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COL4A3BP : ウィキペディア英語版
COL4A3BP

Collagen type IV alpha-3-binding protein, also known as ceramide transfer protein (CERT) or StAR-related lipid transfer protein 11 (STARD11) is a protein that in humans is encoded by the ''COL4A3BP'' gene.〔(【引用サイトリンク】 url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10087 )〕 The protein contains a pleckstrin homology domain at its amino terminus and a START domain towards the end of the molecule. It is a member of the StarD2 subfamily of START domain proteins.
== Function and structure ==

Ceramide transferase protein (or CERT) is responsible for the transfer of ceramide from the endoplasmic reticulum (ER) to the Golgi apparatus. Ceramide plays a very important role in the metabolism and biosynthesis of sphingolipid. More specifically, it is synthesized at the ER, then is transferred by CERT to Golgi where it is converted to sphingomyelin (SM).
There are two pathways through which this transfer takes place: a major pathway, which is ATP and cytosol-dependent and a minor pathway, which is ATP- and cytosol-independent.〔
CERT is a 68kDa protein that consists of three different parts, each of which with a special role:
# Pleckstrin homology domain (PH): It is the aminoterminal domain and it consists of about 100 aminoacid residues.〔 The main function of this part of CERT is to recognize and bind various phosphatidyloinositol phosphates (PIPs) with different level of specificity. The isomers of PIPs are distributed to various organelles: PI-4,5-diphosphate goes to the plasma membrane, PI-3-monophosphate to endosomes and PI-4-monophosphate to Golgi. PH domain of wild-type CERT has been found to recognize specifically PI4P and therefore CERT targets the Golgi apparatus or the trans-Golgi network.
# START domain: It consists of about 210 amino acid residues and has an important role in the transfer of ceramide, which is that it can recognize specifically only the natural D-erythro isomer of ceramide and extract it from the membrane.〔
# FFAT motif (two phenylalanines in an acidic tract, that has a conserved sequence "EFFDAxE"): It is a short domain situated between PH and START domain and is the one responsible for the interaction of CERT with ER. More specifically, it binds to the ER resident type II membrane protein, vesicle-associated membrane protein (VAMP) associated protein (VAP), an interaction that is necessary for the transfer of ceramide from the ER to Golgi.
All of these domains are important for the transfer of ceramide, since first of all CERT will extract newly synthesized ceramide from the membrane with the help of its START domain. Then, ceramide will be transferred through the cytosol towards Golgi because of the interaction between the PH domain and PI4P. Finally, interaction with ER is facilitated through the binding of the FFAT motif with Vesicle-associated membrane protein.

抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)
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