CRYM

CRYM
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2I99
Identifiers
Aliases	CRYM , DFNA40, THBP, crystallin mu
External IDs	OMIM: 123740 MGI: 102675 HomoloGene: 1424 GeneCards: CRYM
Gene location (Human) Chr. Chromosome 16 (human) [1] Band 16p12.2 Start 21,238,874 bp [1] End 21,303,083 bp [1]
Gene location (Mouse) Chr. Chromosome 7 (mouse) [2] Band 7 F2|7 64.47 cM Start 119,785,603 bp [2] End 119,801,334 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar vermis frontal pole Brodmann area 10 orbitofrontal cortex nucleus accumbens Brodmann area 9 caudate nucleus middle temporal gyrus right ventricle Brodmann area 46 Top expressed in hippocampus proper olfactory tubercle nucleus accumbens subiculum lip Region I of hippocampus proper superior frontal gyrus saccule prefrontal cortex hair follicle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function oxidoreductase activity hormone binding protein binding protein homodimerization activity transcription corepressor activity NADP binding thyroid hormone binding thiomorpholine-carboxylate dehydrogenase activity oxidoreductase activity, acting on the CH-NH2 group of donors, NAD or NADP as acceptor Cellular component cytoplasm extracellular exosome mitochondrion nucleus peroxisomal matrix cytosol Biological process thyroid hormone transport negative regulation of transcription by RNA polymerase II sensory perception of sound lysine catabolic process thyroid hormone metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1428 12971 Ensembl ENSG00000103316 ENSMUSG00000030905 UniProt Q14894 O54983 RefSeq (mRNA) NM_001014444 NM_001888 NM_001376256 NM_016669 RefSeq (protein) NP_001879 NP_001363185 NP_057878 Location (UCSC) Chr 16: 21.24 – 21.3 Mb Chr 7: 119.79 – 119.8 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Mu-crystallin homolog also known as NADP-regulated thyroid-hormone-binding protein (THBP) is a protein that in humans is encoded by the CRYM gene. Multiple alternatively spliced transcript variants have been found for this gene. ^{[5] [6]}

Function

Crystallins are separated into two classes: taxon-specific and ubiquitous. The former class is also called phylogenetically-restricted crystallins. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. This gene encodes a taxon-specific crystallin protein that binds NADPH and has sequence similarity to bacterial ornithine cyclodeaminases. The encoded protein does not perform a structural role in lens tissue, and instead it binds thyroid hormone for possible regulatory or developmental roles. ^[6]

Its enzyme function has been determined as a ketimine reductase, reducing cyclic ketimines to their reduced forms. Either NADH or NADPH can be used as cofactor. The most active substrate at pH 5.0 is aminoethylcysteine ketimine (AECK), however at neutral pH (pH 7.2) the most active substrate is 1-piperideine-2-carboxylate which is an important part of the pipecolic acid pathway. The active form of thyroxine, T₃, has been found to be a potent inhibitor at nanomolar concentrations. ^[7]

Besides its role in lens biology, CRYM seems also to be involved in thyroid hormone signalling in other tissues. It could be demonstrated that CRYM mutations may cause deafness through thyroid hormone binding effects on the fibrocytes of the cochlea. ^[8] Disruption of the CRYM gene leads to decreased T₃ concentrations in both tissues and serum without alteration of peripheral T₃ action in vivo. ^{[9] [10]}

The existence of intracellular thyroid hormone binding proteins has been postulated from mathematical modelling of pituitary-thyroid homeostasis. ^[11] Binding properties have been assumed to be similar to those of extracellular binding proteins, ^[12] however it is not clear, if THBP is the only intracellular thyroid hormone binding protein.

