Reviewed,
UniProtKB/Swiss-Prot Q99502 (EYA1_HUMAN)
Last modified
February 9, 2010.
Version 84.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: Eyes absent homolog 1 EC=3.1.3.48 | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Complete proteome] | ||
| Taxonomic identifier | 9606 [NCBI] | ||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 592 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Tyrosine phosphatase that specifically dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph). 'Tyr-142' phosphorylation of histone H2AX plays a central role in DNA repair and acts as a mark that distinguishes between apoptotic and repair responses to genotoxic stress. Promotes efficient DNA repair by dephosphorylating H2AX, promoting the recruitment of DNA repair complexes containing MDC1. Its function as histone phosphatase probably explains its role in transcription regulation during organogenesis. Seems to coactivate SIX2, SIX4 and SIX5. May be required for normal development of branchial arches, ear and kidney. Ref.7 |
| Catalytic activity | Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.7 |
| Cofactor | Binds 1 Mg2+ ion per subunit By similarity. |
| Subunit structure | Probably interacts with SIX2, SIX4 and SIX5 By similarity. |
| Subcellular location | Cytoplasm By similarity. Nucleus. Note: Localizes at sites of DNA damage at double-strand breaks (DSBs). Ref.7 Ref.5 |
| Tissue specificity | In the embryo, highly expressed in kidney with lower levels in brain. Weakly expressed in lung. In the adult, highly expressed in heart and skeletal muscle. Weakly expressed in brain and liver. No expression in eye or kidney. |
| Developmental stage | Detected in cytoplasm of somite cells at the beginning of fourth week of development. Detected in cytoplasm of limb bud cell between the sixth and eighth week of development. Ref.5 |
| Involvement in disease | Defects in EYA1 are the cause of branchiootorenal syndrome type 1 (BOR1) [MIM:113650]; also known as Melnick-Fraser syndrome. BOR is an autosomal dominant disorder manifested by various combinations of preauricular pits, branchial fistulae or cysts, lacrimal duct stenosis, hearing loss, structural defects of the outer, middle, or inner ear, and renal dysplasia. Associated defects include asthenic habitus, long narrow facies, constricted palate, deep overbite, and myopia. Hearing loss may be due to mondini type cochlear defect and stapes fixation. Penetrance of BOR syndrome is high, although expressivity can be extremely variable. Ref.1 Ref.8 Ref.9 Ref.10 Ref.12 Defects in EYA1 are the cause of otofaciocervical syndrome [MIM:166780]. The syndrome is characterized by trophic alterations of the facies and shoulder girdle in addition to the malformations seen in BOR. Ref.11 Ref.14 Defects in EYA1 are the cause of branchiootic syndrome type 1 (BOS1) [MIM:602588]; also known as BO syndrome type 1 or branchiootic dysplasia. Individuals with BOS1 are affected by the same branchial and otic anomalies as those seen in individuals with BOR1, but lack renal anomalies. Ref.6 Ref.13 Ref.15 |
| Sequence similarities | Belongs to the HAD-like hydrolase superfamily. EYA family. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform EYA1A (identifier: Q99502-1) 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 EYA1B (identifier: Q99502-2) The sequence of this isoform differs from the canonical sequence as follows: 1-41: MEMQDLTSPHSRLSGSSESPSGPKLGNSHINSNSMTPNGTE → MLLFPQVA |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 592 | 592 | Eyes absent homolog 1 | PRO_0000218643 | |||||
Sites | |||||||||
| Active site | 328 | 1 | Nucleophile Probable | ||||||
| Active site | 330 | 1 | Proton donor By similarity | ||||||
| Metal binding | 328 | 1 | Magnesium By similarity | ||||||
| Metal binding | 330 | 1 | Magnesium By similarity | ||||||
