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P48964 (MPIP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 101. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
M-phase inducer phosphatase 1

EC=3.1.3.48
Alternative name(s):
Dual specificity phosphatase Cdc25A
Gene names
Name:Cdc25a
Synonyms:Cdc25m3
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length514 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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.

Catalytic activity

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Enzyme regulation

Stimulated by B-type cyclins. Stimulated by PIM1-mediated phosphorylation By similarity.

Subunit structure

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.

Tissue specificity

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

Developmental stage

First detected at the blastocyst stage. Ref.1

Domain

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.

Post-translational modification

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.

Sequence similarities

Belongs to the MPI phosphatase family.

Contains 1 rhodanese domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 514514M-phase inducer phosphatase 1
PRO_0000198642

Regions

Domain366 – 472107Rhodanese
Motif73 – 8311Phosphodegron
Motif140 – 1423KEN box

Sites

Active site4211 By similarity

Amino acid modifications

Modified residue751Phosphoserine; by CHEK1 By similarity
Modified residue781Phosphoserine; by NEK11 By similarity
Modified residue811Phosphoserine; by NEK11 By similarity
Modified residue871Phosphoserine; by NEK11 By similarity
Modified residue1231Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residue1721Phosphoserine; by CHEK1 By similarity
Modified residue2711Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residue2841Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residue4971Phosphothreonine; by CHEK1 By similarity
Modified residue5031Phosphoserine; by PLK3 By similarity
Modified residue5091Phosphoserine; by PLK3 By similarity

Experimental info

Sequence conflict61E → S in AAA85580. Ref.1
Sequence conflict9 – 102HR → P in AAA85580. Ref.1
Sequence conflict231P → S in AAA85580. Ref.1
Sequence conflict1281H → Q in AAA85580. Ref.1
Sequence conflict1381E → K in AAA85580. Ref.1
Sequence conflict147 – 16014FKKPI…RHIYE → PKKQYDLHLSSHLQ in AAA85580. Ref.1
Sequence conflict165 – 1684PFTH → LYTQ in AAA85580. Ref.1
Sequence conflict174 – 1763PAR → QLG in AAA85580. Ref.1
Sequence conflict1931I → T in AAA85580. Ref.1
Sequence conflict2181M → L in AAA85580. Ref.1
Sequence conflict226 – 2294SCMA → TSMV in AAA85580. Ref.1
Sequence conflict2481C → LR in AAA85580. Ref.1
Sequence conflict3651G → S in AAA85580. Ref.1
Sequence conflict5031S → R in AAA85580. Ref.1

Sequences

Sequence LengthMass (Da)Tools
P48964 [UniParc].

Last modified September 18, 2013. Version 2.
Checksum: 7D7AD1CB4C39ACF6

FASTA51457,806
        10         20         30         40         50         60 
MELGPEPPHR RRLFFACSPT PAPQPTGKML FGASAAGGLS PVTNLTVTMD QLEGLGSDCE 

        70         80         90        100        110        120 
KMEVRNNSSL QRMGSSESTD SGFCLDSPGP LDSKENLEIS LTRINSLPQK LLGCSPALKR 

       130        140        150        160        170        180 
SHSDSLDHDT FHLIDQDENK ENEAFEFKKP IRPASRHIYE ESKDPFTHRQ NSAPARMLSS 

       190        200        210        220        230        240 
NESESGNFSP LFIPQSPVKA TLSDEDDGFI DLLDGENMKN DEETPSCMAS LWTAPLVMRR 

       250        260        270        280        290        300 
PANLADRCGL FDSPSPCGSS TRAVLKRADR SHEEPPRGTK RRKSVPSPVK AKADVPEPAQ 

       310        320        330        340        350        360 
LPSQSLSLMS SPKGTIENIL DSDPRDLIGD FSKGYLFNTV SGKHQDLKYI SPEIMASVLN 

       370        380        390        400        410        420 
GKFAGLIKEF VIIDCRYPYE YEGGHIKGAV NLHMEEEVED FLLKNPIVPT DGKRVIVVFH 

       430        440        450        460        470        480 
CEFSSERGPR MCRYVRERDR LGNEYPKLHY PELYVLKGGY KEFFLKCQSH CEPPSYRPMH 

       490        500        510 
HEDFKEDLKK FRTKSRTWAG EKSKREMYSR LKKL 

« Hide

References

« Hide 'large scale' references
[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.
[2]"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. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U27323 mRNA. Translation: AAA85580.1.
CT573087 Genomic DNA. No translation available.
RefSeqNP_031684.3. NM_007658.3.
UniGeneMm.307103.

3D structure databases

ProteinModelPortalP48964.
ModBaseSearch...
MobiDBSearch...

PTM databases

PhosphoSiteP48964.

Proteomic databases

PRIDEP48964.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000094324; ENSMUSP00000091882; ENSMUSG00000032477.
GeneID12530.
KEGGmmu:12530.

Organism-specific databases

CTD993.
MGIMGI:103198. Cdc25a.

Phylogenomic databases

eggNOGCOG5105.
GeneTreeENSGT00390000018747.
HOVERGENHBG052501.
KOK06645.
OMANLTVTMD.
OrthoDBEOG7288R1.
PhylomeDBP48964.
TreeFamTF101056.

Gene expression databases

CleanExMM_CDC25A.
GenevestigatorP48964.

Family and domain databases

Gene3D3.40.250.10. 1 hit.
InterProIPR000751. MPI_Phosphatase.
IPR001763. Rhodanese-like_dom.
[Graphical view]
PfamPF06617. M-inducer_phosp. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]
PRINTSPR00716. MPIPHPHTASE.
SMARTSM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMSSF52821. SSF52821. 1 hit.
PROSITEPS50206. RHODANESE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio281558.
PROP48964.
SOURCESearch...

Entry information

Entry nameMPIP1_MOUSE
AccessionPrimary (citable) accession number: P48964
Secondary accession number(s): E9PVD0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 18, 2013
Last modified: April 16, 2014
This is version 101 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot