolation and cloning of exendin precursor cDNAs from single samples of venom from the Mexican beaded lizard (Heloderma horridum) and the Gila monster (Heloderma suspectum)."
    Chen T., Kwok H., Ivanyi C., Shaw C.
    Toxicon 47:288-295(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 48-86, MASS SPECTROMETRY.
    Tissue: Venom.
  4. "Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas."
    Eng J., Kleinman W.A., Singh L., Singh G., Raufman J.-P.
    J. Biol. Chem. 267:7402-7405(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 48-86.
    Tissue: Venom.
  5. "Cloning and functional expression of the human islet GLP-1 receptor. Demonstration that exendin-4 is an agonist and exendin-(9-39) an antagonist of the receptor."
    Thorens B., Porret A., Buehler L., Deng S., Morel P., Widmann C.
    Diabetes 42:1678-1682(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Novel venom proteins produced by differential domain-expression strategies in beaded lizards and gila monsters (genus Heloderma)."
    Fry B.G., Roelants K., Winter K., Hodgson W.C., Griesman L., Kwok H.F., Scanlon D., Karas J., Shaw C., Wong L., Norman J.A.
    Mol. Biol. Evol. 27:395-407(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SYNTHESIS OF 48-86, FUNCTION.
  7. "The development of Byetta (exenatide) from the venom of the Gila monster as an anti-diabetic agent."
    Furman B.L.
    Toxicon 59:464-471(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW, PHARMACEUTICAL.
  8. "Exenatide extended-release: a once weekly treatment for patients with type 2 diabetes."
    Mann K.V., Raskin P.
    Diabetes Metab. Syndr. Obes. 7:229-239(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW, PHARMACEUTICAL.
  9. "Exendin-4 and glucagon-like-peptide-1: NMR structural comparisons in the solution and micelle-associated states."
    Neidigh J.W., Fesinmeyer R.M., Prickett K.S., Andersen N.H.
    Biochemistry 40:13188-13200(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 48-86.

Entry informationi

Entry nameiEXE4_HELSU
AccessioniPrimary (citable) accession number: P26349
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: July 15, 1998
Last modified: July 6, 2016
This is version 84 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
Annotation programAnimal Toxin Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Pharmaceutical

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.