| Metal binding | 556 | 1 | Magnesium By similarity | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 41 | 41 | MEMQD…PNGTE → MLLFPQVA in isoform EYA1B. | VSP_001486 | |||||
| Natural variant | 20 | 1 | P → A: dbSNP rs1445404. | VAR_024439 | |||||
| Natural variant | 242 | 1 | S → G in BOS1. Ref.13 | VAR_044452 | |||||
| Natural variant | 363 | 1 | E → K in anterior segment anomalies. Ref.9 | VAR_016864 | |||||
| Natural variant | 426 | 1 | G → S in BOR1; with cataract. Ref.9 | VAR_016865 | |||||
| Natural variant | 429 | 1 | D → G in BOR1. Ref.12 | VAR_016866 | |||||
| Natural variant | 440 | 1 | R → Q in BOR1. Ref.8 | VAR_016867 | |||||
| Natural variant | 487 | 1 | S → P in BOR1. Ref.1 | VAR_005203 | |||||
| Natural variant | 505 | 1 | L → R in BOR1. Ref.1 | VAR_005204 | |||||
| Natural variant | 547 | 1 | R → G in anterior segment anomalies; with cataract. Ref.9 | VAR_016868 | |||||
| Natural variant | 583 | 1 | L → P in BOR1. Ref.10 | VAR_016869 | |||||
Experimental info | |||||||||
| Mutagenesis | 328 | 1 | D → A: Loss of tyrosine phosphatase activity toward H2AX. Ref.7 | ||||||
Sequences
| ||||||||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1." Abdelhak S., Kalatzis V., Heilig R., Compain S., Samson D., Vincent C., Levi-Acobas F., Cruaud C., le Merrer M., Mathieu M., Koenig R., Vigneron J., Weissenbach J., Petit C., Weil D. Hum. Mol. Genet. 6:2247-2255(1997) [PubMed: 9361030] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, VARIANTS BOR1 PRO-487 AND ARG-505. Tissue: Embryo. |
| [2] | "A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family." Abdelhak S., Kalatzis V., Heilig R., Compain S., Samson D., Vincent C., Weil D., Cruaud C., Sahly I., Leibovici M., Bitner-Glindzicz M., Francis M., Lacombe D., Vigneron J., Charachon R., Boven K., Bedbeder P., van Regemorter N., Weissenbach J., Petit C. Nat. Genet. 15:157-164(1997) [PubMed: 9020840] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM EYA1A). Tissue: Embryo. |
| [3] | "DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. Lander E.S.Nature 439:331-335(2006) [PubMed: 16421571] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. |
| [5] | "Six and Eya expression during human somitogenesis and MyoD gene family activation." Fougerousse F., Durand M., Lopez S., Suel L., Demignon J., Thornton C., Ozaki H., Kawakami K., Barbet P., Beckmann J.S., Maire P. J. Muscle Res. Cell Motil. 23:255-264(2002) [PubMed: 12500905] [Abstract] Cited for: SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE. |
| [6] | "BOR and BO syndromes are allelic defects of EYA1." Vincent C., Kalatzis V., Abdelhak S., Chaib H., Compain S., Helias J., Vaneecloo F.M., Petit C. Eur. J. Hum. Genet. 5:242-246(1997) [PubMed: 9359046] [Abstract] Cited for: INVOLVEMENT IN BOS1. |
| [7] | "Tyrosine dephosphorylation of H2AX modulates apoptosis and survival decisions." Cook P.J., Ju B.G., Telese F., Wang X., Glass C.K., Rosenfeld M.G. Nature 458:591-596(2009) [PubMed: 19234442] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-328. |
| [8] | "Branchio-oto-renal syndrome: identification of novel mutations, molecular characterization, mutation distribution, and prospects for genetic testing." Kumar S., Deffenbacher K., Cremers C.W.R.J., Van Camp G., Kimberling W.J. Genet. Test. 1:243-251(1998) [PubMed: 10464653] [Abstract] Cited for: VARIANT BOR1 GLN-440. |
| [9] | "Mutations of a human homologue of the Drosophila eyes absent gene (EYA1) detected in patients with congenital cataracts and ocular anterior segment anomalies." Azuma N., Hirakiyama A., Inoue T., Asaka A., Yamada M. Hum. Mol. Genet. 9:363-366(2000) [PubMed: 10655545] [Abstract] Cited for: VARIANTS ANTERIOR SEGMENT ANOMALIES LYS-363 AND GLY-547, VARIANT BOR1 SER-426. |
| [10] | "Importance of clinical evaluation and molecular testing in the branchio-oto-renal (BOR) syndrome and overlapping phenotypes." Rickard S., Boxer M., Trompeter R., Bitner-Glindzicz M. J. Med. Genet. 37:623-627(2000) [PubMed: 10991693] [Abstract] Cited for: VARIANT BOR1 PRO-583. |
