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CRX
Identifiers
Aliases	CRX, CORD2, CRD, LCA7, OTX3, cone-rod homeobox
External IDs	OMIM: 602225; MGI: 1194883; HomoloGene: 467; GeneCards: CRX; OMA:CRX - orthologs
Gene location (Human) Chr. Chromosome 19 (human) Band 19q13.33 Start 47,819,779 bp End 47,843,330 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7 A2|7 8.6 cM Start 15,599,872 bp End 15,613,893 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in retinal pigment epithelium gonad testicle Epithelium of choroid plexus right lobe of liver granulocyte monocyte upper respiratory tract gallbladder mucosa of nose Top expressed in neural layer of retina outer nuclear layer inner nuclear layer pineal gland epithelium of lens retinal pigment epithelium photoreceptor layer of retina Ileal epithelium lumbar spinal ganglion corneal stroma More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA-binding transcription activator activity, RNA polymerase II-specific DNA binding leucine zipper domain binding protein binding sequence-specific DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus Biological process circadian rhythm nervous system development animal organ morphogenesis positive regulation of transcription by RNA polymerase II response to stimulus positive regulation of photoreceptor cell differentiation transcription, DNA-templated multicellular organism development cell differentiation regulation of transcription, DNA-templated visual perception transcription by RNA polymerase II Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 1406 12951 Ensembl ENSG00000105392 ENSMUSG00000041578 UniProt O43186 O54751 RefSeq (mRNA) NM_000554 NM_001113330 NM_007770 RefSeq (protein) NP_000545 NP_001106801 NP_031796 Location (UCSC) Chr 19: 47.82 – 47.84 Mb Chr 7: 15.6 – 15.61 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

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.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000105392 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000041578 – 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. Freund CL, Gregory-Evans CY, Furukawa T, Papaioannou M, Looser J, Ploder L, et al. (Nov 1997). "Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor". Cell. 91 (4): 543–53. doi:10.1016/S0092-8674(00)80440-7. hdl:10261/270606. PMID 9390563. S2CID 5755412.
6. Freund CL, Wang QL, Chen S, Muskat BL, Wiles CD, Sheffield VC, et al. (Apr 1998). "De novo mutations in the CRX homeobox gene associated with Leber congenital amaurosis". Nature Genetics. 18 (4): 311–2. doi:10.1038/ng0498-311. PMID 9537410. S2CID 22131800.
7. ^ "Entrez Gene: CRX cone-rod homeobox".
8. Tran NM, Zhang A, Zhang X, Huecker JB, Hennig AK, Chen S (Feb 6, 2014). "Mechanistically Distinct Mouse Models for CRX-Associated Retinopathy". PLOS Genet. 10 (2): e1004111. doi:10.1371/journal.pgen.1004111. PMC 3916252. PMID 24516401.
9. Clanor PB, Buchholz CN, Hayes JE, Friedman MA, White AM, Enke RA, et al. (March 23, 2022). "Structural and functional analysis of the human cone-rod homeobox transcription factor". Proteins. 90 (8): 1584–1593. doi:10.1002/prot.26332. PMC 9271546. PMID 35255174.
10. Germot A, Lecointre G, Plouhinec JL, Le Mentec C, Girardot F, Mazan S (September 2001). "Structural evolution of Otx genes in craniates". Molecular Biology and Evolution. 18 (9): 1668–78. doi:10.1093/oxfordjournals.molbev.a003955. PMID 11504847.
11. Maeso I, Dunwell TL, Wyatt CD, Marlétaz F, Vető B, Bernal JA, et al. (June 2016). "Evolutionary origin and functional divergence of totipotent cell homeobox genes in eutherian mammals". BMC Biology. 14 (1): 45. doi:10.1186/s12915-016-0267-0. PMC 4904359. PMID 27296695.

Further reading

• Paunescu K, Preising MN, Janke B, Wissinger B, Lorenz B (Jul 2007). "Genotype-phenotype correlation in a German family with a novel complex CRX mutation extending the open reading frame". Ophthalmology. 114 (7): 1348–1357.e1. doi:10.1016/j.ophtha.2006.10.034. PMID 17320181.
• Evans K, Fryer A, Inglehearn C, Duvall-Young J, Whittaker JL, Gregory CY, et al. (Feb 1994). "Genetic linkage of cone-rod retinal dystrophy to chromosome 19q and evidence for segregation distortion". Nature Genetics. 6 (2): 210–3. doi:10.1038/ng0294-210. PMID 8162077. S2CID 333926.
• Chen S, Wang QL, Nie Z, Sun H, Lennon G, Copeland NG, et al. (Nov 1997). "Crx, a novel Otx-like paired-homeodomain protein, binds to and transactivates photoreceptor cell-specific genes". Neuron. 19 (5): 1017–30. doi:10.1016/S0896-6273(00)80394-3. PMID 9390516. S2CID 18485264.
• Swain PK, Chen S, Wang QL, Affatigato LM, Coats CL, Brady KD, et al. (Dec 1997). "Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration". Neuron. 19 (6): 1329–36. doi:10.1016/S0896-6273(00)80423-7. PMID 9427255. S2CID 409482.
• Sohocki MM, Sullivan LS, Mintz-Hittner HA, Birch D, Heckenlively JR, Freund CL, et al. (Nov 1998). "A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene". American Journal of Human Genetics. 63 (5): 1307–15. doi:10.1086/302101. PMC 1377541. PMID 9792858.
• Swaroop A, Wang QL, Wu W, Cook J, Coats C, Xu S, et al. (Feb 1999). "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. doi:10.1093/hmg/8.2.299. PMID 9931337.
• Bessant DA, Payne AM, Mitton KP, Wang QL, Swain PK, Plant C, et al. (Apr 1999). "A mutation in NRL is associated with autosomal dominant retinitis pigmentosa". Nature Genetics. 21 (4): 355–6. doi:10.1038/7678. PMID 10192380. S2CID 28621258.
• Yanagi Y, Masuhiro Y, Mori M, Yanagisawa J, Kato S (Mar 2000). "p300/CBP acts as a coactivator of the cone-rod homeobox transcription factor". Biochemical and Biophysical Research Communications. 269 (2): 410–4. doi:10.1006/bbrc.2000.2304. PMID 10708567.
• Zhu X, Craft CM (Jul 2000). "Modulation of CRX transactivation activity by phosducin isoforms". Molecular and Cellular Biology. 20 (14): 5216–26. doi:10.1128/MCB.20.14.5216-5226.2000. PMC 85970. PMID 10866677.
• Mitton KP, Swain PK, Chen S, Xu S, Zack DJ, Swaroop A (Sep 2000). "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. doi:10.1074/jbc.M003658200. PMID 10887186.
• Bibb LC, Holt JK, Tarttelin EE, Hodges MD, Gregory-Evans K, Rutherford A, et al. (Jul 2001). "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. doi:10.1093/hmg/10.15.1571. PMID 11468275.
• La Spada AR, Fu YH, Sopher BL, Libby RT, Wang X, Li LY, et al. (Sep 2001). "Polyglutamine-expanded ataxin-7 antagonizes CRX function and induces cone-rod dystrophy in a mouse model of SCA7". Neuron. 31 (6): 913–27. doi:10.1016/S0896-6273(01)00422-6. PMID 11580893. S2CID 51784415.
• Rivolta C, Peck NE, Fulton AB, Fishman GA, Berson EL, Dryja TP (Dec 2001). "Novel frameshift mutations in CRX associated with Leber congenital amaurosis". Human Mutation. 18 (6): 550–1. doi:10.1002/humu.1243. PMID 11748859. S2CID 37801650.
• Koenekoop RK, Loyer M, Dembinska O, Beneish R (Mar 2002). "Visual improvement in Leber congenital amaurosis and the CRX genotype". Ophthalmic Genetics. 23 (1): 49–59. doi:10.1076/opge.23.1.49.2200. PMID 11910559. S2CID 21536673.
• Chen S, Wang QL, Xu S, Liu I, Li LY, Wang Y, et al. (Apr 2002). "Functional analysis of cone-rod homeobox (CRX) mutations associated with retinal dystrophy". Human Molecular Genetics. 11 (8): 873–84. doi:10.1093/hmg/11.8.873. PMID 11971869.
• Nakamura M, Ito S, Miyake Y (Sep 2002). "Novel de novo mutation in CRX gene in a Japanese patient with leber congenital amaurosis". American Journal of Ophthalmology. 134 (3): 465–7. doi:10.1016/S0002-9394(02)01542-8. PMID 12208271.
• Lines MA, Hébert M, McTaggart KE, Flynn SJ, Tennant MT, MacDonald IM (Oct 2002). "Electrophysiologic and phenotypic features of an autosomal cone-rod dystrophy caused by a novel CRX mutation". Ophthalmology. 109 (10): 1862–70. doi:10.1016/S0161-6420(02)01187-9. PMID 12359607.
• Hodges MD, Vieira H, Gregory-Evans K, Gregory-Evans CY (Nov 2002). "Characterization of the genomic and transcriptional structure of the CRX gene: substantial differences between human and mouse". Genomics. 80 (5): 531–42. 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 U.S. 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.

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