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Protein

M-phase inducer phosphatase 1

Gene

CDC25A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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.

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Enzyme regulationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei4311

GO - Molecular functioni

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cell proliferation Source: UniProtKB
  • cellular response to UV Source: UniProtKB
  • DNA replication Source: Reactome
  • G1/S transition of mitotic cell cycle Source: Reactome
  • G2/M transition of mitotic cell cycle Source: Reactome
  • mitotic nuclear division Source: UniProtKB-KW
  • regulation of cell cycle Source: Reactome
  • regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
  • 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

BioCyciZFISH:HS08989-MONOMER.
BRENDAi3.1.3.48. 2681.
ReactomeiR-HSA-113507. E2F-enabled inhibition of pre-replication complex formation.
R-HSA-113510. E2F mediated regulation of DNA replication.
R-HSA-1538133. G0 and Early G1.
R-HSA-156711. Polo-like kinase mediated events.
R-HSA-157881. Cyclin B2 mediated events.
R-HSA-176187. Activation of ATR in response to replication stress.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-69202. Cyclin E associated events during G1/S transition.
R-HSA-69205. G1/S-Specific Transcription.
R-HSA-69273. Cyclin A/B1 associated events during G2/M transition.
R-HSA-69601. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
R-HSA-69610. p53-Independent DNA Damage Response.
R-HSA-69656. Cyclin A:Cdk2-associated events at S phase entry.
SIGNORiP30304.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:1725. CDC25A.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi76S → A: Abolishes ubiquitination and impairs CHEK1-dependent degradation following checkpoint activation. 2 Publications1
Mutagenesisi79S → A: Abrogates interactions with BTRC and FBXW11 and prevents ubiquitination. 1 Publication1
Mutagenesisi81D → A: Abrogates interactions with BTRC and FBXW11 and prevents ubiquitination. 1 Publication1
Mutagenesisi82S → A: Abrogates interactions with BTRC and FBXW11 and prevents ubiquitination. 1 Publication1
Mutagenesisi124S → A: Abrogates phosphorylation by CHEK2 and infrared-induced degradation. Increases basal stability and impairs CHEK1-dependent degradation following checkpoint activation; when associated with A-178; A-279 and A-293. 4 Publications1
Mutagenesisi141 – 143KEN → AAA: Prevents ubiquitination and subsequent degradation by the APC/C ubiquitin ligase complex. 1 Publication3
Mutagenesisi178S → A: Increases basal stability and impairs CHEK1-dependent degradation following checkpoint activation; when associated with A-124; A-279 and A-293. Abrogates 14-3-3 protein binding. 3 Publications1
Mutagenesisi279S → A: Increases basal stability and impairs CHEK1-dependent degradation following checkpoint activation; when associated with A-124; A-178 and A-293. 1 Publication1
Mutagenesisi293S → A: Increases basal stability and impairs CHEK1-dependent degradation following checkpoint activation; when associated with A-124; A-178 and A-279. 1 Publication1
Mutagenesisi431C → S: Abolishes phosphatase activity. 2 Publications1
Mutagenesisi507T → A: Abrogates 14-3-3 protein binding; increases binding to cyclin B1. 1 Publication1
Mutagenesisi513S → A: Increased stability following IR treatment. 1 Publication1
Mutagenesisi513S → D: Mimicks phosphorylation state, leading to promote degradation following IR treatment. 1 Publication1
Mutagenesisi514K → L: Abrogates binding to CCNB1; when associated with L-520. 1 Publication1
Mutagenesisi519S → A: Increased stability following IR treatment. 1 Publication1
Mutagenesisi519S → D: Mimicks phosphorylation state, leading to promote degradation following IR treatment. 1 Publication1
Mutagenesisi520R → L: Abrogates binding to CCNB1; when associated with L-514. 1 Publication1

Organism-specific databases

DisGeNETi993.
OpenTargetsiENSG00000164045.
PharmGKBiPA26259.

Chemistry databases

ChEMBLiCHEMBL3775.

Polymorphism and mutation databases

BioMutaiCDC25A.
DMDMi50403734.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001986411 – 524M-phase inducer phosphatase 1Add BLAST524

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei76Phosphoserine; by CHEK12 Publications1
Modified residuei79Phosphoserine; by NEK111 Publication1
Modified residuei82Phosphoserine; by NEK112 Publications1
Modified residuei88Phosphoserine; by NEK112 Publications1
Modified residuei107PhosphoserineCombined sources1
Modified residuei124Phosphoserine; by CHEK1 and CHEK25 Publications1
Modified residuei178Phosphoserine; by CHEK13 Publications1
Modified residuei279Phosphoserine; by CHEK1 and CHEK21 Publication1
Modified residuei293Phosphoserine; by CHEK1 and CHEK21 Publication1
Modified residuei321PhosphoserineCombined sources1
Modified residuei507Phosphothreonine; by CHEK11 Publication1
Modified residuei513Phosphoserine; by PLK31 Publication1
Modified residuei519Phosphoserine; by PLK31 Publication1

Post-translational modificationi

Phosphorylated by CHEK1 on Ser-76, Ser-124, Ser-178, Ser-279, Ser-293 and Thr-507 during checkpoint mediated cell cycle arrest. Also phosphorylated by CHEK2 on Ser-124, Ser-279, and Ser-293 during checkpoint mediated cell cycle arrest. Phosphorylation on Ser-178 and Thr-507 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CDC25A. Phosphorylation on Ser-76, Ser-124, Ser-178, Ser-279 and Ser-293 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.11 Publications
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.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP30304.
MaxQBiP30304.
PaxDbiP30304.
PeptideAtlasiP30304.
PRIDEiP30304.

PTM databases

DEPODiP30304.
iPTMnetiP30304.
PhosphoSitePlusiP30304.

Expressioni

Gene expression databases

BgeeiENSG00000164045.
CleanExiHS_CDC25A.
ExpressionAtlasiP30304. baseline and differential.
GenevisibleiP30304. HS.

Organism-specific databases

HPAiHPA005855.

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.4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RAF1P040494EBI-747671,EBI-365996
YWHABP319468EBI-747671,EBI-359815
YWHAZP631042EBI-747671,EBI-347088

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107428. 52 interactors.
DIPiDIP-166N.
IntActiP30304. 37 interactors.
MINTiMINT-124723.
STRINGi9606.ENSP00000303706.

Chemistry databases

BindingDBiP30304.

Structurei

Secondary structure

1524
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi341 – 344Combined sources4
Helixi362 – 369Combined sources8
Turni370 – 376Combined sources7
Beta strandi377 – 384Combined sources8
Helixi388 – 392Combined sources5
Helixi405 – 411Combined sources7
Turni412 – 414Combined sources3
Beta strandi423 – 430Combined sources8
Beta strandi432 – 436Combined sources5
Helixi437 – 451Combined sources15
Beta strandi463 – 466Combined sources4
Helixi469 – 477Combined sources9
Helixi478 – 480Combined sources3
Beta strandi481 – 484Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1C25X-ray2.30A337-496[»]
ProteinModelPortaliP30304.
SMRiP30304.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30304.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini376 – 482RhodanesePROSITE-ProRule annotationAdd BLAST107

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi74 – 84PhosphodegronAdd BLAST11
Motifi141 – 143KEN box3

Domaini

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.1 Publication

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG3772. Eukaryota.
COG5105. LUCA.
GeneTreeiENSGT00390000018747.
HOGENOMiHOG000082672.
HOVERGENiHBG052501.
InParanoidiP30304.
KOiK06645.
OMAiRGCLHSH.
OrthoDBiEOG091G0H0D.
PhylomeDBiP30304.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P30304-1) [UniParc]FASTAAdd to basket
Also known as: CDC25A1

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MELGPEPPHR RRLLFACSPP PASQPVVKAL FGASAAGGLS PVTNLTVTMD
60 70 80 90 100
QLQGLGSDYE QPLEVKNNSN LQRMGSSEST DSGFCLDSPG PLDSKENLEN
110 120 130 140 150
PMRRIHSLPQ KLLGCSPALK RSHSDSLDHD IFQLIDPDEN KENEAFEFKK
160 170 180 190 200
PVRPVSRGCL HSHGLQEGKD LFTQRQNSAP ARMLSSNERD SSEPGNFIPL
210 220 230 240 250
FTPQSPVTAT LSDEDDGFVD LLDGENLKNE EETPSCMASL WTAPLVMRTT
260 270 280 290 300
NLDNRCKLFD SPSLCSSSTR SVLKRPERSQ EESPPGSTKR RKSMSGASPK
310 320 330 340 350
ESTNPEKAHE TLHQSLSLAS SPKGTIENIL DNDPRDLIGD FSKGYLFHTV
360 370 380 390 400
AGKHQDLKYI SPEIMASVLN GKFANLIKEF VIIDCRYPYE YEGGHIKGAV
410 420 430 440 450
NLHMEEEVED FLLKKPIVPT DGKRVIVVFH CEFSSERGPR MCRYVRERDR
460 470 480 490 500
LGNEYPKLHY PELYVLKGGY KEFFMKCQSY CEPPSYRPMH HEDFKEDLKK
510 520
FRTKSRTWAG EKSKREMYSR LKKL
Length:524
Mass (Da):59,087
Last modified:July 19, 2004 - v2
Checksum:iB2F6B792D4E6122B
GO
Isoform 2 (identifier: P30304-2) [UniParc]FASTAAdd to basket
Also known as: CDC25A2

The sequence of this isoform differs from the canonical sequence as follows:
     144-183: Missing.

Show »
Length:484
Mass (Da):54,551
Checksum:iAE6326F34B704D4B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti6 – 10EPPHR → SPAP in AAA58415 (PubMed:1836978).Curated5
Sequence conflicti180 – 181PA → QL in AAA58415 (PubMed:1836978).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02093288S → F.1 PublicationCorresponds to variant rs3731499dbSNPEnsembl.1
Natural variantiVAR_023532182R → G.1 PublicationCorresponds to variant rs6771386dbSNPEnsembl.1
Natural variantiVAR_023533182R → W.Corresponds to variant rs6771386dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000860144 – 183Missing in isoform 2. 2 PublicationsAdd BLAST40

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81933 mRNA. Translation: AAA58415.1.
AY137580 mRNA. Translation: AAN11305.1.
AF527417 Genomic DNA. Translation: AAM77917.1.
BC007401 mRNA. Translation: AAH07401.1.
BC018642 mRNA. Translation: AAH18642.1.
AF277722 mRNA. Translation: AAG41884.1.
CCDSiCCDS2760.1. [P30304-1]
CCDS2761.1. [P30304-2]
PIRiA41648.
RefSeqiNP_001780.2. NM_001789.2. [P30304-1]
NP_963861.1. NM_201567.1. [P30304-2]
XP_011532618.1. XM_011534316.1. [P30304-1]
UniGeneiHs.437705.

Genome annotation databases

EnsembliENST00000302506; ENSP00000303706; ENSG00000164045. [P30304-1]
ENST00000351231; ENSP00000343166; ENSG00000164045. [P30304-2]
GeneIDi993.
KEGGihsa:993.
UCSCiuc003csh.2. human. [P30304-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M81933 mRNA. Translation: AAA58415.1.
AY137580 mRNA. Translation: AAN11305.1.
AF527417 Genomic DNA. Translation: AAM77917.1.
BC007401 mRNA. Translation: AAH07401.1.
BC018642 mRNA. Translation: AAH18642.1.
AF277722 mRNA. Translation: AAG41884.1.
CCDSiCCDS2760.1. [P30304-1]
CCDS2761.1. [P30304-2]
PIRiA41648.
RefSeqiNP_001780.2. NM_001789.2. [P30304-1]
NP_963861.1. NM_201567.1. [P30304-2]
XP_011532618.1. XM_011534316.1. [P30304-1]
UniGeneiHs.437705.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1C25X-ray2.30A337-496[»]
ProteinModelPortaliP30304.
SMRiP30304.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107428. 52 interactors.
DIPiDIP-166N.
IntActiP30304. 37 interactors.
MINTiMINT-124723.
STRINGi9606.ENSP00000303706.

Chemistry databases

BindingDBiP30304.
ChEMBLiCHEMBL3775.

PTM databases

DEPODiP30304.
iPTMnetiP30304.
PhosphoSitePlusiP30304.

Polymorphism and mutation databases

BioMutaiCDC25A.
DMDMi50403734.

Proteomic databases

EPDiP30304.
MaxQBiP30304.
PaxDbiP30304.
PeptideAtlasiP30304.
PRIDEiP30304.

Protocols and materials databases

DNASUi993.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000302506; ENSP00000303706; ENSG00000164045. [P30304-1]
ENST00000351231; ENSP00000343166; ENSG00000164045. [P30304-2]
GeneIDi993.
KEGGihsa:993.
UCSCiuc003csh.2. human. [P30304-1]

Organism-specific databases

CTDi993.
DisGeNETi993.
GeneCardsiCDC25A.
HGNCiHGNC:1725. CDC25A.
HPAiHPA005855.
MIMi116947. gene.
neXtProtiNX_P30304.
OpenTargetsiENSG00000164045.
PharmGKBiPA26259.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3772. Eukaryota.
COG5105. LUCA.
GeneTreeiENSGT00390000018747.
HOGENOMiHOG000082672.
HOVERGENiHBG052501.
InParanoidiP30304.
KOiK06645.
OMAiRGCLHSH.
OrthoDBiEOG091G0H0D.
PhylomeDBiP30304.
TreeFamiTF101056.

Enzyme and pathway databases

BioCyciZFISH:HS08989-MONOMER.
BRENDAi3.1.3.48. 2681.
ReactomeiR-HSA-113507. E2F-enabled inhibition of pre-replication complex formation.
R-HSA-113510. E2F mediated regulation of DNA replication.
R-HSA-1538133. G0 and Early G1.
R-HSA-156711. Polo-like kinase mediated events.
R-HSA-157881. Cyclin B2 mediated events.
R-HSA-176187. Activation of ATR in response to replication stress.
R-HSA-5689880. Ub-specific processing proteases.
R-HSA-69202. Cyclin E associated events during G1/S transition.
R-HSA-69205. G1/S-Specific Transcription.
R-HSA-69273. Cyclin A/B1 associated events during G2/M transition.
R-HSA-69601. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
R-HSA-69610. p53-Independent DNA Damage Response.
R-HSA-69656. Cyclin A:Cdk2-associated events at S phase entry.
SIGNORiP30304.

Miscellaneous databases

ChiTaRSiCDC25A. human.
EvolutionaryTraceiP30304.
GeneWikiiCDC25A.
GenomeRNAii993.
PROiP30304.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000164045.
CleanExiHS_CDC25A.
ExpressionAtlasiP30304. baseline and differential.
GenevisibleiP30304. HS.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiMPIP1_HUMAN
AccessioniPrimary (citable) accession number: P30304
Secondary accession number(s): Q8IZH5, Q96IL3, Q9H2F2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: July 19, 2004
Last modified: November 30, 2016
This is version 167 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.