P43220 · GLP1R_HUMAN
- ProteinGlucagon-like peptide 1 receptor
- GeneGLP1R
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids463 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
G-protein coupled receptor for glucagon-like peptide 1 (GLP-1) (PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449, PubMed:7517895, PubMed:8216285, PubMed:8405712).
Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels (PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449, PubMed:7517895, PubMed:8216285, PubMed:8405712).
Plays a role in regulating insulin secretion in response to GLP-1 (By similarity).
Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels (PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449, PubMed:7517895, PubMed:8216285, PubMed:8405712).
Plays a role in regulating insulin secretion in response to GLP-1 (By similarity).
Miscellaneous
Selective recognition of glucagon-like peptide over glucagon is determined by residues located at the C-terminal end of the glucagon-like peptide.
Activity regulation
The allosteric modulators NNC0640, PF-06372222 and MK-0893 inhibit the increase of intracellular cAMP levels in response to GLP-1.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 121 | Interaction with the endogenous ligand GLP-1 | ||||
Sequence: R | ||||||
Site | 128 | Interaction with the endogenous ligand GLP-1 | ||||
Sequence: E |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Cellular Component | plasma membrane | |
Molecular Function | glucagon receptor activity | |
Molecular Function | glucagon-like peptide 1 receptor activity | |
Molecular Function | peptide hormone binding | |
Molecular Function | transmembrane signaling receptor activity | |
Biological Process | activation of adenylate cyclase activity | |
Biological Process | adenylate cyclase-activating G protein-coupled receptor signaling pathway | |
Biological Process | cAMP-mediated signaling | |
Biological Process | cell surface receptor signaling pathway | |
Biological Process | hormone secretion | |
Biological Process | learning or memory | |
Biological Process | negative regulation of blood pressure | |
Biological Process | positive regulation of blood pressure | |
Biological Process | positive regulation of cytosolic calcium ion concentration | |
Biological Process | post-translational protein targeting to membrane, translocation | |
Biological Process | regulation of heart contraction | |
Biological Process | response to psychosocial stress |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGlucagon-like peptide 1 receptor
- Short namesGLP-1 receptor; GLP-1-R; GLP-1R
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP43220
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 24-139 | Extracellular | ||||
Sequence: RPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEE | ||||||
Transmembrane | 140-164 | Helical; Name=1 | ||||
Sequence: QLLFLYIIYTVGYALSFSALVIASA | ||||||
Topological domain | 165-175 | Cytoplasmic | ||||
Sequence: ILLGFRHLHCT | ||||||
Transmembrane | 176-201 | Helical; Name=2 | ||||
Sequence: RNYIHLNLFASFILRALSVFIKDAAL | ||||||
Topological domain | 202-227 | Extracellular | ||||
Sequence: KWMYSTAAQQHQWDGLLSYQDSLSCR | ||||||
Transmembrane | 228-251 | Helical; Name=3 | ||||
Sequence: LVFLLMQYCVAANYYWLLVEGVYL | ||||||
Topological domain | 252-265 | Cytoplasmic | ||||
Sequence: YTLLAFSVLSEQWI | ||||||
Transmembrane | 266-290 | Helical; Name=4 | ||||
Sequence: FRLYVSIGWGVPLLFVVPWGIVKYL | ||||||
Topological domain | 291-305 | Extracellular | ||||
Sequence: YEDEGCWTRNSNMNY | ||||||
Transmembrane | 306-328 | Helical; Name=5 | ||||
Sequence: WLIIRLPILFAIGVNFLIFVRVI | ||||||
Topological domain | 329-348 | Cytoplasmic | ||||
Sequence: CIVVSKLKANLMCKTDIKCR | ||||||
Transmembrane | 349-370 | Helical; Name=6 | ||||
Sequence: LAKSTLTLIPLLGTHEVIFAFV | ||||||
Topological domain | 371-383 | Extracellular | ||||
Sequence: MDEHARGTLRFIK | ||||||
Transmembrane | 384-404 | Helical; Name=7 | ||||
Sequence: LFTELSFTSFQGLMVAILYCF | ||||||
Topological domain | 405-463 | Cytoplasmic | ||||
Sequence: VNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSLSSGATAGSSMYTATCQASCS |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_018924 | 7 | in dbSNP:rs10305420 | |||
Sequence: P → L | ||||||
Natural variant | VAR_018925 | 20 | in dbSNP:rs10305421 | |||
Sequence: R → K | ||||||
Mutagenesis | 32 | No effect on stimulation of cAMP accumulation and on GLP-1 binding. | ||||
Sequence: L → A | ||||||
Natural variant | VAR_018926 | 44 | in dbSNP:rs2295006 | |||
Sequence: R → H | ||||||
Mutagenesis | 69 | Abolishes stimulation of cAMP accumulation in response to GLP-1. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 88 | Abolishes stimulation of cAMP accumulation in response to GLP-1. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 89 | Abolishes stimulation of cAMP accumulation in response to GLP-1. | ||||
Sequence: L → A | ||||||
Mutagenesis | 90 | Strongly decreased stimulation of cAMP accumulation in response to GLP-1. | ||||
Sequence: P → A | ||||||
Mutagenesis | 121 | Strongly decreased stimulation of cAMP accumulation in response to GLP-1. | ||||
Sequence: R → A | ||||||
Mutagenesis | 127 | No effect on stimulation of cAMP accumulation in response to GLP-1. | ||||
Sequence: E → A | ||||||
Mutagenesis | 128 | Slightly decreases stimulation of cAMP accumulation in response to GLP-1. | ||||
Sequence: E → A | ||||||
Mutagenesis | 128 | No effect on stimulation of cAMP accumulation in response to GLP-1. | ||||
Sequence: E → Q | ||||||
Natural variant | VAR_018927 | 131 | in dbSNP:rs3765467 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_018928 | 168 | in dbSNP:rs6923761 | |||
Sequence: G → S | ||||||
Mutagenesis | 176 | Decreases sensitivity to GLP-1. | ||||
Sequence: R → Q | ||||||
Natural variant | VAR_015098 | 260 | in dbSNP:rs1042044 | |||
Sequence: L → F | ||||||
Natural variant | VAR_018929 | 316 | in dbSNP:rs10305492 | |||
Sequence: A → T | ||||||
Mutagenesis | 317 | Causes the formation of an artifactual disulfide bond that abolishes signaling in response to GLP-1 binding; when associated with C-361. | ||||
Sequence: I → C | ||||||
Natural variant | VAR_018930 | 333 | in dbSNP:rs10305493 | |||
Sequence: S → C | ||||||
Mutagenesis | 352 | Abolishes inhibition by negative allosteric modulators. | ||||
Sequence: S → A | ||||||
Mutagenesis | 355 | Abolishes inhibition by the negative allosteric modulators NNC0640 and PF-06372222, but does not abolish inhibition by MK-0893. | ||||
Sequence: T → A | ||||||
Mutagenesis | 361 | Causes the formation of an artifactual disulfide bond that abolishes signaling in response to GLP-1 binding; when associated with C-317. | ||||
Sequence: G → C | ||||||
Natural variant | VAR_018931 | 421 | in dbSNP:rs10305510 | |||
Sequence: R → Q |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 484 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-23 | |||||
Sequence: MAGAPGPLRLALLLLGMVGRAGP | ||||||
Chain | PRO_0000012835 | 24-463 | Glucagon-like peptide 1 receptor | |||
Sequence: RPQGATVSLWETVQKWREYRRQCQRSLTEDPPPATDLFCNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSECEESKRGERSSPEEQLLFLYIIYTVGYALSFSALVIASAILLGFRHLHCTRNYIHLNLFASFILRALSVFIKDAALKWMYSTAAQQHQWDGLLSYQDSLSCRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQWIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGCWTRNSNMNYWLIIRLPILFAIGVNFLIFVRVICIVVSKLKANLMCKTDIKCRLAKSTLTLIPLLGTHEVIFAFVMDEHARGTLRFIKLFTELSFTSFQGLMVAILYCFVNNEVQLEFRKSWERWRLEHLHIQRDSSMKPLKCPTSSLSSGATAGSSMYTATCQASCS | ||||||
