ID AGRG6_HUMAN Reviewed; 1221 AA. AC Q86SQ4; Q5TGN7; Q6DHZ4; Q6F3F5; Q6F3F6; Q6F3F7; Q6F3F8; Q6MZU7; Q8IXA4; AC Q8NC14; Q96JW0; DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 24-JAN-2024, entry version 184. DE RecName: Full=Adhesion G-protein coupled receptor G6; DE AltName: Full=Developmentally regulated G-protein-coupled receptor {ECO:0000303|PubMed:15189448}; DE AltName: Full=G-protein coupled receptor 126; DE AltName: Full=Vascular inducible G protein-coupled receptor {ECO:0000303|PubMed:15225624}; DE Contains: DE RecName: Full=ADGRG6 N-terminal fragment; DE Short=ADGRG6-NTF; DE Contains: DE RecName: Full=ADGRG6 C-terminal fragment; DE Short=ADGRG6-CTF; DE Flags: Precursor; GN Name=ADGRG6 {ECO:0000312|HGNC:HGNC:13841}; GN Synonyms=DREG, GPR126, VIGR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), TISSUE SPECIFICITY, SUBCELLULAR RP LOCATION, INDUCTION, AND GLYCOSYLATION. RC TISSUE=Vein; RX PubMed=15225624; DOI=10.1016/j.febslet.2004.05.038; RA Stehlik C., Kroismayr R., Dorfleutner A., Binder B.R., Lipp J.; RT "VIGR -- a novel inducible adhesion family G-protein coupled receptor in RT endothelial cells."; RL FEBS Lett. 569:149-155(2004). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3 AND 4), PROTEIN SEQUENCE OF RP 469-483 AND 841-845, SUBCELLULAR LOCATION, MUTAGENESIS OF ARG-468; SER-469; RP CYS-803; CYS-822; CYS-835; CYS-837 AND THR-841, PROTEOLYTIC PROCESSING, RP CLEAVAGE BY FURIN-LIKE CONVERTASE, AND VARIANT ARG-1127. RX PubMed=15189448; DOI=10.1111/j.1356-9597.2004.00743.x; RA Moriguchi T., Haraguchi K., Ueda N., Okada M., Furuya T., Akiyama T.; RT "DREG, a developmentally regulated G protein-coupled receptor containing RT two conserved proteolytic cleavage sites."; RL Genes Cells 9:549-560(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ARG-1127. RC TISSUE=Uterus; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND VARIANTS GLN-230 RP AND ARG-1127. RC TISSUE=Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 646-1221, AND VARIANT ARG-1127. RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 710-1221 (ISOFORM 3), AND VARIANT ARG-1127. RX PubMed=12565841; DOI=10.1016/s0006-291x(03)00026-3; RA Fredriksson R., Gloriam D.E.I., Hoeglund P.J., Lagerstroem M.C., RA Schioeth H.B.; RT "There exist at least 30 human G-protein-coupled receptors with long RT Ser/Thr-rich N-termini."; RL Biochem. Biophys. Res. Commun. 301:725-734(2003). RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1032-1221, AND VARIANT ARG-1127. RA Ji D., Cheng J., Wang J., Dong J., Yang Q., Dang X., Liu Y.; RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases. RN [9] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-324. RC TISSUE=Bile; RX PubMed=15084671; DOI=10.1074/mcp.m400015-mcp200; RA Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., RA Argani P., Goggins M.G., Maitra A., Pandey A.; RT "A proteomic analysis of human bile."; RL Mol. Cell. Proteomics 3:715-728(2004). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-143; ASN-438 AND ASN-445. RC TISSUE=Plasma; RX PubMed=16335952; DOI=10.1021/pr0502065; RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., RA Smith R.D.; RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, RT hydrazide chemistry, and mass spectrometry."; RL J. Proteome Res. 4:2070-2080(2005). RN [11] RP INVOLVEMENT IN STATURE AS A QUANTITATIVE TRAIT. RX PubMed=18391950; DOI=10.1038/ng.125; RA Lettre G., Jackson A.U., Gieger C., Schumacher F.R., Berndt S.I., Sanna S., RA Eyheramendy S., Voight B.F., Butler J.L., Guiducci C., Illig T., RA Hackett R., Heid I.M., Jacobs K.B., Lyssenko V., Uda M., Boehnke M., RA Chanock S.J., Groop L.C., Hu F.B., Isomaa B., Kraft P., Peltonen L., RA Salomaa V., Schlessinger D., Hunter D.J., Hayes R.B., Abecasis G.R., RA Wichmann H.