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P48965 (MPIP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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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
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length525 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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.

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 CHEK2; mediates CDC25A phosphorylation and degradation in response to infrared-induced DNA damages By similarity. Interacts with PIM1. Ref.2

Domain

The phosphodegron motif mediates interaction with specific F-box proteins when phosphorylated. Putative phosphorylation sites at Ser-79 and Ser-82 appear to be essential for this interaction By similarity.

Post-translational modification

Phosphorylated by CHEK1 on Ser-76, Ser-124, Ser-178, Ser-283, Ser-296 and Thr-508 during checkpoint mediated cell cycle arrest. Also phosphorylated by CHEK2 on Ser-124, Ser-283, and Ser-296 during checkpoint mediated cell cycle arrest. Phosphorylation on Ser-178 and Thr-508 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CDC25A. Phosphorylation on Ser-76, Ser-124, Ser-178, Ser-283 and Ser-296 may also promote ubiquitin-dependent proteolysis of CDC25A by the SCF complex. Phosphorylation of CDC25A at Ser-76 by CHEK1 primes it for subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 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. Ref.2

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 – 525525M-phase inducer phosphatase 1
PRO_0000198643

Regions

Domain377 – 483107Rhodanese
Motif74 – 8411Phosphodegron
Motif141 – 1433KEN box

Sites

Active site4321 By similarity

Amino acid modifications

Modified residue761Phosphoserine; by CHEK1 By similarity
Modified residue791Phosphoserine; by NEK11 By similarity
Modified residue821Phosphoserine; by NEK11 By similarity
Modified residue881Phosphoserine; by NEK11 By similarity
Modified residue1241Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residue1781Phosphoserine; by CHEK1 By similarity
Modified residue2831Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residue2961Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residue5081Phosphothreonine; by CHEK1 By similarity
Modified residue5141Phosphoserine; by PLK3 By similarity
Modified residue5201Phosphoserine; by PLK3 By similarity

Sequences

Sequence LengthMass (Da)Tools
P48965 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: A60EC0AF46D63A9C

FASTA52559,218
        10         20         30         40         50         60 
MELGPEPPHR RRLLFTCSPT PAPQPTGKVQ FGASRAGGLS PVTNLTVTMD QLEGLGSDYE 

        70         80         90        100        110        120 
KPMDVRNSSS LQRMGSSEST DSGFCLDSPG PLDSKENLEI SLRRINCLPQ KLLGCSPALK 

       130        140        150        160        170        180 
RSHSDSLDHD IFQLIDQDEN KENEAFEFKK PIRPASRGCL NAHVHEESKD PFTHRQNSAP 

       190        200        210        220        230        240 
ARMLSSNESD ISESGNFSPL FTPQSPVKAS LSDEDDGFID LLDGENLKND EETPSCMSSL 

       250        260        270        280        290        300 
WTAPLVMRRP TNLADRCGLF DSPSPCSSTS SCSTRAVKRA DRSHEESPRG TKRRKSSEAS 

       310        320        330        340        350        360 
PVKADVPEPT QLPHQSLSLT SFPKGTIENI FHSDPRDLIG DFSKGYLFHT VSGKHQDLKY 

       370        380        390        400        410        420 
ISPEIMASVL NGKFANLIKE FVIIDCRYPY EYEGGHIKGA VNLHMEEEVE EFLLKKPIVP 

       430        440        450        460        470        480 
ADGKRVIVVF HCEFSSERGP RMCRYVRERD RLGNEYPKLH YPELYVLKGG YKEFFLKCQS 

       490        500        510        520 
HCEPPSYRPM HHEDFKEDLK KFRTKSRTWA GEKSKREMYS RLKKL 

« Hide

References

[1]"Cdc25A is a novel phosphatase functioning early in the cell cycle."
Jinno S., Suto K., Nagata A., Igarashi M., Kanaoka Y., Nojima H., Okayama H.
EMBO J. 13:1549-1556(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: NRK49F.
[2]"Physical and functional interactions between Pim-1 kinase and Cdc25A phosphatase. Implications for the Pim-1-mediated activation of the c-Myc signaling pathway."
Mochizuki T., Kitanaka C., Noguchi K., Muramatsu T., Asai A., Kuchino Y.
J. Biol. Chem. 274:18659-18666(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIM1, PHOSPHORYLATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D16236 mRNA. Translation: BAA03761.1.
RefSeqNP_598255.1. NM_133571.1.
UniGeneRn.11390.

3D structure databases

ProteinModelPortalP48965.
SMRP48965. Positions 338-497.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000028141.

PTM databases

PhosphoSiteP48965.

Proteomic databases

PRIDEP48965.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID171102.
KEGGrno:171102.
UCSCRGD:621498. rat.

Organism-specific databases

CTD993.
RGD621498. Cdc25a.

Phylogenomic databases

eggNOGCOG5105.
HOGENOMHOG000082672.
HOVERGENHBG052501.
InParanoidP48965.
KOK06645.
PhylomeDBP48965.

Gene expression databases

GenevestigatorP48965.

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

NextBio621782.
PROP48965.

Entry information

Entry nameMPIP1_RAT
AccessionPrimary (citable) accession number: P48965
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: April 16, 2014
This is version 93 of the entry and version 1 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