StAR-related transfer domain
Encyclopedia
START is a lipid-binding domain in StAR, HD-ZIP and signalling proteins. The archetypical domain is found in StAR (Steroidogenic acute regulatory protein
), a mitochondrial protein that is synthesized in steroid
-producing cells. StAR and initiates steroid production by mediating the delivery of cholesterol to the first enzyme in steroidogenic pathway. The START domain is critical for this activity, perhaps through the binding of cholesterol. Following the discovery of StAR, 15 START-domain-containing proteins (termed STARD1 through STARD15) were subsequently identified in vertebrates as well as other that are related.
Thousands of proteins containing at least one START domain have been determined in invertebrates, bacteria
and plants to form a larger superfamily, variously known as START, Bet v1
-like or SRPBCC (START/RHOalphaC/PITP
/Bet v1/CoxG/CalC) domain proteins, all of which bind hydrophobic ligands. In the case of plants, many of the START proteins fall into the category of putative lipid/sterol-binding homeodomain (HD) transcription factors or HD-START proteins.
Representatives of the START domain family bind different substances or ligands such as sterols (e.g., StAR or STARD1) and lipids like phosphatidylcholine
(phosphatidylcholine transfer protein
, also called PCTP or STARD2) and have enzymatic activities. Ligand binding by the START domain in multidomain proteins can also regulate the activities of the other domains, such as the RhoGAP domain
, the homeodomain and the thioesterase
domain.
shows an alpha/beta fold built around an U-shaped incomplete beta-barrel. Most importantly, the interior of the protein encompasses a 26 x 12 x 11 Angstroms hydrophobic tunnel that is apparently large enough to bind a single cholesterol molecule. The START domain structure revealed an unexpected similarity to that of the birch pollen allergen Bet v 1 and to bacterial polyketide
cyclase
s/aromatases.
An exception is StarD9 whose activity remains unknown. Other proteins also exist in the human with domains that are members of the START-based superfamily such as PITP, but are not part of the START domain itself.
Steroidogenic acute regulatory protein
The steroidogenic acute regulatory protein, commonly referred to as StAR , is a transport protein that regulates cholesterol transfer within the mitochondria, which is the rate-limiting step in the production of steroid hormones...
), a mitochondrial protein that is synthesized in steroid
Steroid
A steroid is a type of organic compound that contains a characteristic arrangement of four cycloalkane rings that are joined to each other. Examples of steroids include the dietary fat cholesterol, the sex hormones estradiol and testosterone, and the anti-inflammatory drug dexamethasone.The core...
-producing cells. StAR and initiates steroid production by mediating the delivery of cholesterol to the first enzyme in steroidogenic pathway. The START domain is critical for this activity, perhaps through the binding of cholesterol. Following the discovery of StAR, 15 START-domain-containing proteins (termed STARD1 through STARD15) were subsequently identified in vertebrates as well as other that are related.
Thousands of proteins containing at least one START domain have been determined in invertebrates, bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and plants to form a larger superfamily, variously known as START, Bet v1
Bet v I allergen
Bet v I allergen is a family of protein allergens. Allergies are hypersensitivity reactions of the immune system to specific substances called allergens that, in most people, result in no symptoms....
-like or SRPBCC (START/RHOalphaC/PITP
Phosphatidylinositol transfer protein
Phosphatidylinositol transfer protein or priming in exocytosis protein 3 is a ubiquitous cytosolic domain involved in transport of phospholipids from their site of synthesis in the endoplasmic reticulum and Golgi to othercell membranes....
/Bet v1/CoxG/CalC) domain proteins, all of which bind hydrophobic ligands. In the case of plants, many of the START proteins fall into the category of putative lipid/sterol-binding homeodomain (HD) transcription factors or HD-START proteins.
Representatives of the START domain family bind different substances or ligands such as sterols (e.g., StAR or STARD1) and lipids like phosphatidylcholine
Phosphatidylcholine
Phosphatidylcholines are a class of phospholipids that incorporate choline as a headgroup.They are a major component of biological membranes and can be easily obtained from a variety of readily available sources such as egg yolk or soy beans from which they are mechanically extracted or chemically...
(phosphatidylcholine transfer protein
Phosphatidylcholine transfer protein
Phosphatidylcholine transfer protein also known as StAR-related lipid transfer domain protein 2 is a specific intracellular phospholipid binding protein that can transfer phosphatidylcholine between different membranes in the cytosol....
, also called PCTP or STARD2) and have enzymatic activities. Ligand binding by the START domain in multidomain proteins can also regulate the activities of the other domains, such as the RhoGAP domain
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;...
