AGRG1_RAT
ID AGRG1_RAT Reviewed; 687 AA.
AC Q8K3V3;
DT 15-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Adhesion G-protein coupled receptor G1;
DE AltName: Full=G-protein coupled receptor 56;
DE Contains:
DE RecName: Full=ADGRG1 N-terminal fragment;
DE Short=ADGRG1 NT;
DE AltName: Full=GPR56 N-terminal fragment;
DE Short=GPR56 NT;
DE Short=GPR56(N);
DE AltName: Full=GPR56 extracellular subunit;
DE AltName: Full=GPR56 subunit alpha;
DE Contains:
DE RecName: Full=ADGRG1 C-terminal fragment;
DE Short=ADGRG1 CT;
DE AltName: Full=GPR56 C-terminal fragment;
DE Short=GPR56 CT;
DE Short=GPR56(C);
DE AltName: Full=GPR56 seven-transmembrane subunit;
DE Short=GPR56 7TM;
DE AltName: Full=GPR56 subunit beta;
DE Flags: Precursor;
GN Name=Adgrg1 {ECO:0000312|RGD:628617}; Synonyms=Gpr56;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kuehnen P., Seufert J.;
RT "Inhibition of rat serpentine receptor mRNA expression by leptin in insulin
RT producing pancreatic beta-cells.";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP SUBUNIT, AND PROTEOLYTIC PROCESSING.
RX PubMed=21708946; DOI=10.1074/jbc.m111.247973;
RA Paavola K.J., Stephenson J.R., Ritter S.L., Alter S.P., Hall R.A.;
RT "The N terminus of the adhesion G protein-coupled receptor GPR56 controls
RT receptor signaling activity.";
RL J. Biol. Chem. 286:28914-28921(2011).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Receptor involved in cell adhesion and probably in cell-cell
CC interactions. Mediates cell matrix adhesion in developing neurons and
CC hematopoietic stem cells. Receptor for collagen III/COL3A1 in the
CC developing brain and involved in regulation of cortical development,
CC specifically in maintenance of the pial basement membrane integrity and
CC in cortical lamination. Binding to the COL3A1 ligand inhibits neuronal
CC migration and activates the RhoA pathway by coupling to GNA13 and
CC possibly GNA12. Plays a role in the maintenance of hematopoietic stem
CC cells and/or leukemia stem cells in bone marrow niche. Plays an
CC essential role in testis development. Plays a critical role in
CC tumourigenesis. {ECO:0000250|UniProtKB:Q8K209,
CC ECO:0000250|UniProtKB:Q9Y653}.
CC -!- ACTIVITY REGULATION: ADGRG1 NT is proposed to inhibit receptor
CC signaling; its interactions with extracellular ligands and /or
CC homophilic ADGRG1 NT interactions may relieve the inhibition. Following
CC ligand binding to the N-terminal fragment, the N-terminal fragment is
CC released from the seven-transmembrane C-terminal fragment to unveil a
CC new N-terminal stalk, which then stimulates G-protein-dependent
CC signaling activity. The N-terminal stalk has also been shown to be
CC dispensable for at least some G-protein-dependent signaling.
CC {ECO:0000250|UniProtKB:Q9Y653}.
CC -!- SUBUNIT: Heterodimer of 2 chains generated by proteolytic processing;
CC the large extracellular N-terminal fragment (ADGRG1 NT) and the
CC membrane-bound C-terminal fragment (ADGRG1 CT) predominantly remain
CC associated and non-covalently linked. ADGRG1 NT self-associates in a
CC trans-trans manner; the homophilic interaction enhances receptor
CC signaling. ADGRG1 CT interacts with ARRB2; the interaction is impaired
CC by ADGRG1 NT. Interacts with TGM2; TGM2 probably is not a ADGRG1 ligand
CC and the interaction is reported controversial. Part of a GPCR-
CC tetraspanin complex at least consisting of ADGRG1, CD81, eventually
CC CD9, and GNA11 in which CD81 is enhancing the association of ADGRG1
CC with GNA11. Interacts with heparin; leading to the reduction of ADGRG1
CC shedding. Interacts with COL3A1 (By similarity).
CC {ECO:0000250|UniProtKB:Q9Y653}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9Y653};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- SUBCELLULAR LOCATION: [ADGRG1 N-terminal fragment]: Secreted
CC {ECO:0000250|UniProtKB:Q9Y653}.
CC -!- SUBCELLULAR LOCATION: [ADGRG1 C-terminal fragment]: Membrane raft
CC {ECO:0000250|UniProtKB:Q9Y653}. Note=Interaction with its ligand COL3A1
CC leads to the release of ADGRG1 NT from the membrane and triggers the
CC association of ADGRG1 CT with lipid rafts.
CC {ECO:0000250|UniProtKB:Q9Y653}.
CC -!- PTM: Autoproteolytically cleaved into 2 fragments; the large
CC extracellular N-terminal fragment and the membrane-bound C-terminal
CC fragment predominantly remain associated and non-covalently linked.
CC Shedding to yield the secreted ADGRG1 N-terminal fragment seems also to
CC involve metalloprotease(s). {ECO:0000269|PubMed:21708946}.
CC -!- PTM: N-glycosylated. Contains sialic acid residues.
CC {ECO:0000250|UniProtKB:Q9Y653}.
CC -!- PTM: Ubiquitinated. Undergoes polyubiquitination upon activation.
CC {ECO:0000250|UniProtKB:Q9Y653}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family. LN-TM7
CC subfamily. {ECO:0000305}.
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DR EMBL; AF529886; AAM94855.1; -; mRNA.
DR AlphaFoldDB; Q8K3V3; -.
DR SMR; Q8K3V3; -.
DR STRING; 10116.ENSRNOP00000020921; -.
DR MEROPS; P02.008; -.
DR GlyGen; Q8K3V3; 7 sites, 2 N-linked glycans (1 site).
DR iPTMnet; Q8K3V3; -.
DR PhosphoSitePlus; Q8K3V3; -.
DR PaxDb; Q8K3V3; -.
DR PRIDE; Q8K3V3; -.
DR UCSC; RGD:628617; rat.
DR RGD; 628617; Adgrg1.
DR eggNOG; KOG4193; Eukaryota.
DR InParanoid; Q8K3V3; -.
DR PhylomeDB; Q8K3V3; -.
DR PRO; PR:Q8K3V3; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0097451; C:glial limiting end-foot; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB.
DR GO; GO:0050840; F:extracellular matrix binding; ISS:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; ISS:UniProtKB.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB.
DR GO; GO:0007420; P:brain development; ISO:RGD.
DR GO; GO:0007155; P:cell adhesion; ISS:UniProtKB.
DR GO; GO:0016477; P:cell migration; ISS:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IEA:InterPro.
DR GO; GO:0021801; P:cerebral cortex radial glia-guided migration; ISS:UniProtKB.
DR GO; GO:0021796; P:cerebral cortex regionalization; ISO:RGD.
DR GO; GO:0061484; P:hematopoietic stem cell homeostasis; ISO:RGD.
DR GO; GO:0021819; P:layer formation in cerebral cortex; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:2001223; P:negative regulation of neuron migration; ISS:UniProtKB.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; ISO:RGD.
DR GO; GO:0035025; P:positive regulation of Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:0070528; P:protein kinase C signaling; ISS:UniProtKB.
DR GO; GO:0007266; P:Rho protein signal transduction; ISS:UniProtKB.
DR GO; GO:0072520; P:seminiferous tubule development; ISO:RGD.
DR GO; GO:0010573; P:vascular endothelial growth factor production; ISS:UniProtKB.
DR Gene3D; 2.60.220.50; -; 1.
DR InterPro; IPR040950; GAIN_A.
DR InterPro; IPR046338; GAIN_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR000832; GPCR_2_secretin-like.
DR InterPro; IPR003910; GPR1/GPR3/GPR5.
DR InterPro; IPR000203; GPS.
DR InterPro; IPR040679; PLL.
DR Pfam; PF00002; 7tm_2; 1.
DR Pfam; PF18619; GAIN_A; 1.
DR Pfam; PF01825; GPS; 1.
DR Pfam; PF18587; PLL; 1.
DR PRINTS; PR00249; GPCRSECRETIN.
DR PRINTS; PR01422; GPR56ORPHANR.
DR SMART; SM00303; GPS; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
DR PROSITE; PS50221; GPS; 1.
PE 1: Evidence at protein level;
KW Cell adhesion; Cell membrane; Developmental protein; Differentiation;
KW G-protein coupled receptor; Glycoprotein; Heparin-binding; Membrane;
KW Neurogenesis; Receptor; Reference proteome; Secreted; Signal; Transducer;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000250|UniProtKB:Q9Y653"
FT CHAIN 26..687
FT /note="Adhesion G-protein coupled receptor G1"
FT /evidence="ECO:0000250|UniProtKB:Q9Y653"
FT /id="PRO_0000012885"
FT CHAIN 26..?382
FT /note="ADGRG1 N-terminal fragment"
FT /evidence="ECO:0000250|UniProtKB:Q9Y653"
FT /id="PRO_0000423096"
FT CHAIN ?383..687
FT /note="ADGRG1 C-terminal fragment"
FT /id="PRO_0000423097"
FT TOPO_DOM 26..402
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 424..442
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 443..463
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 464..471
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 472..492
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 493..512
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 513..533
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 534..570
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 571..591
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 592..603
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 604..624
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 625..630
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 631..651
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 652..687
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 343..394
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT REGION 664..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 26..33
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:Q9Y653"
FT BINDING 190..200
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250|UniProtKB:Q9Y653"
FT SITE 382..383
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9Y653"
FT CARBOHYD 39
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 171
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 234
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 303
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 324
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 687 AA; 77252 MW; 79C8A64FC572856D CRC64;
MAVQVLLQMV YFLLTLLFLV QGAHGASPRE DFRFCGQRNQ TQQSTLHYDQ TSEPHIFVWN
TDESLTIRAP FPAAPDIPYF FPEPRGLYHF CLYWSRHTGR LHLRYGKNDY LLSSRASNLL
CYRKQEESLK QGAPLVATSV SSWQSPQNTS LPGAPSFIFS FHNAPHKVSH NASVNMCDLK
KELQLLSKFL QHPHKASKRP SAAFISQQLQ NLESKLTSVS FLGDTLSFEE NRVNATVWKL
PPTAGLEDLQ IHSQQEEEQS EVQAYSVLLP RAVFQQTRGR RRDAAKRLLV VDFSSQALFQ
DKNSSQVLGE KVLGIVVQNT KVTNLSDPVV LTFQHQPQPK NVTLQCVFWV EDPASSSTGS
WSSEGCETVS RDTQTSCLCN HLTYFAVLMV SSMEVEATHK HYLTLLSYVG CVISALACVF
TIAAYLCTRR KSRDYTIKVH MNLLLAVFLL DVSFLLSEPV ALMGSEAACR TSAMFLHFSL
LACLSWMGLE GYNLYRLVVE VFGTYVPGYL LKLSTVGWGF PVFLVTLVAL VDVNNYGPII
LAVRRTPDHV IYPSMCWIRD SVVSYVTNLG LFSLVFLFNM AMLATMVVQI LRLRPHSQKW
PHVLTLLGLS LVLGLPWALV FFSFASGTFQ LVIIYLFSIM TSFQGFLIFL WYWSMRFQAQ
GGPSPLKNNS DSAKLPISSG STSSSRI
