AGRG6_HUMAN
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 03-AUG-2022, entry version 176.
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}; 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};
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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 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; Q86SQ4; -.
DR PeptideAtlas; Q86SQ4; -.
DR PRIDE; Q86SQ4; -.
DR ProteomicsDB; 69609; -. [Q86SQ4-1]
DR ProteomicsDB; 69610; -. [Q86SQ4-2]
DR ProteomicsDB; 69611; -. [Q86SQ4-3]
DR ProteomicsDB; 69612; -. [Q86SQ4-4]
DR Antibodypedia; 1571; 216 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 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; SNLSCDV; -.
DR OrthoDB; 148879at2759; -.
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; 8 hits in 1068 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 163 other tissues.
DR ExpressionAtlas; Q86SQ4; baseline and differential.
DR Genevisible; Q86SQ4; HS.
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:0016021; C:integral component of membrane; TAS:GDB.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
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; cd00041; CUB; 1.
DR Gene3D; 2.60.120.290; -; 1.
DR Gene3D; 2.60.220.50; -; 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.
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 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; SSF49854; SSF49854; 1.
DR SUPFAM; SSF49899; SSF49899; 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.
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 autoprocessing/
FT 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
