[1]	NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING, AND VARIANTS BOR1 PRO-487 AND ARG-505. TISSUE=Embryo; DOI=10.1093/hmg/6.13.2247; PubMed=9361030 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Clustering of mutations responsible for branchio-oto-renal (BOR) syndrome in the eyes absent homologous region (eyaHR) of EYA1."; Hum. Mol. Genet. 6:2247-2255(1997).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM EYA1A). TISSUE=Embryo; DOI=10.1038/ng0297-157; PubMed=9020840 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifies a novel gene family."; Nat. Genet. 15:157-164(1997).
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. DOI=10.1038/nature04406; PubMed=16421571 [NCBI, ExPASy, EBI, Israel, Japan] 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., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.; "DNA sequence and analysis of human chromosome 8."; Nature 439:331-335(2006).
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. DOI=10.1023/A:1020990825644; PubMed=12500905 [NCBI, ExPASy, EBI, Israel, Japan] Fougerousse F., Durand M., Lopez S., Suel L., Demignon J., Thornton C., Ozaki H., Kawakami K., Barbet P., Beckmann J.S., Maire P.; "Six and Eya expression during human somitogenesis and MyoD gene family activation."; J. Muscle Res. Cell Motil. 23:255-264(2002).
[6]	INVOLVEMENT IN BOS1. PubMed=9359046 [NCBI, ExPASy, EBI, Israel, Japan] Vincent C., Kalatzis V., Abdelhak S., Chaib H., Compain S., Helias J., Vaneecloo F.M., Petit C.; "BOR and BO syndromes are allelic defects of EYA1."; Eur. J. Hum. Genet. 5:242-246(1997).
[7]	VARIANT BOR1 GLN-440. PubMed=10464653 [NCBI, ExPASy, EBI, Israel, Japan] Kumar S., Deffenbacher K., Cremers C.W.R.J., Van Camp G., Kimberling W.J.; "Branchio-oto-renal syndrome: identification of novel mutations, molecular characterization, mutation distribution, and prospects for genetic testing."; Genet. Test. 1:243-251(1998).
[8]	VARIANTS ANTERIOR SEGMENT ANOMALIES LYS-363 AND GLY-547, AND VARIANT BOR1 SER-426. DOI=10.1093/hmg/9.3.363; PubMed=10655545 [NCBI, ExPASy, EBI, Israel, Japan] Azuma N., Hirakiyama A., Inoue T., Asaka A., Yamada M.; "Mutations of a human homologue of the Drosophila eyes absent gene (EYA1) detected in patients with congenital cataracts and ocular anterior segment anomalies."; Hum. Mol. Genet. 9:363-366(2000).
[9]	VARIANT BOR1 PRO-583. DOI=10.1136/jmg.37.8.623; PubMed=10991693 [NCBI, ExPASy, EBI, Israel, Japan] Rickard S., Boxer M., Trompeter R., Bitner-Glindzicz M.; "Importance of clinical evaluation and molecular testing in the branchio-oto-renal (BOR) syndrome and overlapping phenotypes."; J. Med. Genet. 37:623-627(2000).
[10]	INVOLVEMENT IN OTOFACIOCERVICAL SYNDROME. DOI=10.1007/s004390100495; PubMed=11409867 [NCBI, ExPASy, EBI, Israel, Japan] Rickard S., Parker M., van't Hoff W., Barnicoat A., Russell-Eggitt I., Winter R.M., Bitner-Glindzicz M.; "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."; Hum. Genet. 108:398-403(2001).
[11]	VARIANT BOR1 GLY-429. DOI=10.1007/s100380170033; PubMed=11558900 [NCBI, ExPASy, EBI, Israel, Japan] Namba A., Abe S., Shinkawa H., Kimberling W.J., Usami S.; "Genetic features of hearing loss associated with ear anomalies: PDS and EYA1 mutation analysis."; J. Hum. Genet. 46:518-521(2001).
[12]	VARIANT BOS1 GLY-242. DOI=10.1080/0036554021000028103; PubMed=12701758 [NCBI, ExPASy, EBI, Israel, Japan] Yashima T., Noguchi Y., Ishikawa K., Mizusawa H., Kitamura K.; "Mutation of the EYA1 gene in patients with branchio-oto syndrome."; Acta Otolaryngol. 123:279-282(2003).
[13]	INVOLVEMENT IN OTOFACIOCERVICAL SYNDROME. DOI=10.1111/j.1529-8817.2005.00204.x; PubMed=16441263 [NCBI, ExPASy, EBI, Israel, Japan] Estefania E., Ramirez-Camacho R., Gomar M., Trinidad A., Arellano B., Garcia-Berrocal J.R., Verdaguer J.M., Vilches C.; "Point mutation of an EYA1-gene splice site in a patient with oto-facio-cervical syndrome."; Ann. Hum. Genet. 70:140-144(2006).
[14]	INVOLVEMENT IN BOS1. DOI=10.1002/ajmg.a.31285; PubMed=16691597 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Identification of a novel EYA1 mutation presenting in a newborn with laryngomalacia, glossoptosis, retrognathia, and pectus excavatum."; Am. J. Med. Genet. A 140:1343-1345(2006).

