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ADGRA2 Membrane Protein Introduction

Introduction of ADGRA2

ADGRA2, also known as adhesion G protein-coupled receptor A2 or tumor endothelial marker 5, is a protein that encoded by the human GPR124 gene. Together with two other members of the GPCR protein family, Adgra1 (Gpr123) and Adgra3 (Gpr125), the three genes form a special group of adhesion G protein-coupled receptors A. It has been reported that the extracellular part of Adgra2 contains a leucine-rich repeat (LRR), an immunoglobulin domain (IG), a hormone receptor domain and a G protein-coupled receptor proteolytic site (GPS). And the intracellular part is characterized by a PDZ binding domain.

Basic Information of ADGRA2
Protein Name Adhesion G protein-coupled receptor A2
Gene Name ADGRA2
Aliases G-protein coupled receptor 124, Tumor endothelial marker 5
Organism Homo sapiens (Human)
UniProt ID Q96PE1
Transmembrane Times 7
Length (aa) 1338
Sequence MGAGGRRMRGAPARLLLPLLPWLLLLLAPEARGAPGCPLSIRSCKCSGERPKGLSGGVPGPARRRVVCSG
GDLPEPPEPGLLPNGTVTLLLSNNKITGLRNGSFLGLSLLEKLDLRNNIISTVQPGAFLGLGELKRLDLS
NNRIGCLTSETFQGLPRLLRLNISGNIFSSLQPGVFDELPALKVVDLGTEFLTCDCHLRWLLPWAQNRSL
QLSEHTLCAYPSALHAQALGSLQEAQLCCEGALELHTHHLIPSLRQVVFQGDRLPFQCSASYLGNDTRIR
WYHNRAPVEGDEQAGILLAESLIHDCTFITSELTLSHIGVWASGEWECTVSMAQGNASKKVEIVVLETSA
SYCPAERVANNRGDFRWPRTLAGITAYQSCLQYPFTSVPLGGGAPGTRASRRCDRAGRWEPGDYSHCLYT
NDITRVLYTFVLMPINASNALTLAHQLRVYTAEAASFSDMMDVVYVAQMIQKFLGYVDQIKELVEVMVDM
ASNLMLVDEHLLWLAQREDKACSRIVGALERIGGAALSPHAQHISVNARNVALEAYLIKPHSYVGLTCTA
FQRREGGVPGTRPGSPGQNPPPEPEPPADQQLRFRCTTGRPNVSLSSFHIKNSVALASIQLPPSLFSSLP
AALAPPVPPDCTLQLLVFRNGRLFHSHSNTSRPGAAGPGKRRGVATPVIFAGTSGCGVGNLTEPVAVSLR
HWAEGAEPVAAWWSQEGPGEAGGWTSEGCQLRSSQPNVSALHCQHLGNVAVLMELSAFPREVGGAGAGLH
PVVYPCTALLLLCLFATIITYILNHSSIRVSRKGWHMLLNLCFHIAMTSAVFAGGITLTNYQMVCQAVGI
TLHYSSLSTLLWMGVKARVLHKELTWRAPPPQEGDPALPTPSPMLRFYLIAGGIPLIICGITAAVNIHNY
RDHSPYCWLVWRPSLGAFYIPVALILLITWIYFLCAGLRLRGPLAQNPKAGNSRASLEAGEELRGSTRLR
GSGPLLSDSGSLLATGSARVGTPGPPEDGDSLYSPGVQLGALVTTHFLYLAMWACGALAVSQRWLPRVVC
SCLYGVAASALGLFVFTHHCARRRDVRASWRACCPPASPAAPHAPPRALPAAAEDGSPVFGEGPPSLKSS
PSGSSGHPLALGPCKLTNLQLAQSQVCEAGAAAGGEGEPEPAGTRGNLAHRHPNNVHHGRRAHKSRAKGH
RAGEACGKNRLKALRGGAAGALELLSSESGSLHNSPTDSYLGSSRNSPGAGLQLEGEPMLTPSEGSDTSA
APLSEAGRAGQRRSASRDSLKGGGALEKESHRRSYPLNAASLNGAPKGGKYDDVTLMGAEVASGGCMKTG
LWKSETTV

Function of ADGRA2 Membrane Protein

As a member of the G protein-coupled receptor family which are characterized by seven 7 transmembrane helices, ADGRA2 receives signals from various extracellular ligands such as photons, hormones, and small molecules and translate them into several intracellular signaling cascades. The expression of ADGRA2 has been found in several human tissues, especially in the blood vessels of tumors. Studies have suggested that there is a correlation between ADGRA2 and the development of hypertension as ADGRA2 is associated with Vascular Endothelial Growth Factor (VEGF)-dependent and independent cell migration events. It has been reported that GPR124 is essential for numerous biological processes, including invasion and migration of blood vessels into neuroepithelium, establishment of BBB properties, and expansion of the cerebral cortex. Moreover, ADGRA2 is also an important regulator of neurovasculature development and a potential drug target for cerebrovascular diseases.

The human adhesion GPCR family.Fig.1 The human adhesion GPCR family.

Application of ADGRA2 Membrane Protein in Literature

1. Seigfried FA, et.al. Expression of the adhesion G protein-coupled receptor A2 (adgra2) during Xenopus laevis development. Gene Expression Patterns. 2018, 28: 54-61. PubMed ID: 29462671

This article proves that the role of ADGRA2 in embryogenesis which indicates a good starting point for further functional studies during early vertebrate development.

2. Hernández-Vásquez MN, et.al. Cell adhesion controlled by adhesion G protein-coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo-Dock. Journal of Biological Chemistry. 2017, 292(29): 12178-91. PubMed ID: 28600358

This article reveals that ADGRA2 could promote cell adhesion through Elmo-Dock and ITSN which constitutes a previously unrecognized complex involved in ADGRA2-dependent angiogenic responses.

3. Calderón-Zamora L, et.al. Possible involvement of orphan receptors GPR88 and GPR124 in the development of hypertension in spontaneously hypertensive rat. Clinical and Experimental Hypertension. 2017, 39(6): 513-9. PubMed ID: 28678544

This report finds that the expression of ADGRA2 in rat tissues is dependent on the age and development of hypertension which indicates that ADGRA2 receptor may be involved in the development or maintenance of high blood pressure.

4. Bostaille N, et.al. Molecular insights into Adgra2/Gpr124 and Reck intracellular trafficking. Biology open. 2016, 5(12): 1874-81. PubMed ID: 27979830

This article evaluates the manner of the ADGRA2 trafficking appearance by using CRISPR/Cas9 engineered cells. It indicates that ADGRA2 trafficking occurs in a Reck-independent manner and Reck reaches the plasma membrane regardless of ADGRA2 expression and location.

ADGRA2 Preparation Options

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