Sorting nexin

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.

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
SCOP2	1h6h / SCOPe / SUPFAM
OPM superfamily	57
OPM protein	4on3
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Sorting nexin, N-terminal domain
Identifiers
Symbol	Sorting_nexin
Pfam	PF03700
InterPro	IPR005329
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Vps5 C terminal like (BAR domain)
Identifiers
Symbol	Vps5
Pfam	PF09325
InterPro	IPR015404
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

Sorting nexin, C terminal domain
Identifiers
Symbol	Nexin_C
Pfam	PF08628
InterPro	IPR013937
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

WASP-binding domain of Sorting nexin protein
Identifiers
Symbol	BAR3-WASP
Pfam	PF10456
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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	-	FERM_M[9]
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.