Q99502 (EYA1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eyes absent homolog 1
EC=3.1.3.48

Gene names

Name:

EYA1

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	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.10
Catalytic activity	Protein tyrosine phosphate + H2O = protein tyrosine + phosphate. Ref.10
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.10
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.7
Post-translational modification	Sumoylated by SUMO1 By similarity.
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.11 Ref.12 Ref.13 Ref.14 Ref.16 Defects in EYA1 are the cause of otofaciocervical syndrome (OFCS) [MIM:166780]. The syndrome is characterized by trophic alterations of the facies and shoulder girdle in addition to the malformations seen in BOR. Ref.6 Ref.8 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.5 Ref.9 Ref.15
Sequence similarities	Belongs to the HAD-like hydrolase superfamily. EYA family.

Ontologies

Keywords
Biological process	DNA damage DNA repair Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation
Ligand	Magnesium Metal-binding
Molecular function	Activator Chromatin regulator Developmental protein Hydrolase Protein phosphatase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	anatomical structure morphogenesis Traceable author statement. Source: ProtInc double-strand break repair Inferred from mutant phenotype Ref.10. Source: UniProtKB histone dephosphorylation Inferred from direct assay Ref.10. Source: UniProtKB multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW positive regulation of DNA repair Inferred from mutant phenotype Ref.10. Source: UniProtKB protein sumoylation Inferred from sequence or structural similarity. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to ionizing radiation Inferred from direct assay Ref.10. Source: UniProtKB sensory perception of sound Traceable author statement. Source: ProtInc transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay Ref.10. Source: UniProtKB
Molecular function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein tyrosine phosphatase activity Inferred from direct assay Ref.10. Source: UniProtKB
Complete GO annotation...

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. Corresponds to variant rs1445404 [ dbSNP | Ensembl ].		VAR_024439
	Natural variant	95	1	P → S in BOR1. Ref.16		VAR_064942
	Natural variant	140	1	G → S in BOR1. Ref.16		VAR_064943
	Natural variant	242	1	S → G in BOS1. Ref.15		VAR_044452
	Natural variant	363	1	E → K in anterior segment anomalies. Ref.12		VAR_016864
	Natural variant	363	1	E → V in BOR1. Ref.16		VAR_064944
	Natural variant	426	1	G → S in BOR1; with cataract. Ref.12		VAR_016865
	Natural variant	429	1	D → G in BOR1. Ref.14		VAR_016866
	Natural variant	440	1	R → Q in BOR1. Ref.11 Ref.16		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	514	1	L → P in BOR1. Ref.16		VAR_064945
	Natural variant	527	1	Y → C in BOR1. Ref.16		VAR_064946
	Natural variant	547	1	R → G in anterior segment anomalies; with cataract. Ref.12		VAR_016868
	Natural variant	569	1	M → T in BOR1. Ref.16		VAR_064947
	Natural variant	583	1	L → P in BOR1. Ref.13		VAR_016869
Experimental info
	Mutagenesis	328	1	D → A: Loss of tyrosine phosphatase activity toward H2AX. Ref.10

