DNAJC5
Encyclopedia
DnaJ homolog subfamily C member 5, also known as cysteine string protein or CSP is a protein
, that in humans encoded by the DNAJC5 gene
. It was first described in 1990.
is has 198 amino acid
s with a predicted molecular weight of 22.149 kiloDalton
s (kDa). The weight of the mature protein is 34kDa.
This gene is highly conserved and found both in invertebrate
s and vertebrate
s. In humans, a pseudogene
of this gene is located on the short arm of chromosome 8.
coated vesicles. It is also found on secretory vesicles in endocrine, neuroendocrine and exocrine cells. This protein makes up ~1% of the protein content of the synaptic vesicle
s. DNAJC5 appears to have a role in stimulated exocytosis
.
activity of 70 kDa heat shock protein
s (Hsp70
). DNAJC5 is a guanine nucleotide exchange factor
for Gα
proteins. CSPα plays a role in membrane trafficking
and protein folding
, and has been shown to have anti-neurodegenerative
properties. It is known to play a role in cystic fibrosis
and Huntington's disease
.
This protein has been proposed as a key element of the synaptic molecular machinery devoted to the rescue of synaptic proteins that have been unfolded by activity dependent stress. Syntaxin 1A, a plasma membrane SNARE
(soluble N-ethylmaleimide-sensitive factor attachment protein receptor) critical for neurotransmission, forms a complex with CSPα, a G protein
and an N-type calcium channel
. Huntingtin
may be able displace both syntaxin 1A and CSPα from N-type channels. CSP interacts with the calcium sensor protein synaptotagmin 9
via its linker domain.
Huntingtin-interacting protein 14
, a palmitoyl transferase, is required for exocytosis and targeting of CSP to synaptic vesicles. The palmitoyl residues are transferred to the cysteine residues. If these resides are mutated membrane targeting is reduced or lost. The rat CSP forms a complex with Sgt (SGTA
) and Hsc70 (HSPA8) located on the synaptic vesicle
surface. This complex functions as an ATP-dependent chaperone that reactivates denatured substrates. Furthermore the Csp/Sgt/Hsc70 complex appears to be important for maintenance of normal synapse
s.
Its expression may be increased with the use of lithium
. Quercetin
promotes formation of stable CSPα-CSPα dimers.
with the cystic fibrosis transmembrane conductance regulator
.
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...
, that in humans encoded by the DNAJC5 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
. It was first described in 1990.
Gene
In humans, the gene is located on the long arm of chromosome 20 (20q13.33) on the Watson (positive strand). The gene is 40,867 bases in length and the encoded proteinProtein
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...
is has 198 amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s with a predicted molecular weight of 22.149 kiloDalton
Dalton
Dalton may refer to:-In Canada:* Dalton, Algoma District, Ontario* Dalton Armoury, a Canadian Forces facility primarily used by the Queen's Own Rifles of Canada- In the United Kingdom :* Dalton, Cumbria, England* Dalton, Dumfries and Galloway, Scotland...
s (kDa). The weight of the mature protein is 34kDa.
This gene is highly conserved and found both in invertebrate
Invertebrate
An invertebrate is an animal without a backbone. The group includes 97% of all animal species – all animals except those in the chordate subphylum Vertebrata .Invertebrates form a paraphyletic group...
s and vertebrate
Vertebrate
Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...
s. In humans, a pseudogene
Pseudogene
Pseudogenes are dysfunctional relatives of known genes that have lost their protein-coding ability or are otherwise no longer expressed in the cell...
of this gene is located on the short arm of chromosome 8.
Structure
The organisation of the protein is as follows:- an N-terminus phosphorylation site for protein kinase A
- a J domainChaperone DnaJIn molecular biology, chaperone DnaJ, also known as Hsp40 , is a molecular chaperone protein. It is expressed in a wide variety of organisms from bacteria to humans.-Function:...
(~70 amino acids) - a linker region
- a cysteineCysteineCysteine 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...
motif consisting of 13–15 cysteines within a stretch of 25 amino acids. It is heavily palmitoylated in the cysteine string motif. - a less conserved C-terminal domain
Tissue distribution
This protein is abundant in neural tissue and displays a characteristic localization to synaptic and clathrinClathrin
Clathrin is a protein that plays a major role in the formation of coated vesicles. Clathrin was first isolated and named by Barbara Pearse in 1975. It forms a triskelion shape composed of three clathrin heavy chains and three light chains. When the triskelia interact they form a polyhedral lattice...
coated vesicles. It is also found on secretory vesicles in endocrine, neuroendocrine and exocrine cells. This protein makes up ~1% of the protein content of the synaptic vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
s. DNAJC5 appears to have a role in stimulated exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
.
