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UniProt functional annotation for O00167 | ||
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| UniProt code: O00167. |
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| Organism: | |
Homo sapiens (Human). |
| Taxonomy: | |
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo. |
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| Function: | |
Functions both as protein phosphatase and as transcriptional coactivator for SIX1, and probably also for SIX2, SIX4 and SIX5 (PubMed:12500905, PubMed:23435380). Tyrosine phosphatase that dephosphorylates 'Tyr-142' of histone H2AX (H2AXY142ph) and promotes efficient DNA repair via the recruitment of DNA repair complexes containing MDC1. '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 (PubMed:19351884). Its function as histone phosphatase may contribute to its function in transcription regulation during organogenesis. Plays an important role in hypaxial muscle development together with SIX1 and DACH2; in this it is functionally redundant with EYA1 (PubMed:12500905). {ECO:0000269|PubMed:12500905, ECO:0000269|PubMed:19351884, ECO:0000269|PubMed:21706047, ECO:0000269|PubMed:23435380}. |
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| Catalytic activity: | |
Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] + phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA- COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620; EC=3.1.3.48; Evidence={ECO:0000269|PubMed:19351884}; |
| Cofactor: | |
Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:19858093}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:19858093}; |
| Biophysicochemical properties: | |
Kinetic parameters: KM=1.9 uM for H2AXY142ph {ECO:0000269|PubMed:19351884}; KM=80 uM for H2AXS139ph {ECO:0000269|PubMed:19351884}; |
| Subunit: | |
Interacts with DACH2 and SIX1, and probably with SIX2, SIX4 and SIX5. Interacts with CAPN8 (By similarity). Interacts with GNAZ and GNAI2; this precludes interaction with SIX1. {ECO:0000250, ECO:0000269|PubMed:10906137, ECO:0000269|PubMed:19351884, ECO:0000269|PubMed:19497856, ECO:0000269|PubMed:19858093, ECO:0000269|PubMed:23435380}. |
| Subcellular location: | |
Cytoplasm {ECO:0000269|PubMed:10906137, ECO:0000269|PubMed:12500905}. Nucleus {ECO:0000269|PubMed:10906137, ECO:0000269|PubMed:12500905, ECO:0000269|PubMed:19497856}. Note=Retained in the cytoplasm via interaction with GNAZ and GNAI2 (PubMed:10906137). Interaction with SIX1, SIX2, SIX4 or SIX5 is required for translocation to the nucleus (PubMed:10906137, PubMed:12500905). {ECO:0000269|PubMed:10906137, ECO:0000269|PubMed:12500905}. |
| Tissue specificity: | |
Highest expression in muscle with lower levels in kidney, placenta, pancreas, brain and heart. {ECO:0000269|PubMed:9195991}. |
| 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. {ECO:0000269|PubMed:12500905}. |
| Similarity: | |
Belongs to the HAD-like hydrolase superfamily. EYA family. {ECO:0000305}. |
| Sequence caution: | |
Sequence=AAH13882.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; |
Annotations taken from UniProtKB at the EBI.