-E., Mohlke K.L., Hirschhorn J.N.; RT "Identification of ten loci associated with height highlights new RT biological pathways in human growth."; RL Nat. Genet. 40:584-591(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1165, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [13] RP SUBCELLULAR LOCATION, AND FUNCTION. RX PubMed=24227709; DOI=10.1523/jneurosci.1809-13.2013; RA Mogha A., Benesh A.E., Patra C., Engel F.B., Schoeneberg T., Liebscher I., RA Monk K.R.; RT "Gpr126 functions in Schwann cells to control differentiation and RT myelination via G-protein activation."; RL J. Neurosci. 33:17976-17985(2013). RN [14] RP STACHEL MOTIF, AND MUTAGENESIS OF SER-813; GLY-815; ASN-818 AND THR-819. RX PubMed=25533341; DOI=10.1016/j.celrep.2014.11.036; RA Liebscher I., Schoen J., Petersen S.C., Fischer L., Auerbach N., RA Demberg L.M., Mogha A., Coester M., Simon K.U., Rothemund S., Monk K.R., RA Schoeneberg T.; RT "A tethered agonist within the ectodomain activates the adhesion G protein- RT coupled receptors GPR126 and GPR133."; RL Cell Rep. 9:2018-2026(2014). RN [15] RP FUNCTION, INVOLVEMENT IN LCCS9, VARIANTS LCCS9 GLU-741 AND GLU-769, AND RP CHARACTERIZATION OF VARIANT LCCS9 GLU-741. RX PubMed=26004201; DOI=10.1016/j.ajhg.2015.04.014; RA Ravenscroft G., Nolent F., Rajagopalan S., Meireles A.M., Paavola K.J., RA Gaillard D., Alanio E., Buckland M., Arbuckle S., Krivanek M., Maluenda J., RA Pannell S., Gooding R., Ong R.W., Allcock R.J., Carvalho E.D., RA Carvalho M.D., Kok F., Talbot W.S., Melki J., Laing N.G.; RT "Mutations of GPR126 are responsible for severe arthrogryposis multiplex RT congenita."; RL Am. J. Hum. Genet. 96:955-961(2015). RN [16] RP VARIANT GLN-1057, AND CHARACTERIZATION OF VARIANT GLN-1057. RX PubMed=27509131; DOI=10.1371/journal.pone.0160765; RA Kitagaki J., Miyauchi S., Asano Y., Imai A., Kawai S., Michikami I., RA Yamashita M., Yamada S., Kitamura M., Murakami S.; RT "A Putative association of a single nucleotide polymorphism in GPR126 with RT aggressive periodontitis in a japanese population."; RL PLoS ONE 11:E0160765-E0160765(2016). CC -!- FUNCTION: G-protein coupled receptor which is activated by type IV CC collagen, a major constituent of the basement membrane (By similarity). CC Couples to G(i)-proteins as well as G(s)-proteins (PubMed:24227709). CC Essential for normal differentiation of promyelinating Schwann cells CC and for normal myelination of axons (PubMed:24227709). Regulates CC neural, cardiac and ear development via G-protein- and/or N-terminus- CC dependent signaling (By similarity). May act as a receptor for PRNP CC which may promote myelin homeostasis (By similarity). CC {ECO:0000250|UniProtKB:C6KFA3, ECO:0000269|PubMed:24227709, CC ECO:0000269|PubMed:26004201}. CC -!- SUBUNIT: Interacts with Laminin-2; this interaction stabilizes the CC receptor in an inactive state. Laminin-2 polymerization could CC facilitate ADGRG6-NTF removal, thereby exposing the tethered agonist to CC drive myelination. Interacts with PRNP. {ECO:0000250|UniProtKB:Q6F3F9}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15189448, CC ECO:0000269|PubMed:15225624, ECO:0000269|PubMed:24227709}; Multi-pass CC membrane protein {ECO:0000255}. Note=Detected on the cell surface of CC activated but not resting umbilical vein. CC {ECO:0000269|PubMed:15225624}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; CC IsoId=Q86SQ4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q86SQ4-2; Sequence=VSP_010747; CC Name=3; CC IsoId=Q86SQ4-3; Sequence=VSP_010748; CC Name=4; CC IsoId=Q86SQ4-4; Sequence=VSP_010747, VSP_010748; CC -!- TISSUE SPECIFICITY: Expressed in placenta and to a lower extent in CC pancreas and liver. Detected in aortic endothelial cells but not in CC skin microvascular endothelial cells. {ECO:0000269|PubMed:15225624}. CC -!- INDUCTION: Up-regulated by bacterial lipopolysaccharides (LPS) and CC thrombin, but not by other inflammatory stimuli in primary umbilical CC veins. {ECO:0000269|PubMed:15225624}. CC -!- DOMAIN: A short peptide sequence (termed the Stachel sequence) in the CC C-terminal part of the extra-cellular domain (ECD) functions as a CC tethered agonist. Upon structural changes within the ECD, e.g. due to CC extracellular ligand binding or mechanical movements, this CC intramolecular agonist is exposed to the 7TM domain, triggering G- CC protein activation. {ECO:0000269|PubMed:25533341}. CC -!- PTM: Proteolytically cleaved into 2 conserved sites: one in the GPS CC domain (S1 site) and the other in the middle of the extracellular CC domain (S2 site). The proteolytic cleavage at S1 site generates an CC extracellular subunit and a seven-transmembrane subunit. Furin is CC involved in the cleavage of the S2 site generating a soluble fragment. CC Processing at the GPS domain occurred independent of and probably prior CC to the cleavage at the S2 site. Proteolytic cleavage is required for CC activation of the receptor. {ECO:0000269|PubMed:15189448, CC ECO:0000269|PubMed:26004201}. CC -!- PTM: Highly glycosylated. {ECO:0000269|PubMed:15225624}. CC -!- POLYMORPHISM: Genetic variations in ADGRG6 influences stature as a CC quantitative trait (STQTL) [MIM:606255]. Adult height is an easily CC observable and highly heritable complex continuous trait. Because of CC this, it is a model trait for studying genetic influence on CC quantitative traits. {ECO:0000269|PubMed:18391950}. CC -!- DISEASE: Lethal congenital contracture syndrome 9 (LCCS9) [MIM:616503]: CC A form of lethal congenital contracture syndrome, an autosomal CC recessive disorder characterized by degeneration of anterior horn CC neurons, extreme skeletal muscle atrophy and congenital non-progressive CC joint contractures. The contractures can involve the upper or lower CC limbs and/or the vertebral column, leading to various degrees of CC flexion or extension limitations evident at birth. CC {ECO:0000269|PubMed:26004201}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family. CC Adhesion G-protein coupled receptor (ADGR) subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAO13250.1; Type=Miscellaneous discrepancy; Note=Sequencing errors.; Evidence={ECO:0000305}; CC Sequence=BAB55406.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC11393.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=CAE45930.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF216967; AAO13250.1; ALT_SEQ; mRNA. DR EMBL; AB183546; BAD27571.1; -; mRNA. DR EMBL; AB183547; BAD27572.1; -; mRNA. DR EMBL; AB183548; BAD27573.1; -; mRNA. DR EMBL; AB183549; BAD27574.1; -; mRNA. DR EMBL; BX640971; CAE45986.1; -; mRNA. DR EMBL; BX640873; CAE45930.1; ALT_INIT; mRNA. DR EMBL; AL033377; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL360007; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC075798; AAH75798.1; -; mRNA. DR EMBL; AK027843; BAB55406.1; ALT_INIT; mRNA. DR EMBL; AK075087; BAC11393.1; ALT_INIT; mRNA. DR EMBL; AY181244; AAO27356.1; -; mRNA. DR EMBL; AY426673; AAR88427.1; -; mRNA. DR CCDS; CCDS47489.1; -. [Q86SQ4-3] DR CCDS; CCDS47490.1; -. [Q86SQ4-1] DR CCDS; CCDS47491.1; -. [Q86SQ4-2] DR CCDS; CCDS55064.1; -. [Q86SQ4-4] DR RefSeq; NP_001027566.1; NM_001032394.2. [Q86SQ4-2] DR RefSeq; NP_001027567.1; NM_001032395.2. [Q86SQ4-4] DR RefSeq; NP_065188.4; NM_020455.5. [Q86SQ4-1] DR RefSeq; NP_940971.1; NM_198569.2. [Q86SQ4-3] DR AlphaFoldDB; Q86SQ4; -. DR SASBDB; Q86SQ4; -. DR SMR; Q86SQ4; -. DR BioGRID; 121449; 110. DR IntAct; Q86SQ4; 2. DR STRING; 9606.ENSP00000356581; -. DR ChEMBL; CHEMBL4523884; -. DR MEROPS; P02.017; -. DR GlyConnect; 1287; 19 N-Linked glycans (8 sites). DR GlyCosmos; Q86SQ4; 26 sites, 19 glycans. DR GlyGen; Q86SQ4; 26 sites, 19 N-linked glycans (8 sites). DR iPTMnet; Q86SQ4; -. DR PhosphoSitePlus; Q86SQ4; -. DR SwissPalm; Q86SQ4; -. DR BioMuta; ADGRG6; -. DR DMDM; 215274152; -. DR EPD; Q86SQ4; -. DR jPOST; Q86SQ4; -. DR MassIVE; Q86SQ4; -. DR MaxQB; Q86SQ4; -. DR PaxDb; 9606-ENSP00000356581; -. DR PeptideAtlas; Q86SQ4; -. DR ProteomicsDB; 69609; -. [Q86SQ4-1] DR ProteomicsDB; 69610; -. [Q86SQ4-2] DR ProteomicsDB; 69611; -. [Q86SQ4-3] DR ProteomicsDB; 69612; -. [Q86SQ4-4] DR Antibodypedia; 1571; 237 antibodies from 28 providers. DR DNASU; 57211; -. DR Ensembl; ENST00000230173.10; ENSP00000230173.6; ENSG00000112414.15. [Q86SQ4-1] DR Ensembl; ENST00000296932.13; ENSP00000296932.8; ENSG00000112414.15. [Q86SQ4-2] DR Ensembl; ENST00000367608.6; ENSP00000356580.2; ENSG00000112414.15. [Q86SQ4-4] DR Ensembl; ENST00000367609.8; ENSP00000356581.3; ENSG00000112414.15. [Q86SQ4-3] DR GeneID; 57211; -. DR KEGG; hsa:57211; -. DR MANE-Select; ENST00000367609.8; ENSP00000356581.3; NM_198569.3; NP_940971.2. [Q86SQ4-3] DR UCSC; uc010khc.4; human. [Q86SQ4-1] DR AGR; HGNC:13841; -. DR CTD; 57211; -. DR DisGeNET; 57211; -. DR GeneCards; ADGRG6; -. DR HGNC; HGNC:13841; ADGRG6. DR HPA; ENSG00000112414; Tissue enhanced (liver, placenta). DR MalaCards; ADGRG6; -. DR MIM; 606255; phenotype. DR MIM; 612243; gene. DR MIM; 616503; phenotype. DR neXtProt; NX_Q86SQ4; -. DR OpenTargets; ENSG00000112414; -. DR PharmGKB; PA134878328; -. DR VEuPathDB; HostDB:ENSG00000112414; -. DR eggNOG; KOG4193; Eukaryota. DR GeneTree; ENSGT00940000155621; -. DR HOGENOM; CLU_002753_3_3_1; -. DR InParanoid; Q86SQ4; -. DR OMA; AVHHPIC; -. DR OrthoDB; 3026989at2759; -. DR PhylomeDB; Q86SQ4; -. DR TreeFam; TF321769; -. DR PathwayCommons; Q86SQ4; -. DR Reactome; R-HSA-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination. DR SignaLink; Q86SQ4; -. DR BioGRID-ORCS; 57211; 11 hits in 1152 CRISPR screens. DR ChiTaRS; ADGRG6; human. DR GeneWiki; GPR126; -. DR GenomeRNAi; 57211; -. DR Pharos; Q86SQ4; Tbio. DR PRO; PR:Q86SQ4; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q86SQ4; Protein. DR Bgee; ENSG00000112414; Expressed in endometrium epithelium and 165 other cell types or tissues. DR ExpressionAtlas; Q86SQ4; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:MGI. DR GO; GO:0005737; C:cytoplasm; IDA:MGI. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; TAS:GDB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0005518; F:collagen binding; ISS:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; TAS:Reactome. DR GO; GO:0050840; F:extracellular matrix binding; ISS:UniProtKB. DR GO; GO:0004930; F:G protein-coupled receptor activity; IMP:UniProtKB. DR GO; GO:0043236; F:laminin binding; ISS:UniProtKB. DR GO; GO:0007189; P:adenylate cyclase-activating G protein-coupled receptor signaling pathway; IBA:GO_Central. DR GO; GO:0019933; P:cAMP-mediated signaling; IMP:UniProtKB. DR GO; GO:0007166; P:cell surface receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0060347; P:heart trabecula formation; IBA:GO_Central. DR GO; GO:0042552; P:myelination; IMP:UniProtKB. DR GO; GO:0022011; P:myelination in peripheral nervous system; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:Reactome. DR GO; GO:0014037; P:Schwann cell differentiation; IMP:UniProtKB. DR CDD; cd15996; 7tmB2_GPR126; 1. DR CDD; cd00041; CUB; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 2.60.220.50; -; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR Gene3D; 2.60.120.290; Spermadhesin, CUB domain; 1. