Interacts with BRCA1, CLSPN, FBXO6, PPM1D, RAD51, TIMELESS, XPO1/CRM1 and YWHAZ/14-3-3 zeta. Interacts with FEM1B.
Function:
Required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Inhibition of CDC25 activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Binds to and phosphorylates RAD51 at 'Thr-309', which may enhance the association of RAD51 with chromatin and promote DNA repair by homologous recombination. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may affect chromatin assembly during S phase or DNA repair. May also phosphorylate multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and enhances suppression of cellular proliferation. Phosphorylates NEK6 and NEK11. Phosphorylation of CDC25A at Ser-76 primes it for subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 by NEK11.
Subcellular Location:
Nucleus
Cytoplasm
Cytoplasm
cytoskeleton
centrosome
Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B.
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1);FUNCTION IN PHOSPHORYLATION OF CDC25A; CDC25B AND CDC25C;INTERACTION WITH CDC25A; CDC25B AND CDC25C;SUBCELLULAR LOCATION;TISSUE SPECIFICITY;MUTAGENESIS OF ASP-130;VARIANT VAL-471
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1);TISSUE SPECIFICITY;SUBCELLULAR LOCATION;VARIANT VAL-471
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];VARIANT VAL-471
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2);ALTERNATIVE SPLICING
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3);VARIANT VAL-471
NIEHS SNPs program
Submitted (2002-07) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];VARIANTS GLN-156 AND VAL-471
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1);VARIANT VAL-471
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA];VARIANT VAL-471
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1);VARIANT VAL-471
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Cited for: FUNCTION IN PHOSPHORYLATION OF TP53;MUTAGENESIS OF ASP-130
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Cited for: FUNCTION IN DNA REPLICATION;PHOSPHORYLATION BY ATR;MUTAGENESIS OF ASP-130
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Cited for: PHOSPHORYLATION AT SER-317 AND SER-345;MUTAGENESIS OF ASP-130; SER-317; SER-345; SER-357; SER-366 AND SER-468
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Cited for: FUNCTION IN DNA DAMAGE RESPONSE;PHOSPHORYLATION AT SER-317 AND SER-345;MUTAGENESIS OF LYS-38
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Cited for: FUNCTION IN CDC25A TURNOVER;PHOSPHORYLATION AT SER-317 AND SER-345;MUTAGENESIS OF SER-317 AND SER-345
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Cited for: FUNCTION IN PHOSPHORYLATION OF TLK1;PHOSPHORYLATION AT SER-317
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Cited for: FUNCTION IN CDC25A TURNOVER;MUTAGENESIS OF ASP-130
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Cited for: PHOSPHORYLATION AT SER-317;MUTAGENESIS OF ASP-130; SER-317 AND SER-345
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Cited for: FUNCTION IN CDC25A TURNOVER;PHOSPHORYLATION AT SER-345
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Cited for: INTERACTION WITH YWHAZ AND XPO1;SUBCELLULAR LOCATION;ASSOCIATION WITH CHROMATIN;PHOSPHORYLATION AT SER-317 AND SER-345;MUTAGENESIS OF SER-317; PHE-344; SER-345 AND MET-353
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Cited for: FUNCTION IN MITOSIS;FUNCTION IN PHOSPHORYLATION OF CDC25A
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Cited for: DOMAIN;MITOTIC PHOSPHORYLATION;PHOSPHORYLATION AT SER-345;MUTAGENESIS OF LYS-38
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Cited for: FUNCTION IN MITOSIS;SUBCELLULAR LOCATION;MUTAGENESIS OF ASP-130
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Cited for: INTERACTION WITH CLSPN;PHOSPHORYLATION AT SER-296; SER-317 AND SER-345
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Cited for: INTERACTION WITH PPM1D;PHOSPHORYLATION AT SER-317 AND SER-345;DEPHOSPHORYLATION BY PPM1D
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Cited for: FUNCTION IN PHOSPHORYLATION OF TP53;FUNCTION IN TP53-DEPENDENT TRANSCRIPTION
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Cited for: FUNCTION IN HOMOLOGOUS RECOMBINATION REPAIR;FUNCTION IN PHOSPHORYLATION OF RAD51;INTERACTION WITH RAD51;MUTAGENESIS OF SER-317 AND SER-345
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Cited for: FUNCTION IN MITOTIC EXIT;PHOSPHORYLATION AT SER-345
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Cited for: FUNCTION IN TP53 ACTIVATION;FUNCTION IN PHOSPHORYLATION OF MDM4
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Cited for: FUNCTION IN PHOSPHORYLATION OF CLSPN;INTERACTION WITH CLSPN
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Cited for: FUNCTION IN DNA CROSS-LINKS REPAIR;FUNCTION IN PHOSPHORYLATION OF FANCE
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Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-436
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: FUNCTION IN REPLICATION FORK MAINTENANCE;FUNCTION IN PCNA UBIQUITINATION
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: FUNCTION IN RAD51-MEDIATED DNA REPAIR;FUNCTION IN PHOSPHORYLATION OF BRCA2 AND RAD51
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-296 AND SER-301;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION AT SER-345;UBIQUITINATION AT LYS-436;INTERACTION WITH FBXO6;MUTAGENESIS OF SER-345; ARG-372; ARG-376; ARG-379 AND LYS-436
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-296 AND SER-301;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-223 AND MET-312
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