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Protein

Adhesion G-protein coupled receptor G6

Gene

Adgrg6

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

G-protein coupled receptor which is activated by type IV collagen, a major constituent of the basement membrane. Essential for normal differentiation of promyelinating Schwann cells and for normal myelination of axons these functions are mediated via G-protein-signaling pathways (PubMed:24227709, PubMed:21613327). Regulates also neural, cardiac and ear development via G-protein- and/or N-terminus-dependent signaling. May act as a receptor for PRNP which may promote myelin homeostasis (PubMed:27501152).By similarity3 Publications
ADGRG6 N-terminal fragment: Plays an important role in heart developmention (PubMed:24082093). Necessary and sufficient for axon sorting by Schwann cells independently of the ADGRG6-CTF (PubMed:25695270).2 Publications

GO - Molecular functioni

GO - Biological processi

  • cAMP-mediated signaling Source: UniProtKB
  • cell surface receptor signaling pathway Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • heart trabecula formation Source: UniProtKB
  • mitochondrion organization Source: UniProtKB
  • myelination Source: UniProtKB
  • myelination in peripheral nervous system Source: UniProtKB
  • positive regulation of adenylate cyclase activity involved in G-protein coupled receptor signaling pathway Source: UniProtKB
  • Schwann cell differentiation Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Names & Taxonomyi

Protein namesi
Recommended name:
Adhesion G-protein coupled receptor G6
Alternative name(s):
Developmentally regulated G-protein-coupled receptor1 Publication
G-protein coupled receptor 126
Cleaved into the following 2 chains:
ADGRG6 N-terminal fragment2 Publications
Short name:
ADGRG6-NTF
ADGRG6 C-terminal fragment2 Publications
Short name:
ADGRG6-CTF
Gene namesi
Name:Adgrg6Imported
Synonyms:Dreg, Gm222, Gpr126
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1916151. Adgrg6.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini31 – 832ExtracellularSequence analysisAdd BLAST802
Transmembranei833 – 853Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini854 – 873CytoplasmicSequence analysisAdd BLAST20
Transmembranei874 – 894Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini895 – 899ExtracellularSequence analysis5
Transmembranei900 – 920Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini921 – 940CytoplasmicSequence analysisAdd BLAST20
Transmembranei941 – 961Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini962 – 994ExtracellularSequence analysisAdd BLAST33
Transmembranei995 – 1015Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini1016 – 1039CytoplasmicSequence analysisAdd BLAST24
Transmembranei1040 – 1060Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini1061 – 1062ExtracellularSequence analysis2
Transmembranei1063 – 1083Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini1084 – 1165CytoplasmicSequence analysisAdd BLAST82

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Disruption phenotypei

Deficient mice die during organogenesis. Mutant embryos show signs of myocardial wall thinning, hypotrabeculation, defective mitochondrial and circulatory failure.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 30Sequence analysisAdd BLAST30
ChainiPRO_000030388831 – 1165Adhesion G-protein coupled receptor G6Add BLAST1135
ChainiPRO_000043859831 – 440ADGRG6 N-terminal fragment1 PublicationAdd BLAST410
ChainiPRO_0000438599441 – 1165ADGRG6 C-terminal fragment1 PublicationAdd BLAST725

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi41 ↔ 67PROSITE-ProRule annotation
Disulfide bondi94 ↔ 111PROSITE-ProRule annotation
Glycosylationi121N-linked (GlcNAc...)Sequence analysis1
Glycosylationi143N-linked (GlcNAc...)Sequence analysis1
Glycosylationi258N-linked (GlcNAc...)Sequence analysis1
Glycosylationi314N-linked (GlcNAc...)1 Publication1
Glycosylationi324N-linked (GlcNAc...)Sequence analysis1
Glycosylationi353N-linked (GlcNAc...)Sequence analysis1
Glycosylationi370N-linked (GlcNAc...)Sequence analysis1
Glycosylationi410N-linked (GlcNAc...)Sequence analysis1
Glycosylationi417N-linked (GlcNAc...)Sequence analysis1
Glycosylationi424N-linked (GlcNAc...)Sequence analysis1
Glycosylationi458N-linked (GlcNAc...)Sequence analysis1
Glycosylationi462N-linked (GlcNAc...)Sequence analysis1
Glycosylationi478N-linked (GlcNAc...)Sequence analysis1
Glycosylationi536N-linked (GlcNAc...)Sequence analysis1
Glycosylationi549N-linked (GlcNAc...)Sequence analysis1
Glycosylationi563N-linked (GlcNAc...)Sequence analysis1
Glycosylationi570N-linked (GlcNAc...)Sequence analysis1
Glycosylationi665N-linked (GlcNAc...)Sequence analysis1
Glycosylationi674N-linked (GlcNAc...)Sequence analysis1
Glycosylationi720N-linked (GlcNAc...)Sequence analysis1
Glycosylationi746N-linked (GlcNAc...)Sequence analysis1
Glycosylationi781N-linked (GlcNAc...)Sequence analysis1
Glycosylationi788N-linked (GlcNAc...)Sequence analysis1
Modified residuei1135PhosphoserineCombined sources1
Modified residuei1138PhosphoserineCombined sources1

Post-translational modificationi

Proteolytically cleaved into 2 conserved sites: one in the GPS domain (S1 site) and the other in the middle of the extracellular domain (S2 site). The proteolytic cleavage at S1 site generates an N-terminal fragment (NTF) and a seven-transmembrane-containing C-terminal fragment (CTF). The membrane-bound CTF can act as an independent receptor and the soluble NTF can act as a ligand or coreceptor. Furin is involved in the cleavage of the S2 site generating a soluble fragment. Processing at the GPS domain occurred independent of and probably prior to the cleavage at the S2 site. Proteolytic cleavage is required for activation of the receptor (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei440 – 441Cleavage; by furin like-convertase1 Publication2
Sitei810 – 811Cleavage1 Publication2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ6F3F9.
PaxDbiQ6F3F9.
PeptideAtlasiQ6F3F9.
PRIDEiQ6F3F9.

PTM databases

iPTMnetiQ6F3F9.
PhosphoSitePlusiQ6F3F9.

Expressioni

Tissue specificityi

Expressed at high levels in the heart, somite and otic vesicle during embryogenesis and in adult lung.2 Publications

Gene expression databases

BgeeiENSMUSG00000039116.
CleanExiMM_GPR126.
ExpressionAtlasiQ6F3F9. baseline and differential.
GenevisibleiQ6F3F9. MM.

Interactioni

Subunit structurei

Interacts with Laminin-2; this interaction stabilizes the receptor in an inactive state (PubMed:25695270). Laminin-2 polymerization could facilitate ADGRG6-NTF removal, thereby exposing the tethered agonist to drive myelination (PubMed:25695270). Interacts with PRNP (PubMed:27501152).2 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000043055.

Structurei

3D structure databases

ProteinModelPortaliQ6F3F9.
SMRiQ6F3F9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 149CUBPROSITE-ProRule annotationAdd BLAST109
Domaini150 – 355PentaxinAdd BLAST206
Domaini770 – 822GPSPROSITE-ProRule annotationAdd BLAST53

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni41 – 822Inhibits receptor signaling in absence of type IV collagenBy similarityAdd BLAST782
Regioni41 – 355Mediates interaction with type IV collagenBy similarityAdd BLAST315
Regioni446 – 807Mediates interaction with laminin-21 PublicationAdd BLAST362

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi812 – 820STACHELBy similarity9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1123 – 1165Ser-richAdd BLAST43

Sequence similaritiesi

Contains 1 CUB domain.PROSITE-ProRule annotation
Contains 1 GPS domain.PROSITE-ProRule annotation
Contains 1 pentaxin domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
KOG4193. Eukaryota.
ENOG410XSD2. LUCA.
GeneTreeiENSGT00830000128227.
HOGENOMiHOG000112768.
HOVERGENiHBG051778.
InParanoidiQ6F3F9.
KOiK08463.
OrthoDBiEOG091G00P5.
PhylomeDBiQ6F3F9.
TreeFamiTF321769.