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR000859; CUB_dom. DR InterPro; IPR046338; GAIN_dom_sf. DR InterPro; IPR017981; GPCR_2-like_7TM. DR InterPro; IPR000832; GPCR_2_secretin-like. DR InterPro; IPR017983; GPCR_2_secretin-like_CS. DR InterPro; IPR000203; GPS. DR InterPro; IPR001759; Pentraxin-related. DR InterPro; IPR035914; Sperma_CUB_dom_sf. DR PANTHER; PTHR12011; ADHESION G-PROTEIN COUPLED RECEPTOR; 1. DR PANTHER; PTHR12011:SF290; ADHESION G-PROTEIN COUPLED RECEPTOR G6; 1. DR Pfam; PF00002; 7tm_2; 1. DR Pfam; PF00431; CUB; 1. DR Pfam; PF01825; GPS; 1. DR Pfam; PF00354; Pentaxin; 1. DR PRINTS; PR00249; GPCRSECRETIN. DR SMART; SM00042; CUB; 1. DR SMART; SM00303; GPS; 1. DR SMART; SM00159; PTX; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF81321; Family A G protein-coupled receptor-like; 1. DR SUPFAM; SSF49854; Spermadhesin, CUB domain; 1. DR PROSITE; PS01180; CUB; 1. DR PROSITE; PS00650; G_PROTEIN_RECEP_F2_2; 1. DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1. DR PROSITE; PS50221; GPS; 1. DR PROSITE; PS51828; PTX_2; 1. DR Genevisible; Q86SQ4; HS. PE 1: Evidence at protein level; KW Alternative splicing; Cell membrane; Cleavage on pair of basic residues; KW Direct protein sequencing; Disease variant; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Membrane; Phosphoprotein; KW Receptor; Reference proteome; Signal; Transducer; Transmembrane; KW Transmembrane helix. FT SIGNAL 1..37 FT /evidence="ECO:0000255" FT CHAIN 38..1221 FT /note="Adhesion G-protein coupled receptor G6" FT /id="PRO_0000012902" FT CHAIN 38..840 FT /note="ADGRG6 N-terminal fragment" FT /evidence="ECO:0000305|PubMed:15189448" FT /id="PRO_0000438596" FT CHAIN 841..1221 FT /note="ADGRG6 C-terminal fragment" FT /evidence="ECO:0000305|PubMed:15189448" FT /id="PRO_0000438597" FT TOPO_DOM 38..862 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 863..883 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 884..903 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 904..924 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 925..929 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 930..950 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 951..970 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 971..991 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 992..1024 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1025..1045 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 1046..1069 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 1070..1090 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 1091..1092 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 1093..1113 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 1114..1221 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 41..149 FT /note="CUB" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DOMAIN 154..356 FT /note="Pentraxin (PTX)" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01172" FT DOMAIN 800..852 FT /note="GPS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098" FT REGION 41..852 FT /note="Inhibits receptor signaling in absence of type IV FT collagen" FT /evidence="ECO:0000250|UniProtKB:C6KFA3" FT REGION 41..355 FT /note="Mediates interaction with type IV collagen" FT /evidence="ECO:0000250|UniProtKB:C6KFA3" FT REGION 473..837 FT /note="Mediates interaction with laminin-2" FT /evidence="ECO:0000250|UniProtKB:Q6F3F9" FT REGION 1156..1176 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 842..850 FT /note="Stachel" FT /evidence="ECO:0000269|PubMed:25533341" FT SITE 467..468 FT /note="Cleavage; by furin like-convertase" FT /evidence="ECO:0000269|PubMed:15189448" FT SITE 840..841 FT /note="Cleavage" FT /evidence="ECO:0000269|PubMed:15189448" FT MOD_RES 1165 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 1168 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6F3F9" FT CARBOHYD 121 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 143 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952" FT CARBOHYD 206 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 258 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 314 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 324 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:15084671" FT CARBOHYD 353 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 438 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952" FT CARBOHYD 445 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16335952" FT CARBOHYD 452 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 485 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 488 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 505 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 563 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 593 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 600 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 605 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 667 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 673 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 695 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 704 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 750 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 776 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 811 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 818 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 41..67 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DISULFID 94..111 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059" FT DISULFID 186..254 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01172" FT VAR_SEQ 380..407 FT /note="Missing (in isoform 2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:15189448, FT ECO:0000303|PubMed:15225624, ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:17974005" FT /id="VSP_010747" FT VAR_SEQ 1193..1221 FT /note="NVSYEHSFNKSGSLRQCFHGQVLVKTGPC -> SASMDKSLSKLAHADGDQT FT SIIPVHQVIDKVKGYCNAHSDNFYKNIIMSDTFSHSTKF (in isoform 3 and FT isoform 4)" FT /evidence="ECO:0000303|PubMed:12565841, FT ECO:0000303|PubMed:15189448, ECO:0000303|PubMed:15225624, FT ECO:0000303|PubMed:15489334" FT /id="VSP_010748" FT VARIANT 123 FT /note="S -> G (in dbSNP:rs17280293)" FT /id="VAR_054128" FT VARIANT 230 FT /note="K -> Q (in dbSNP:rs11155242)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_024478" FT VARIANT 741 FT /note="V -> E (in LCCS9; decreases the FT autoprocessing/cleavage of the receptor)" FT /evidence="ECO:0000269|PubMed:26004201" FT /id="VAR_075146" FT VARIANT 769 FT /note="V -> E (in LCCS9; dbSNP:rs793888525)" FT /evidence="ECO:0000269|PubMed:26004201" FT /id="VAR_075147" FT VARIANT 1057 FT /note="R -> Q (found in patients with aggressive FT periodontitis; impairs cAMP production; abrogates