Comments

FUNCTION: Thought to play a role in transcription regulation during organogenesis through its intrinsic protein phosphatase activity. Seems to coactivate SIX2, SIX4 and SIX5 (By similarity). May be required for normal development of branchial arches, ear and kidney.
CATALYTIC ACTIVITY: Protein tyrosine phosphate + H₂O = protein tyrosine + phosphate.
COFACTOR: Magnesium (By similarity).
SUBUNIT: Probably interacts with SIX2, SIX4 and SIX5 (By similarity).
SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By similarity).
ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.

Name EYA1A

Isoform ID Q99502-1

This is the isoform sequence displayed in this entry.

Name EYA1B

Isoform ID Q99502-2

Features which should be applied to build the isoform sequence: VSP_001486.
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: At the begin of fourth week of development detected in cytoplasm of somite cells. Between the sixth and eighth week of development detected in cytoplasm of limb bud cells.
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.
DISEASE: 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.
DISEASE: 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.
SIMILARITY: Belongs to the EYA family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.genetests.org/query?gene=EYA1";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

Y10260; CAA71309.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ000097; CAA03922.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ000098; CAA03923.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AC016465; -; NOT_ANNOTATED_CDS; Genomic_DNA.	[EMBL / GenBank / DDBJ]
BC121799; AAI21800.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

RefSeq

NP_000494.2; -.
NP_742055.1; -.

UniGene

Hs.491997

3D structure databases

ModBase

Q99502.

Organism-specific databases

HIX0025545; -.

HGNC:3519; EYA1.

113650; phenotype. [NCBI / EBI]
166780; phenotype. [NCBI / EBI]
601653; gene. [NCBI / EBI]
602588; phenotype. [NCBI / EBI]

Orphanet

107; BOR syndrome.
52429; Branchio-otic syndrome.
2792; Otofaciocervical syndrome.

PharmGKB

PA27931; -.

GeneCards

Q99502.

Gene expression databases

ArrayExpress

Q99502; -.

CleanEx

HS_EYA1; -.

GermOnline

ENSG00000104313; Homo sapiens.

Ontologies

GO:0009653;	Biological process: anatomical structure morphogenesis (traceable author statement from ProtInc).
GO:0007605;	Biological process: sensory perception of sound (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR005834; Dehalogen-like_hydro.
IPR006545; EYA.
Graphical view of domain structure.

Pfam

PF00702; Hydrolase; 1.
Pfam graphical view of domain structure.

TIGRFAMs

TIGR01658; EYA-cons_domain; 1.

BLOCKS

Q99502.

