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P48964

- MPIP1_MOUSE

UniProt

P48964 - MPIP1_MOUSE

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Protein

M-phase inducer phosphatase 1

Gene

Cdc25a

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at transcript leveli

Functioni

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).By similarity

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Enzyme regulationi

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

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei421 – 4211By similarity

GO - Molecular functioni

  1. protein tyrosine phosphatase activity Source: UniProtKB-EC

GO - Biological processi

  1. cellular response to UV Source: Ensembl
  2. mitotic nuclear division Source: UniProtKB-KW
  3. response to radiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Enzyme and pathway databases

ReactomeiREACT_199110. G0 and Early G1.
REACT_204269. E2F-enabled inhibition of pre-replication complex formation.
REACT_206803. Cyclin A/B1 associated events during G2/M transition.
REACT_209377. Cyclin B2 mediated events.
REACT_223647. Cyclin A:Cdk2-associated events at S phase entry.

Names & Taxonomyi

Protein namesi
Recommended name:
M-phase inducer phosphatase 1 (EC:3.1.3.48)
Alternative name(s):
Dual specificity phosphatase Cdc25A
Gene namesi
Name:Cdc25a
Synonyms:Cdc25m3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:103198. Cdc25a.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: MGI
  2. nucleus Source: MGI
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 514514M-phase inducer phosphatase 1PRO_0000198642Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei75 – 751Phosphoserine; by CHEK1By similarity
Modified residuei78 – 781Phosphoserine; by NEK11By similarity
Modified residuei81 – 811Phosphoserine; by NEK11By similarity
Modified residuei87 – 871Phosphoserine; by NEK11By similarity
Modified residuei123 – 1231Phosphoserine; by CHEK1 and CHEK2By similarity
Modified residuei172 – 1721Phosphoserine; by CHEK1By similarity
Modified residuei271 – 2711Phosphoserine; by CHEK1 and CHEK2By similarity
Modified residuei284 – 2841Phosphoserine; by CHEK1 and CHEK2By similarity
Modified residuei497 – 4971Phosphothreonine; by CHEK1By similarity
Modified residuei503 – 5031Phosphoserine; by PLK3By similarity
Modified residuei509 – 5091Phosphoserine; by PLK3By similarity

Post-translational modificationi

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).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).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP48964.

PTM databases

PhosphoSiteiP48964.

Expressioni

Tissue specificityi

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.1 Publication

Developmental stagei

First detected at the blastocyst stage.1 Publication

Gene expression databases

CleanExiMM_CDC25A.
GenevestigatoriP48964.

Interactioni

Subunit structurei

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).By similarity

Structurei

3D structure databases

ProteinModelPortaliP48964.
SMRiP48964. Positions 327-486.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini366 – 472107RhodanesePROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi73 – 8311PhosphodegronAdd
BLAST
Motifi140 – 1423KEN box

Domaini

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).By similarity

Sequence similaritiesi

Belongs to the MPI phosphatase family.Curated
Contains 1 rhodanese domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5105.
GeneTreeiENSGT00390000018747.
HOVERGENiHBG052501.
InParanoidiP48964.
KOiK06645.
OMAiNLTVTMD.
OrthoDBiEOG7288R1.
PhylomeDBiP48964.
TreeFamiTF101056.

Family and domain databases

Gene3Di3.40.250.10. 1 hit.
InterProiIPR000751. MPI_Phosphatase.
IPR001763. Rhodanese-like_dom.
[Graphical view]
PfamiPF06617. M-inducer_phosp. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]
PRINTSiPR00716. MPIPHPHTASE.
SMARTiSM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMiSSF52821. SSF52821. 1 hit.
PROSITEiPS50206. RHODANESE_3. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P48964-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MELGPEPPHR RRLFFACSPT PAPQPTGKML FGASAAGGLS PVTNLTVTMD
60 70 80 90 100
QLEGLGSDCE KMEVRNNSSL QRMGSSESTD SGFCLDSPGP LDSKENLEIS
110 120 130 140 150
LTRINSLPQK LLGCSPALKR SHSDSLDHDT FHLIDQDENK ENEAFEFKKP
160 170 180 190 200
IRPASRHIYE ESKDPFTHRQ NSAPARMLSS NESESGNFSP LFIPQSPVKA
210 220 230 240 250
TLSDEDDGFI DLLDGENMKN DEETPSCMAS LWTAPLVMRR PANLADRCGL
260 270 280 290 300
FDSPSPCGSS TRAVLKRADR SHEEPPRGTK RRKSVPSPVK AKADVPEPAQ
310 320 330 340 350
LPSQSLSLMS SPKGTIENIL DSDPRDLIGD FSKGYLFNTV SGKHQDLKYI
360 370 380 390 400
SPEIMASVLN GKFAGLIKEF VIIDCRYPYE YEGGHIKGAV NLHMEEEVED
410 420 430 440 450
FLLKNPIVPT DGKRVIVVFH CEFSSERGPR MCRYVRERDR LGNEYPKLHY
460 470 480 490 500
PELYVLKGGY KEFFLKCQSH CEPPSYRPMH HEDFKEDLKK FRTKSRTWAG
510
EKSKREMYSR LKKL
Length:514
Mass (Da):57,806
Last modified:September 18, 2013 - v2
Checksum:i7D7AD1CB4C39ACF6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti6 – 61E → S in AAA85580. (PubMed:7635051)Curated
Sequence conflicti9 – 102HR → P in AAA85580. (PubMed:7635051)Curated
Sequence conflicti23 – 231P → S in AAA85580. (PubMed:7635051)Curated
Sequence conflicti128 – 1281H → Q in AAA85580. (PubMed:7635051)Curated
Sequence conflicti138 – 1381E → K in AAA85580. (PubMed:7635051)Curated
Sequence conflicti147 – 16014FKKPI…RHIYE → PKKQYDLHLSSHLQ in AAA85580. (PubMed:7635051)CuratedAdd
BLAST
Sequence conflicti165 – 1684PFTH → LYTQ in AAA85580. (PubMed:7635051)Curated
Sequence conflicti174 – 1763PAR → QLG in AAA85580. (PubMed:7635051)Curated
Sequence conflicti193 – 1931I → T in AAA85580. (PubMed:7635051)Curated
Sequence conflicti218 – 2181M → L in AAA85580. (PubMed:7635051)Curated
Sequence conflicti226 – 2294SCMA → TSMV in AAA85580. (PubMed:7635051)Curated
Sequence conflicti248 – 2481C → LR in AAA85580. (PubMed:7635051)Curated
Sequence conflicti365 – 3651G → S in AAA85580. (PubMed:7635051)Curated
Sequence conflicti503 – 5031S → R in AAA85580. (PubMed:7635051)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U27323 mRNA. Translation: AAA85580.1.
CT573087 Genomic DNA. No translation available.
CCDSiCCDS23559.1.
RefSeqiNP_031684.3. NM_007658.3.
UniGeneiMm.307103.

Genome annotation databases

EnsembliENSMUST00000094324; ENSMUSP00000091882; ENSMUSG00000032477.
GeneIDi12530.
KEGGimmu:12530.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U27323 mRNA. Translation: AAA85580.1 .
CT573087 Genomic DNA. No translation available.
CCDSi CCDS23559.1.
RefSeqi NP_031684.3. NM_007658.3.
UniGenei Mm.307103.

3D structure databases

ProteinModelPortali P48964.
SMRi P48964. Positions 327-486.
ModBasei Search...
MobiDBi Search...

PTM databases

PhosphoSitei P48964.

Proteomic databases

PRIDEi P48964.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000094324 ; ENSMUSP00000091882 ; ENSMUSG00000032477 .
GeneIDi 12530.
KEGGi mmu:12530.

Organism-specific databases

CTDi 993.
MGIi MGI:103198. Cdc25a.

Phylogenomic databases

eggNOGi COG5105.
GeneTreei ENSGT00390000018747.
HOVERGENi HBG052501.
InParanoidi P48964.
KOi K06645.
OMAi NLTVTMD.
OrthoDBi EOG7288R1.
PhylomeDBi P48964.
TreeFami TF101056.

Enzyme and pathway databases

Reactomei REACT_199110. G0 and Early G1.
REACT_204269. E2F-enabled inhibition of pre-replication complex formation.
REACT_206803. Cyclin A/B1 associated events during G2/M transition.
REACT_209377. Cyclin B2 mediated events.
REACT_223647. Cyclin A:Cdk2-associated events at S phase entry.

Miscellaneous databases

NextBioi 281558.
PROi P48964.
SOURCEi Search...

Gene expression databases

CleanExi MM_CDC25A.
Genevestigatori P48964.

Family and domain databases

Gene3Di 3.40.250.10. 1 hit.
InterProi IPR000751. MPI_Phosphatase.
IPR001763. Rhodanese-like_dom.
[Graphical view ]
Pfami PF06617. M-inducer_phosp. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view ]
PRINTSi PR00716. MPIPHPHTASE.
SMARTi SM00450. RHOD. 1 hit.
[Graphical view ]
SUPFAMi SSF52821. SSF52821. 1 hit.
PROSITEi PS50206. RHODANESE_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.

Entry informationi

Entry nameiMPIP1_MOUSE
AccessioniPrimary (citable) accession number: P48964
Secondary accession number(s): E9PVD0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: September 18, 2013
Last modified: October 29, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3