The PX domain is a phosphoinositide-binding

structural domain In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of s ...

involved in targeting of proteins to cell membranes. This domain was first found in P40phox and p47phox domains of

NADPH oxidase NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) is a membrane-bound enzyme complex that faces the extracellular space. It can be found in the plasma membrane as well as in the membranes of phagosomes used by neutrophil white ...

(phox stands for phagocytic oxidase). It was also identified in many other proteins involved in membrane trafficking, including nexins,

Phospholipase D Phospholipase D (EC 3.1.4.4, lipophosphodiesterase II, lecithinase D, choline phosphatase, PLD; systematic name phosphatidylcholine phosphatidohydrolase) is an enzyme of the phospholipase superfamily that catalyses the following reaction : a p ...

, and phosphoinositide-3-

kinase In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...

s. The PX domain is structurally conserved in

eukaryote Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacter ...

s, although amino acid sequences show little similarity. PX domains interact primarily with PtdIns(3)P lipids. However some of them bind to

phosphatidic acid Phosphatidic acids are anionic phospholipids important to cell signaling and direct activation of lipid-gated ion channels. Hydrolysis of phosphatidic acid gives rise to one molecule each of glycerol and phosphoric acid and two molecules of fatty ac ...

PtdIns(3,4)P2 Phosphatidylinositol (3,4)-bisphosphate (PtdIns(3,4)''P''2) is a minor phospholipid component of cell membranes, yet an important second messenger. The generation of PtdIns(3,4)''P''2 at the plasma membrane activates a number of important cell sig ...

PtdIns(3,5)P2 Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively p ...

PtdIns(4,5)P2 Phosphatidylinositol 4,5-bisphosphate or PtdIns(4,5)''P''2, also known simply as PIP2 or PI(4,5)P2, is a minor phospholipid component of cell membranes. PtdIns(4,5)''P''2 is enriched at the plasma membrane where it is a substrate for a number of ...

, and PtdIns(3,4,5)P3. The PX-domain can also interact with other domains and proteins.

Human proteins containing this domain

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 inter ...

s contain this domain. Other examples include: * HS1BP3 *

KIF16B Kinesin family member 16B, also known as KIF16B, is a protein which in humans is encoded by the ''KIF16B'' gene. See also * Kinesin A kinesin is a protein belonging to a class of motor proteins found in eukaryotic cells. Kinesins move al ...

(SNX23) * NCF1;

NCF1C Putative neutrophil cytosol factor 1C is a protein that in humans is encoded by the ''NCF1C'' gene. It relates to a type of white blood cell called a neutrophil. The Neutrophil Cytosolic Factor 1C (NCF1C) gene is responsible for encoding the 4 ...

;

NCF4 Neutrophil cytosol factor 4 is a protein that in humans is encoded by the ''NCF4'' gene. Function The protein encoded by this gene is a cytosolic regulatory component of the superoxide-producing phagocyte NADPH-oxidase, a multicomponent enzym ...

;

NISCH Nischarin is a protein that in humans is encoded by the ''NISCH'' gene. Function This gene encodes a nonadrenergic imidazoline-1 receptor protein that localizes to the inner layer of the plasma membrane as well as early and recycling endosome ...

PIK3C2A Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing alpha polypeptide is an enzyme that in humans is encoded by the ''PIK3C2A'' gene. The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases p ...

;

PIK3C2B Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing beta polypeptide is an enzyme that in humans is encoded by the ''PIK3C2B'' gene. Function The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. P ...

;

PIK3C2G Phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing gamma polypeptide is an enzyme that in humans is encoded by the ''PIK3C2G'' gene. The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases ...

; PLD1; PLD2; PXK * RPS6KC1 *

SGK3 Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the ''SGK3'' gene. Function This gene is a member of the serine/threonine protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The ...

;

SH3PXD2A SH3 and PX domain-containing protein 2A is a protein that in humans is encoded by the ''SH3PXD2A'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meanin ...

; SNAG1; SNX9

References

{{Protein domains Peripheral membrane proteins Protein domains