P32243 (OTX2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Homeobox protein OTX2

Alternative name(s):
Orthodenticle homolog 2

Gene names

Name:

OTX2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	289 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Involvement in disease	Defects in OTX2 are the cause of microphthalmia syndromic type 5 (MCOPS5) [MIM:610125]. Microphthalmia is a clinically heterogeneous disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Up to 80% of cases of microphthalia occur in association with syndromes that include non-ocular abnormalities. MCOPS5 patients manifest unilateral or bilateral microphthalmia/clinical anophthalmia and variable additional features including coloboma, microcornea, cataract, retinal dystrophy, hypoplasia or agenesis of the optic nerve, agenesis of the corpus callosum, developmental delay, joint laxity, hypotonia, and seizures. Ref.8 Ref.11 Defects in OTX2 are the cause of pituitary hormone deficiency combined type 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. Ref.10
Sequence similarities	Belongs to the paired homeobox family. Bicoid subfamily. Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation Microphthalmia
Domain	Homeobox
Ligand	DNA-binding
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	axon guidance Inferred from direct assay. Source: UniProtKB forebrain development Traceable author statement. Source: UniProtKB midbrain development Traceable author statement. 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 primitive streak formation Inferred from sequence or structural similarity. Source: UniProtKB protein complex assembly Inferred from direct assay. Source: UniProtKB regulation of fibroblast growth factor receptor signaling pathway Traceable author statement. Source: UniProtKB regulation of smoothened signaling pathway Traceable author statement. Source: UniProtKB
Cellular component	growth cone Inferred from direct assay. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell protein complex Inferred from direct assay. Source: UniProtKB
Molecular function	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Inferred from direct assay. Source: UniProtKB eukaryotic initiation factor 4E binding Traceable author statement. 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 289	289	Homeobox protein OTX2		PRO_0000049210
Regions
	DNA binding	38 – 97	60	Homeobox
	Compositional bias	95 – 101	7	Poly-Gln
Natural variations
	Alternative sequence	32	1	P → PGPWASCPA in isoform 2.		VSP_021006
	Natural variant	89	1	R → G in MCOPS5. Ref.8		VAR_029354
	Natural variant	90	1	R → 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.11		VAR_065952
	Natural variant	133	1	P → T in MCOPS5. Ref.8		VAR_029355
	Natural variant	134	1	P → A in MCOPS5. Ref.8		VAR_029356
	Natural variant	225	1	N → S in CPHD6; acts as a dominant inhibitor of the HESX1 gene. Ref.10		VAR_065953

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: 66B86D5EAD6E2E7A	FASTA	289	31,636
	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
	Isoform 2 [UniParc]. Checksum: DB4A3AE99DDA6F6A	FASTA	297	32,406
	10 20 30 40 50 60 MMSYLKQPPY AVNGLSLTTS GMDLLHPSVG YPGPWASCPA ATPRKQRRER TTFTRAQLDV 70 80 90 100 110 120 LEALFAKTRY PDIFMREEVA LKINLPESRV QVWFKNRRAK CRQQQQQQQN GGQNKVRPAK 130 140 150 160 170 180 KKTSPAREVS SESGTSGQFT PPSSTSVPTI ASSSAPVSIW SPASISPLSD PLSTSSSCMQ 190 200 210 220 230 240 RSYPMTYTQA SGYSQGYAGS TSYFGGMDCG SYLTPMHHQL PGPGATLSPM GTNAVTSHLN 250 260 270 280 290 QSPASLSTQG YGASSLGFNS TTDCLDYKDQ TASWKLNFNA DCLDYKDQTS SWKFQVL

References

	« Hide 'large scale' referencesShow '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: 8101484] [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: 10372988] [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. , 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: 14702039] [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. , 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: 15489334] [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. , Fitzpatrick D.R., van Heyningen V., Hanson I.M. Am. J. Hum. Genet. 76:1008-1022(2005) [PubMed: 15846561] [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. , Fitzpatrick D.R., van Heyningen V., Hanson I.M. Am. J. Hum. Genet. 77:334-334(2005)
[10]	"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: 18728160] [Abstract] Cited for: VARIANT CPHD6 SER-225, CHARACTERIZATION OF VARIANT CPHD6 SER-225.
[11]	"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: 20396904] [Abstract] Cited for: VARIANT MCOPS5 SER-90, CHARACTERIZATION OF VARIANT MCOPS5 SER-90.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.
IPI	IPI00027683. IPI00172654.
RefSeq	NP_068374.1. NM_021728.2. NP_758840.1. NM_172337.1.
UniGene	Hs.288655.
3D structure databases
ProteinModelPortal	P32243.
SMR	P32243. Positions 12-106.
ModBase	Search...
Protein-protein interaction databases
IntAct	P32243. 1 interaction.
MINT	MINT-2861458.
STRING	P32243.
Polymorphism databases
DMDM	417427.
Proteomic databases
PRIDE	P32243.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000408990; ENSP00000386185; ENSG00000165588. ENST00000446043; ENSP00000407086; ENSG00000165588.
GeneID	5015.
KEGG	hsa:5015.
UCSC	uc001xcp.1. human. uc001xcq.1. human.
Organism-specific databases
CTD	5015.
GeneCards	GC14M057267.
HGNC	HGNC:8522. OTX2.
HPA	HPA000633.
MIM	600037. gene. 610125. phenotype. 613986. phenotype.
neXtProt	NX_P32243.
Orphanet	95494. Combined pituitary hormone deficiencies, genetic forms. 3157. Septo-optic dysplasia. 178364. Syndromic microphthalmia type 5.
PharmGKB	PA32849.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG12232.
GeneTree	ENSGT00600000084183.
HOVERGEN	HBG004028.
OMA	ESRVQXE.
Gene expression databases
ArrayExpress	P32243.
Bgee	P32243.
CleanEx	HS_OTX2.
Genevestigator	P32243.
GermOnline	ENSG00000165588. Homo sapiens.
Family and domain databases
InterPro	IPR001356. Homeobox. IPR017970. Homeobox_CS. IPR009057. Homeodomain-like. IPR012287. Homeodomain-rel. IPR003022. Otx2_TF. IPR003025. Otx_TF. IPR013851. Otx_TF_C. [Graphical view]
Gene3D	G3DSA:1.10.10.60. Homeodomain-rel. 1 hit.
KO	K09326.
Pfam	PF00046. Homeobox. 1 hit. PF03529. TF_Otx. 1 hit. [Graphical view]
PRINTS	PR01257. OTX2HOMEOBOX. PR01255. OTXHOMEOBOX.
SMART	SM00389. HOX. 1 hit. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	19304.
SOURCE	Search...

Entry information

Entry name

OTX2_HUMAN

Accession

Primary (citable) accession number: P32243
Secondary accession number(s): B2RAN5 , Q6GTV3, Q9HAW3, Q9P2R1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	October 1, 1993
Last modified:	January 25, 2012
This is version 119 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.