, the homeodomain and the thioesterase
Thioesterase
Thioesterases are enzymes which belong to the Esterase family. Esterases, in turn, are one type of the several hydrolases known.Thioesterases exhibit Esterase activity specifically at a thiol group.Thioesterases or thiolester hydrolases are identified as members of E.C.3.1.2.-Examples:Acetyl-coA...
domain.
Structure
The crystal structure of START domain of human MLN64MLN64
StAR-related lipid transfer domain protein 3 also known as metastatic lymph node 64 protein is a late endosomal integral membrane protein involved in cholesterol transport.-Function:...
shows an alpha/beta fold built around an U-shaped incomplete beta-barrel. Most importantly, the interior of the protein encompasses a 26 x 12 x 11 Angstroms hydrophobic tunnel that is apparently large enough to bind a single cholesterol molecule. The START domain structure revealed an unexpected similarity to that of the birch pollen allergen Bet v 1 and to bacterial polyketide
Polyketide
Polyketides are secondary metabolites from bacteria, fungi, plants, and animals. Polyketides are usually biosynthesized through the decarboxylative condensation of malonyl-CoA derived extender units in a similar process to fatty acid synthesis...
cyclase
Cyclase
A cyclase is an enzyme, almost always a lyase, that catalyzes a chemical reaction to form a cyclic compound. Important cyclase enzymes include:* Adenylyl cyclase, which forms cyclic AMP from adenosine triphosphate...
s/aromatases.
Human proteins containing the START domain
START domain-containing proteins in the human are divided into five subfamilies.An exception is StarD9 whose activity remains unknown. Other proteins also exist in the human with domains that are members of the START-based superfamily such as PITP, but are not part of the START domain itself.
Cholesterol/oxysterol binding StarD1/D3 subfamily
These proteins are primarily concerned with cholesterol transport- StAR (STARD1)
- MLN64 (STARD3)
StarD4 subfamily
These proteins are involved in cholesterol and oxysterol transport- STARD4STARD4StAR-related lipid transfer protein 4 is a soluble protein involved in cholesterol transport. It can transfer up to 7 sterol molecules per minute between artificial membranes.-Function:...
- STARD5STARD5StAR-related lipid transfer protein 5 is a protein that in humans is encoded by the STARD5 gene. The protein is a 213 amino acids long, consisting almost entirely of a StAR-related transfer domain...
- STARD6
Phospholipid/sphingolipid binding StarD2 subfamily
- PCTP (STARD2)
- STARD7STARD7StAR-related lipid transfer domain protein 7 or gestational trophoblastic tumor gene-1 is a lipid transporter that specifically binds and transports phosphatidylcholine between membranes.-Function and tissue distribution :...
- STARD10STARD10StAR-related lipid transfer protein 10 or PCTP-like protein is a lipid transfer protein that in humans is encoded by the STARD10 gene. The protein derives its name from the fact that the molecule contains a START domain. As part of the StarD2 subfamily, StarD10 can transport the lipids...
- COL4A3BPCOL4A3BPCollagen type IV alpha-3-binding protein, ceramide transfer protein or StAR-related lipid transfer protein 11 is a protein that in humans is encoded by the COL4A3BP gene. The protein contains a pleckstrin homology domain at its amino terminus and a START domain towards the end of the molecule...
(STARD11)
SAM-RhoGAP-START subfamily
These proteins contain both the START domain and Rho-GTPase signaling activity- STARD8STARD8StAR-related lipid transfer domain protein 8 also known as deleted in liver cancer 3 protein is a protein that in humans is encoded by the STARD8 gene and is a member of the DLC family.-Structure and function:...
(DLC-3) - DLC1DLC1Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 is a protein which in humans is encoded by the DLC1 gene....
(STARD12) - STARD13STARD13StAR-related lipid transfer domain protein 13 also known as deleted in liver cancer 2 protein is a protein that in humans is encoded by the STARD13 gene and a member of the DLC family of proteins.-Function and structure:...
(DLC-2)
Acyl-CoA thioesterase subfamily
The members of this subfamily possess the START domain and thioesterase activity- ACOT11ACOT11Acyl-coenzyme A thioesterase 11 also known as StAR-related lipid transfer protein 14 is an enzyme that in humans is encoded by the ACOT11 gene.-Further reading:...
(STARD14) - ACOT12ACOT12Acyl-coenzyme A thioesterase 12 or StAR-related lipid transfer protein 15 is an enzyme that in humans is encoded by the ACOT12 gene. The protein contains a StAR-related lipid transfer domain.-Further reading:...
(STARD15)