Family and domain databases

CDDicd00041. CUB. 1 hit.
Gene3Di2.60.120.290. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR000859. CUB_dom.
IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
IPR000203. GPS.
IPR001759. Pentaxin-related.
[Graphical view]
PfamiPF00002. 7tm_2. 1 hit.
PF00431. CUB. 1 hit.
PF01825. GPS. 1 hit.
[Graphical view]
PRINTSiPR00249. GPCRSECRETIN.
SMARTiSM00042. CUB. 1 hit.
SM00303. GPS. 1 hit.
SM00159. PTX. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEiPS01180. CUB. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
PS50221. GPS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q6F3F9-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMFDTLGKRC CPWRLKPSAL LFLFVLCVTC VPLSVCGCGS CRLVLSNPSG
60 70 80 90 100
TFTSPCYPND YPNTQSCSWT LRAPAGYIIQ ITFNDFDIEE APNCIYDSLS
110 120 130 140 150
LDNGESQTKF CGATAKGLSF NSSVNEMHVS FSSDFSIQKK GFNASYIRVA
160 170 180 190 200
VSLRNQKVIL PQTLDAYQVS VAKSISIPEL KAFTLCFEAS KVGNEGGDWT
210 220 230 240 250
AFSYSDESLT QLLSLEKASN GYFLSISGSR CLLNNALPVK DKEDIFTENL
260 270 280 290 300
EQLCLVWNNS WGSIGINFKK NYETVPCDST ISAVVPGDGT LLLGSDRDEV
310 320 330 340 350
ASLRGSIYNF RLWNFTMDLK ALSNLSCSVS GNVIDWHNDF WSISTQALKA
360 370 380 390 400
EGNLSCGSYL IQLPAAELTN CSELGTLCQD GIMYRISVVI HNDFNHPEVK
410 420 430 440 450
VQTKVAEWLN STFQNWNYTV YVVNISFHQK VGEDRMKVKR DIMDDDKRLV
460 470 480 490 500
LWALLVYNAT NNVSLNEEKI KQKLMTNNAS LEDGLRLCEV DVNQLGMCSA
510 520 530 540 550
LEDPDGFSWP ATLPSVYKQP CPNKPGFFMT RACLSNGTST FWGPVDTSNC
560 570 580 590 600
SRQSNEVANE ILNQTGDGQN LTSANINSIV EKVKRIVNKE ENIDITLGST
610 620 630 640 650
LMNIFSNILS SSDSDLLESS TEALKTIDEL AFKIDLNSTP HVNIETQNLA
660 670 680 690 700
LGVSSLIPGT NAPSNFSIGL PSNNESYFQM DFGNGQTDPL ASVILPPNLL
710 720 730 740 750
ENLSPEDSVL VRRAQFTFFN KTGLFQDVGS QRKVLVSYVM ACSIGNITIQ
760 770 780 790 800
NLKDPVQIKI KHTRTQEVHH PICAFWDMNK NKSFGGWNTS GCVAHSDLDA
810 820 830 840 850
GETICLCSHF THFGVLMDLP RSASQIDGRN TKVLTFITYI GCGISAIFSA
860 870 880 890 900
ATLLTYVAFE KLRRDYPSKI LMNLSSALLF LNLIFLLDGW VTSFGVAGLC
910 920 930 940 950
TAVAALLHFF LLATFTWMGL EAIHMYIALV KVFNTYIHRY ILKFCIIGWG
960 970 980 990 1000
LPALVVSIIL VSRRQNEVYG KESYGKDQDD EFCWIQDPVV FYVSCAGYFG
1010 1020 1030 1040 1050
VMFFLNVAMF IVVMVQICGR NGKRSNRTLR EEVLRNLRSV VSLTFLLGMT
1060 1070 1080 1090 1100
WGFAFFAWGP LNIPFMYLFS IFNSLQGLFI FIFHCAMKEN VQKQWRRHLC
1110 1120 1130 1140 1150
CGRFRLADNS DWSKTATNII KKSSDNLGKS LSSSSIGSNS TYLTSKSKSS
1160
STTYFKRNSH SDNFS
Length:1,165
Mass (Da):129,721
Last modified:August 16, 2004 - v1
Checksum:iB5CC5CDEAA42CB50
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB183545 mRNA. Translation: BAD27570.1.
BC046534 mRNA. Translation: AAH46534.1.
CCDSiCCDS35848.1.
RefSeqiNP_001002268.1. NM_001002268.3.
UniGeneiMm.440142.

