Biology:CRX (gene)

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Cone-rod homeobox protein is a protein that in humans is encoded by the CRX gene.

Function

The protein encoded by this gene is a photoreceptor-specific transcription factor which plays a role in the differentiation of photoreceptor cells. This homeodomain protein is necessary for the maintenance of normal cone and rod function. Mutations in this gene are associated with photoreceptor degeneration, Leber's congenital amaurosis type III and the autosomal dominant cone-rod dystrophy 2. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined.

Mammalian CRX encodes a 299 amino acid protein containing a DNA binding homeodomain (HD) near its N-terminus followed by glutamine rich (Gln), and basic amino acid regions, then a C-terminal transactivation domain (AD). While structural biochemistry has demonstrated that the CRX HD adopts a canonical homeodomain protein fold, the AD is predicted to be flexible and disordered. The structural attributes of the CRX AD have yet to be solved.

Evolution

CRX is a divergent duplicate of OTX produced during the 2 rounds of vertebrate whole genome duplication.

In the eutherian mammals, CRX has again duplicated by tandem gene duplication, with six ancestral duplicates, which are collectively referred to as ETCHbox genes.

Further reading

• "Genotype-phenotype correlation in a German family with a novel complex CRX mutation extending the open reading frame". Ophthalmology 114 (7): 1348–1357.e1. Jul 2007. doi:10.1016/j.ophtha.2006.10.034. PMID 17320181. 
• "Genetic linkage of cone-rod retinal dystrophy to chromosome 19q and evidence for segregation distortion". Nature Genetics 6 (2): 210–3. Feb 1994. doi:10.1038/ng0294-210. PMID 8162077. 
• "Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes". Neuron 19 (5): 1017–30. Nov 1997. doi:10.1016/S0896-6273(00)80394-3. PMID 9390516. 
• "Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration". Neuron 19 (6): 1329–36. Dec 1997. doi:10.1016/S0896-6273(00)80423-7. PMID 9427255. 
• "A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene". American Journal of Human Genetics 63 (5): 1307–15. Nov 1998. doi:10.1086/302101. PMID 9792858. 
• "Leber congenital amaurosis caused by a homozygous mutation (R90W) in the homeodomain of the retinal transcription factor CRX: direct evidence for the involvement of CRX in the development of photoreceptor function". Human Molecular Genetics 8 (2): 299–305. Feb 1999. doi:10.1093/hmg/8.2.299. PMID 9931337. 
• "A mutation in NRL is associated with autosomal dominant retinitis pigmentosa". Nature Genetics 21 (4): 355–6. Apr 1999. doi:10.1038/7678. PMID 10192380. 
• "p300/CBP acts as a coactivator of the cone-rod homeobox transcription factor". Biochemical and Biophysical Research Communications 269 (2): 410–4. Mar 2000. doi:10.1006/bbrc.2000.2304. PMID 10708567. 
• "Modulation of CRX transactivation activity by phosducin isoforms". Molecular and Cellular Biology 20 (14): 5216–26. Jul 2000. doi:10.1128/MCB.20.14.5216-5226.2000. PMID 10866677. 
• "The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation". The Journal of Biological Chemistry 275 (38): 29794–9. Sep 2000. doi:10.1074/jbc.M003658200. PMID 10887186. 
• "Temporal and spatial expression patterns of the CRX transcription factor and its downstream targets. Critical differences during human and mouse eye development". Human Molecular Genetics 10 (15): 1571–9. Jul 2001. doi:10.1093/hmg/10.15.1571. PMID 11468275. 
• "Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7". Neuron 31 (6): 913–27. Sep 2001. doi:10.1016/S0896-6273(01)00422-6. PMID 11580893. 
• "Novel frameshift mutations in CRX associated with Leber congenital amaurosis". Human Mutation 18 (6): 550–1. Dec 2001. doi:10.1002/humu.1243. PMID 11748859. 
• "Visual improvement in Leber congenital amaurosis and the CRX genotype". Ophthalmic Genetics 23 (1): 49–59. Mar 2002. doi:10.1076/opge.23.1.49.2200. PMID 11910559. 
• "Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal dystrophy". Human Molecular Genetics 11 (8): 873–84. Apr 2002. doi:10.1093/hmg/11.8.873. PMID 11971869. 
• "Novel de novo mutation in CRX gene in a Japanese patient with leber congenital amaurosis". American Journal of Ophthalmology 134 (3): 465–7. Sep 2002. doi:10.1016/S0002-9394(02)01542-8. PMID 12208271. 
• "Electrophysiologic and phenotypic features of an autosomal cone-rod dystrophy caused by a novel CRX mutation". Ophthalmology 109 (10): 1862–70. Oct 2002. doi:10.1016/S0161-6420(02)01187-9. PMID 12359607. 
• "Characterization of the genomic and transcriptional structure of the CRX gene: substantial differences between human and mouse". Genomics 80 (5): 531–42. Nov 2002. doi:10.1016/S0888-7543(02)96854-0. PMID 12408971. 

External links

• GeneReviews/NCBI/NIH/UW entry on Retinitis Pigmentosa Overview
• CRX+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human CRX genome location and CRX gene details page in the UCSC Genome Browser.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.