Cell cycle control protein 50C (CDC50C, also known as TMEM30C) is one of the CDC50 (CDC50A/B/C) proteins []. CDC50A and CDC50B are accessory components of the phospholipid-transporting ATPase (P4-ATPase) complex which catalyses the hydrolysis of ATP coupled to the transport of phospholipids across the membrane []. The function of CDC50C is not clear. Unlike the broad expression of CDC50A and CDC50B, CDC50C is expressed specifically in mouse testis [, ]. However, no full-length transcripts of CDC50C have been found in humans [].
Phospholipid-transporting ATPase ID (also known as ATP8B2 or ATPID) belongs to the IV subfamily of the P-type ATPases family, whose members transport phospholipids across the membrane. The function of ATP8B2 is not clear. It can bind either CDC50A or CDC50B as its accessory protein required for its function []. ATP8B2 is expressed throughout the body [].
Probable phospholipid-transporting ATPase IM (also known as ATP8B4) belongs to subfamily IV of the P-type ATPases family, whose members transport phospholipids across the membrane. It appears to be a component of a P4-ATPase flippase complex and can bind either CDC50A or CDC50B as its accessory protein []. ATPase IM is expressed throughout the brain and may be involved in Alzheimer's disease [].
Cell cycle control protein 50A (CDC50A, also known as TMEM30A) is an accessory component of the phospholipid-transporting ATPase (P4-ATPase) complex which catalyses the hydrolysis of ATP coupled to the transport of phospholipids across the membrane []. It can interact with several P4-ATPases, such as ATP8A1, ATP8A2, ATP8B1, ATP8B2, ATP11A, ATP11B and ATP11C [, , ]. CDC50A is a terminal-glycosylated glycoprotein and is expressed in hepatocytes and liver sinusoidal endothelial cells. In pancreas and stomach, it localises to secretory vesicles, while in kidney, it localises to the apical region of proximal convoluted tubules of the cortex []. In human carcinoma cells, CDC50A plays a key role in the uptake of the anticancer drug perifosine [].
Phospholipid-transporting ATPase IF (also known as ATP11B) belongs to subfamily IV of the P-type ATPases (P4-ATPase) family, whose members transport phospholipids across the membrane. ATP11B is ubiquitously expressed and binds CDC50A as its beta-subunit []. It is the catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of intracellular membranes [].
Phospholipid-transporting ATPase IG (also known as ATP11C) belongs to subfamily IV of the P-type ATPases (P4-ATPase) family, whose members transport phospholipids across the membrane. ATP11C is ubiquitously expressed and binds CDC50A as its beta-subunit []. In mice, ATP11C plays an important role in the proper development of B-cell lymphocytes [, , ]. In human cells, ATP11C can function as a phosphatidylserine (PtdSer) flippase at the plasma membrane. During apoptosis, the inactivation of ATP11C is required for cells to expose and display apoptotic PtdSer, which then serves as an "eat me"signal for macrophages to engulf the cells [].
Phospholipid-transporting ATPase IK (also known as ATP8B3 orATP1K) belongs to the subfamily IV of the P-type ATPases family, whose members transport phospholipids across the membrane. The function of ATP8B3 is not clear. Unlike other type IV members (ATP8B1,2,4), ATP8B3 does not seem to interact with either CDC50A or CDC50B []. It is exclusively expressed in the testis where it localises to the acrosomes of spermatids, the organelle which develops in the anterior half of the head of spermatozoa []. However, the disruption of ATP8B3 in mice does not affect sperm morphology or fertilisation rate [].
Phospholipid-transporting ATPase VB (also known as ATP10B) belongs to the IV subfamily of the P-type ATPases (P4-ATPase) family. P4-ATPases are phospholipid flippases that translocate phospholipids from the exoplasmic (lumenal) to the cytoplasmic leaflet of cellular membranes. ATP10C requires CDC50A for its exit from the endoplasmic reticulum (ER) and final subcellular localisation []. ATP10B is the catalytic component of a P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of glucosylceramide (GlcCer) from the outer to the inner leaflet of lysosome membranes [].
Probable phospholipid-transporting ATPase IH (also known as ATP11A) belongs to the IV subfamily of the P-type ATPases (P4-ATPase) family, whose members transport phospholipids across the membrane. Most P4-ATPases are known to associate with an accessory or beta-subunit known as CDC50 to form a heteromeric complex. ATP11A is ubiquitously expressed and only binds CDC50A as its beta-subunit [, ]. ATP11A is a catalytic component of a P4-ATPase flippase complex which catalyzes the hydrolysis of ATP coupled to the transport of aminophospholipids, phosphatidylserines (PS) and phosphatidylethanolamines (PE), from the outer to the inner leaflet of the plasma membrane [, , , , ].
Phospholipid-transporting ATPase IC (also known as ATP8B1 or ATPIC) belongs to subfamily IV of the P-type ATPases family, whose members transport phospholipids across the membrane. ATP8B1 can bind either CDC50A or CDC50B as its accessory protein for endoplasmic reticulum exit and plasma membrane lipid flippase activity [, , ].In hepatocytes, ATP8B1 localises in the canalicular membrane, where it may maintain the membrane integrity and to the function of ABCB4, an ABC floppase that play a role in bile export []. In the epithelial Caco-2 cells, ATP8B1 is required for apical protein expression and microvillus formation in polarised epithelial cells []. Mutations in ATP8B1 cause two forms of intrahepatic cholestasis, progressive familial intrahepatic cholestasis (PFIC) and benign recurrent intrahepatic cholestasis (BFIC) []. It is involved in the correct apical membrane localization of CDC42, CFTR and SLC10A2 [].
Phospholipid-transporting ATPase VA (also known as ATP10A or ATP10C) belongs to the IV subfamily of the P-type ATPases (P4-ATPase) family. P4-ATPases are phospholipid flippases that translocate phospholipids from the exoplasmic (lumenal) to the cytoplasmic leaflet of lipid bilayers. ATP10A is a catalytic component of P4-ATPase flippase complex, which catalyzes the hydrolysis of ATP coupled to the transport of phosphatidylcholine (PC) from the outer to the inner leaflet of the plasma membrane. However, it has low flippase activity toward glucosylceramide (GlcCer) []. ATP10A has also been shown to initiate inward plasma membrane bending and recruitment of Bin/amphiphysin/Rvs (BAR) domain-containing proteins involved in membrane tubulation and cell trafficking []. ATP10A requires CDC50A for its exit from the endoplasmic reticulum (ER) and final subcellular localisation []. ATP10A has been linked to diseases such as Angelman syndrome []and type 2 diabetes [].