Genome annotation databases

Ensembl

ENSG00000104313; Homo sapiens. [Contig view]

GeneID

2138; -.

KEGG

hsa:2138; -.

Phylogenomic databases

HOVERGEN

Q99502; -.

Other

EYA1; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Activator; Alternative splicing; Cytoplasm; Deafness; Developmental protein; Disease mutation; Hydrolase; Magnesium; Nucleus; Polymorphism; Protein phosphatase; Transcription; Transcription regulation.

Features

Feature table viewer

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 592`	`592`	`Eyes absent homolog 1.`	`PRO_0000218643`
`VAR_SEQ`	`1 41`		`MEMQDLTSPHSRLSGSSESPSGPKLGNSHINSNSMT` `PNGTE -> MLLFPQVA (in isoform EYA1B).`	`VSP_001486`
`VARIANT`	`20 20`	`1`	`P -> A (in dbSNP:rs1445404 [NCBI]).`	`VAR_024439`
`VARIANT`	`242 242`	`1`	`S -> G (in BOS1).`	`VAR_044452`
`VARIANT`	`363 363`	`1`	`E -> K (in anterior segment anomalies).`	`VAR_016864`
`VARIANT`	`426 426`	`1`	`G -> S (in BOR1; with cataract).`	`VAR_016865`
`VARIANT`	`429 429`	`1`	`D -> G (in BOR1).`	`VAR_016866`
`VARIANT`	`440 440`	`1`	`R -> Q (in BOR1).`	`VAR_016867`
`VARIANT`	`487 487`	`1`	`S -> P (in BOR1).`	`VAR_005203`
`VARIANT`	`505 505`	`1`	`L -> R (in BOR1).`	`VAR_005204`
`VARIANT`	`547 547`	`1`	`R -> G (in anterior segment anomalies; with cataract).`	`VAR_016868`
`VARIANT`	`583 583`	`1`	`L -> P (in BOR1).`	`VAR_016869`

Sequence information

Length: 592 AA [This is the length of the unprocessed precursor]

Molecular weight: 64593 Da [This is the MW of the unprocessed precursor]

CRC64: D62365F81EB692E2 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MEMQDLTSPH SRLSGSSESP SGPKLGNSHI NSNSMTPNGT EVKTEPMSSS ETASTTADGS 

        70         80         90        100        110        120 
LNNFSGSAIG SSSFSPRPTH QFSPPQIYPS NRPYPHILPT PSSQTMAAYG QTQFTTGMQQ 

       130        140        150        160        170        180 
ATAYATYPQP GQPYGISSYG ALWAGIKTEG GLSQSQSPGQ TGFLSYGTSF STPQPGQAPY 

       190        200        210        220        230        240 
SYQMQGSSFT TSSGIYTGNN SLTNSSGFNS SQQDYPSYPS FGQGQYAQYY NSSPYPAHYM 

       250        260        270        280        290        300 
TSSNTSPTTP STNATYQLQE PPSGITSQAV TDPTAEYSTI HSPSTPIKDS DSDRLRRGSD 

       310        320        330        340        350        360 
GKSRGRGRRN NNPSPPPDSD LERVFIWDLD ETIIVFHSLL TGSYANRYGR DPPTSVSLGL 

       370        380        390        400        410        420 
RMEEMIFNLA DTHLFFNDLE ECDQVHIDDV SSDDNGQDLS TYNFGTDGFP AAATSANLCL 

       430        440        450        460        470        480 
ATGVRGGVDW MRKLAFRYRR VKEIYNTYKN NVGGLLGPAK REAWLQLRAE IEALTDSWLT 

       490        500        510        520        530        540 
LALKALSLIH SRTNCVNILV TTTQLIPALA KVLLYGLGIV FPIENIYSAT KIGKESCFER 

       550        560        570        580        590 
IIQRFGRKVV YVVIGDGVEE EQGAKKHAMP FWRISSHSDL MALHHALELE YL

Q99502 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools