AGRG6_DANRE
ID AGRG6_DANRE Reviewed; 1185 AA.
AC C6KFA3;
DT 02-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-SEP-2009, sequence version 1.
DT 03-AUG-2022, entry version 70.
DE RecName: Full=Adhesion G-protein coupled receptor G6;
DE AltName: Full=G-protein coupled receptor 126;
DE Contains:
DE RecName: Full=ADGRG6 N-terminal fragment {ECO:0000303|PubMed:24082093};
DE Short=ADGRG6-NTF;
DE Contains:
DE RecName: Full=ADGRG6 C-terminal fragment {ECO:0000303|PubMed:24082093};
DE Short=ADGRG6-CTF;
DE Flags: Precursor;
GN Name=adgrg6; Synonyms=gpr126;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND TISSUE
RP SPECIFICITY.
RX PubMed=19745155; DOI=10.1126/science.1173474;
RA Monk K.R., Naylor S.G., Glenn T.D., Mercurio S., Perlin J.R., Dominguez C.,
RA Moens C.B., Talbot W.S.;
RT "A G protein-coupled receptor is essential for Schwann cells to initiate
RT myelination.";
RL Science 325:1402-1405(2009).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND VARIANTS ASN-963 AND LEU-969.
RX PubMed=24067352; DOI=10.1242/dev.098061;
RA Geng F.S., Abbas L., Baxendale S., Holdsworth C.J., Swanson A.G.,
RA Slanchev K., Hammerschmidt M., Topczewski J., Whitfield T.T.;
RT "Semicircular canal morphogenesis in the zebrafish inner ear requires the
RT function of gpr126 (lauscher), an adhesion class G protein-coupled receptor
RT gene.";
RL Development 140:4362-4374(2013).
RN [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION (ADGRG6 N-TERMINAL FRAGMENT).
RX PubMed=24082093; DOI=10.1073/pnas.1304837110;
RA Patra C., van Amerongen M.J., Ghosh S., Ricciardi F., Sajjad A.,
RA Novoyatleva T., Mogha A., Monk K.R., Muehlfeld C., Engel F.B.;
RT "Organ-specific function of adhesion G protein-coupled receptor GPR126 is
RT domain-dependent.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:16898-16903(2013).
RN [4]
RP FUNCTION, AND MUTAGENESIS OF 831-GLY-ILE-832.
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND REGION.
RX PubMed=25118328; DOI=10.1126/scisignal.2005347;
RA Paavola K.J., Sidik H., Zuchero J.B., Eckart M., Talbot W.S.;
RT "Type IV collagen is an activating ligand for the adhesion G protein-
RT coupled receptor GPR126.";
RL Sci. Signal. 7:RA76-RA76(2014).
RN [6]
RP FUNCTION (ADGRG6 N-TERMINAL FRAGMENT).
RX PubMed=25695270; DOI=10.1016/j.neuron.2014.12.057;
RA Petersen S.C., Luo R., Liebscher I., Giera S., Jeong S.J., Mogha A.,
RA Ghidinelli M., Feltri M.L., Schoeneberg T., Piao X., Monk K.R.;
RT "The adhesion GPCR GPR126 has distinct, domain-dependent functions in
RT Schwann cell development mediated by interaction with laminin-211.";
RL Neuron 85:755-769(2015).
CC -!- FUNCTION: G-protein coupled receptor which is activated by type IV
CC collagen, a major constituent of the basement membrane. Couples to
CC G(i)-proteins as well as G(s)-proteins (PubMed:25118328). Essential for
CC normal differentiation of promyelinating Schwann cells and for normal
CC myelination of axons (PubMed:19745155). Also plays a role in inner ear
CC development (PubMed:24067352). {ECO:0000250|UniProtKB:Q86SQ4,
CC ECO:0000269|PubMed:19745155, ECO:0000269|PubMed:24067352,
CC ECO:0000269|PubMed:25118328}.
