CLPB

8157020480ENSG00000162129ENSMUSG00000001829Q9H078Q60649NM_001258392NM_001258393NM_001258394NM_030813NM_009191NM_001363991NP_001245321NP_001245322NP_001245323NP_110440NP_033217NP_001350920Caseinolytic peptidase B protein homolog(CLPB), also known as mitochondrial AAA ATPase chaperonin, is an enzyme that in humans is encoded by the CLPB gene, which encodes an ATP-dependent chaperone. CLPB is localized in mitochondria and widely expressed in human tissues. High expression in adult brain and low expression in granulocyte is found. It is a chaperone involved in disaggregating proteins and also has a role in de novo protein synthesis under mild stress conditions. Mutations in 'CLPB' gene could cause autosomal recessive metabolic disorder with intellectual disability/developmental delay, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria. Caseinolytic peptidase B protein homolog(CLPB), also known as mitochondrial AAA ATPase chaperonin, is an enzyme that in humans is encoded by the CLPB gene, which encodes an ATP-dependent chaperone. CLPB is localized in mitochondria and widely expressed in human tissues. High expression in adult brain and low expression in granulocyte is found. It is a chaperone involved in disaggregating proteins and also has a role in de novo protein synthesis under mild stress conditions. Mutations in 'CLPB' gene could cause autosomal recessive metabolic disorder with intellectual disability/developmental delay, congenital neutropenia, progressive brain atrophy, movement disorder, cataracts, and 3-methylglutaconic aciduria. The CLPB gene has 19 exons and is located at the chromosome band 11q13.4. CLPB has five isoforms due to alternative splicing. Isoform 1 is considered to have the 'canonical' sequence. The protein is 78.7 kDa in size and composed of 707 amino acids. It contains an N-terminal mitochondrial targeting sequence (1-36 amino acids). After processing, the mature mitochondrial protein has a theoretical pI of 8.53. CLPB has a specific C-terminal D2 domain and proteins with this domain form the sub-family of Caseinolytic peptidase (Clp) proteins, also called HSP100. The domain composition of human CLPB is different from that of microbial or plant orthologs. Notably, the presence of ankyrin repeats replaced the first of two ATPase domains found in bacteria and fungi. CLPB belongs to the large AAA+ superfamily. The unifying characteristic of this family is the hydrolysis of ATP through the AAA+ domain to produce energy required to catalyze protein unfolding, disassembly and disaggregation. CLPB cooperates with HSP70 and its in vivo ATPase activity has been confirmed. This protein contributes to the thermotolerance of cells and appears to be required for mitochondrial function by acting as a protein chaperone. The interaction with protein like HAX1 suggests that human CLPB may be involved in apoptosis. In humans, the presence of ankyrin repeats replaced the first of two ATPase domains found in bacteria and fungi, which might have evolved to ensure more elaborate substrate recognition or to support a putative chaperone function. With only one ATPase domain, CLPB is postulated competent in the use of ATP hydrolysis energy for threading unfolded polypeptide through the central channel of the hexamer ring. Neonatal encephalopathy is a kind of severe neurological impairment in the newborn with no specific clinical sign at the early stage of life, and its diagnosis remains a challenge. This neonatal encephalopathy includes a heterogeneous group of 3- methylgutaconic aciduria syndromes and loss of CLPB function is reported to be one of the causes. Knocking down 'CLPB' gene in the zebrafish induced reduction of growth and increment of motor activity, which is similar to the signs observed in patients. Its loss may lead to a broad phenotypic spectrum encompassing intellectual disability/developmental delay, congenital neutropenia, progressive brain atrophy, movement disorder, and bilateral cataracts, with 3-methylglutaconic aciduria. Further investigation into CLPB may shed a new light on the diagnosis of this disease.