Adgrf5
entrez
224792
canonical
uniprot
G5E8Q8
canonical
ensembl
ENSMUSG00000056492
resolver
ensp
ENSMUSP00000109229
resolver
ensp
ENSMUSP00000153049
resolver
ensp
ENSMUSP00000153373
resolver
ensp
ENSMUSP00000275818
resolver
ensp
ENSMUSP00000275819
resolver
ensp
ENSMUSP00000275821
resolver
ensp
ENSMUSP00000275822
resolver
enst
ENSMUST00000113599
resolver
enst
ENSMUST00000226087
resolver
genesymbol
Adgrf5
resolver
genesymbol_syn
Gpr116
resolver
uniprot_entry
AGRF5_MOUSE
resolver
activity_regulation
ACTIVITY REGULATION: As an adhesion G protein-coupled receptor (aGPCR) exhibits a large N-terminal extracellular domain containing highly conserved GPCR autoproteolysis-inducing (GAIN) domain. During synthesis, intracellular autoproteolytic processing of nascent chain within the GAIN domain generates a mature protein, consisting of an N-terminal fragment that is non-covalently linked to the C-terminal fragment. The mature protein is routed to the plasma membrane where the N- and C-terminal fragments remain associated, forming the holoreceptor. Dissociation of the aGPCR fragments stimulates G protein signaling through the action of the tethered-peptide agonist stalk that is occluded within the GAIN domain in the holoreceptor form. This dissociation might be induced by ligand binding, such as that of sFNDC4. {ECO:0000305}.
uniprot
proteins
amino_acid_sequence
MRSPRTFTFYFLLLVICSSEAALSTPTEPIVQPSILQEHELAGEELLRPKRAAAAGDRVAEEYMVDIEISFENVSFLESIRAHLNNLSFPIRGTEADILNIAMTTVCTPAGNDLLCFCEKGYQWSEERCLHSLTCQDYDSALPGGYCSCLKGLPPQGPFCQLPEAFITLKLKVRLNIGFQEDLKNTSSALYRSYKTDLERAFRAGYRTLPGFRSVTVTQFTKGSVVVNYVVRVTSAPLPGSIHKANEQVIQNLNHTYKMDYNSFQGTPSNETKFTVIPEFIFEGDNVTLECETEFVTSNTSWYYGEKRSDIQNSDKYSIHTTVINNISLITRLTIYNFTQHDAGMYGCNVTLDIFEYGTVRKLDVTPIRILAKEERKVVCDNHPISLNCCSENIANWSSIEWKQEGKISILGNPESDLESSCSTYTLKADGTQCPSGSSGTTVIYTCEFVSAYGARGSKNIAVTFTSVANLTITRDPISVSEGQSFSITCLSDVSSFDEVYWNTSAGIKIHPRFYTMRRYQDGAESVLMVKTSTREWNGTYHCIFRYKNSYSIATKDVTVHPLPLVSDIMMDPLEASGLCTSSHQFKCCVEEDAGEEYAVTFHVDSSSFPAEREVIGKQACYTYSLPANLPRCPKDIAVFCHFTNAANSSVRSPSMKLKLIPRENVTCQDPIIGIGDPGKVIQKLCQFSGVYGSPGQAIGGTVTYKCVGTQWKEESRACISAPINGLLQVAKALIKSPTQDQKLPTYLRDLSVSAGKEEQDIRSSPGSLGAIISILDLLSTVPTQVNSEMMRDILATINVILDKSALNSWEKLLQQQSNQSSQFLHSVERFSQALQLGDSTPPFLAHPNVQMKSMVIKRGHPQIYQQQFIFKDSDLWGDVAIDECQLGNLQPDSSIVTVAFPTLKAILAQDVQRKTSSNSLVMTTTVSHNIVKPFRISMTFKNNHRSGGKPQCVFWNFSLANNTGGWDSSGCSVEDDGRDNRDRVFCKCNHLTSFSILMSPDSPDPGSLLKILLDIISYIGLGFSIVSLAACLVVEAMVWKSVTKNRTSYMRHICIVNIAFCLLIADIWFIVAGAIHDGRYPLNETACVAATFFIHFFYLSVFFWMLTLGLMLFYRLIFILHDASKSTQKAIAFSLGYGCPLIISSITVGVTQPQEVYMRKNACWLNWEDTRALLAFAIPALIIVVVNVSITVVVITKILRPSIGDKPGKQEKSSLFQISKSIGVLTPLLGLTWGFGLATVIQGSNAVFHIIFTLLNAFQGLFILLFGCLWDQKVQEALLHKFSLSRWSSQHSKSTSIGSSTPVFSMSSPISRRFNNLFGKTGTYNVSTPETTSSSLENSSSAYSLLN
uniprot
proteins
function
FUNCTION: Adhesion G protein-coupled receptor (PubMed:23590306, PubMed:23684610, PubMed:23922714, PubMed:28570277). In alveolar type II (ATII or AT2) cells, required for normal lung surfactant homeostasis (PubMed:23590306, PubMed:23684610, PubMed:23922714, PubMed:28570277). Modulation of both surfactant secretion and uptake by ATII cells is mediated by the downstream activation of GNAQ/GNA11 proteins and may be a consequence of increased cortical F-actin assembly induced by ADGRF5 activation (PubMed:28570277). In the kidney, may play a role in the regulation of acid excretion into the primary urine, possibly by regulating the surface expression of V-ATPase proton pump (PubMed:33004624). As a receptor for soluble FNDC4 (sFNDC4), required for proper systemic glucose tolerance, specifically sensitizing white adipose tissue to insulin. Also plays a role in sFNDC4-induced decrease of local inflammation in white adipose tissue (PubMed:22971422, PubMed:34016966). {ECO:0000269|PubMed:22971422, ECO:0000269|PubMed:23590306, ECO:0000269|PubMed:23684610, ECO:0000269|PubMed:23922714, ECO:0000269|PubMed:28570277, ECO:0000269|PubMed:33004624, ECO:0000269|PubMed:34016966}.
