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P32243 (OTX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein OTX2
Alternative name(s):
Orthodenticle homolog 2
Gene names
Name:OTX2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Probably plays a role in the development of the brain and the sense organs. Can bind to the BCD target sequence (BTS): 5'-TCTAATCCC-3'.

Subcellular location

Nucleus Probable.

Tissue specificity

Expressed in brain.

Developmental stage

Embryo. Expression in the retina peaks at fetal days 48-54. At 6-, 8- and 10-week old, in the retina, the expression is strongest in the retinal pigment epithelium (at protein level). Ref.10

Involvement in disease

Microphthalmia, syndromic, 5 (MCOPS5) [MIM:610125]: Patients manifest unilateral or bilateral microphthalmia/clinical anophthalmia and variable additional features including pituitary dysfunction, coloboma, microcornea, cataract, retinal dystrophy, hypoplasia or agenesis of the optic nerve, agenesis of the corpus callosum, developmental delay, joint laxity, hypotonia, and seizures. Microphthalmia is a disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues (anophthalmia). In many cases, microphthalmia/anophthalmia occurs in association with syndromes that include non-ocular abnormalities.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.12

Pituitary hormone deficiency, combined, 6 (CPHD6) [MIM:613986]: Combined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD6 patients manifest neonatal hypoglycemia, and deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.11

Sequence similarities

Belongs to the paired homeobox family. Bicoid subfamily.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
Microphthalmia
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processaxon guidance

Inferred from direct assay PubMed 16267555. Source: UniProtKB

cell fate specification

Inferred from electronic annotation. Source: Ensembl

diencephalon morphogenesis

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral pattern formation

Inferred from electronic annotation. Source: Ensembl

endoderm development

Inferred from electronic annotation. Source: Ensembl

eye photoreceptor cell fate commitment

Inferred from electronic annotation. Source: Ensembl

forebrain development

Traceable author statement PubMed 15705863. Source: UniProtKB

inner ear morphogenesis

Inferred from electronic annotation. Source: Ensembl

metencephalon development

Inferred from electronic annotation. Source: Ensembl

midbrain development

Traceable author statement PubMed 15705863. Source: UniProtKB

positive regulation of embryonic development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gastrulation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 20530484. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

primitive streak formation

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex assembly

Inferred from direct assay PubMed 20530484. Source: UniProtKB

regulation of fibroblast growth factor receptor signaling pathway

Traceable author statement PubMed 15705863. Source: UniProtKB

regulation of smoothened signaling pathway

Traceable author statement PubMed 15705863. Source: UniProtKB

somite rostral/caudal axis specification

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

growth cone

Inferred from direct assay PubMed 16267555. Source: UniProtKB

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

protein complex

Inferred from direct assay PubMed 20530484. Source: UniProtKB

   Molecular_functionRNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription

Inferred from direct assay PubMed 20530484. Source: UniProtKB

eukaryotic initiation factor 4E binding

Traceable author statement PubMed 15705863. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P32243-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P32243-2)

The sequence of this isoform differs from the canonical sequence as follows:
     32-32: P → PGPWASCPA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 289289Homeobox protein OTX2
PRO_0000049210

Regions

DNA binding38 – 9760Homeobox
Compositional bias95 – 1017Poly-Gln

Natural variations

Alternative sequence321P → PGPWASCPA in isoform 2.
VSP_021006
Natural variant891R → G in MCOPS5. Ref.8
VAR_029354
Natural variant901R → S in MCOPS5; does not affect the expression or nuclear localization of the protein but inhibits its DNA-binding activity as well as its transactivation capability; the protein is non-functional. Ref.12
VAR_065952
Natural variant1331P → T in MCOPS5. Ref.8
VAR_029355
Natural variant1341P → A in MCOPS5. Ref.8
VAR_029356
Natural variant2251N → S in CPHD6; acts as a dominant inhibitor of the HESX1 gene. Ref.11
VAR_065953

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: 66B86D5EAD6E2E7A

FASTA28931,636
        10         20         30         40         50         60 
MMSYLKQPPY AVNGLSLTTS GMDLLHPSVG YPATPRKQRR ERTTFTRAQL DVLEALFAKT 

        70         80         90        100        110        120 
RYPDIFMREE VALKINLPES RVQVWFKNRR AKCRQQQQQQ QNGGQNKVRP AKKKTSPARE 

       130        140        150        160        170        180 
VSSESGTSGQ FTPPSSTSVP TIASSSAPVS IWSPASISPL SDPLSTSSSC MQRSYPMTYT 

       190        200        210        220        230        240 
QASGYSQGYA GSTSYFGGMD CGSYLTPMHH QLPGPGATLS PMGTNAVTSH LNQSPASLST 

       250        260        270        280 
QGYGASSLGF NSTTDCLDYK DQTASWKLNF NADCLDYKDQ TSSWKFQVL 

« Hide

Isoform 2 [UniParc].

Checksum: DB4A3AE99DDA6F6A
Show »

FASTA29732,406

References

« Hide 'large scale' references
[1]"A vertebrate gene related to orthodenticle contains a homeodomain of the bicoid class and demarcates anterior neuroectoderm in the gastrulating mouse embryo."
Simeone A., Acampora D., Mallamaci A., Stornaiuolo A., D'Apice M.R., Nigro V., Boncinelli E.
EMBO J. 12:2735-2747(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]Perrault I., Rozet J.-M., Gerber S., Munnich A., Kaplan J.
Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Elements regulating the transcription of human interstitial retinoid-binding protein (IRBP) gene in cultured retinoblastoma cells."
Fong S.L., Fong W.B.
Curr. Eye Res. 18:283-291(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Retina.
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Cerebellum.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORM 2).
Tissue: Eye.
[7]Kitano T., Kobayakawa H., Saitou N.
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 171-283.
[8]"Heterozygous mutations of OTX2 cause severe ocular malformations."
Ragge N.K., Brown A.G., Poloschek C.M., Lorenz B., Henderson R.A., Clarke M.P., Russell-Eggitt I., Fielder A., Gerrelli D., Martinez-Barbera J.P., Ruddle P., Hurst J., Collin J.R., Salt A., Cooper S.T., Thompson P.J., Sisodiya S.M., Williamson K.A. expand/collapse author list , Fitzpatrick D.R., van Heyningen V., Hanson I.M.
Am. J. Hum. Genet. 76:1008-1022(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MCOPS5 GLY-89; THR-133 AND ALA-134.
[9]Erratum
Ragge N.K., Brown A.G., Poloschek C.M., Lorenz B., Henderson R.A., Clarke M.P., Russell-Eggitt I., Fielder A., Gerrelli D., Martinez-Barbera J.P., Ruddle P., Hurst J., Collin J.R., Salt A., Cooper S.T., Thompson P.J., Sisodiya S.M., Williamson K.A. expand/collapse author list , Fitzpatrick D.R., van Heyningen V., Hanson I.M.
Am. J. Hum. Genet. 77:334-334(2005)
[10]"Expression of the homeobox genes PAX6, OTX2, and OTX1 in the early human fetal retina."
Larsen K.B., Lutterodt M., Rath M.F., Moeller M.
Int. J. Dev. Neurosci. 27:485-492(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: DEVELOPMENTAL STAGE.
[11]"A novel dominant negative mutation of OTX2 associated with combined pituitary hormone deficiency."
Diaczok D., Romero C., Zunich J., Marshall I., Radovick S.
J. Clin. Endocrinol. Metab. 93:4351-4359(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPHD6 SER-225, CHARACTERIZATION OF VARIANT CPHD6 SER-225.
[12]"A novel loss-of-function mutation in OTX2 in a patient with anophthalmia and isolated growth hormone deficiency."
Ashkenazi-Hoffnung L., Lebenthal Y., Wyatt A.W., Ragge N.K., Dateki S., Fukami M., Ogata T., Phillip M., Gat-Yablonski G.
Hum. Genet. 127:721-729(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MCOPS5 SER-90, CHARACTERIZATION OF VARIANT MCOPS5 SER-90.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF298117 Genomic DNA. Translation: AAG16243.1.
AF093138 mRNA. Translation: AAD31385.1.
AK314271 mRNA. Translation: BAG36932.1.
CH471061 Genomic DNA. Translation: EAW80692.1.
BC032579 mRNA. Translation: AAH32579.1.
AB037505 Genomic DNA. Translation: BAA90425.1.
RefSeqNP_001257452.1. NM_001270523.1.
NP_001257453.1. NM_001270524.1.
NP_001257454.1. NM_001270525.1.
NP_068374.1. NM_021728.3.
NP_758840.1. NM_172337.2.
UniGeneHs.288655.
Hs.741558.

3D structure databases

ProteinModelPortalP32243.
SMRP32243. Positions 12-106.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111055. 6 interactions.
IntActP32243. 2 interactions.
MINTMINT-2861458.
STRING9606.ENSP00000343819.

PTM databases

PhosphoSiteP32243.

Proteomic databases

PaxDbP32243.
PRIDEP32243.

Protocols and materials databases

DNASU5015.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000339475; ENSP00000343819; ENSG00000165588. [P32243-2]
ENST00000408990; ENSP00000386185; ENSG00000165588. [P32243-1]
ENST00000555006; ENSP00000452336; ENSG00000165588. [P32243-1]
GeneID5015.
KEGGhsa:5015.
UCSCuc001xcp.4. human. [P32243-1]

Organism-specific databases

CTD5015.
GeneCardsGC14M057267.
HGNCHGNC:8522. OTX2.
HPAHPA000633.
MIM600037. gene.
610125. phenotype.
613986. phenotype.
neXtProtNX_P32243.
Orphanet990. Agnathia - holoprosencephaly - situs inversus.
95494. Combined pituitary hormone deficiencies, genetic forms.
2542. Isolated anophthalmia - microphthalmia.
3157. Septo-optic dysplasia.
178364. Syndromic microphthalmia type 5.
PharmGKBPA32849.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG245767.
HOGENOMHOG000082677.
HOVERGENHBG004028.
KOK09326.
OMAKGPWASC.
OrthoDBEOG74J98P.
PhylomeDBP32243.
TreeFamTF351179.

Gene expression databases

ArrayExpressP32243.
BgeeP32243.
CleanExHS_OTX2.
GenevestigatorP32243.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR003022. Otx2_TF.
IPR003025. Otx_TF.
IPR013851. Otx_TF_C.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
PF03529. TF_Otx. 1 hit.
[Graphical view]
PRINTSPR01257. OTX2HOMEOBOX.
PR01255. OTXHOMEOBOX.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiOrthodenticle_homeobox_2.
GenomeRNAi5015.
NextBio19304.
PROP32243.
SOURCESearch...

Entry information

Entry nameOTX2_HUMAN
AccessionPrimary (citable) accession number: P32243
Secondary accession number(s): B2RAN5 expand/collapse secondary AC list , Q6GTV3, Q9HAW3, Q9P2R1
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: April 16, 2014
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM