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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...

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.