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O43186

- CRX_HUMAN

UniProt

O43186 - CRX_HUMAN

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Protein

Cone-rod homeobox protein

Gene

CRX

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Transcription factor that binds and transactivates the sequence 5'-TAATC[CA]-3' which is found upstream of several photoreceptor-specific genes, including the opsin genes. Acts synergistically with other transcription factors, such as NRL, RORB and RAX, to regulate photoreceptor cell-specific gene transcription. Essential for the maintenance of mammalian photoreceptors.1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi39 – 9860HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. chromatin binding Source: Ensembl
  2. leucine zipper domain binding Source: UniProtKB
  3. nuclear hormone receptor binding Source: UniProtKB
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  6. sequence-specific DNA binding transcription factor activity Source: UniProtKB

GO - Biological processi

  1. circadian rhythm Source: Ensembl
  2. organ morphogenesis Source: ProtInc
  3. positive regulation of photoreceptor cell differentiation Source: Ensembl
  4. positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  5. regulation of transcription, DNA-templated Source: UniProtKB
  6. response to stimulus Source: UniProtKB-KW
  7. retina development in camera-type eye Source: Ensembl
  8. visual perception Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Activator, Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis, Sensory transduction, Transcription, Transcription regulation, Vision

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Cone-rod homeobox protein
Gene namesi
Name:CRX
Synonyms:CORD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:2383. CRX.

Subcellular locationi

Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

  1. nucleus Source: UniProtKB
  2. transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Leber congenital amaurosis 7 (LCA7) [MIM:613829]: A severe dystrophy of the retina, typically becoming evident in the first years of life. Visual function is usually poor and often accompanied by nystagmus, sluggish or near-absent pupillary responses, photophobia, high hyperopia and keratoconus.3 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti42 – 421E → K Found in a patient with LCA7. 1 Publication
VAR_067189
Natural varianti88 – 881K → N in LCA7; reduces NRL transactivation and reduces steady state levels of CRX and NRL; altered localization to the cytoplasm. 1 Publication
VAR_063919
Natural varianti90 – 901R → W in LCA7; reduced DNA-binding ability, transcriptional synergy and interaction with NRL. 1 Publication
VAR_008714
Natural varianti146 – 1494Missing in LCA7. 1 Publication
VAR_007947
Cone-rod dystrophy 2 (CORD2) [MIM:120970]: An inherited retinal dystrophy characterized by retinal pigment deposits visible on fundus examination, predominantly in the macular region, and initial loss of cone photoreceptors followed by rod degeneration. This leads to decreased visual acuity and sensitivity in the central visual field, followed by loss of peripheral vision. Severe loss of vision occurs earlier than in retinitis pigmentosa.3 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411R → W in CORD2; exhibits reduced DNA binding, transcriptional synergy and interaction with NRL. 1 Publication
VAR_003750
Natural varianti80 – 801E → A in CORD2. 2 Publications
Corresponds to variant rs28939682 [ dbSNP | Ensembl ].
VAR_003751
Natural varianti242 – 2421V → M in CORD2. 1 Publication
VAR_007949
Retinitis pigmentosa (RP) [MIM:268000]: A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411R → Q in RP. 2 Publications
VAR_007946
Natural varianti122 – 1221G → D in RP.
Corresponds to variant rs61748441 [ dbSNP | Ensembl ].
VAR_008282

Keywords - Diseasei

Cone-rod dystrophy, Disease mutation, Leber congenital amaurosis, Retinitis pigmentosa

Organism-specific databases

MIMi120970. phenotype.
268000. phenotype.
613829. phenotype.
Orphaneti1872. Cone rod dystrophy.
65. Leber congenital amaurosis.
791. Retinitis pigmentosa.
PharmGKBiPA26903.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 299299Cone-rod homeobox proteinPRO_0000048862Add
BLAST

Proteomic databases

PaxDbiO43186.
PRIDEiO43186.

PTM databases

PhosphoSiteiO43186.

Expressioni

Tissue specificityi

Retina.

Gene expression databases

BgeeiO43186.
CleanExiHS_CRX.
GenevestigatoriO43186.

Organism-specific databases

HPAiHPA036762.
HPA036763.

Interactioni

Subunit structurei

Interacts (via the homeobox) with NRL (via the leucine-zipper domain). Interacts with PDC, RAX2, RORB and SCA7.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
taxP034103EBI-748171,EBI-9676218From a different organism.

Protein-protein interaction databases

BioGridi107796. 15 interactions.
IntActiO43186. 7 interactions.
MINTiMINT-1442706.
STRINGi9606.ENSP00000221996.

Structurei

3D structure databases

ProteinModelPortaliO43186.
SMRiO43186. Positions 34-95.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the paired homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG324074.
GeneTreeiENSGT00760000118908.
HOGENOMiHOG000082677.
HOVERGENiHBG004028.
InParanoidiO43186.
KOiK09337.
OMAiQTKARPA.
PhylomeDBiO43186.
TreeFamiTF351179.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR013851. Otx_TF_C.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
PF03529. TF_Otx. 1 hit.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O43186-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MMAYMNPGPH YSVNALALSG PSVDLMHQAV PYPSAPRKQR RERTTFTRSQ
60 70 80 90 100
LEELEALFAK TQYPDVYARE EVALKINLPE SRVQVWFKNR RAKCRQQRQQ
110 120 130 140 150
QKQQQQPPGG QAKARPAKRK AGTSPRPSTD VCPDPLGISD SYSPPLPGPS
160 170 180 190 200
GSPTTAVATV SIWSPASESP LPEAQRAGLV ASGPSLTSAP YAMTYAPASA
210 220 230 240 250
FCSSPSAYGS PSSYFSGLDP YLSPMVPQLG GPALSPLSGP SVGPSLAQSP
260 270 280 290
TSLSGQSYGA YSPVDSLEFK DPTGTWKFTY NPMDPLDYKD QSAWKFQIL
Length:299
Mass (Da):32,261
Last modified:June 1, 1998 - v1
Checksum:i46747C09277A0864
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti41 – 411R → Q in RP. 2 Publications
VAR_007946
Natural varianti41 – 411R → W in CORD2; exhibits reduced DNA binding, transcriptional synergy and interaction with NRL. 1 Publication
VAR_003750
Natural varianti42 – 421E → K Found in a patient with LCA7. 1 Publication
VAR_067189
Natural varianti80 – 801E → A in CORD2. 2 Publications
Corresponds to variant rs28939682 [ dbSNP | Ensembl ].
VAR_003751
Natural varianti88 – 881K → N in LCA7; reduces NRL transactivation and reduces steady state levels of CRX and NRL; altered localization to the cytoplasm. 1 Publication
VAR_063919
Natural varianti90 – 901R → W in LCA7; reduced DNA-binding ability, transcriptional synergy and interaction with NRL. 1 Publication
VAR_008714
Natural varianti122 – 1221G → D in RP.
Corresponds to variant rs61748441 [ dbSNP | Ensembl ].
VAR_008282
Natural varianti141 – 1411S → F in a breast cancer sample; somatic mutation. 1 Publication
VAR_036438
Natural varianti146 – 1494Missing in LCA7. 1 Publication
VAR_007947
Natural varianti154 – 1541T → A.1 Publication
VAR_067190
Natural varianti158 – 1581A → T.1 Publication
Corresponds to variant rs61748445 [ dbSNP | Ensembl ].
VAR_007948
Natural varianti242 – 2421V → M in CORD2. 1 Publication
VAR_007949

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024711 Genomic DNA. Translation: AAB88418.1.
BT007364 mRNA. Translation: AAP36028.1.
AC008745 Genomic DNA. No translation available.
BC016664 mRNA. No translation available.
BC053672 mRNA. No translation available.
DQ426868 mRNA. Translation: ABD90533.1.
CCDSiCCDS12706.1.
RefSeqiNP_000545.1. NM_000554.4.
UniGeneiHs.617342.
Hs.633434.
Hs.639114.

Genome annotation databases

EnsembliENST00000221996; ENSP00000221996; ENSG00000105392.
ENST00000539067; ENSP00000445565; ENSG00000105392.
GeneIDi1406.
KEGGihsa:1406.
UCSCiuc002phq.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Mutations of the CRX gene

Retina International's Scientific Newsletter

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024711 Genomic DNA. Translation: AAB88418.1 .
BT007364 mRNA. Translation: AAP36028.1 .
AC008745 Genomic DNA. No translation available.
BC016664 mRNA. No translation available.
BC053672 mRNA. No translation available.
DQ426868 mRNA. Translation: ABD90533.1 .
CCDSi CCDS12706.1.
RefSeqi NP_000545.1. NM_000554.4.
UniGenei Hs.617342.
Hs.633434.
Hs.639114.

3D structure databases

ProteinModelPortali O43186.
SMRi O43186. Positions 34-95.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107796. 15 interactions.
IntActi O43186. 7 interactions.
MINTi MINT-1442706.
STRINGi 9606.ENSP00000221996.

PTM databases

PhosphoSitei O43186.

Proteomic databases

PaxDbi O43186.
PRIDEi O43186.

Protocols and materials databases

DNASUi 1406.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000221996 ; ENSP00000221996 ; ENSG00000105392 .
ENST00000539067 ; ENSP00000445565 ; ENSG00000105392 .
GeneIDi 1406.
KEGGi hsa:1406.
UCSCi uc002phq.4. human.

Organism-specific databases

CTDi 1406.
GeneCardsi GC19P048359.
GeneReviewsi CRX.
HGNCi HGNC:2383. CRX.
HPAi HPA036762.
HPA036763.
MIMi 120970. phenotype.
268000. phenotype.
602225. gene.
613829. phenotype.
neXtProti NX_O43186.
Orphaneti 1872. Cone rod dystrophy.
65. Leber congenital amaurosis.
791. Retinitis pigmentosa.
PharmGKBi PA26903.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG324074.
GeneTreei ENSGT00760000118908.
HOGENOMi HOG000082677.
HOVERGENi HBG004028.
InParanoidi O43186.
KOi K09337.
OMAi QTKARPA.
PhylomeDBi O43186.
TreeFami TF351179.