Genome annotation databases

EnsembliENSMUST00000041168; ENSMUSP00000043055; ENSMUSG00000039116.
GeneIDi215798.
KEGGimmu:215798.
UCSCiuc007elk.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB183545 mRNA. Translation: BAD27570.1.
BC046534 mRNA. Translation: AAH46534.1.
CCDSiCCDS35848.1.
RefSeqiNP_001002268.1. NM_001002268.3.
UniGeneiMm.440142.

3D structure databases

ProteinModelPortaliQ6F3F9.
SMRiQ6F3F9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000043055.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ6F3F9.
PhosphoSitePlusiQ6F3F9.

Proteomic databases

MaxQBiQ6F3F9.
PaxDbiQ6F3F9.
PeptideAtlasiQ6F3F9.
PRIDEiQ6F3F9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000041168; ENSMUSP00000043055; ENSMUSG00000039116.
GeneIDi215798.
KEGGimmu:215798.
UCSCiuc007elk.1. mouse.

Organism-specific databases

CTDi57211.
MGIiMGI:1916151. Adgrg6.

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
KOG4193. Eukaryota.
ENOG410XSD2. LUCA.
GeneTreeiENSGT00830000128227.
HOGENOMiHOG000112768.
HOVERGENiHBG051778.
InParanoidiQ6F3F9.
KOiK08463.
OrthoDBiEOG091G00P5.
PhylomeDBiQ6F3F9.
TreeFamiTF321769.

Miscellaneous databases

PROiQ6F3F9.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039116.
CleanExiMM_GPR126.
ExpressionAtlasiQ6F3F9. baseline and differential.
GenevisibleiQ6F3F9. MM.

Family and domain databases

CDDicd00041. CUB. 1 hit.
Gene3Di2.60.120.290. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR000859. CUB_dom.
IPR017981. GPCR_2-like.
IPR001879. GPCR_2_extracellular_dom.
IPR000832. GPCR_2_secretin-like.
IPR017983. GPCR_2_secretin-like_CS.
IPR000203. GPS.
IPR001759. Pentaxin-related.
[Graphical view]
PfamiPF00002. 7tm_2. 1 hit.
PF00431. CUB. 1 hit.
PF01825. GPS. 1 hit.
[Graphical view]
PRINTSiPR00249. GPCRSECRETIN.
SMARTiSM00042. CUB. 1 hit.
SM00303. GPS. 1 hit.
SM00159. PTX. 1 hit.
[Graphical view]
SUPFAMiSSF49854. SSF49854. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEiPS01180. CUB. 1 hit.
PS00650. G_PROTEIN_RECEP_F2_2. 1 hit.
PS50227. G_PROTEIN_RECEP_F2_3. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
PS50221. GPS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAGRG6_MOUSE
AccessioniPrimary (citable) accession number: Q6F3F9
Secondary accession number(s): Q811E4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: August 16, 2004
Last modified: November 30, 2016
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.