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Protein

Homeobox protein OTX2

Gene

OTX2

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

Functioni

Transcription factor probably involved in the development of the brain and the sense organs. Can bind to the bicoid/BCD target sequence (BTS): 5'-TCTAATCCC-3'.1 Publication

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi38 – 97HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

GO - Biological processi

  • axon guidance Source: UniProtKB
  • dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
  • forebrain development Source: UniProtKB
  • midbrain development Source: UniProtKB
  • positive regulation of embryonic development Source: UniProtKB
  • positive regulation of gastrulation Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • primitive streak formation Source: UniProtKB
  • protein complex assembly Source: UniProtKB
  • regulation of fibroblast growth factor receptor signaling pathway Source: UniProtKB
  • regulation of smoothened signaling pathway Source: UniProtKB

Keywordsi

Molecular functionDevelopmental protein, DNA-binding

Enzyme and pathway databases

SIGNORiP32243.

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein OTX2
Alternative name(s):
Orthodenticle homolog 2
Gene namesi
Name:OTX2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:8522. OTX2.

Subcellular locationi

GO - Cellular componenti

  • growth cone Source: UniProtKB
  • nucleus Source: ParkinsonsUK-UCL
  • protein complex Source: UniProtKB

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Microphthalmia, syndromic, 5 (MCOPS5)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionPatients 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.
See also OMIM:610125
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02935489R → G in MCOPS5. 1 PublicationCorresponds to variant dbSNP:rs104894464Ensembl.1
Natural variantiVAR_06595290R → 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. 1 Publication1
Natural variantiVAR_029355133P → T in MCOPS5. 1 PublicationCorresponds to variant dbSNP:rs376333965Ensembl.1
Natural variantiVAR_029356134P → A in MCOPS5. 1 PublicationCorresponds to variant dbSNP:rs753783256Ensembl.1
Pituitary hormone deficiency, combined, 6 (CPHD6)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCombined 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.
See also OMIM:613986
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078446134P → R in CPHD6; unknown pathological significance; loss of transcriptional activity, when tested on bicoid binding sites; decreases transactivation mediated by the wild-type protein, when tested on bicoid binding sites; no effect on DNA-binding. 1 PublicationCorresponds to variant dbSNP:rs199761861Ensembl.1
Natural variantiVAR_065953225N → S in CPHD6; acts as a dominant inhibitor of the HESX1 gene. 1 PublicationCorresponds to variant dbSNP:rs370761964Ensembl.1
Retinal dystrophy, early-onset, with or without pituitary dysfunction (RDEOP)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant ocular disease characterized by pattern dystrophy of the retinal pigment epithelium, and photoreceptor degeneration. Mild developmental anomalies include optic nerve head dysplasia, microcornea, and Rathke's cleft cyst. Some patients manifest pituary dysfunction.
See also OMIM:610125
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07379379E → K in RDEOP. 1 PublicationCorresponds to variant dbSNP:rs786205224Ensembl.1

Keywords - Diseasei

Disease mutation, Microphthalmia

Organism-specific databases

DisGeNETi5015.
GeneReviewsiOTX2.
MalaCardsiOTX2.
MIMi610125. phenotype.
613986. phenotype.
OpenTargetsiENSG00000165588.
Orphaneti990. Agnathia - holoprosencephaly - situs inversus.
95494. Combined pituitary hormone deficiencies, genetic forms.
2542. Isolated anophthalmia - microphthalmia.
3157. Septo-optic dysplasia.
178364. Syndromic microphthalmia type 5.
PharmGKBiPA32849.

Polymorphism and mutation databases

BioMutaiOTX2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000492101 – 289Homeobox protein OTX2Add BLAST289

Proteomic databases

EPDiP32243.
PaxDbiP32243.
PeptideAtlasiP32243.
PRIDEiP32243.

PTM databases

iPTMnetiP32243.
PhosphoSitePlusiP32243.

Expressioni

Developmental stagei

At Carnegie stage (CS) 14, widely expressed throughout the telencephalon and mesencephalon, with a sharp cutoff at the midbrain-hindbrain boundary. At CS16, found in the lamina terminalis and the floor of the telencephalon. At CS16-CS19, in the developing eye, strongly expressed in the retinal pigment epithelium layer and more weakly in the neural retina, not expressed in the optic nerve itself (at protein level). Retinal expression peaks between CS19 and CS21 and decline in older fetuses. At CS22, detected in the choroid plexus, the dorsal thalamus, and the roof of the mesencephalon. In the developing nasal structures, expressed in the olfactory epithelium of the nasal pits at CS18.2 Publications

Gene expression databases

BgeeiENSG00000165588.
CleanExiHS_OTX2.
ExpressionAtlasiP32243. baseline and differential.
GenevisibleiP32243. HS.

Organism-specific databases

HPAiHPA000633.

Interactioni

Binary interactionsi

Show more details

GO - Molecular functioni

  • eukaryotic initiation factor 4E binding Source: UniProtKB

Protein-protein interaction databases

BioGridi111055. 10 interactors.
IntActiP32243. 41 interactors.
MINTiMINT-2861458.
STRINGi9606.ENSP00000343819.

Structurei

3D structure databases

ProteinModelPortaliP32243.
SMRiP32243.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi95 – 101Poly-Gln7

Sequence similaritiesi

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG2251. Eukaryota.
ENOG4111XIJ. LUCA.
GeneTreeiENSGT00820000126963.
HOGENOMiHOG000082677.
HOVERGENiHBG004028.
InParanoidiP32243.
KOiK18490.
OMAiSTADCLD.
PhylomeDBiP32243.
TreeFamiTF351179.

Family and domain databases

InterProiView protein in InterPro
IPR009057. Homeobox-like.
IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR003022. Otx2_TF.
IPR003025. Otx_TF.
IPR013851. Otx_TF_C.
PfamiView protein in Pfam
PF00046. Homeobox. 1 hit.
PF03529. TF_Otx. 1 hit.
PRINTSiPR01257. OTX2HOMEOBOX.
PR01255. OTXHOMEOBOX.
SMARTiView protein in SMART
SM00389. HOX. 1 hit.
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiView protein in PROSITE
PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P32243-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MMSYLKQPPY AVNGLSLTTS GMDLLHPSVG YPATPRKQRR ERTTFTRAQL
60 70 80 90 100
DVLEALFAKT RYPDIFMREE VALKINLPES RVQVWFKNRR AKCRQQQQQQ
110 120 130 140 150
QNGGQNKVRP AKKKTSPARE VSSESGTSGQ FTPPSSTSVP TIASSSAPVS
160 170 180 190 200
IWSPASISPL SDPLSTSSSC MQRSYPMTYT QASGYSQGYA GSTSYFGGMD
210 220 230 240 250
CGSYLTPMHH QLPGPGATLS PMGTNAVTSH LNQSPASLST QGYGASSLGF
260 270 280
NSTTDCLDYK DQTASWKLNF NADCLDYKDQ TSSWKFQVL
Length:289
Mass (Da):31,636
Last modified:October 1, 1993 - v1
Checksum:i66B86D5EAD6E2E7A
GO
Isoform 2 (identifier: P32243-2) [UniParc]FASTAAdd to basket

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

Show »
Length:297
Mass (Da):32,406
Checksum:iDB4A3AE99DDA6F6A
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07379379E → K in RDEOP. 1 PublicationCorresponds to variant dbSNP:rs786205224Ensembl.1
Natural variantiVAR_02935489R → G in MCOPS5. 1 PublicationCorresponds to variant dbSNP:rs104894464Ensembl.1
Natural variantiVAR_06595290R → 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. 1 Publication1
Natural variantiVAR_029355133P → T in MCOPS5. 1 PublicationCorresponds to variant dbSNP:rs376333965Ensembl.1
Natural variantiVAR_029356134P → A in MCOPS5. 1 PublicationCorresponds to variant dbSNP:rs753783256Ensembl.1
Natural variantiVAR_078446134P → R in CPHD6; unknown pathological significance; loss of transcriptional activity, when tested on bicoid binding sites; decreases transactivation mediated by the wild-type protein, when tested on bicoid binding sites; no effect on DNA-binding. 1 PublicationCorresponds to variant dbSNP:rs199761861Ensembl.1
Natural variantiVAR_065953225N → S in CPHD6; acts as a dominant inhibitor of the HESX1 gene. 1 PublicationCorresponds to variant dbSNP:rs370761964Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_02100632P → PGPWASCPA in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41960.1. [P32243-1]
CCDS9728.1. [P32243-2]
RefSeqiNP_001257452.1. NM_001270523.1. [P32243-1]
NP_001257453.1. NM_001270524.1. [P32243-1]
NP_001257454.1. NM_001270525.1. [P32243-2]
NP_068374.1. NM_021728.3. [P32243-2]
NP_758840.1. NM_172337.2. [P32243-1]
UniGeneiHs.288655.
Hs.741558.

Genome annotation databases

EnsembliENST00000339475; ENSP00000343819; ENSG00000165588. [P32243-2]
ENST00000408990; ENSP00000386185; ENSG00000165588. [P32243-1]
ENST00000555006; ENSP00000452336; ENSG00000165588. [P32243-1]
GeneIDi5015.
KEGGihsa:5015.
UCSCiuc001xcp.5. human. [P32243-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiOTX2_HUMAN
AccessioniPrimary (citable) accession number: P32243
Secondary accession number(s): B2RAN5
, Q6GTV3, Q9HAW3, Q9P2R1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: August 30, 2017
This is version 172 of the entry and version 1 of the sequence. See 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 14
    Human chromosome 14: 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