CC -!- FUNCTION: [ADGRG6 N-terminal fragment]: Plays an important role in
CC heart development (PubMed:24082093). Necessary and sufficient for axon
CC sorting by Schwann cells independently of the ADGRG6-CTF
CC (PubMed:25695270). {ECO:0000269|PubMed:24082093,
CC ECO:0000269|PubMed:25695270}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:25118328};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed in Schwann cells of the posterior lateral
CC line nerve and in brain. {ECO:0000269|PubMed:19745155}.
CC -!- DEVELOPMENTAL STAGE: Detected from 30 hours post-fertilization to 4
CC days post-fertilization in Schwann cells of the posterior lateral line
CC nerve. {ECO:0000269|PubMed:19745155}.
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 -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein results in
CC defects in semicircular canal formation inner ear (PubMed:24067352).
CC {ECO:0000269|PubMed:24067352, ECO:0000269|PubMed:24082093}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 2 family.
CC Adhesion G-protein coupled receptor (ADGR) subfamily. {ECO:0000305}.
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DR EMBL; GQ202546; ACS94979.1; -; mRNA.
DR RefSeq; NP_001156763.1; NM_001163291.1.
DR AlphaFoldDB; C6KFA3; -.
DR SASBDB; C6KFA3; -.
DR SMR; C6KFA3; -.
DR STRING; 7955.ENSDARP00000109070; -.
DR PaxDb; C6KFA3; -.
DR GeneID; 561970; -.
DR KEGG; dre:561970; -.
DR CTD; 57211; -.
DR ZFIN; ZDB-GENE-041014-357; adgrg6.
DR eggNOG; KOG4193; Eukaryota.
DR InParanoid; C6KFA3; -.
DR OrthoDB; 148879at2759; -.
DR Reactome; R-DRE-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination.
DR PRO; PR:C6KFA3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005518; F:collagen binding; IDA:UniProtKB.
DR GO; GO:0050840; F:extracellular matrix binding; IDA:UniProtKB.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IDA: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; IDA:UniProtKB.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0043583; P:ear development; IDA:UniProtKB.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0007507; P:heart development; IDA:UniProtKB.
DR GO; GO:0060347; P:heart trabecula formation; IMP:ZFIN.
DR GO; GO:0007005; P:mitochondrion organization; IMP:ZFIN.
DR GO; GO:0042552; P:myelination; IDA:UniProtKB.
DR GO; GO:0022011; P:myelination in peripheral nervous system; IMP:ZFIN.
DR GO; GO:0048932; P:myelination of posterior lateral line nerve axons; IMP:ZFIN.
DR GO; GO:0001503; P:ossification; IMP:ZFIN.
DR GO; GO:0032290; P:peripheral nervous system myelin formation; IMP:ZFIN.
DR GO; GO:1903670; P:regulation of sprouting angiogenesis; IMP:ZFIN.
DR GO; GO:0014037; P:Schwann cell differentiation; ISS:UniProtKB.
DR GO; GO:0060879; P:semicircular canal fusion; IMP:ZFIN.
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 Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Membrane; Receptor; Reference proteome; Signal; Transducer; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..32
FT /evidence="ECO:0000255"
FT CHAIN 33..1185
FT /note="Adhesion G-protein coupled receptor G6"
FT /id="PRO_0000391719"
FT CHAIN 33..827
FT /note="ADGRG6 N-terminal fragment"
FT /evidence="ECO:0000250|UniProtKB:Q6F3F9"
FT /id="PRO_0000438600"
FT CHAIN 828..1185
FT /note="ADGRG6 C-terminal fragment"
FT /evidence="ECO:0000250|UniProtKB:Q6F3F9"
FT /id="PRO_0000438601"
FT TOPO_DOM 33..849
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 850..870
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 871..886
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 887..907
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 908..915
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 916..936
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 937..957
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 958..978
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 979..1013
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1014..1034
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1035..1057
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1058..1080
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1081..1083
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1084..1106
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1107..1185
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 41..149
FT /note="CUB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00059"
FT DOMAIN 154..355
FT /note="Pentraxin (PTX)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01172"
FT DOMAIN 787..839
FT /note="GPS"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00098"
FT REGION 41..839
FT /note="Inhibits receptor signaling in absence of type IV
FT collagen"
FT /evidence="ECO:0000269|PubMed:25118328"
FT REGION 41..354
FT /note="Mediates interaction with type IV collagen"
FT /evidence="ECO:0000269|PubMed:25118328"
FT REGION 1138..1160
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 829..837
FT /note="Stachel"
FT /evidence="ECO:0000250|UniProtKB:Q86SQ4"
FT SITE 827..828
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q86SQ4"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 121
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 429
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 470
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 539
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 550
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 562
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 565
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 613
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 680
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 691
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 719
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 763
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 799
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 185..248
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01172"
FT VARIANT 963
FT /note="I -> N (in lau; allele tb233c; semicircular canal
FT defects)"
FT /evidence="ECO:0000269|PubMed:24067352"
FT VARIANT 969
FT /note="P -> L (in lau; allele tk256a; semicircular canal
FT defects)"
FT /evidence="ECO:0000269|PubMed:24067352"
FT MUTAGEN 831..832
FT /note="Missing: In stl215; mutants developp swollen ears,
FT fail to express mbp and do not myelinate peripheral axons."