uniprot
proteins
mass_dalton
149387
uniprot
proteins
mutagenesis
MUTAGEN 991; /note="H->A: Loss of autocatalytic cleavage; exhibits higher levels of saturated phosphatidylcholine in the bronchoalveolar lavage fluid, when tested in 8 week-old transgenic mice, a phenotype similar to that of knockout animals, suggesting loss of function in vivo; does not affect localization at the plasma membrane; does not affect the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 993..995; /note="TSF->AAA: Loss of activation, as measured by inositol phosphate conversion."; /evidence="ECO:0000269|PubMed:28570277"; MUTAGEN 993; /note="T->A: No effect on protein expression; no effect on location at the plasma membrane; no effect on inositol monophosphate conversion; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 994; /note="S->A: No effect on protein expression; no effect on location at the plasma membrane; no effect on inositol monophosphate conversion; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 995; /note="F->A: Complete inhibition of basal inositol monophosphate formation, when tested in transfected HEK293 cells; no effect on protein expression; no effect on location at the plasma membrane; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 996..998; /note="SIL->AAA: Loss of activation, as measured by inositol phosphate conversion."; /evidence="ECO:0000269|PubMed:28570277"; MUTAGEN 996; /note="S->A: No effect on protein expression; no effect on location at the plasma membrane; no effect on inositol monophosphate conversion; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 997; /note="I->A: Decreased basal inositol monophosphate formation, when tested in transfected HEK293 cells; no effect on protein expression; no effect on location at the plasma membrane; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 998; /note="L->A: Complete inhibition of basal inositol monophosphate formation, when tested in transfected HEK293 cells; no effect on protein expression; no effect on location at the plasma membrane; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 999..1001; /note="MSP->AAA: Loss of activation, as measured by inositol phosphate conversion."; /evidence="ECO:0000269|PubMed:28570277"; MUTAGEN 999; /note="M->A: Complete inhibition of basal inositol monophosphate formation, when tested in transfected HEK293 cells; no effect on protein expression; no effect on location at the plasma membrane; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1000; /note="S->A: No effect on protein expression; no effect on location at the plasma membrane; no effect on inositol monophosphate conversion; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1001; /note="P->A: No effect on protein expression; no effect on location at the plasma membrane; no effect on inositol monophosphate conversion; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1002..1004; /note="DSP->AAA: Loss of activation, as measured by inositol phosphate conversion."; /evidence="ECO:0000269|PubMed:28570277"; MUTAGEN 1002; /note="D->A: Decreased basal inositol monophosphate formation, when tested in transfected HEK293 cells; no effect on protein expression; no effect on location at the plasma membrane; Decreased inositol monophosphate formation, when tested in transfected HEK293 cells; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1003; /note="S->A: Decreased basal inositol monophosphate formation, when tested in transfected HEK293 cells; no effect on protein expression; no effect on location at the plasma membrane; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1004; /note="P->A: Decreased basal inositol monophosphate formation, when tested in transfected HEK293 cells; no effect on protein expression; no effect on location at the plasma membrane; no effect on the response to exogenously added agonistic peptide."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1005..1007; /note="DPG->AAA: No effect on activation, as measured by inositol phosphate conversion."; /evidence="ECO:0000269|PubMed:28570277"; MUTAGEN 1158; /note="Y->A: Unresponsive to exogenous ligand-mediated activation; no effect on location at the plasma membrane."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1158; /note="Y->F: Exogenous ligand-mediated activation similar to wild-type, albeit with lower potency; no effect on location at the plasma membrane."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1160; /note="R->A,K: Unresponsive to exogenous ligand-mediated activation."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1165; /note="W->A,F,V,Y: Loss of, or strong reduction, in exogenous ligand-mediated activation."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1166; /note="L->A,I: Unresponsive to exogenous ligand-mediated activation; no effect on location at the plasma membrane."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1240; /note="T->A: Unresponsive to exogenous ligand-mediated activation; no effect on location at the plasma membrane."; /evidence="ECO:0000269|PubMed:36073784"; MUTAGEN 1240; /note="T->S: Exogenous ligand-mediated activation maintained, although with decreased efficacy compared to wild-type."; /evidence="ECO:0000269|PubMed:36073784
uniprot
proteins
post_translational_modification
PTM: Highly glycosylated. {ECO:0000250|UniProtKB:Q9WVT0}.; PTM: Proteolytically cleaved at multiple sites: one in the GPS region of the GAIN-B domain (S1 site) and the other in the SEA domain (S2 site). The proteolytic cleavage at S1 site generates an extracellular subunit and a seven-transmembrane subunit. The proteolytic cleavage at S2 site generates a fragment that undergoes proteolytic cleavage by the processing enzyme furin. {ECO:0000250|UniProtKB:Q9WVT0}.
uniprot
proteins
protein_family
Adhesion G protein-coupled receptor (ADGR) subfamily
uniprot
proteins
protein_family
G protein-coupled receptor 2 family
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22837050
uniprot
proteins
pubmed
22971422
uniprot
proteins
pubmed
23590306
uniprot
proteins
pubmed
23684610
uniprot
proteins
pubmed
23922714
uniprot
proteins
pubmed
26394398
uniprot
proteins
pubmed
28154189
uniprot
proteins
pubmed
28570277
uniprot
proteins
pubmed
33004624
uniprot
proteins
pubmed
34016966
uniprot
proteins
pubmed
36073784
uniprot
proteins
pubmed
38228886
uniprot
proteins
sequence_length
1348
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:36073784}; Multi-pass membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 1020..1040; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1056..1076; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1093..1113; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1131..1151; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1176..1196; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1222..1242; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 1251..1271; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins