P48964 (MPIP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified April 16, 2014. Version 101. History...
Names and origin
|Protein names||Recommended name:|
M-phase inducer phosphatase 1
Dual specificity phosphatase Cdc25A
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||514 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Directly dephosphorylates CDK1 and stimulates its kinase activity. Also dephosphorylates CDK2 in complex with cyclin E, in vitro By similarity. Phosphorylation by PIM1 leads to an increase in phosphatase activity By similarity.
Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.
Stimulated by B-type cyclins. Stimulated by PIM1-mediated phosphorylation By similarity.
Interacts with CCNB1/cyclin B1. Interacts with YWHAE/14-3-3 epsilon when phosphorylated. Interacts with CUL1 specifically when CUL1 is neddylated and active. Interacts with BTRC/BTRCP1 and FBXW11/BTRCP2. Interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage. Interacts with PIM1. Interacts with CHEK2; mediates CDC25A phosphorylation and degradation in response to infrared-induced DNA damages By similarity.
Ubiquitously expressed in most developing tissue. High levels in the testis and lower levels in the ovary, particularly in germ cells. Lower levels also in kidney, liver, heart and muscle. Ref.1
First detected at the blastocyst stage. Ref.1
The phosphodegron motif mediates interaction with specific F-box proteins when phosphorylated. Putative phosphorylation sites at Ser-78 and Ser-81 appear to be essential for this interaction By similarity.
Phosphorylated by CHEK1 on Ser-75, Ser-123, Ser-172, Ser-271, Ser-284 and Thr-497 during checkpoint mediated cell cycle arrest. Also phosphorylated by CHEK2 on Ser-123, Ser-271, and Ser-284 during checkpoint mediated cell cycle arrest. Phosphorylation on Ser-172 and Thr-497 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CDC25A. Phosphorylation on Ser-75, Ser-123, Ser-172, Ser-271 and Ser-284 may also promote ubiquitin-dependent proteolysis of CDC25A by the SCF complex. Phosphorylation of CDC25A at Ser-75 by CHEK1 primes it for subsequent phosphorylation at Ser-75, Ser-81 and Ser-87 by NEK11. Phosphorylation by NEK11 is required for BTRC-mediated polyubiquitination and degradation. Phosphorylation by PIM1 leads to an increase in phosphatase activity. Phosphorylated by PLK3 following DNA damage, leading to promote its ubiquitination and degradation By similarity.
Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex that contains FZR1/CDH1 during G1 phase leading to its degradation by the proteasome. Ubiquitinated by a SCF complex containing BTRC and FBXW11 during S phase leading to its degradation by the proteasome. Deubiquitination by USP17L2/DUB3 leads to its stabilization By similarity.
Belongs to the MPI phosphatase family.
Contains 1 rhodanese domain.
|Biological process||Cell cycle|
|Technical term||Complete proteome|
|Gene Ontology (GO)|
|Biological_process||cellular response to UV|
Inferred from electronic annotation. Source: Ensemblmitosis
Inferred from electronic annotation. Source: UniProtKB-KWresponse to radiation
Inferred from sequence or structural similarity. Source: UniProtKB
|Molecular_function||protein tyrosine phosphatase activity|
Inferred from electronic annotation. Source: UniProtKB-EC
|Complete GO annotation...|
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 514||514||M-phase inducer phosphatase 1||PRO_0000198642|
|Domain||366 – 472||107||Rhodanese|
|Motif||73 – 83||11||Phosphodegron|
|Motif||140 – 142||3||KEN box|
|Active site||421||1||By similarity|
Amino acid modifications
|Modified residue||75||1||Phosphoserine; by CHEK1 By similarity|
|Modified residue||78||1||Phosphoserine; by NEK11 By similarity|
|Modified residue||81||1||Phosphoserine; by NEK11 By similarity|
|Modified residue||87||1||Phosphoserine; by NEK11 By similarity|
|Modified residue||123||1||Phosphoserine; by CHEK1 and CHEK2 By similarity|
|Modified residue||172||1||Phosphoserine; by CHEK1 By similarity|
|Modified residue||271||1||Phosphoserine; by CHEK1 and CHEK2 By similarity|
|Modified residue||284||1||Phosphoserine; by CHEK1 and CHEK2 By similarity|
|Modified residue||497||1||Phosphothreonine; by CHEK1 By similarity|
|Modified residue||503||1||Phosphoserine; by PLK3 By similarity|
|Modified residue||509||1||Phosphoserine; by PLK3 By similarity|
|Sequence conflict||6||1||E → S in AAA85580. Ref.1|
|Sequence conflict||9 – 10||2||HR → P in AAA85580. Ref.1|
|Sequence conflict||23||1||P → S in AAA85580. Ref.1|
|Sequence conflict||128||1||H → Q in AAA85580. Ref.1|
|Sequence conflict||138||1||E → K in AAA85580. Ref.1|
|Sequence conflict||147 – 160||14||FKKPI…RHIYE → PKKQYDLHLSSHLQ in AAA85580. Ref.1|
|Sequence conflict||165 – 168||4||PFTH → LYTQ in AAA85580. Ref.1|
|Sequence conflict||174 – 176||3||PAR → QLG in AAA85580. Ref.1|
|Sequence conflict||193||1||I → T in AAA85580. Ref.1|
|Sequence conflict||218||1||M → L in AAA85580. Ref.1|
|Sequence conflict||226 – 229||4||SCMA → TSMV in AAA85580. Ref.1|
|Sequence conflict||248||1||C → LR in AAA85580. Ref.1|
|Sequence conflict||365||1||G → S in AAA85580. Ref.1|
|Sequence conflict||503||1||S → R in AAA85580. Ref.1|
|||"Two CDC25 homologues are differentially expressed during mouse development."|
Wickramasinghe D., Becker S., Ernst M.K., Resnick J.L., Centanni J.M., Tessarollo L., Grabel L.B., Donovan P.J.
Development 121:2047-2056(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
|||"Lineage-specific biology revealed by a finished genome assembly of the mouse."|
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|+||Additional computationally mapped references.|
|U27323 mRNA. Translation: AAA85580.1.|
CT573087 Genomic DNA. No translation available.
|RefSeq||NP_031684.3. NM_007658.3. |
3D structure databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000094324; ENSMUSP00000091882; ENSMUSG00000032477. |
|MGI||MGI:103198. Cdc25a. |
Gene expression databases
Family and domain databases
|Gene3D||220.127.116.11. 1 hit. |
|InterPro||IPR000751. MPI_Phosphatase. |
|Pfam||PF06617. M-inducer_phosp. 1 hit. |
PF00581. Rhodanese. 1 hit.
|PRINTS||PR00716. MPIPHPHTASE. |
|SMART||SM00450. RHOD. 1 hit. |
|SUPFAM||SSF52821. SSF52821. 1 hit. |
|PROSITE||PS50206. RHODANESE_3. 1 hit. |
|Accession||Primary (citable) accession number: P48964|
Secondary accession number(s): E9PVD0
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|