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Protein

M-phase inducer phosphatase 3

Gene

CDC25C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle. When phosphorylated, highly effective in activating G2 cells into prophase. Directly dephosphorylates CDK1 and activates its kinase activity.1 Publication

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei377By similarity1

GO - Molecular functioni

  • phosphoprotein phosphatase activity Source: Reactome
  • protein kinase binding Source: UniProtKB
  • protein tyrosine phosphatase activity Source: GO_Central
  • WW domain binding Source: BHF-UCL

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protein phosphatase
Biological processCell cycle, Cell division, Host-virus interaction, Mitosis

Enzyme and pathway databases

BRENDAi3.1.3.48 2681
ReactomeiR-HSA-156711 Polo-like kinase mediated events
R-HSA-176187 Activation of ATR in response to replication stress
R-HSA-5625740 RHO GTPases activate PKNs
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
SIGNORiP30307

Names & Taxonomyi

Protein namesi
Recommended name:
M-phase inducer phosphatase 3 (EC:3.1.3.48)
Alternative name(s):
Dual specificity phosphatase Cdc25C
Gene namesi
Name:CDC25C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000158402.18
HGNCiHGNC:1727 CDC25C
MIMi157680 gene
neXtProtiNX_P30307

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi129S → V: Loss of phosphorylation. Severely impairs PLK1-binding. 1 Publication1
Mutagenesisi130T → A: Loss of phosphorylation. Severely impairs PLK1-binding. 1 Publication1
Mutagenesisi191S → A: Facilitates nuclear exclusion. 1 Publication1
Mutagenesisi191S → D: Mimicks phosphorylation state, leading to enhanced accumulation in the nucleus. 1 Publication1
Mutagenesisi352E → K: Partial loss of HIV-1 Vpr binding. 1 Publication1
Mutagenesisi359K → E: No effect on HIV-1 Vpr binding. 1 Publication1

Organism-specific databases

DisGeNETi995
OpenTargetsiENSG00000158402
PharmGKBiPA100

Chemistry databases

ChEMBLiCHEMBL2378

Polymorphism and mutation databases

BioMutaiCDC25C
DMDMi116242631

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001986472 – 473M-phase inducer phosphatase 3Add BLAST472

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei20PhosphoserineCombined sources1
Modified residuei38PhosphoserineCombined sources1
Modified residuei48PhosphothreonineCombined sources1 Publication1
Modified residuei57PhosphoserineCombined sources1
Modified residuei61PhosphoserineCombined sources1
Modified residuei64PhosphoserineCombined sources1
Modified residuei67PhosphothreonineCombined sources1 Publication1
Modified residuei122Phosphoserine; by CDK11 Publication1
Modified residuei129Phosphoserine1 Publication1
Modified residuei130Phosphothreonine1 Publication1
Modified residuei168PhosphoserineCombined sources1 Publication1
Modified residuei191Phosphoserine; by PLK31 Publication1
Modified residuei198Phosphoserine; by PLK31 Publication1
Modified residuei214Phosphoserine; by CDK11 Publication1
Modified residuei216Phosphoserine; by CHEK1, CHEK2, BRSK1 and MAPK14Combined sources3 Publications1
Modified residuei472PhosphoserineCombined sources1
Isoform 4 (identifier: P30307-3)
Modified residuei61Phosphoserine1
Isoform 5 (identifier: P30307-4)
Modified residuei61Phosphoserine1

Post-translational modificationi

Phosphorylated by CHEK1 and MAPK14 at Ser-216. This phosphorylation creates a binding site for 14-3-3 protein and inhibits the phosphatase. Phosphorylated by PLK4. Phosphorylated by PLK1, leading to activate the phosphatase activity. Phosphorylation by PLK3 at Ser-191 promotes nuclear translocation. Ser-198 is a minor phosphorylation site. Was initially reported to be phosphorylated by PLK3 at Ser-216 (PubMed:10557092). However, such phosphorylation by PLK3 was not confirmed by other groups. Phosphorylation at Thr-48, Thr-67, Ser-122, Thr-130, Ser-168 and Ser-214 occurs at G2 and G2-M transition and is probably catalyzed by CDK1. Ser-168 phosphorylation levels are lower than those at the other 5 CDK1 sites. Phosphorylation by CDK1 leads to increased activity.8 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP30307
PaxDbiP30307
PeptideAtlasiP30307
PRIDEiP30307
ProteomicsDBi54658
54659 [P30307-2]
54660 [P30307-3]
54661 [P30307-4]

PTM databases

DEPODiP30307
iPTMnetiP30307
PhosphoSitePlusiP30307

Expressioni

Developmental stagei

Expressed predominantly in G2 phase.

Gene expression databases

BgeeiENSG00000158402 Expressed in 92 organ(s), highest expression level in testis
CleanExiHS_CDC25C
ExpressionAtlasiP30307 baseline and differential
GenevisibleiP30307 HS

Organism-specific databases

HPAiCAB003800
HPA066991

Interactioni

Subunit structurei

Interacts with MAPK14 and 14-3-3 proteins. When phosphorylated on Ser-129 and/or Thr-130, interacts with PLK1.2 Publications
(Microbial infection) Interacts with HIV-1 Vpr; this interaction inactivates CDC25C phosphatase activity.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107430, 103 interactors
DIPiDIP-24183N
IntActiP30307, 18 interactors
MINTiP30307
STRINGi9606.ENSP00000321656

Chemistry databases

BindingDBiP30307

Structurei

Secondary structure

1473
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP30307
SMRiP30307
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP30307

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini321 – 428RhodanesePROSITE-ProRule annotationAdd BLAST108

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni334 – 379HIV-1 Vpr binding siteAdd BLAST46

Sequence similaritiesi

Belongs to the MPI phosphatase family.Curated

Phylogenomic databases

eggNOGiKOG3772 Eukaryota
COG5105 LUCA
GeneTreeiENSGT00390000018747
HOVERGENiHBG052501
InParanoidiP30307
KOiK05867
OMAiSKAWEGE
OrthoDBiEOG091G0H0D
PhylomeDBiP30307
TreeFamiTF101056

Family and domain databases

CDDicd01530 Cdc25, 1 hit
Gene3Di3.40.250.10, 1 hit
InterProiView protein in InterPro
IPR000751 MPI_Phosphatase
IPR001763 Rhodanese-like_dom
IPR036873 Rhodanese-like_dom_sf
PfamiView protein in Pfam
PF06617 M-inducer_phosp, 1 hit
PF00581 Rhodanese, 1 hit
PRINTSiPR00716 MPIPHPHTASE
SMARTiView protein in SMART
SM00450 RHOD, 1 hit
SUPFAMiSSF52821 SSF52821, 1 hit
PROSITEiView protein in PROSITE
PS50206 RHODANESE_3, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P30307-1) [UniParc]FASTAAdd to basket
Also known as: CDC25C1

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
MSTELFSSTR EEGSSGSGPS FRSNQRKMLN LLLERDTSFT VCPDVPRTPV
60 70 80 90 100
GKFLGDSANL SILSGGTPKR CLDLSNLSSG EITATQLTTS ADLDETGHLD
110 120 130 140 150
SSGLQEVHLA GMNHDQHLMK CSPAQLLCST PNGLDRGHRK RDAMCSSSAN
160 170 180 190 200
KENDNGNLVD SEMKYLGSPI TTVPKLDKNP NLGEDQAEEI SDELMEFSLK
210 220 230 240 250
DQEAKVSRSG LYRSPSMPEN LNRPRLKQVE KFKDNTIPDK VKKKYFSGQG
260 270 280 290 300
KLRKGLCLKK TVSLCDITIT QMLEEDSNQG HLIGDFSKVC ALPTVSGKHQ
310 320 330 340 350
DLKYVNPETV AALLSGKFQG LIEKFYVIDC RYPYEYLGGH IQGALNLYSQ
360 370 380 390 400
EELFNFFLKK PIVPLDTQKR IIIVFHCEFS SERGPRMCRC LREEDRSLNQ
410 420 430 440 450
YPALYYPELY ILKGGYRDFF PEYMELCEPQ SYCPMHHQDH KTELLRCRSQ
460 470
SKVQEGERQL REQIALLVKD MSP
Length:473
Mass (Da):53,365
Last modified:October 17, 2006 - v2
Checksum:i0658A1F1B9B8996A
GO
Isoform 2 (identifier: P30307-2) [UniParc]FASTAAdd to basket
Also known as: CDC25C2

The sequence of this isoform differs from the canonical sequence as follows:
     124-153: Missing.

