Rab (G-protein)
Encyclopedia
The Rab family of protein
s is a member of the Ras superfamily
of monomer
ic G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab GTPases regulate many steps of membrane traffic, including vesicle formation, vesicle movement along actin
and tubulin
networks, and membrane fusion. These processes make up the route through which cell surface proteins are trafficked from the Golgi to the plasma membrane and are recycled. Surface protein recycling returns proteins to the surface whose function involves carrying another protein or substance inside the cell, such as the transferrin receptor, or serves as a means of regulating the number of a certain type of protein molecules on the surface.
s in the C-terminus. Rab escort proteins (REPs) deliver newly-synthesized and prenylated Rab to its destination membrane by binding the hydrophobic, insoluble prenyl groups and carrying Rab through the cytoplasm. The lipid
prenyl groups can then insert into the membrane, anchoring Rab at the cytoplasmic face of a vesicle or the plasma membrane. Because Rab proteins are anchored to the membrane through a flexible C-terminal region, they can be thought of as a 'balloon on a string'.
Like other GTPase
s, Rabs switch between two conformations, an inactive form bound to GDP
(guanosine diphosphate), and an active form bound to GTP
(guanosine triphosphate). A GDP/GTP exchange factor (GEF) catalyzes the conversion from GDP-bound to GTP-bound forms, and GTP hydrolysis to GDP is catalyzed by a GTPase-activating protein (GAP). REPs carry only the GDP-bound form of Rab, and Rab effectors, proteins with which Rab interacts and through which it functions, only bind the GTP-bound form of Rab. Rab effectors are very heterogeneous, and each Rab isoform has many effectors through which it carries out multiple functions.
After membrane fusion, Rab is recycled back to its membrane of origin. A GDP dissociation inhbitor (GDI) binds the prenyl groups of the inactive, GDP-bound form of Rab, inhibits the exchange of GDP for GTP (which would reactivate the Rab) and delivers Rab to its original membrane.
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s is a member of the Ras superfamily
Ras superfamily
The Ras superfamily is a protein superfamily of small GTPases, which are all related, to a degree, to the Ras protein subfamily .There are more than a hundred proteins in the Ras superfamily...
of monomer
Monomer
A monomer is an atom or a small molecule that may bind chemically to other monomers to form a polymer; the term "monomeric protein" may also be used to describe one of the proteins making up a multiprotein complex...
ic G proteins. Approximately 70 types of Rabs have now been identified in humans. Rab GTPases regulate many steps of membrane traffic, including vesicle formation, vesicle movement along actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
and tubulin
Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...
networks, and membrane fusion. These processes make up the route through which cell surface proteins are trafficked from the Golgi to the plasma membrane and are recycled. Surface protein recycling returns proteins to the surface whose function involves carrying another protein or substance inside the cell, such as the transferrin receptor, or serves as a means of regulating the number of a certain type of protein molecules on the surface.
Function
Rab proteins are peripheral membrane proteins, anchored to a membrane via a lipid group covalently linked to an amino acid. Specifically, Rabs are anchored via prenyl groups on two cysteineCysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
s in the C-terminus. Rab escort proteins (REPs) deliver newly-synthesized and prenylated Rab to its destination membrane by binding the hydrophobic, insoluble prenyl groups and carrying Rab through the cytoplasm. The lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
prenyl groups can then insert into the membrane, anchoring Rab at the cytoplasmic face of a vesicle or the plasma membrane. Because Rab proteins are anchored to the membrane through a flexible C-terminal region, they can be thought of as a 'balloon on a string'.
Like other GTPase
GTPase
GTPases are a large family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate . The GTP binding and hydrolysis takes place in the highly conserved G domain common to all GTPases.-Functions:...
s, Rabs switch between two conformations, an inactive form bound to GDP
Guanosine diphosphate
Guanosine diphosphate, abbreviated GDP, is a nucleoside diphosphate. It is an ester of pyrophosphoric acid with the nucleoside guanosine. GDP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase guanine....
(guanosine diphosphate), and an active form bound to GTP
Guanosine triphosphate
Guanosine-5'-triphosphate is a purine nucleoside triphosphate. It can act as a substrate for the synthesis of RNA during the transcription process...
(guanosine triphosphate). A GDP/GTP exchange factor (GEF) catalyzes the conversion from GDP-bound to GTP-bound forms, and GTP hydrolysis to GDP is catalyzed by a GTPase-activating protein (GAP). REPs carry only the GDP-bound form of Rab, and Rab effectors, proteins with which Rab interacts and through which it functions, only bind the GTP-bound form of Rab. Rab effectors are very heterogeneous, and each Rab isoform has many effectors through which it carries out multiple functions.
After membrane fusion, Rab is recycled back to its membrane of origin. A GDP dissociation inhbitor (GDI) binds the prenyl groups of the inactive, GDP-bound form of Rab, inhibits the exchange of GDP for GTP (which would reactivate the Rab) and delivers Rab to its original membrane.
Clinical significance
Defects in protein prenylation can cause pathologies such as choroideremiaChoroideremia
Choroideremia is an X-linked recessive retinal degenerative disease that leads to the degeneration of the choriocapillaris, the retinal pigment epithelium, and the photoreceptor of the eye....
.
Types of Rab proteins
There are approximately 70 different Rabs that have been identified in humans thus far. They are mostly involved in vesicle trafficking. Their complexity can be understood if thought of as address labels for vesicle trafficking, defining the identity and routing of vesicles.| Name | Subcellular location |
|---|---|
| RAB1 (YPT1) | ER, golgi complex |
| RAB2 | ER, cis-golgi network |
| RAB3A RAB3A Ras-related protein Rab-3A is a protein that in humans is encoded by the RAB3A gene.-Interactions:RAB3A has been shown to interact with CHM, RPH3A and RIMS1.-Further reading:... |
secretory and synaptic vesicles |
| RAB4 | early endosomes |
| RAB5A RAB5A Ras-related protein Rab-5A is a protein that in humans is encoded by the RAB5A gene.-Interactions:RAB5A has been shown to interact with RABEP1, SDCBP, ZFYVE20 and CHML.-Further reading:... |
clathrin-coated vesicles, plasma membranes |
| RAB5C RAB5C Ras-related protein Rab-5C is a protein that in humans is encoded by the RAB5C gene. RAB5C belongs to the Ras-related protein family.-Further reading:... |
early endosomes |
| RAB6 | medial- and trans-golgi network |
| RAB7 | late endosomes |
| RAB8 | basolateral secretory vesicles |
| RAB9 | late endosome, trans-golgi network |
| RAB11 | recycling endosomes |
| RAB18 RAB18 Ras-related protein Rab-18 is a protein that in humans is encoded by the RAB18 gene.Rab18 is a ubiquitously expressed protein with particularly high expression in brain and adipose tissue. Rab18 was first characterised as an endosomal protein in epithelial cells of mouse kidney and intestines... |
lipid droplets, golgi, endoplasmic reticulum |
| RAB39a | binds Caspase-1 in inflammasome |
| SEC4 | secretory vesicles |