Disulfide bond | 46↔71 | |||||
Sequence: CQRSLTEDPPPATDLFCNRTFDEYAC | ||||||
Disulfide bond | 62↔104 | |||||
Sequence: CNRTFDEYACWPDGEPGSFVNVSCPWYLPWASSVPQGHVYRFC | ||||||
Glycosylation | 63 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 82 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 85↔126 | |||||
Sequence: CPWYLPWASSVPQGHVYRFCTAEGLWLQKDNSSLPWRDLSEC | ||||||
Glycosylation | 115 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 226↔296 | |||||
Sequence: CRLVFLLMQYCVAANYYWLLVEGVYLYTLLAFSVLSEQWIFRLYVSIGWGVPLLFVVPWGIVKYLYEDEGC | ||||||
Modified residue | 341 | ADP-ribosylcysteine | ||||
Sequence: C | ||||||
Modified residue | 348 | ADP-ribosylarginine | ||||
Sequence: R |
Post-translational modification
N-glycosylation enhances cell surface expression and lengthens receptor half-life by preventing degradation in the ER.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
May form homodimers and heterodimers with GIPR.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P43220 | CYSRT1 A8MQ03 | 3 | EBI-7466542, EBI-3867333 | |
BINARY | P43220 | KRTAP1-1 Q07627 | 3 | EBI-7466542, EBI-11959885 | |
BINARY | P43220 | KRTAP1-3 Q8IUG1 | 3 | EBI-7466542, EBI-11749135 | |
BINARY | P43220 | KRTAP10-7 P60409 | 3 | EBI-7466542, EBI-10172290 | |
BINARY | P43220 | KRTAP10-8 P60410 | 3 | EBI-7466542, EBI-10171774 | |
BINARY | P43220 | KRTAP10-9 P60411 | 3 | EBI-7466542, EBI-10172052 | |
BINARY | P43220 | KRTAP17-1 Q9BYP8 | 3 | EBI-7466542, EBI-11988175 | |
BINARY | P43220 | KRTAP5-9 P26371 | 3 | EBI-7466542, EBI-3958099 | |
BINARY | P43220 | NOTCH2NLA Q7Z3S9 | 3 | EBI-7466542, EBI-945833 | |
BINARY | P43220 | NOTCH2NLC P0DPK4 | 3 | EBI-7466542, EBI-22310682 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 352-355 | Important for allosteric inhibitor binding | ||||
Sequence: STLT |
Sequence similarities
Belongs to the G-protein coupled receptor 2 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Protein family/group databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length463
- Mass (Da)53,026
- Last updated2010-11-02 v2
- ChecksumEE7C0EAE29931F5D
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 12 | in Ref. 1; AAA03614, 4; no nucleotide entry and 10; AAB64013 | ||||
Sequence: L → V | ||||||
Sequence conflict | 136-137 | in Ref. 1; AAA03614 | ||||
Sequence: SP → WG | ||||||
Sequence conflict | 137 | in Ref. 4; no nucleotide entry | ||||
Sequence: P → R | ||||||
Sequence conflict | 151 | in Ref. 1; AAA03614 | ||||
Sequence: G → A | ||||||
Sequence conflict | 221 | in Ref. 5; AAA63787 | ||||
Sequence: Q → L | ||||||
Sequence conflict | 289 | in Ref. 1; AAA03614 | ||||
Sequence: Y → I | ||||||
Sequence conflict | 316 | in Ref. 2; AAA62471/AAC50050 | ||||
Sequence: A → G |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U01104 EMBL· GenBank· DDBJ | AAA03614.1 EMBL· GenBank· DDBJ | mRNA | ||
U01157 EMBL· GenBank· DDBJ | AAA62471.1 EMBL· GenBank· DDBJ | mRNA | ||
U01156 EMBL· GenBank· DDBJ | AAC50050.1 EMBL· GenBank· DDBJ | mRNA | ||
L23503 EMBL· GenBank· DDBJ | AAA17021.1 EMBL· GenBank· DDBJ | mRNA | ||
U10037 EMBL· GenBank· DDBJ | AAA63787.1 EMBL· GenBank· DDBJ | mRNA | ||
AB065685 EMBL· GenBank· DDBJ | BAC05908.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY439112 EMBL· GenBank· DDBJ | AAR05444.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL035690 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC112126 EMBL· GenBank· DDBJ | AAI12127.1 EMBL· GenBank· DDBJ | mRNA | ||
BC113493 EMBL· GenBank· DDBJ | AAI13494.1 EMBL· GenBank· DDBJ | mRNA | ||
U66062 EMBL· GenBank· DDBJ | AAB64013.1 EMBL· GenBank· DDBJ | Genomic DNA |