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ADGRD1 Membrane Protein Introduction

Introduction of ADGRD1

ADGRD1, also known as G-protein coupled receptor 133 (GPR133) or G-protein coupled receptor PGR25 (PGR25), is a protein encoded by the human GPR133 gene. It belongs to the adhesion-GPCR family which is characterized by an extended extracellular region with a variable number of protein domains coupled to a TM7 domain via a domain known as the GPCR-Autoproteolysis INducing (GAIN) domain. Moreover, it also has high basal activity with high expression levels at the cell surface.

Basic Information of ADGRD1
Protein Name Adhesion G-protein coupled receptor D1
Gene Name ADGRD1
Aliases G-protein coupled receptor 133, G-protein coupled receptor PGR25
Organism Homo sapiens (Human)
UniProt ID Q6QNK2
Transmembrane Times 7
Length (aa) 906
Sequence MEKLLRLCCWYSWLLLFYYNFQVRGVYSRSQDHPGFQVLASASHYWPLENVDGIHELQDTTGASRTHKLT
VLPSRNATFVYSNDSAYSNLSATVDIVEGKVNKGIYLKEEKGVTLLYYGRYNSSCISKPEQCGPEGVTFS
FFWKTQGEQSRPIPSAYGGQVISNGFKVCSSGGRGSVELYTRDNSMTWEASFSPPGPYWTHVLFTWKSKE
GLKVYVNGTLSTSDPSGKVSRDYGESNVNLVIGSEQDQAKCYENGAFDEFIIWERALTPDEIAMYFTAAI
GKHALLSSTLPSLFMTSTASPVMPTDAYHPIITNLTEERKTFQSPGVILSYLQNVSLSLPSKSLSEQTAL
NLTKTFLKAVGEILLLPGWIALSEDSAVVLSLIDTIDTVMGHVSSNLHGSTPQVTVEGSSAMAEFSVAKI
LPKTVNSSHYRFPAHGQSFIQIPHEAFHRHAWSTVVGLLYHSMHYYLNNIWPAHTKIAEAMHHQDCLLFA
TSHLISLEVSPPPTLSQNLSGSPLITVHLKHRLTRKQHSEATNSSNRVFVYCAFLDFSSGEGVWSNHGCA
LTRGNLTYSVCRCTHLTNFAILMQVVPLELARGHQVALSSISYVGCSLSVLCLVATLVTFAVLSSVSTIR
NQRYHIHANLSFAVLVAQVLLLISFRLEPGTTPCQVMAVLLHYFFLSAFAWMLVEGLHLYSMVIKVFGSE
DSKHRYYYGMGWGFPLLICIISLSFAMDSYGTSNNCWLSLASGAIWAFVAPALFVIVVNIGILIAVTRVI
SQISADNYKIHGDPSAFKLTAKAVAVLLPILGTSWVFGVLAVNGCAVVFQYMFATLNSLQGLFIFLFHCL
LNSEVRAAFKHKTKVWSLTSSSARTSNAKPFHSDLMNGTRPGMASTKLSPWDKSSHSAHRVDLSAV

Function of ADGRD1 Membrane Protein

Studies have found that ADGRD1, an orphan adhesion G-protein-coupled receptor (GPCR), is enriched in CD133-expressing GBM cells with enhanced tumorigenic potential. ADGRD1 is also found in the hypoxic areas of pseudopalisading necrosis in human biospecimens. Recently, studies reveal that there are strong associations between GPR133 and various biological processes, including but not limited to human weight, HIV-1 pathogenesis, the heat shock response, and sporadic amyotrophic lateral sclerosis. Moreover, GPR133 is experimentally proven to activate the adenylate cyclase pathway by binding to Gαqs4 (Gα protein) and involve in cyclic adenosine monophosphate (cAMP)-stimulated cell proliferation. And ADGRD1 could couple to the Gs protein/adenylyl cyclase signaling pathway and is activated by a tethered agonist.

Adhesion G protein-coupled receptors possess structural elements of adhesion molecules and GPCRs.Fig.1 Adhesion G protein-coupled receptors possess structural elements of adhesion molecules and GPCRs. (Cazorla-Vázquez, et.al. 2018)

Application of ADGRD1 Membrane Protein in Literature

1. Bayin NS, et.al. GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth. Oncogenesis. 2016, 5(10): e263. PubMed ID: 5117849

This article suggests that GPR133 is an important mediator of the hypoxic response in GBM and has significant protumorigenic functions. And it may be used as a novel molecular target in GBM and possibly other malignancies where hypoxia is fundamental to pathogenesis.

2. Fischer L, et.al. Functional relevance of naturally occurring mutations in adhesion G protein-coupled receptor ADGRD1 (GPR133). BMC Genomics. 2016, 17(1): 609. PubMed ID: 4982218

This article reveals that there is a variety of functionally relevant ADGRD1 variants in the human population which may cause clinically relevant phenotypes while being compatible with life when heterozygous.

3. Frenster JD, et.al. GPR133 Promotes Glioblastoma Growth in Hypoxia. Neurosurgery. 2017, 64: 177-81. PubMed ID: 28899043

This article suggests that GPR133 plays an important protumorigenic role in GBM, particularly in the context of hypoxia. And it can be used as a novel therapeutic target.

4. Liebscher I, et.al. A tethered agonist within the ectodomain activates the adhesion G protein-coupled receptors GPR126 and GPR133. Cell reports. 2014, 9(6): 2018-26. PubMed ID: 25533341

This article indicates a mode of aGPCR activation and may prompt the development of specific ligands for this currently untargeted GPCR family.

5. Bohnekamp J, Schöneberg T. Cell adhesion receptor GPR133 couples to Gs protein. Journal of Biological Chemistry. 2011, 286(49): 41912-6. PubMed ID: 22025619

This article demonstrates that GPR133, a member of the adhesion GPCR subfamily, activates the G(s) protein/adenylyl cyclase pathway.

ADGRD1 Preparation Options

With advanced Magic™ membrane protein production platform and experienced scientists, we offer many flexible options for membrane protein preparation. In order to obtain the specific target protein, we provide both reconstitution forms as well as multiple active formats for worldwide customers. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-ADGRD1 antibody development services.


Creative Biolabs is dedicated to offering the most high-quality membrane protein preparation service for worldwide customers. For years, we have been making constant efforts to satisfy our customers with innovative technology and superior service. If you are interested in the service we can provide, please feel free to contact us for more information.

Reference

  1. Cazorla-Vázquez,et.al. (2018). Adhesion GPCRs in Kidney Development and Disease. Frontiers in Cell and Developmental Biology, 6, 9.

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