Miscellaneous databases

ChiTaRSi CRX. human.
GeneWikii CRX_(gene).
GenomeRNAii 1406.
NextBioi 5749.
PROi O43186.
SOURCEi Search...

Gene expression databases

Bgeei O43186.
CleanExi HS_CRX.
Genevestigatori O43186.

Family and domain databases

Gene3Di 1.10.10.60. 1 hit.
InterProi IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR013851. Otx_TF_C.
[Graphical view ]
Pfami PF00046. Homeobox. 1 hit.
PF03529. TF_Otx. 1 hit.
[Graphical view ]
SMARTi SM00389. HOX. 1 hit.
[Graphical view ]
SUPFAMi SSF46689. SSF46689. 1 hit.
PROSITEi PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor."
    Freund C.L., Gregory-Evans C.Y., Furukawa T., Papaioannou M., Looser J., Ploder L., Bellingham J., Ng D., Herbrick J.-A.S., Duncan A., Scherer S.W., Tsui L.-C., Loutradis-Anagnostou A., Jacobson S.G., Cepko C.L., Bhattacharya S.S., McInnes R.R.
    Cell 91:543-553(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CORD2 ALA-80.
  2. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Eye.
  5. "Mapping of transcription start sites of human retina expressed genes."
    Roni V., Carpio R., Wissinger B.
    BMC Genomics 8:42-42(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-54.
    Tissue: Retina.
  6. "Both PCE-1/RX and OTX/CRX interactions are necessary for photoreceptor-specific gene expression."
    Kimura A., Singh D., Wawrousek E.F., Kikuchi M., Nakamura M., Shinohara T.
    J. Biol. Chem. 275:1152-1160(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. "The leucine zipper of NRL interacts with the CRX homeodomain. A possible mechanism of transcriptional synergy in rhodopsin regulation."
    Mitton K.P., Swain P.K., Chen S., Xu S., Zack D.J., Swaroop A.
    J. Biol. Chem. 275:29794-29799(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NRL, CHARACTERIZATION OF VARIANT CORD2 TRP-41, CHARACTERIZATION OF VARIANT LCA7 TRP-90.
  8. Cited for: INTERACTION WITH RAX2.
  9. "Mutations in the cone-rod homeobox gene are associated with the cone-rod dystrophy photoreceptor degeneration."
    Swain P.K., Chen S., Wang Q.-L., Affatigato L.M., Coats C.L., Brady K.D., Fishman G.A., Jacobson S.G., Swaroop A., Stone E., Sieving P.A., Zack D.J.
    Neuron 19:1329-1336(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CORD2 TRP-41 AND MET-242, VARIANT RP GLN-41, VARIANT THR-158.
  10. "A range of clinical phenotypes associated with mutations in CRX, a photoreceptor transcription-factor gene."
    Sohocki M.M., Sullivan L.S., Mintz-Hittner H.A., Birch D., Heckenlively J.R., Freund C.L., McInnes R.R., Daiger S.P.
    Am. J. Hum. Genet. 63:1307-1315(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT RP GLN-41, VARIANT CORD2 ALA-80, VARIANT LCA7 146-LEU--PRO-149 DEL.
  11. "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."
    Swaroop A., Wang Q.-L., Wu W., Cook J., Coats C., Xu S., Chen S., Zack D.J., Sieving P.A.
    Hum. Mol. Genet. 8:299-305(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT LCA7 TRP-90.
  12. Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-141.
  13. "Molecular characterization of Leber congenital amaurosis in Koreans."
    Seong M.W., Kim S.Y., Yu Y.S., Hwang J.M., Kim J.Y., Park S.S.
    Mol. Vis. 14:1429-1436(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT ALA-154.
  14. "Two novel CRX mutant proteins causing autosomal dominant Leber congenital amaurosis interact differently with NRL."
    Nichols L.L. II, Alur R.P., Boobalan E., Sergeev Y.V., Caruso R.C., Stone E.M., Swaroop A., Johnson M.A., Brooks B.P.
    Hum. Mutat. 31:E1472-E1483(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT LCA7 ASN-88, CHARACTERIZATION OF VARIANT LCA7 ASN-88.
  15. "Detection of variants in 15 genes in 87 unrelated Chinese patients with Leber congenital amaurosis."
    Li L., Xiao X., Li S., Jia X., Wang P., Guo X., Jiao X., Zhang Q., Hejtmancik J.F.
    PLoS ONE 6:E19458-E19458(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT LYS-42.

Entry informationi

Entry nameiCRX_HUMAN
AccessioniPrimary (citable) accession number: O43186
Secondary accession number(s): Q0QD45
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: June 1, 1998
Last modified: October 29, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3