2.A.94 The Phosphate Permease (Pho1) Family

Pho1 of A. thaliana (TC# 2.A.94.1.1) is a member of the PHO1 family (11 paralogues in A. thaliana). It functions in inorganic phosphate transport and homeostasis. Pho1 catalyzes efflux of phosphate from epidermal and cortical cells into the xylem (Quaghebeur and Rengel, 2004; Stefanovic et al., 2007). The SPX superfamily domain is an N-terminal soluble domain. These proteins belong to the EXS (Erd1/Xpr1/Syg1) superfamily. Recently it has been suggested that XPR1 is a  regulator of cellular phosphate homeostasis rather than a Pi exporter (Burns et al. 2024).

Erd1 (TC# 2.A.94.1.7) is a member of the Pho1 family and is of 362 aas possibly with 7 TMSs in a 1 + 2 + 3 + 1 TMS arrangement, where the first 3 TMSs are stronly hydrophobic, but the last 4 are only moderately hydrophobic. It is required for the retention of luminal endoplasmic reticulum/Golgi proteins and affects glycoprotein processing in the Golgi apparatus. Protein glycosylation in the Golgi is a sequential process that requires proper distribution of transmembrane glycosyltransferases in the appropriate Golgi compartments. Some of the cytosolic machinery required for the steady-state localization of some Golgi enzymes is known. Erd1 facilitates Golgi glycosyltransferase recycling by directly interacting with both the Golgi enzymes and the cytosolic receptor, Vps74 (Q06385) (Sardana et al. 2021). Loss of Erd1 function results in mislocalization of Golgi enzymes to the vacuole/lysosome. Thus, Erd1 forms an integral part of the recycling machinery and ensures productive recycling of several early Golgi enzymes as well as how the localization of Golgi glycosyltransferases is spatially and temporally regulated.

The generalized reaction catalyzed by Pho1 is:

Pi (cells) → Pi (xylem)

This family belongs to the IT Superfamily.


This family belongs to the IT Superfamily.
 

References:

Anheim, M., U. López-Sánchez, D. Giovannini, A.C. Richard, J. Touhami, L. N''Guyen, G. Rudolf, A. Thibault-Stoll, T. Frebourg, D. Hannequin, D. Campion, J.L. Battini, M. Sitbon, and G. Nicolas. (2016). XPR1 mutations are a rare cause of primary familial brain calcification. J Neurol 263: 1559-1564.
Burns, D., R. Berlinguer-Palmini, and A. Werner. (2024). XPR1: a regulator of cellular phosphate homeostasis rather than a Pi exporter. Pflugers Arch 476: 861-869.
Giovannini, D., J. Touhami, P. Charnet, M. Sitbon, and J.L. Battini. (2013). Inorganic phosphate export by the retrovirus receptor XPR1 in metazoans. Cell Rep 3: 1866-1873.
Hamburger, D., E. Rezzonico, J. MacDonald-Comber Petétot, C. Somerville, and Y. Poirier. (2002). Identification and characterization of the Arabidopsis PHO1 gene involved in phosphate loading to the xylem. Plant Cell 14: 889-902.
Legati, A., D. Giovannini, G. Nicolas, U. López-Sánchez, B. Quintáns, J.R. Oliveira, R.L. Sears, E.M. Ramos, E. Spiteri, M.J. Sobrido, &.#.1.9.3.;. Carracedo, C. Castro-Fernández, S. Cubizolle, B.L. Fogel, C. Goizet, J.C. Jen, S. Kirdlarp, A.E. Lang, Z. Miedzybrodzka, W. Mitarnun, M. Paucar, H. Paulson, J. Pariente, A.C. Richard, N.S. Salins, S.A. Simpson, P. Striano, P. Svenningsson, F. Tison, V.K. Unni, O. Vanakker, M.W. Wessels, S. Wetchaphanphesat, M. Yang, F. Boller, D. Campion, D. Hannequin, M. Sitbon, D.H. Geschwind, J.L. Battini, and G. Coppola. (2015). Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export. Nat. Genet. 47: 579-581.
Quaghebeur, M., and Z. Rengel. (2004). Arsenic uptake, translocation and speciation in pho1 and pho2 mutants of Arabidopsis thaliana. Physiol. Plant. 120: 280-286.
Sardana, R., C.M. Highland, B.E. Straight, C.F. Chavez, J.C. Fromme, and S.D. Emr. (2021). Golgi membrane protein Erd1 Is essential for recycling a subset of Golgi glycosyltransferases. Elife 10:.
Stefanovic, A., C. Ribot, H. Rouached, Y. Wang, J. Chong, L. Belbahri, S. Delessert, and Y. Poirier. (2007). Members of the PHO1 gene family show limited functional redundancy in phosphate transfer to the shoot, and are regulated by phosphate deficiency via distinct pathways. Plant J. 50: 982-994.
Wild, R., R. Gerasimaite, J.Y. Jung, V. Truffault, I. Pavlovic, A. Schmidt, A. Saiardi, H.J. Jessen, Y. Poirier, M. Hothorn, and A. Mayer. (2016). Control of eukaryotic phosphate homeostasis by inositol polyphosphate sensor domains. Science 352: 986-990.
Zhang, W., Y. Chen, Z. Guan, Y. Wang, M. Tang, Z. Du, J. Zhang, M. Cheng, J. Zuo, Y. Liu, Q. Wang, Y. Liu, D. Zhang, P. Yin, L. Ma, and Z. Liu. (2025). Structural insights into the mechanism of phosphate recognition and transport by XPR1. Nat Commun 16: 18.
Examples:

TC#NameOrganismal TypeExample
2.A.94.1.1

Putative phosphate transporter, Pho1 (one of ten paralogues) (782 aas; 10 or 11 TMSs) (Hamburger et al., 2002)

Plants

Pho1 of Arabidopsis thaliana (Q8S403)

 
2.A.94.1.2

Xenotropic and polytropic murine-leukemia virus receptor Xpr1 of 671 aas and 11 or 12 TMSs. XPR1 senses intracellular Pi levels via its SPX domain and downregulates cellular Pi uptake via the C-terminal domain; it may not be a transporter (Burns et al. 2024).

Insects

Xpr1 of Culex pipiens (XP_001850310)

 
2.A.94.1.3

Pho1 homologue of 396 aas and probably either 10 or 11 TMSs, ERD1.

ERD1 of Cercospora beticola

 
2.A.94.1.4

EXS-domain-containing protein of 565 aas and probably 10 or 11 TMSs.

EXS protein of Mortierella elongata

 
2.A.94.1.5

EXS family protein of 414 aas and 8 - 11 TMSs.

EXS protein of Tetrahymena thermophila

 
2.A.94.1.6

The Xenotropic and polytropic retrovirus receptor 1, the XPR1 or SLC53A1 protein, also called SYG1 or XR of 696 aas and 10 - 12 TMSs. XPR1 exports inorganic phosphate in metazoans (Giovannini et al. 2013) and is associated with Primary Familial Brain Calcification (PFBC, formerly known as Fahr disease or Idiopathic Basal Ganglia Calcification in idiopathic forms) (Legati et al. 2015 and Anheim et al. 2016). It binds inositol hexakisphosphate (Ins6P) and similar inositol polyphosphates, such as 5-diphospho-inositol pentakisphosphate (5-InsP7), important intracellular signaling molecules (Wild et al. 2016). It has been associated with Primary Familial Brain Calcification (PFBC) (Monfrini et al. 2023).  XPR1 senses intracellular Pi levels via its SPX domain and downregulates cellular Pi uptake via the C-terminal domain; it may not be a transporter (Burns et al. 2024).  However, Zhang et al. 2025 provided structural insights into the mechanism of phosphate recognition and transport by XPR1.

XPR1 of Homo sapiens

 
2.A.94.1.7

Erd1 of 362 aas, possibly with 7 TMSs in a 1 + 2 + 3 + 1 TMS arrangement, where the first 3 TMSs are stronly hydrophobic, but the last 4 are only moderately hydrophobic. It is required for the retention of luminal endoplasmic reticulum/Golgi proteins and affects glycoprotein processing in the Golgi apparatus. Protein glycosylation in the Golgi is a sequential process that requires proper distribution of transmembrane glycosyltransferase enzymes in the appropriate Golgi compartments. Some of the cytosolic machinery required for the steady-state localization of some Golgi enzymes are known. Erd1 facilitates Golgi glycosyltransferase recycling by directly interacting with both the Golgi enzymes and the cytosolic receptor, Vps74 (Sardana et al. 2021). Loss of Erd1 function results in mislocalization of Golgi enzymes to the vacuole/lysosome. Erd1 forms an integral part of the recycling machinery while ensuring productive recycling of several early Golgi enzymes. It also determines how the localization of Golgi glycosyltransferases is spatially and temporally regulated (Sardana et al. 2021).

 

Erd1 of Saccharomyces cerevisiae