| [11] | "Oto-facio-cervical (OFC) syndrome is a contiguous gene deletion syndrome involving EYA1: molecular analysis confirms allelism with BOR syndrome and further narrows the Duane syndrome critical region to 1 cM." Rickard S., Parker M., van't Hoff W., Barnicoat A., Russell-Eggitt I., Winter R.M., Bitner-Glindzicz M. Hum. Genet. 108:398-403(2001) [PubMed: 11409867] [Abstract] Cited for: INVOLVEMENT IN OTOFACIOCERVICAL SYNDROME. |
| [12] | "Genetic features of hearing loss associated with ear anomalies: PDS and EYA1 mutation analysis." Namba A., Abe S., Shinkawa H., Kimberling W.J., Usami S. J. Hum. Genet. 46:518-521(2001) [PubMed: 11558900] [Abstract] Cited for: VARIANT BOR1 GLY-429. |
| [13] | "Mutation of the EYA1 gene in patients with branchio-oto syndrome." Yashima T., Noguchi Y., Ishikawa K., Mizusawa H., Kitamura K. Acta Oto-Laryngol. 123:279-282(2003) [PubMed: 12701758] [Abstract] Cited for: VARIANT BOS1 GLY-242. |
| [14] | "Point mutation of an EYA1-gene splice site in a patient with oto-facio-cervical syndrome." Estefania E., Ramirez-Camacho R., Gomar M., Trinidad A., Arellano B., Garcia-Berrocal J.R., Verdaguer J.M., Vilches C. Ann. Hum. Genet. 70:140-144(2006) [PubMed: 16441263] [Abstract] Cited for: INVOLVEMENT IN OTOFACIOCERVICAL SYNDROME. |
| [15] | "Identification of a novel EYA1 mutation presenting in a newborn with laryngomalacia, glossoptosis, retrognathia, and pectus excavatum." Spruijt L., Hoefsloot L.H., van Schaijk G.H.W.H., van Waardenburg D., Kremer B., Brackel H.J.L., de Die-Smulders C.E.M. Am. J. Med. Genet. A 140:1343-1345(2006) [PubMed: 16691597] [Abstract] Cited for: INVOLVEMENT IN BOS1. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | Y10260 Genomic DNA. Translation: CAA71309.1. AJ000097 mRNA. Translation: CAA03922.1. AJ000098 mRNA. Translation: CAA03923.1. AC016465 Genomic DNA. No translation available. BC121799 mRNA. Translation: AAI21800.1. |
| IPI | IPI00328572. IPI00940365. |
| RefSeq | NP_000494.2. NP_742055.1. NP_742057.1. |
| UniGene | Hs.491997 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q99502. |
PTM databases | |
| PhosphoSite | Q99502. |
Proteomic databases | |
| PRIDE | Q99502. |
Genome annotation databases | |
| Ensembl | ENST00000340726; ENSP00000342626; ENSG00000104313; Homo sapiens. [Genome view] ENST00000388742; ENSP00000373394; ENSG00000104313; Homo sapiens. [Genome view] |
| GeneID | 2138. |
| KEGG | hsa:2138. |
| UCSC | uc003xys.2. human. uc003xyt.2. human. |
Organism-specific databases | |
| CTD | 2138. |
| GeneCards | GC08M072272. |
| H-InvDB | HIX0025545. |
| HGNC | HGNC:3519. EYA1. |
| MIM | 113650. phenotype. 166780. phenotype. 601653. gene. 602588. phenotype. |
| Orphanet | 107. BOR syndrome. 52429. Branchio-otic syndrome. 2792. Otofaciocervical syndrome. |
| PharmGKB | PA27931. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG10399. |
| HOGENOM | HBG445616. |
| HOVERGEN | Q99502. |
| InParanoid | Q99502. |
| OMA | GMQQATA. |
Enzyme and pathway databases | |
| BRENDA | 3.1.3.48. 247. |
Gene expression databases | |
| ArrayExpress | Q99502. |
| Bgee | Q99502. |
| CleanEx | HS_EYA1. |
| Genevestigator | Q99502. |
| GermOnline | ENSG00000104313. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR005834. Dehalogen-like_hydro. IPR006545. EYA. [Graphical view] |
| Pfam | PF00702. Hydrolase. 1 hit. [Graphical view] |
| TIGRFAMs | TIGR01658. EYA-cons_domain. 1 hit. |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 8639. |
| SOURCE | Search... |
Entry information
| Entry name | EYA1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q99502 Secondary accession number(s): A6NHQ0, Q0P516 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 8 Human chromosome 8: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


