Sorting nexin

PX domain

Structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate.[1]
Identifiers
Symbol PX
Pfam PF00787
InterPro IPR001683
SMART PX
PROSITE PDOC50195
SCOP 1h6h
SUPERFAMILY 1h6h
Sorting nexin, N-terminal domain
Identifiers
Symbol Sorting_nexin
Pfam PF03700
InterPro IPR005329
Vps5 C terminal like (BAR domain)
Identifiers
Symbol Vps5
Pfam PF09325
InterPro IPR015404
Sorting nexin, C terminal domain
Identifiers
Symbol Nexin_C
Pfam PF08628
InterPro IPR013937

Sorting nexins are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain (a phospholipid-binding motif) or through protein–protein interactions with membrane-associated protein complexes[2][3] Some members of this family have been shown to facilitate protein sorting.

Family members

In humans, sorting nexins are transcribed from the following genes:

Genes Domain Composition
N-terminus Mid-1 Mid-2 Mid-3 C-terminus
SNX1, SNX2 Sorting_nexin_N – PX – BAR[4] (Vps5)
SNX4, SNX7, SNX8, SNX30 – – PX – BAR[4] (Vsp5)
SNX5, SNX6, SNX32 – – PX – BAR[4]
SNX9, SNX18, SNX33 SH3 – PX – BAR[4] (BAR_3_WASP_bdg)[5]
SNX13, SNX14, SNX19, SNX25 PXA[6] RGS PX – Nexin_C
SNX15 – – PX – MIT[7]
SNX17, SNX31 – – PX RA[8] FERM_M[9]
SNX23 kinesin_motor SMAD_FHA[10] PX – –
SNX26 – – PX SH3 RhoGAP
SNX27 PDZ – PX - RA
SNX28 – – PX SH3 SH3
SNX3, SNX10, SNX11, SNX12, SNX16, SNX20, SNX21, SNX22, SNX24, SNX29 – – PX – –

Structure

Sorting nexins either consist solely of a PX domain (e.g. SNX3) or have a modular structure made up of the PX and additional domains.

A subgroup of sorting nexins (comprising, in humans, SNX1, SNX2, SNX4, SNX5, SNX6, SNX7, SNX8, SNX9, SNX18, SNX30, SNX32 and SNX33) possess a BAR domain at their C-terminus. (The BAR domain of SNXs 1, 2, 4, 7, 8 and 30 is classified by pfam as 'Vps5 C terminal like'.)

An example of a sorting nexin domain structure can be seen here for SNX1:

  1. NTD – N-terminal domain
  2. PX domain
  3. CTD – C-terminal BAR domain
Schematic diagram of the 1D structures of a representative sorting nexin, the sorting nexin 1 (SNX1). NTD = N-terminal SNX domain, PX = PX domain, CTD = C-terminal BAR domain.

References

  1. ↑ Bravo J, Karathanassis D, Pacold CM, et al. (October 2001). "The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate". Mol. Cell. 8 (4): 829–39. doi:10.1016/S1097-2765(01)00372-0. PMID 11684018.
  2. ↑ Dixon JE, Worby CA (2002). "Sorting out the cellular functions of sorting nexins". Nat. Rev. Mol. Cell Biol. 3 (12): 919–931. doi:10.1038/nrm974. PMID 12461558.
  3. ↑ Worby CA, Dixon JE (2002). "Sorting out the cellular functions of sorting nexins". Nat. Rev. Mol. Cell Biol. 3 (12): 919–31. doi:10.1038/nrm974. PMID 12461558.
  4. 1 2 3 4 Frost A, Unger VM, De Camilli P (April 2009). "The BAR domain superfamily: membrane-molding macromolecules". Cell. 137 (2): 191–196. doi:10.1016/j.cell.2009.04.010. PMID 19379681.
  5. ↑ BAR_3_WASP_bdg: WASP-binding domain of Sorting nexin protein, Pfam PF10456
  6. ↑ PXA: PXA domain, Pfam PF02194
  7. ↑ MIT: MIT (microtubule interacting and transport) domain, Pfam PF04212
  8. ↑ RA: Ras association (RalGDS/AF-6) domain, Pfam PF00788
  9. ↑ FERM_M: FERM central domain, Pfam PF00373
  10. ↑ SMAD_FHA: SMAD/FHA domain, InterPro: IPR008984


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