References

1. GRCh38: Ensembl release 89: ENSG00000103316 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000030905 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Chen H, Phillips HA, Callen DF, Kim RY, Wistow GJ, Antonarakis SE (Feb 1993). "Localization of the human gene for mu-crystallin to chromosome 16p". Genomics. 14 (4): 1115–6. doi: 10.1016/S0888-7543(05)80143-0 . PMID   1478656.
6. "Entrez Gene: CRYM crystallin, mu".
7. Hallen A, Cooper AJ, Jamie JF, Haynes PA, Willows RD (February 2011). "Mammalian forebrain ketimine reductase identified as μ-crystallin; potential regulation by thyroid hormones". J Neurochem. 118 (3): 379–387. doi:10.1111/j.1471-4159.2011.07220.x. PMID   21332720. S2CID   2081522.
8. Oshima A, Suzuki S, Takumi Y, Hashizume K, Abe S, Usami S (June 2006). "CRYM mutations cause deafness through thyroid hormone binding properties in the fibrocytes of the cochlea". J. Med. Genet. 43 (6): e25. doi:10.1136/jmg.2005.034397. PMC   2564543 . PMID   16740909.
9. Abe S, Katagiri T, Saito-Hisaminato A, Usami S, Inoue Y, Tsunoda T, Nakamura Y (January 2003). "Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues". Am. J. Hum. Genet. 72 (1): 73–82. doi:10.1086/345398. PMC   420014 . PMID   12471561.
10. Suzuki S, Suzuki N, Mori J, Oshima A, Usami S, Hashizume K (April 2007). "micro-Crystallin as an intracellular 3,5,3'-triiodothyronine holder in vivo". Mol. Endocrinol. 21 (4): 885–94. doi: 10.1210/me.2006-0403 . PMID   17264173.
11. Dietrich JW (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Entwicklung und klinische Anwendung eines nichtlinearen Modells[The pituitary-thyroid control loop. Development and clinical application of a nonlinear model] (in German). Berlin: Logos-Verlag. ISBN   3-89722-850-5.
12. Dietrich JW, Tesche A, Pickardt CR, Mitzdorf U (2004). "Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis". Cybernetics and Systems. 35 (4): 315–31. doi:10.1080/01969720490443354. S2CID   13421388.

External links

• Human CRYM genome location and CRYM gene details page in the UCSC Genome Browser .

Further reading

• Kim RY, Gasser R, Wistow GJ (1992). "mu-crystallin is a mammalian homologue of Agrobacterium ornithine cyclodeaminase and is expressed in human retina". Proc. Natl. Acad. Sci. U.S.A. 89 (19): 9292–6. Bibcode:1992PNAS...89.9292K. doi: 10.1073/pnas.89.19.9292 . PMC   50112 . PMID   1384048.
• Vié MP, Blanchet P, Samson M, et al. (1996). "High affinity thyroid hormone-binding protein in human kidney: kinetic characterization and identification by photoaffinity labeling". Endocrinology. 137 (11): 4563–70. doi:10.1210/en.137.11.4563. PMID   8895318.
• Segovia L, Horwitz J, Gasser R, Wistow G (1998). "Two roles for mu-crystallin: a lens structural protein in diurnal marsupials and a possible enzyme in mammalian retinas". Mol. Vis. 3: 9. PMID   9285773.
• Vié MP, Evrard C, Osty J, et al. (1998). "Purification, molecular cloning, and functional expression of the human nicodinamide-adenine dinucleotide phosphate-regulated thyroid hormone-binding protein". Mol. Endocrinol. 11 (11): 1728–36. doi: 10.1210/mend.11.11.9915 . PMID   9328354.
• Loftus BJ, Kim UJ, Sneddon VP, et al. (1999). "Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q". Genomics. 60 (3): 295–308. doi:10.1006/geno.1999.5927. PMID   10493829.
• Abe S, Katagiri T, Saito-Hisaminato A, et al. (2003). "Identification of CRYM as a candidate responsible for nonsyndromic deafness, through cDNA microarray analysis of human cochlear and vestibular tissues". Am. J. Hum. Genet. 72 (1): 73–82. doi:10.1086/345398. PMC   420014 . PMID   12471561.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Reed PW, Corse AM, Porter NC, et al. (2007). "Abnormal expression of mu-crystallin in facioscapulohumeral muscular dystrophy". Exp. Neurol. 205 (2): 583–6. doi:10.1016/j.expneurol.2007.03.009. PMID   17451686. S2CID   32811393.