FT /evidence="ECO:0000269|PubMed:25533341"
SQ SEQUENCE 1185 AA; 130813 MW; E9D8FDE1D349E8FA CRC64;
MISFISGRWW RWKFQNTLAV FLLLICLSTS VAQSCQSSTS CNVVLTDSQG SFTSPCYPND
YPPSQSCNWT IQAPAGFIVQ ITFLDFELEE AQGCIYDRVV VKTGTSDAKF CGLTANGLTL
NSTGNVMEVF FNSDFSVQKK GFHISYKQVA VTLRNQKVTM PKSSKTILRV SNSISIPVLT
AFTVCFEIAR TAQKATETIF TLSDAAGTSI LAFEKTSNGM ELFIGASYCS VDNLLTSSDI
TATMKPLCLT WTKSSGLIGV YFGGHYFSSI CSASQIYTLQ SGGLLQIAGK GSSSVSVDDQ
NLDGFIYNFR LWDHAMLSSE LSALTCDTVG NVVDWDHSYW TIPGSSTQTD STLSCSTAIT
TLSPGTAGCA SGLGCPATLT VTITSIATTN IIPTNATTHE DIFYRSTLVV TDEQTPDRDA
TAIISQWLNQ TFQNWMYRVY VDGISLQLIT VLSRITTTRQ TYLALLVYKN TTDVNLAEVE
IESMLRSAPA IGNGLTLDSV TVNLMENCQA DEFPVHYRWP ESRPTVTQYV PCFPYKDRNA
SRTCMINRDN YTSFWALPDR GNCTNITSIT VSQENAMDVA VQLADISNNG LSKEELTQVV
TKVMELVNIA KINATLASTV VTIISNVMVS SEDAQKDASE TALKAVDELV QKIEFDGPSL
TISSKNLVVG VSALDTTNFN GSTLSAFIAT NTTDPQIDFD SEAHNALAVV TLPPTLLQNL
SLSQIEKVSR INFMFFGRTG LFQDHQNNGL TLNSYVVASS VGNFTIKNLQ DPVRIEIAHL
EYQKDPNPQC VFWDFNLQNY SGGCNSDGCK VGSDSNSNRT VCLCNHLTHF GILMDVSRAA
ELIDEKNNRV LTFITYIGCG ISAIFSAATL LTYIAFEKLR RDYPSKILMN LSTSLLFLNM
VFLLDGWLAS YEIKELCVTV AVFLHFFLLT SFTWMGLESI HMYIALVKVF NTYIRRYILK
FCIVGWGVPA AIVGIVLAVS KDSYGKNYYG KGKDGQGTSE FCWILNPVVF YVTCVAYFSI
IFLMNVAMFI VVMIQICGRN GKRSNRTLRE DILRNLRSVV SLTFLLGMTW GFAFFAWGPV
SLAFMYLFTI FNSLQGLFIF VFHCALKENV QKQWRRYLCC GKLRLADNSD WSKTATNNTK
KVSSDNLGKS LSSSSFGSTT ANWTSKAKAT LNPFARHSNA DSTLQ