Function
The encoded protein is a member of the J protein family. These proteins function in many cellular processes by regulating the ATPaseATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...
activity of 70 kDa heat shock protein
Heat shock protein
Heat shock proteins are a class of functionally related proteins involved in the folding and unfolding of other proteins. Their expression is increased when cells are exposed to elevated temperatures or other stress. This increase in expression is transcriptionally regulated...
s (Hsp70
Hsp70
The 70 kilodalton heat shock proteins are a family of ubiquitously expressed heat shock proteins. Proteins with similar structure exist in virtually all living organisms...
). DNAJC5 is a guanine nucleotide exchange factor
Guanine nucleotide exchange factor
Guanine nucleotide exchange factors activate monomeric GTPases by stimulating the release of guanosine diphosphate to allow binding of guanosine triphosphate . A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity...
for Gα
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
proteins. CSPα plays a role in membrane trafficking
Protein targeting
Protein targeting or protein sorting is the mechanism by which a cell transports proteins to the appropriate positions in the cell or outside of it. Sorting targets can be the inner space of an organelle, any of several interior membranes, the cell's outer membrane, or its exterior via secretion...
and protein folding
Protein folding
Protein folding is the process by which a protein structure assumes its functional shape or conformation. It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil....
, and has been shown to have anti-neurodegenerative
Neurodegeneration
Neurodegeneration is the umbrella term for the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Huntington’s occur as a result of neurodegenerative processes. As research progresses, many...
properties. It is known to play a role in cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
and Huntington's disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
.
This protein has been proposed as a key element of the synaptic molecular machinery devoted to the rescue of synaptic proteins that have been unfolded by activity dependent stress. Syntaxin 1A, a plasma membrane SNARE
SNARE (protein)
SNARE proteins are a large protein superfamily consisting of more than 60 members in yeast and mammalian cells....
(soluble N-ethylmaleimide-sensitive factor attachment protein receptor) critical for neurotransmission, forms a complex with CSPα, a G protein
G protein
G proteins are a family of proteins involved in transmitting chemical signals outside the cell, and causing changes inside the cell. They communicate signals from many hormones, neurotransmitters, and other signaling factors. G protein-coupled receptors are transmembrane receptors...
and an N-type calcium channel
N-type calcium channel
The N-type calcium channel is a type of voltage-dependent calcium channel. Like the others of this class, the α1 subunit forms the pore through which calcium enters the cell and determines most of the channel's properties...
. Huntingtin
Huntingtin
The Huntingtin gene, also called HTT or HD gene, is the IT15 gene which codes for a protein called the huntingtin protein...
may be able displace both syntaxin 1A and CSPα from N-type channels. CSP interacts with the calcium sensor protein synaptotagmin 9
SYT9
Synaptotagmin-9 is a protein that in humans is encoded by the SYT9 gene.-Interactions:SYT9 has been shown to interact with SYNCRIP, TUBB and TRPV1.-Further reading:...
via its linker domain.
Huntingtin-interacting protein 14
ZDHHC17
Palmitoyltransferase ZDHHC17 is an enzyme that contains a DHHC domain that in humans is encoded by the ZDHHC17 gene.-Interactions:ZDHHC17 has been shown to interact with Huntingtin.-Further reading:...
, a palmitoyl transferase, is required for exocytosis and targeting of CSP to synaptic vesicles. The palmitoyl residues are transferred to the cysteine residues. If these resides are mutated membrane targeting is reduced or lost. The rat CSP forms a complex with Sgt (SGTA
SGTA
Small glutamine-rich tetratricopeptide repeat-containing protein alpha is a protein that in humans is encoded by the SGTA gene. SGTA orthologs have also been identified in several mammals for which complete genome data are available....
) and Hsc70 (HSPA8) located on the synaptic vesicle
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
surface. This complex functions as an ATP-dependent chaperone that reactivates denatured substrates. Furthermore the Csp/Sgt/Hsc70 complex appears to be important for maintenance of normal synapse
Synapse
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another cell...
s.
Its expression may be increased with the use of lithium
Lithium
Lithium is a soft, silver-white metal that belongs to the alkali metal group of chemical elements. It is represented by the symbol Li, and it has the atomic number 3. Under standard conditions it is the lightest metal and the least dense solid element. Like all alkali metals, lithium is highly...
. Quercetin
Quercetin
Quercetin , a flavonol, is a plant-derived flavonoid found in fruits, vegetables, leaves and grains. It also may be used as an ingredient in supplements, beverages or foods.-Occurrence:...
promotes formation of stable CSPα-CSPα dimers.
Interactions
DNAJC5 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with the cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator
Cystic fibrosis transmembrane conductance regulator is a protein that in humans is encoded by the CFTR gene.CFTR is a ABC transporter-class ion channel that transports chloride and thiocyanate ions across epithelial cell membranes...
.