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

PX domain

The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.This domain was first found in P40phox and p47phox domains of NADPH oxidase...

 (a phospholipid

Phospholipid

Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

-binding motif

Structural motif

In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a supersecondary structure, which appears also in a variety of other molecules...

) or through protein-protein interactions with membrane-associated protein complexes Some members of this family have been shown to facilitate protein sorting

Protein targeting

Protein targeting or protein sorting is the mechanism by which a cell transports proteins to the appropriate positions in the cell or outside of it. Sorting targets can be the inner space of an organelle, any of several interior membranes, the cell's outer membrane, or its exterior via secretion...

.

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 SNX1 Sorting nexin-1 is a protein that in humans is encoded by the SNX1 gene. The protein encoded by this gene is a sorting nexin. SNX1 is a component of the retromer complex.- Function :... , SNX2 SNX2 Sorting nexin-2 is a protein that in humans is encoded by the SNX2 gene.-Further reading:...	Sorting_nexin_N	–	PX PX domain The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.This domain was first found in P40phox and p47phox domains of NADPH oxidase...	–	BAR BAR domain BAR domains are highly conserved protein dimerisation domains that occur in many proteins involved in membrane dynamics in a cell. The BAR domain is banana shaped and binds to membrane via its concave face. It is capable of sensing membrane curvature by binding preferentially to curved membranes...  (Vps5)
SNX4 SNX4 Sorting nexin-4 is a protein that in humans is encoded by the SNX4 gene.-Further reading:... , SNX7, SNX8, SNX30	–	–	PX	–	BAR (Vsp5)
SNX5 SNX5 Sorting nexin-5 is a protein that in humans is encoded by the SNX5 gene.This gene encodes a member of the sorting nexin family. Members of this family contain a phox domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking... , SNX6 SNX6 Sorting Nexin 6 also known as SNX6 is a well-conserved membrane-associated protein belonging to the sorting nexin family that is a component of the retromer complex. The protein contains a coiled-coil domain at its C terminus and a PX domain at its N terminus. Binding to PIM1 causes translocation... , SNX32	–	–	PX	–	BAR
SNX9 SNX9 Sorting nexin-9 is a protein that in humans is encoded by the SNX9 gene.-Interactions:SNX9 has been shown to interact with ADAM9, DNM2 and ADAM15.-Further reading:... , SNX18 SNAG1 Sorting nexin-18 is a protein that in humans is encoded by the SNX18 gene.-Further reading:... , SNX33	SH3 SH3 domain The SRC Homology 3 Domain is a small protein domain of about 60 amino acids residues first identified as a conserved sequence in the viral adaptor protein v-Crk and the non-catalytic parts of enzymes such as phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src...	–	PX	–	BAR (BAR_3_WASP_bdg)
SNX13 SNX13 Sorting nexin-13 is a protein that in humans is encoded by the SNX13 gene.-Further reading:... , SNX14, SNX19, SNX25	PXA	RGS Regulator of G protein signalling Regulators of G protein signalling are protein structural domains that activate GTPases for heterotrimeric G-protein alpha-subunits....	PX	–	Nexin_C
SNX15 SNX15 Sorting nexin-15 is a protein that in humans is encoded by the SNX15 gene.-Further reading:...	–	–	PX	–	MIT
SNX17 SNX17 Sorting nexin-17 is a protein that in humans is encoded by the SNX17 gene.-Interactions:SNX17 has been shown to interact with Low density lipoprotein receptor-related protein 8 and LDL receptor.-Further reading:... , SNX31	–	–	PX	RA	FERM_M
SNX23	kinesin motor	SMAD_FHA	PX	–	–
SNX26 SNX26 TC10/CDC42 GTPase-activating protein is an enzyme that in humans is encoded by the SNX26 gene.-Further reading:...	–	–	PX	SH3	RhoGAP RhoGAP domain RhoGAP domain is an evolutionary conserved protein domain ofGTPase activating proteins towards Rho/Rac/Cdc42-like small GTPases.-Human proteins containing this domain :ABR; ARHGAP1; ARHGAP10; ARHGAP11A; ARHGAP11B; ARHGAP12; ARHGAP15; ARHGAP17;...
SNX27 SNX27 Sorting nexin family member 27, also known as SNX27, is a human gene.This gene encodes a member of the sorting nexin family, a diverse group of cytoplasmic and membrane-associated proteins involved in endocytosis of plasma membrane receptors and protein trafficking through these compartments. All...	PDZ	–	PX	-	RA
SNX28 NOXO1 NADPH oxidase organizer 1 is an enzyme that in humans is encoded by the NOXO1 gene.-Further reading:...	–	–	PX	SH3	SH3
SNX3 SNX3 Sorting nexin-3 is a protein that in humans is encoded by the SNX3 gene.-Further reading:... , SNX10, SNX11, SNX12, SNX16, SNX20, SNX21 SNX21 Sorting nexin-21 is a protein that in humans is encoded by the SNX21 gene.-Further reading:... , SNX22, SNX24, SNX29	–	–	PX	–	–

Structure

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

Protein domain

A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...

.

A subgroup of sorting nexins (comprising, in humans, SNX1, SNX2, SNX4, SNX5, SNX6, SNX7, SNX8, SNX9, SNX18, SNX30, SNX32 and SNX33) possess a BAR

BAR domain

BAR domains are highly conserved protein dimerisation domains that occur in many proteins involved in membrane dynamics in a cell. The BAR domain is banana shaped and binds to membrane via its concave face. It is capable of sensing membrane curvature by binding preferentially to curved membranes...

 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
   PX domain
   The PX domain is a phosphoinositide-binding structural domain involved in targeting of proteins to cell membranes.This domain was first found in P40phox and p47phox domains of NADPH oxidase...
   
   
3. CTD – C-terminal BAR domain