Sequences

	Sequence		Length	Mass (Da)
	Isoform EYA1A [UniParc]. Last modified July 15, 1998. Version 2. Checksum: D62365F81EB692E2	FASTA	592	64,593
	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
	Isoform EYA1B [UniParc]. Checksum: 6B638C22438309A8	FASTA	559	61,211
	10 20 30 40 50 60 MLLFPQVAVK TEPMSSSETA STTADGSLNN FSGSAIGSSS FSPRPTHQFS PPQIYPSNRP 70 80 90 100 110 120 YPHILPTPSS QTMAAYGQTQ FTTGMQQATA YATYPQPGQP YGISSYGALW AGIKTEGGLS 130 140 150 160 170 180 QSQSPGQTGF LSYGTSFSTP QPGQAPYSYQ MQGSSFTTSS GIYTGNNSLT NSSGFNSSQQ 190 200 210 220 230 240 DYPSYPSFGQ GQYAQYYNSS PYPAHYMTSS NTSPTTPSTN ATYQLQEPPS GITSQAVTDP 250 260 270 280 290 300 TAEYSTIHSP STPIKDSDSD RLRRGSDGKS RGRGRRNNNP SPPPDSDLER VFIWDLDETI 310 320 330 340 350 360 IVFHSLLTGS YANRYGRDPP TSVSLGLRME EMIFNLADTH LFFNDLEECD QVHIDDVSSD 370 380 390 400 410 420 DNGQDLSTYN FGTDGFPAAA TSANLCLATG VRGGVDWMRK LAFRYRRVKE IYNTYKNNVG 430 440 450 460 470 480 GLLGPAKREA WLQLRAEIEA LTDSWLTLAL KALSLIHSRT NCVNILVTTT QLIPALAKVL 490 500 510 520 530 540 LYGLGIVFPI ENIYSATKIG KESCFERIIQ RFGRKVVYVV IGDGVEEEQG AKKHAMPFWR 550 ISSHSDLMAL HHALELEYL

References

	« Hide 'large scale' referencesShow '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. , 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. 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]	"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.
[6]	"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 OFCS.
[7]	"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.
[8]	"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 OFCS.
[9]	"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.
[10]	"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.
[11]	"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(1997) [PubMed: 10464653] [Abstract] Cited for: VARIANT BOR1 GLN-440.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"Mutation screening of the EYA1, SIX1, and SIX5 genes in a large cohort of patients harboring branchio-oto-renal syndrome calls into question the pathogenic role of SIX5 mutations." Krug P., Moriniere V., Marlin S., Koubi V., Gabriel H.D., Colin E., Bonneau D., Salomon R., Antignac C., Heidet L. Hum. Mutat. 32:183-190(2011) [PubMed: 21280147] [Abstract] Cited for: VARIANTS BOR1 SER-95; SER-140; VAL-363; GLN-440; PRO-514; CYS-527 AND THR-569.
+	Additional computationally mapped references.

Web resources

GeneReviews

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. NM_000503.4. NP_742055.1. NM_172058.2. NP_742057.1. NM_172060.2.
UniGene	Hs.491997.
3D structure databases
ProteinModelPortal	Q99502.
SMR	Q99502. Positions 322-592.
ModBase	Search...
Protein-protein interaction databases
STRING	Q99502.
PTM databases
PhosphoSite	Q99502.
Polymorphism databases
DMDM	3183005.
Proteomic databases
PRIDE	Q99502.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000340726; ENSP00000342626; ENSG00000104313. ENST00000388742; ENSP00000373394; ENSG00000104313.
GeneID	2138.
KEGG	hsa:2138.
UCSC	uc003xys.2. human. uc003xyt.2. human.
Organism-specific databases
CTD	2138.
GeneCards	GC08M072159.
H-InvDB	HIX0025545.
HGNC	HGNC:3519. EYA1.
MIM	113650. phenotype. 166780. phenotype. 601653. gene. 602588. phenotype.
neXtProt	NX_Q99502.
Orphanet	107. BOR syndrome. 52429. Branchio-otic syndrome. 2792. Otofaciocervical syndrome.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG10399.
GeneTree	ENSGT00390000008860.
HOGENOM	HBG445616.
HOVERGEN	HBG002447.
InParanoid	Q99502.
OMA	GQPYGIS.
OrthoDB	EOG4XH000.
PhylomeDB	Q99502.
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]
KO	K15616.
Pfam	PF00702. Hydrolase. 1 hit. [Graphical view]
TIGRFAMs	TIGR01658. EYA-cons_domain. 1 hit.
ProtoNet	Search...
Other
NextBio	8639.
SOURCE	Search...

Entry information

Entry name

EYA1_HUMAN

Accession

Primary (citable) accession number: Q99502
Secondary accession number(s): A6NHQ0, Q0P516

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	January 25, 2012
This is version 102 of the entry and version 2 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.