Xenotropic and polytropic retrovirus receptor 1

XPR1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	5IJH
Identifiers
Aliases	XPR1 , SYG1, X3, IBGC6, xenotropic and polytropic retrovirus receptor 1, SLC53A1
External IDs	OMIM: 605237; MGI: 97932; HomoloGene: 134226; GeneCards: XPR1; OMA:XPR1 - orthologs
Gene location (Human)
Chr.	Chromosome 1 (human)
End	180,890,279 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	155,293,161 bp
RNA expression pattern
	Top expressed in
	myocardium of left ventricle; ; ganglionic eminence; ; secondary oocyte; ; endothelial cell; ; nasal epithelium; ; pancreatic epithelial cell; ; cardiac muscle tissue of right atrium; ; islet of Langerhans; ; Brodmann area 23; ; right ventricle;
	Top expressed in
	median eminence; ; ventromedial nucleus; ; lateral septal nucleus; ; arcuate nucleus; ; habenula; ; ascending aorta; ; dorsomedial hypothalamic nucleus; ; extensor digitorum longus muscle; ; mammillary body; ; triceps brachii muscle;
	More reference expression data
	n/a
Gene ontology
Molecular function	G protein-coupled receptor activity ; transmembrane signaling receptor activity ; phosphate ion transmembrane transporter activity ; inositol hexakisphosphate binding ; virus receptor activity ; efflux transmembrane transporter activity ; signaling receptor activity ;
Cellular component	integral component of membrane ; membrane ; intrinsic component of plasma membrane ; plasma membrane ; cytoplasm ; Golgi apparatus ;
Biological process	viral entry into host cell ; G protein-coupled receptor signaling pathway ; response to virus ; cellular phosphate ion homeostasis ; phosphate ion transmembrane transport ; phosphate ion transport ; cellular response to phosphate starvation ;
	Sources:Amigo / QuickGO
Orthologs
	9213
	19775
	ENSG00000143324
	ENSMUSG00000026469
	Q9UBH6
	Q9Z0U0
	NM_004736 ; NM_001135669 ; NM_001328662
	NM_011273
	NP_001129141 ; NP_001315591 ; NP_004727
	NP_035403
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated October 01, 2024

Gene and physiological roles

Xenotropic and polytropic retrovirus receptor 1 is a protein that in humans is encoded by the XPR1 gene. ^[5] It is a member of the solute carrier (SLC) family, specifically classified as SLC53A1. XPR1 is crucial for maintaining cellular phosphate homeostasis by facilitating the efflux of inorganic phosphate (Pi) from cells.^[6] Mutations in XPR1 that disrupt its phosphate export function are linked to Primary familial brain calcification (PFBC),^[7] a neurological condition characterized by abnormal hydroxyapatite deposits in the brain.

Structures and functions

XPR1 is characterized by a unique architecture that includes a transmembrane domain (TMD) and a cytoplasmic SPX domain. The TMD is composed of multiple transmembrane helices that form a channel-like structure. Recent cryo-electron microscopy (cryo-EM) studies have revealed various conformational states of XPR1, including inactive (closed) and active (open) forms, as well as intermediate states.^[8]^[9] Notably, XPR1 features dual binding sites for Inositol phosphate(IPs) and inositol pyrophosphates (PP-IPs), which regulate its activity.

Electrophysiological studies on XPR1 showed that XPR1 functions primarily as a PP-IPs gated Pi channel,^[9] playing a pivotal role in preventing the accumulation of excess intracellular phosphate, which can lead to metabolic disorders. It responds to the cellular levels of IPs and PP-IPs, with PP-IPs acting as more potent activators of XPR1 compared to IPs. The binding of these signaling molecules induces conformational changes in XPR1, facilitating the opening of the channel and allowing phosphate ions to exit the cell.

Related Research Articles

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

<span class="mw-page-title-main">Inositol trisphosphate receptor</span> Class of transport proteins

Inositol trisphosphate receptor (InsP3R) is a membrane glycoprotein complex acting as a Ca²⁺ channel activated by inositol trisphosphate (InsP3). InsP3R is very diverse among organisms, and is necessary for the control of cellular and physiological processes including cell division, cell proliferation, apoptosis, fertilization, development, behavior, learning and memory. Inositol triphosphate receptor represents a dominant second messenger leading to the release of Ca²⁺ from intracellular store sites. There is strong evidence suggesting that the InsP3R plays an important role in the conversion of external stimuli to intracellular Ca²⁺ signals characterized by complex patterns relative to both space and time, such as Ca²⁺ waves and oscillations.

Inositol phosphates are a group of mono- to hexaphosphorylated inositols. Each form of inositol phosphate is distinguished by the number and position of the phosphate group on the inositol ring.

Pannexins are a family of vertebrate proteins identified by their homology to the invertebrate innexins. While innexins are responsible for forming gap junctions in invertebrates, the pannexins have been shown to predominantly exist as large transmembrane channels connecting the intracellular and extracellular space, allowing the passage of ions and small molecules between these compartments.

<span class="mw-page-title-main">Xenotropic murine leukemia virus–related virus</span> Species of virus

Xenotropic murine leukemia virus–related virus (XMRV) is a retrovirus which was first described in 2006 as an apparently novel human pathogen found in tissue samples from men with prostate cancer. Initial reports erroneously linked the virus to prostate cancer and later to chronic fatigue syndrome (CFS), leading to considerable interest in the scientific and patient communities, investigation of XMRV as a potential cause of multiple medical conditions, and public-health concerns about the safety of the donated blood supply.

Inositol-trisphosphate 3-kinase B is an enzyme that in humans is encoded by the ITPKB gene.

G protein-coupled receptor 6, also known as GPR6, is a protein which in humans is encoded by the GPR6 gene.

P2Y purinoceptor 14 is a protein that in humans is encoded by the P2RY14 gene.

G-protein coupled receptor 3 is a protein that in humans is encoded by the GPR3 gene. The protein encoded by this gene is a member of the G protein-coupled receptor family of transmembrane receptors and is involved in signal transduction.

In enzymology, a polyphosphate kinase, or polyphosphate polymerase, is an enzyme that catalyzes the formation of polyphosphate from ATP, with chain lengths of up to a thousand or more orthophosphate moieties.

Progressive ankylosis protein homolog is a protein that in humans is encoded by the ANKH gene.

Sodium-dependent phosphate transporter 1 is a protein that in humans is encoded by the SLC20A1 gene.

Inositol-trisphosphate 3-kinase A is an enzyme that in humans is encoded by the ITPKA gene.

Receptor-type tyrosine-protein phosphatase delta is an enzyme that, in humans, is encoded by the PTPRD gene.

Sodium-dependent phosphate transporter 2 is a protein that in humans is encoded by the SLC20A2 gene.

Ryanodine receptor 3 is one of a class of ryanodine receptors and a protein that in humans is encoded by the RYR3 gene. The protein encoded by this gene is both a calcium channel and a receptor for the plant alkaloid ryanodine. RYR3 and RYR1 control the resting calcium ion concentration in skeletal muscle.

Tyrosine-protein kinase CSK also known as C-terminal Src kinase is an enzyme that, in humans, is encoded by the CSK gene. This enzyme phosphorylates tyrosine residues located in the C-terminal end of Src-family kinases (SFKs) including SRC, HCK, FYN, LCK, LYN and YES1.

The Pho1 phosphate permease family is a family of phosphate transporters belonging to the ion transporter (IT) superfamily. Representative members of the Pho1 family include the putative phosphate transporter PHO1 of Arabidopsis thaliana, and the xenotropic and polytropic murine-leukemia virus receptor Xpr1 of Metazoa, such as Homo sapein, Drosophila, and Culex pipiens.

Diphosphoinositol pentakisphosphate kinase 2 is a protein that in humans is encoded by the PPIP5K2 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000143324 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026469 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Entrez Gene: Xenotropic and polytropic retrovirus receptor 1" . Retrieved 2017-03-31.
↑ Giovannini, Donatella; Touhami, Jawida; Charnet, Pierre; Sitbon, Marc; Battini, Jean-Luc (2013). "Inorganic Phosphate Export by the Retrovirus Receptor XPR1 in Metazoans". Cell Reports . 3 (6): 1866–1873. doi:10.1016/j.celrep.2013.05.035. PMID 23791524.
↑ Legati, Andrea; Giovannini, Donatella; Nicolas, Gaël; López-Sánchez, Uriel; Quintáns, Beatriz; Oliveira, João R M; Sears, Renee L; Ramos, Eliana Marisa; Spiteri, Elizabeth; Sobrido, María-Jesús; Carracedo, Ángel; Castro-Fernández, Cristina; Cubizolle, Stéphanie; Fogel, Brent L; Goizet, Cyril (2015). "Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export". Nature Genetics . 47 (6): 579–581. doi:10.1038/ng.3289. ISSN 1061-4036. PMC 4516721 . PMID 25938945.
↑ Yan, Rui; Chen, Huiwen; Liu, Chuanyu; Zhao, Jun; Wu, Di; Jiang, Juquan; Gong, Jianke; Jiang, Daohua (2024-09-26). "Human XPR1 structures reveal phosphate export mechanism". Nature. 633 (8031): 960–967. doi:10.1038/s41586-024-07852-9. ISSN 0028-0836. PMID 39169184.
1 2 Lu, Yi; Yue, Chen-Xi; Zhang, Li; Yao, Deqiang; Xia, Ying; Zhang, Qing; Zhang, Xinchen; Li, Shaobai; Shen, Yafeng; Cao, Mi; Guo, Chang-Run; Qin, An; Zhao, Jie; Zhou, Lu; Yu, Ye (2024-09-26). "Structural basis for inositol pyrophosphate gating of the phosphate channel XPR1". Science. doi:10.1126/science.adp3252. ISSN 0036-8075. PMID 39325866.

Xenotropic and polytropic retrovirus receptor 1

Gene and physiological roles

Contents

Structures and functions

Related Research Articles

References

Further reading