FT osteoblastic differentiation; dbSNP:rs536714306)" FT /evidence="ECO:0000269|PubMed:27509131" FT /id="VAR_076965" FT VARIANT 1127 FT /note="Q -> R (in dbSNP:rs1262686)" FT /evidence="ECO:0000269|PubMed:12565841, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15189448, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005, FT ECO:0000269|Ref.8" FT /id="VAR_054129" FT MUTAGEN 468 FT /note="R->A: No cleavage." FT /evidence="ECO:0000269|PubMed:15189448" FT MUTAGEN 469 FT /note="S->A: No effect on cleavage." FT /evidence="ECO:0000269|PubMed:15189448" FT MUTAGEN 803 FT /note="C->S: No cleavage and not detected at the cell FT surface." FT /evidence="ECO:0000269|PubMed:15189448" FT MUTAGEN 813 FT /note="S->A: No effect on G-protein-mediated cAMP release." FT /evidence="ECO:0000269|PubMed:25533341" FT MUTAGEN 815 FT /note="G->A: Abolishes G-protein-mediated cAMP release." FT /evidence="ECO:0000269|PubMed:25533341" FT MUTAGEN 818 FT /note="N->A: Abolishes G-protein-mediated cAMP release." FT /evidence="ECO:0000269|PubMed:25533341" FT MUTAGEN 819 FT /note="T->A: Abolishes G-protein-mediated cAMP release." FT /evidence="ECO:0000269|PubMed:25533341" FT MUTAGEN 822 FT /note="C->S: No cleavage and not detected at the cell FT surface." FT /evidence="ECO:0000269|PubMed:15189448" FT MUTAGEN 835 FT /note="C->S: No cleavage and not detected at the cell FT surface." FT /evidence="ECO:0000269|PubMed:15189448" FT MUTAGEN 837 FT /note="C->S: No cleavage and not detected at the cell FT surface." FT /evidence="ECO:0000269|PubMed:15189448" FT MUTAGEN 841 FT /note="T->A: No cleavage but detected at cell surface." FT /evidence="ECO:0000269|PubMed:15189448" FT MUTAGEN 841 FT /note="T->P: No cleavage and not detected at the cell FT surface." FT /evidence="ECO:0000269|PubMed:15189448" FT CONFLICT 622 FT /note="N -> S (in Ref. 3; CAE45986)" FT /evidence="ECO:0000305" FT CONFLICT 623 FT /note="I -> V (in Ref. 3; CAE45930)" FT /evidence="ECO:0000305" FT CONFLICT 708 FT /note="F -> S (in Ref. 3; CAE45986)" FT /evidence="ECO:0000305" FT CONFLICT 763 FT /note="K -> Q (in Ref. 3; CAE45930)" FT /evidence="ECO:0000305" FT CONFLICT 908 FT /note="L -> P (in Ref. 5; AAH75798)" FT /evidence="ECO:0000305" SQ SEQUENCE 1221 AA; 136695 MW; 1950DE5AE648F1C4 CRC64; MMFRSDRMWS CHWKWKPSPL LFLFALYIMC VPHSVWGCAN CRVVLSNPSG TFTSPCYPND YPNSQACMWT LRAPTGYIIQ ITFNDFDIEE APNCIYDSLS LDNGESQTKF CGATAKGLSF NSSANEMHVS FSSDFSIQKK GFNASYIRVA VSLRNQKVIL PQTSDAYQVS VAKSISIPEL SAFTLCFEAT KVGHEDSDWT AFSYSNASFT QLLSFGKAKS GYFLSISDSK CLLNNALPVK EKEDIFAESF EQLCLVWNNS LGSIGVNFKR NYETVPCDST ISKVIPGNGK LLLGSNQNEI VSLKGDIYNF RLWNFTMNAK ILSNLSCNVK GNVVDWQNDF WNIPNLALKA ESNLSCGSYL IPLPAAELAS CADLGTLCQA TVNSPSTTPP TVTTNMPVTN RIDKQRNDGI IYRISVVIQN ILRHPEVKVQ SKVAEWLNST FQNWNYTVYV VNISFHLSAG EDKIKVKRSL EDEPRLVLWA LLVYNATNNT NLEGKIIQQK LLKNNESLDE GLRLHTVNVR QLGHCLAMEE PKGYYWPSIQ PSEYVLPCPD KPGFSASRIC FYNATNPLVT YWGPVDISNC LKEANEVANQ ILNLTADGQN LTSANITNIV EQVKRIVNKE ENIDITLGST LMNIFSNILS SSDSDLLESS SEALKTIDEL AFKIDLNSTS HVNITTRNLA LSVSSLLPGT NAISNFSIGL PSNNESYFQM DFESGQVDPL ASVILPPNLL ENLSPEDSVL VRRAQFTFFN KTGLFQDVGP QRKTLVSYVM ACSIGNITIQ NLKDPVQIKI KHTRTQEVHH PICAFWDLNK NKSFGGWNTS GCVAHRDSDA SETVCLCNHF THFGVLMDLP RSASQLDARN TKVLTFISYI GCGISAIFSA ATLLTYVAFE KLRRDYPSKI LMNLSTALLF LNLLFLLDGW ITSFNVDGLC IAVAVLLHFF LLATFTWMGL EAIHMYIALV KVFNTYIRRY ILKFCIIGWG LPALVVSVVL ASRNNNEVYG KESYGKEKGD EFCWIQDPVI FYVTCAGYFG VMFFLNIAMF IVVMVQICGR NGKRSNRTLR EEVLRNLRSV VSLTFLLGMT WGFAFFAWGP LNIPFMYLFS IFNSLQGLFI FIFHCAMKEN VQKQWRQHLC CGRFRLADNS DWSKTATNII KKSSDNLGKS LSSSSIGSNS TYLTSKSKSS STTYFKRNSH TDNVSYEHSF NKSGSLRQCF HGQVLVKTGP C //