ADGRA3 Membrane Protein Introduction

Introduction of ADGRA3

ADGRA3, also known as adhesion G protein-coupled receptor A3 or G-protein coupled receptor 125 (GPR125), is a protein that encoded by the human GPR125 gene. As a member of the adhesion G protein-coupled receptor family, ADGRA3 has a long extracellular subunit with protein-protein interacting domains and a GPCR subunit. The last four amino acids (ETTV) of Gpr125 constitute a PDZ-binding motif, which is also found in the transmembrane PCP pathway components Frizzled and Vangl2.

Basic Information of ADGRA3
Protein Name	Adhesion G protein-coupled receptor A3
Gene Name	ADGRA3
Aliases	G-protein coupled receptor 125
Organism	Homo sapiens (Human)
UniProt ID	Q8IWK6
Transmembrane Times	7
Length (aa)	1321
Sequence	MEPPGRRRGRAQPPLLLPLSLLALLALLGGGGGGGAAALPAGCKHDGRPRGAGRAAGAAEGKVVCSSLEL AQVLPPDTLPNRTVTLILSNNKISELKNGSFSGLSLLERLDLRNNLISSIDPGAFWGLSSLKRLDLTNNR IGCLNADIFRGLTNLVRLNLSGNLFSSLSQGTFDYLASLRSLEFQTEYLLCDCNILWMHRWVKEKNITVR DTRCVYPKSLQAQPVTGVKQELLTCDPPLELPSFYMTPSHRQVVFEGDSLPFQCMASYIDQDMQVLWYQD GRIVETDESQGIFVEKNMIHNCSLIASALTISNIQAGSTGNWGCHVQTKRGNNTRTVDIVVLESSAQYCP PERVVNNKGDFRWPRTLAGITAYLQCTRNTHGSGIYPGNPQDERKAWRRCDRGGFWADDDYSRCQYANDV TRVLYMFNQMPLNLTNAVATARQLLAYTVEAANFSDKMDVIFVAEMIEKFGRFTKEEKSKELGDVMVDIA SNIMLADERVLWLAQREAKACSRIVQCLQRIATYRLAGGAHVYSTYSPNIALEAYVIKSTGFTGMTCTVF QKVAASDRTGLSDYGRRDPEGNLDKQLSFKCNVSNTFSSLALKNTIVEASIQLPPSLFSPKQKRELRPTD DSLYKLQLIAFRNGKLFPATGNSTNLADDGKRRTVVTPVILTKIDGVNVDTHHIPVNVTLRRIAHGADAV AARWDFDLLNGQGGWKSDGCHILYSDENITTIQCYSLSNYAVLMDLTGSELYTQAASLLHPVVYTTAIIL LLCLLAVIVSYIYHHSLIRISLKSWHMLVNLCFHIFLTCVVFVGGITQTRNASICQAVGIILHYSTLATV LWVGVTARNIYKQVTKKAKRCQDPDEPPPPPRPMLRFYLIGGGIPIIVCGITAAANIKNYGSRPNAPYCW MAWEPSLGAFYGPASFITFVNCMYFLSIFIQLKRHPERKYELKEPTEEQQRLAANENGEINHQDSMSLSL ISTSALENEHTFHSQLLGASLTLLLYVALWMFGALAVSLYYPLDLVFSFVFGATSLSFSAFFVVHHCVNR EDVRLAWIMTCCPGRSSYSVQVNVQPPNSNGTNGEAPKCPNSSAESSCTNKSASSFKNSSQGCKLTNLQA AAAQCHANSLPLNSTPQLDNSLTEHSMDNDIKMHVAPLEVQFRTNVHSSRHHKNRSKGHRASRLTVLREY AYDVPTSVEGSVQNGLPKSRLGNNEGHSRSRRAYLAYRERQYNPPQQDSSDACSTLPKSSRNFEKPVSTT SKKDALRKPAVVELENQQKSYGLNLAIQNGPIKSNGQEGPLLGTDSTGNVRTGLWKHETTV

Function of ADGRA3 Membrane Protein

During the past years, the expression of ADGRA3 has been found in diverse human tissues, including but not limited to thyroid, liver, and other tissues. It has been reported that ADGRA3 can be used as a novel modulator of the Wnt/planar cell polarity signaling system as it can functionally interact with multiple Wnt/PCP components. What’s more, studies have shown that excess Gpr125 could impair convergence and extension (C&E) movements and the underlying cell and molecular polarities. The reduced Gpr125 function may exacerbate the C&E and facial branchiomotor neuron (FBMN) migration defects of embryos with reduced Wnt/planar cell polarity signaling. Most importantly, this membrane protein may play a role in tumor angiogenesis through its interaction with the human homolog of the Drosophila disc large tumor suppressor gene.

Fig.1 Schematic view of the overall structure of a G protein-coupled receptor (GPCR), with depiction of the connectivity of the intracellular (IL) and extracellular (EL) loops between helices (H). (Fossépré, 2014)

Application of ADGRA3 Membrane Protein in Literature

1. Sachs C, et.al. Evaluation of candidate spermatogonial markers ID4 and GPR125 in testes of adult human cadaveric organ donors. Andrology. 2014, 2(4): 607-14. PubMed ID: 24902969

This article suggests that ADGRA3 is useful for identifying previously unrecognized human spermatogonial subpopulations in conjunction with other putative human stem cell markers, both in younger and older donors.

2. Fu JF, et.al. Involvement of Gpr125 in the myeloid sarcoma formation induced by cooperating MLL/AF10 (OM-LZ) and oncogenic KRAS in a mouse bone marrow transplantation model. International journal of cancer. 2013, 133(8): 1792-802. PubMed ID: 23564351

This article reveals that upregulation of ADGRA3 by cooperating MLL/AF10 (OM-LZ) and KRASG12C could promote cell adhesion and contribute to the MS formation.

3. Li X, et.al. Gpr125 modulates Dishevelled distribution and planar cell polarity signaling. Development. 2013, 140(14): 3028-39. PubMed ID: 23821037

This article reveals the role of ADGRA3 in PCP-mediated processes. The ADGRA3 intracellular domain directly could interact with Dvl. Moreover, ADGRA3 is able to recruit a subset of PCP components into membrane subdomains, suggesting that ADGRA3 may modulate the composition of Wnt/PCP membrane complexes.

4. Pickering C, et.al. The Adhesion GPCR GPR125 is specifically expressed in the choroid plexus and is upregulated following brain injury. BMC Neuroscience. 2008, (1): 97. PubMed ID: 18834514

This article indicates that GPR125 may play a functional role in choroidal and hippocampal response to injury.

5. Seandel M, et.al. Niche players: spermatogonial progenitors marked by GPR125. Cell Cycle. 2008, 7(2): 135-40. PubMed ID: 18256534

This article reveals that GPR125 could be used as a novel target for purifying adult stem and progenitors from tissues, with the goal of developing autologous multipotent cell lines.

ADGRA3 Preparation Options

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Reference

Fossépré, et al. (2014). On the modularity of the intrinsic flexibility of the µ opioid receptor: a computational study. PloS one 9.12: e115856.

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