Show »
Length:443
Mass (Da):50,122
Checksum:i11480DF49B3F04DD
GO
Isoform 3 (identifier: P30307-5)
Also known as: CDC25C3
Sequence is not available
Length:
Mass (Da):
Isoform 4 (identifier: P30307-3) [UniParc]FASTAAdd to basket
Also known as: CDC25C4

The sequence of this isoform differs from the canonical sequence as follows:
     66-123: GTPKRCLDLSNLSSGEITATQLTTSADLDETGHLDSSGLQEVHLAGMNHDQHLMKCSP → SPGFFRTSGSAFSWD

Show »
Length:430
Mass (Da):48,851
Checksum:iF2DDF9DB1653BCEE
GO
Isoform 5 (identifier: P30307-4) [UniParc]FASTAAdd to basket
Also known as: CDC25C5, Cdc25Cdm

The sequence of this isoform differs from the canonical sequence as follows:
     66-123: GTPKRCLDLSNLSSGEITATQLTTSADLDETGHLDSSGLQEVHLAGMNHDQHLMKCSP → SPGFFRTSGSAFSWD
     124-153: Missing.

Show »
Length:400
Mass (Da):45,608
Checksum:i212EA5FD75672289
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
D6RJC2D6RJC2_HUMAN
M-phase inducer phosphatase 3
CDC25C
249Annotation score:
H0Y999H0Y999_HUMAN
M-phase inducer phosphatase 3
CDC25C
258Annotation score:
D6RD20D6RD20_HUMAN
M-phase inducer phosphatase 3
CDC25C
170Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02792214S → N. Corresponds to variant dbSNP:rs11567959Ensembl.1
Natural variantiVAR_02792370R → C3 PublicationsCorresponds to variant dbSNP:rs3734166Ensembl.1
Natural variantiVAR_02792478S → N. Corresponds to variant dbSNP:rs11567962Ensembl.1
Natural variantiVAR_020146297G → R. Corresponds to variant dbSNP:rs11567997Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00086366 – 123GTPKR…MKCSP → SPGFFRTSGSAFSWD in isoform 4 and isoform 5. 2 PublicationsAdd BLAST58
Alternative sequenceiVSP_000864124 – 153Missing in isoform 2 and isoform 5. 2 PublicationsAdd BLAST30

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34065 mRNA Translation: AAA35666.1
AJ304504 mRNA Translation: CAC19192.1
AY497474 Genomic DNA Translation: AAR32098.1
CH471062 Genomic DNA Translation: EAW62145.1
CH471062 Genomic DNA Translation: EAW62149.1
BC019089 mRNA Translation: AAH19089.1
AF277723 mRNA Translation: AAG41885.1
AF277725 mRNA Translation: AAG41887.1
AF277726 mRNA Translation: AAG41888.1
AF312681 mRNA Translation: AAL26835.1
CCDSiCCDS4202.1 [P30307-1]
CCDS4203.1 [P30307-4]
PIRiI59168 A38874
RefSeqiNP_001274511.1, NM_001287582.1 [P30307-1]
NP_001305027.1, NM_001318098.1
NP_001781.2, NM_001790.4 [P30307-1]
NP_073720.1, NM_022809.3 [P30307-4]
XP_011542064.1, XM_011543762.1 [P30307-4]
UniGeneiHs.656

Genome annotation databases

EnsembliENST00000323760; ENSP00000321656; ENSG00000158402 [P30307-1]
ENST00000348983; ENSP00000345205; ENSG00000158402 [P30307-4]
ENST00000415130; ENSP00000392631; ENSG00000158402 [P30307-4]
ENST00000513970; ENSP00000424795; ENSG00000158402 [P30307-1]
ENST00000514555; ENSP00000425470; ENSG00000158402 [P30307-2]
GeneIDi995
KEGGihsa:995
UCSCiuc003lcp.3 human [P30307-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M34065 mRNA Translation: AAA35666.1
AJ304504 mRNA Translation: CAC19192.1
AY497474 Genomic DNA Translation: AAR32098.1
CH471062 Genomic DNA Translation: EAW62145.1
CH471062 Genomic DNA Translation: EAW62149.1
BC019089 mRNA Translation: AAH19089.1
AF277723 mRNA Translation: AAG41885.1
AF277725 mRNA Translation: AAG41887.1
AF277726 mRNA Translation: AAG41888.1
AF312681 mRNA Translation: AAL26835.1
CCDSiCCDS4202.1 [P30307-1]
CCDS4203.1 [P30307-4]
PIRiI59168 A38874
RefSeqiNP_001274511.1, NM_001287582.1 [P30307-1]
NP_001305027.1, NM_001318098.1
NP_001781.2, NM_001790.4 [P30307-1]
NP_073720.1, NM_022809.3 [P30307-4]
XP_011542064.1, XM_011543762.1 [P30307-4]
UniGeneiHs.656

