DnaJ homolog subfamily C member 5, also known as cysteine string protein or CSP is a
protein, that in humans encoded by the DNAJC5gene.[5] It was first described in 1990.[6]
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
protein has 198
amino acids with a predicted molecular weight of 22.149 kilo
daltons (kDa). The weight of the mature protein is 34 kDa.
This protein is abundant in neural tissue and displays a characteristic localization to synaptic and
clathrin 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 vesicles.[8] DNAJC5 appears to have a role in stimulated
exocytosis.[9]
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.[11][12]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.[13] CSP interacts with the calcium sensor protein
synaptotagmin 9 via its linker domain.[14]
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.[15] 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
synapses.[7]
Its expression may be increased with the use of
lithium.[16]Quercetin promotes formation of stable CSPα-CSPα dimers.[17]
Cysteine-string protein increases the calcium sensitivity of neurotransmitter exocytosis.[18]
^Zinsmaier KE, Hofbauer A, Heimbeck G, Pflugfelder GO, Buchner S, Buchner E (November 1990). "A cysteine-string protein is expressed in retina and brain of Drosophila". J. Neurogenet. 7 (1): 15–29.
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10.3109/01677069009084150.
PMID2129171.
Mastrogiacomo A, Gundersen CB (1995). "The nucleotide and deduced amino acid sequence of a rat cysteine string protein". Molecular Brain Research. 28 (1): 12–18.
doi:
10.1016/0169-328x(94)00172-b.
PMID7535880.
Giorgianni F, Beranova-Giorgianni S, Desiderio DM (2004). "Identification and characterization of phosphorylated proteins in the human pituitary". Proteomics. 4 (3): 587–98.
doi:
10.1002/pmic.200300584.
PMID14997482.
S2CID25355914.
Chi A, Valencia JC, Hu ZZ, et al. (2007). "Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes". J. Proteome Res. 5 (11): 3135–44.
doi:
10.1021/pr060363j.
PMID17081065.