Disease relevance of CRYM

• Aberrant intracellular localization of the mutated proteins might cause dysfunction of the CRYM product and result in hearing impairment [1].
• The crystal structure of human CRYM's bacterial homolog Pseudomonas putida ornithine cyclodeaminase and Archaeoglobus fulgidus alanine dehydrogenase have been available, but no CRYM structure has been reported [2].

High impact information on CRYM

• Through cDNA microarray analysis of gene expression in human cochlea and vestibule, we detected strong expression of mu-crystallin (CRYM; also known as "NADP-regulated thyroid hormone-binding protein") only in these inner-ear tissues [1].
• In a subsequent search for mutations of CRYM, among 192 patients with nonsyndromic deafness, we identified two mutations at the C-terminus; one was a de novo change (X315Y) in a patient with unaffected parents, and the other was a missense mutation (K314T) that segregated dominantly in the proband's family [1].
• CRYM knockout loses the reduced nicotinamide adenine dinucleotide phosphate-dependent T(3) binding activity in the cytosol of the brain, kidney, heart, and liver [3].
• The kidney and several other thyroid hormone-responsive tissues contain a NADP-regulated thyroid hormone (TH)-binding protein (THBP), with an apparent molecular mass of 36 kDa on SDS-PAGE, responsible for most of the intracellular high-affinity T3 and T4 binding [4].
• The expressed protein displays the appropriate binding properties, indicating that TH5.9 cDNA encodes the NADP-regulated THBP characterized in human tissues [4].

Biological context of CRYM

• OBJECTIVE: To investigate the mechanism of hearing loss caused by CRYM mutations METHODS: T3 binding activity of mutant mu-crystallin was compared with that of wild-type mu-crystallin, because mu-crystallin is known to be identical to T3 binding protein [5].

Anatomical context of CRYM

• THBP was purified to homogeneity from human kidney cytosol and used to generate proteolytic peptides [4].
• CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea [5].
• In an attempt to investigate the genes expressed during the development of mouse hair follicles, we employed RNA differential display and identified a cDNA encoding micro-crystallin, that is a major component of kangaroo lens and a cytosolic NADP-regulated thyroid hormone-binding protein in human kidney [6].

Associations of CRYM with chemical compounds

• Here, we report the crystal structure of human CRYM bound with NADPH refined to 2.6 A, and there is one dimer in the asymmetric unit [2].

Analytical, diagnostic and therapeutic context of CRYM

• Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues [1].

References