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2OJXX-ray2.85E126-134[»]
3BZIX-ray2.10E126-134[»]
3OP3X-ray2.63A270-462[»]
5M35X-ray2.38C/D207-244[»]
5M36X-ray2.45C/D207-244[»]
5M37X-ray2.35C/D207-226[»]
ProteinModelPortaliP30307
SMRiP30307
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107430, 103 interactors
DIPiDIP-24183N
IntActiP30307, 18 interactors
MINTiP30307
STRINGi9606.ENSP00000321656

Chemistry databases

BindingDBiP30307
ChEMBLiCHEMBL2378

PTM databases

DEPODiP30307
iPTMnetiP30307
PhosphoSitePlusiP30307

Polymorphism and mutation databases

BioMutaiCDC25C
DMDMi116242631

Proteomic databases

EPDiP30307
PaxDbiP30307
PeptideAtlasiP30307
PRIDEiP30307
ProteomicsDBi54658
54659 [P30307-2]
54660 [P30307-3]
54661 [P30307-4]

Protocols and materials databases

DNASUi995
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000323760; ENSP00000321656; ENSG00000158402 [P30307-1]
ENST00000348983; ENSP00000345205; ENSG00000158402 [P30307-4]
ENST00000415130; ENSP00000392631; ENSG00000158402 [P30307-4]
ENST00000513970; ENSP00000424795; ENSG00000158402 [P30307-1]
ENST00000514555; ENSP00000425470; ENSG00000158402 [P30307-2]
GeneIDi995
KEGGihsa:995
UCSCiuc003lcp.3 human [P30307-1]

Organism-specific databases

CTDi995
DisGeNETi995
EuPathDBiHostDB:ENSG00000158402.18
GeneCardsiCDC25C
HGNCiHGNC:1727 CDC25C
HPAiCAB003800
HPA066991
MIMi157680 gene
neXtProtiNX_P30307
OpenTargetsiENSG00000158402
PharmGKBiPA100
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3772 Eukaryota
COG5105 LUCA
GeneTreeiENSGT00390000018747
HOVERGENiHBG052501
InParanoidiP30307
KOiK05867
OMAiSKAWEGE
OrthoDBiEOG091G0H0D
PhylomeDBiP30307
TreeFamiTF101056

Enzyme and pathway databases

BRENDAi3.1.3.48 2681
ReactomeiR-HSA-156711 Polo-like kinase mediated events
R-HSA-176187 Activation of ATR in response to replication stress
R-HSA-5625740 RHO GTPases activate PKNs
R-HSA-6804114 TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest
R-HSA-6804115 TP53 regulates transcription of additional cell cycle genes whose exact role in the p53 pathway remain uncertain
R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
R-HSA-8862803 Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
SIGNORiP30307

Miscellaneous databases

ChiTaRSiCDC25C human
EvolutionaryTraceiP30307
GeneWikiiCDC25C
GenomeRNAii995
PROiPR:P30307
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000158402 Expressed in 92 organ(s), highest expression level in testis
CleanExiHS_CDC25C
ExpressionAtlasiP30307 baseline and differential
GenevisibleiP30307 HS

Family and domain databases

CDDicd01530 Cdc25, 1 hit
Gene3Di3.40.250.10, 1 hit
InterProiView protein in InterPro
IPR000751 MPI_Phosphatase
IPR001763 Rhodanese-like_dom
IPR036873 Rhodanese-like_dom_sf
PfamiView protein in Pfam
PF06617 M-inducer_phosp, 1 hit
PF00581 Rhodanese, 1 hit
PRINTSiPR00716 MPIPHPHTASE
SMARTiView protein in SMART
SM00450 RHOD, 1 hit
SUPFAMiSSF52821 SSF52821, 1 hit
PROSITEiView protein in PROSITE
PS50206 RHODANESE_3, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMPIP3_HUMAN
AccessioniPrimary (citable) accession number: P30307
Secondary accession number(s): D3DQB8
, Q96PL3, Q9H168, Q9H2E8, Q9H2E9, Q9H2F1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: October 17, 2006
Last modified: November 7, 2018
This is version 191 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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