GPR35
entrez
2859
canonical
uniprot
Q9HC97
canonical
ensembl
ENSG00000178623
resolver
ensp
ENSP00000384263
resolver
ensp
ENSP00000411788
resolver
genesymbol
GPR35
resolver
hgnc
HGNC:4492
resolver
uniprot
A8K2J1
resolver
uniprot
B2RA17
resolver
uniprot
J3KR30
resolver
uniprot
O43495
resolver
uniprot
Q17R58
resolver
uniprot
Q4VBN5
resolver
uniprot
Q4ZFV2
resolver
uniprot
Q6FHI8
resolver
uniprot
Q86UH4
resolver
uniprot_entry
A8K2J1_HUMAN
resolver
uniprot_entry
B2RA17_HUMAN
resolver
uniprot_entry
GPR35_HUMAN
resolver
uniprot_sec
J3KR30
resolver
uniprot_sec
O43495
resolver
uniprot_sec
Q17R58
resolver
uniprot_sec
Q4VBN5
resolver
uniprot_sec
Q4ZFV2
resolver
uniprot_sec
Q6FHI8
resolver
uniprot_sec
Q86UH4
resolver
amino_acid_sequence
MNGTYNTCGSSDLTWPPAIKLGFYAYLGVLLVLGLLLNSLALWVFCCRMQQWTETRIYMTNLAVADLCLLCTLPFVLHSLRDTSDTPLCQLSQGIYLTNRYMSISLVTAIAVDRYVAVRHPLRARGLRSPRQAAAVCAVLWVLVIGSLVARWLLGIQEGGFCFRSTRHNFNSMAFPLLGFYLPLAVVVFCSLKVVTALAQRPPTDVGQAEATRKAARMVWANLLVFVVCFLPLHVGLTVRLAVGWNACALLETIRRALYITSKLSDANCCLDAICYYYMAKEFQEASALAVAPSAKAHKSQDSLCVTLA
uniprot
proteins
function
FUNCTION: G protein-coupled receptor that binds to several ligands including the tryptophan metabolite kynurenic acid (KYNA), lysophosphatidic acid (LPA) or 5-hydroxyindoleacetic acid (5-HIAA) with high affinity, leading to rapid and transient activation of numerous intracellular signaling pathways (PubMed:16754668, PubMed:19473985, PubMed:20361937, PubMed:24347166, PubMed:35148838, PubMed:35926043). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of downstream effectors, such as adenylate cyclase (PubMed:19473985, PubMed:35926043). GPR35 can couple with G(i)/G(o)- or G(12)/G(13) classes of G alpha proteins depending on the context, mediating the inhibition of adenylate cyclase or activation Rho small GTPases, respectively (PubMed:19473985, PubMed:35926043, PubMed:36543774). KYNA-binding promotes monocyte adhesion to vascular endothelium under flow conditions, leading to G(i)/GNAI1 activation and inhibition of adenylate cyclase (PubMed:19473985). Involved in cardioprotection during ischemia by promoting mitochondrial remodeling: following KYNA-binding and G(i)/GNAI1 activation, GPR35 is internalized to the outer mitochondrial membrane, where it inhibits mitochondrial adenylate cyclase (ADCY10), allowing ATPIF1 to repress ATP synthase activity (PubMed:35926043). Stimulates lipid metabolism, thermogenic and anti-inflammatory gene expression in adipose tissue once activated by KYNA (By similarity). Plays a role in neutrophil recruitment to sites of inflammation and bacterial clearance through the major serotonin metabolite 5-HIAA that acts as a physiological ligand (PubMed:35148838). In macrophages, activation by lysophosphatidic acid promotes GPR35-induced signaling with a distinct transcriptional profile characterized by TNF production associated with ERK and NF-kappa-B activation (By similarity). In turn, induces chemotaxis of macrophages (By similarity). {ECO:0000250|UniProtKB:Q9ES90, ECO:0000269|PubMed:16754668, ECO:0000269|PubMed:19473985, ECO:0000269|PubMed:20361937, ECO:0000269|PubMed:24347166, ECO:0000269|PubMed:35148838, ECO:0000269|PubMed:35926043, ECO:0000269|PubMed:36543774}.
uniprot
proteins
mass_dalton
34072
uniprot
proteins
mutagenesis
MUTAGEN 20; /note="K->A: Does not affect G protein-coupled receptor signaling in response to ligand-binding."; /evidence="ECO:0000269|PubMed:24347166"; MUTAGEN 81; /note="R->A: Does not affect G protein-coupled receptor signaling in response to ligand-binding."; /evidence="ECO:0000269|PubMed:24347166"; MUTAGEN 100; /note="R->A: Impaired G protein-coupled receptor signaling in response to ligand-binding."; /evidence="ECO:0000269|PubMed:24347166"; MUTAGEN 151; /note="R->A: Impaired G protein-coupled receptor signaling in response to ligand-binding."; /evidence="ECO:0000269|PubMed:24347166, ECO:0000269|PubMed:35926043"; MUTAGEN 164; /note="R->A,L: Impaired G protein-coupled receptor signaling in response to ligand-binding."; /evidence="ECO:0000269|PubMed:24347166"; MUTAGEN 167; /note="R->A: Impaired G protein-coupled receptor signaling in response to ligand-binding."; /evidence="ECO:0000269|PubMed:24347166"; MUTAGEN 240; /note="R->A: Impaired G protein-coupled receptor signaling in response to ligand-binding."; /evidence="ECO:0000269|PubMed:24347166"; MUTAGEN 263; /note="K->A: Does not affect G protein-coupled receptor signaling in response to ligand-binding."; /evidence="ECO:0000269|PubMed:24347166"; MUTAGEN 287; /note="S->A: About 40% loss of ARRB2 recruitment."; /evidence="ECO:0000269|PubMed:35101446"; MUTAGEN 300; /note="S->A: About 50% loss of ARRB2 recruitment."; /evidence="ECO:0000269|PubMed:35101446"; MUTAGEN 303; /note="S->A: Almost complete loss of ARRB2 recruitment."; /evidence="ECO:0000269|PubMed:35101446"; MUTAGEN 307; /note="T->A: About 75% loss of ARRB2 recruitment."; /evidence="ECO:0000269|PubMed:35101446
uniprot
proteins
post_translational_modification
PTM: Multiply phosphorylated in clusters of serines and threonines in the C-terminal tail (PubMed:35101446). Phosphorylation of Ser-300 and Ser-303 is mediated by GRK5 and/or GRK6 (PubMed:37660910). {ECO:0000269|PubMed:35101446, ECO:0000269|PubMed:37660910}.
uniprot
proteins
protein_family
G protein-coupled receptor 1 family
uniprot
proteins
pubmed
11017071
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16754668
uniprot
proteins
pubmed
19473985
uniprot
proteins
pubmed
20361937
uniprot
proteins
pubmed
24347166
uniprot
proteins
pubmed
25411203
uniprot
proteins
pubmed
29068046
uniprot
proteins
pubmed
29875152
uniprot
proteins
pubmed
35101446
uniprot
proteins
pubmed
35148838
uniprot
proteins
pubmed
35926043
uniprot
proteins
pubmed
36543774
uniprot
proteins
pubmed
37660910
uniprot
proteins
pubmed
9479505
uniprot
proteins
sequence_length
309
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16754668, ECO:0000269|PubMed:20361937, ECO:0000269|PubMed:24347166, ECO:0000269|PubMed:35101446, ECO:0000269|PubMed:35926043}; Multi-pass membrane protein {ECO:0000269|PubMed:36543774}. Mitochondrion outer membrane {ECO:0000269|PubMed:35926043}; Multi-pass membrane protein {ECO:0000269|PubMed:36543774}. Note=Internalized to the cytoplasm after exposure to kynurenic acid (PubMed:16754668). Translocates to the outer mitochondrial membrane in response to ischemia (PubMed:35926043). {ECO:0000269|PubMed:16754668, ECO:0000269|PubMed:35926043}.
uniprot
proteins
transmembrane_region
TRANSMEM 18..43; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:36543774, ECO:0007744|PDB:8H8J"; TRANSMEM 57..80; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:36543774, ECO:0007744|PDB:8H8J"; TRANSMEM 87..112; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:36543774, ECO:0007744|PDB:8H8J"; TRANSMEM 134..155; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:36543774, ECO:0007744|PDB:8H8J"; TRANSMEM 170..192; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:36543774, ECO:0007744|PDB:8H8J"; TRANSMEM 219..242; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:36543774, ECO:0007744|PDB:8H8J"; TRANSMEM 257..279; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:36543774, ECO:0007744|PDB:8H8J
uniprot
proteins