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Protein

M-phase inducer phosphatase 3

Gene

CDC25C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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: UniProtKB
  • WW domain binding Source: BHF-UCL

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cell proliferation Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
  • DNA replication Source: Reactome
  • G2/M transition of mitotic cell cycle Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • regulation of cell cycle Source: Reactome
  • regulation of cyclin-dependent protein serine/threonine kinase activity Source: UniProtKB
  • regulation of mitotic nuclear division Source: ProtInc
  • spermatogenesis Source: Ensembl
  • viral process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Cell cycle, Cell division, Host-virus interaction, Mitosis

Enzyme and pathway databases

BioCyciZFISH:HS08286-MONOMER.
BRENDAi3.1.3.48. 2681.
ReactomeiR-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-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 associated events during G2/M transition.
R-HSA-75035. Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
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

HGNCiHGNC:1727. CDC25C.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: Ensembl
Complete GO annotation...

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 residuei61PhosphoserineCombined sources1
Isoform 5 (identifier: P30307-4)
Modified residuei61PhosphoserineCombined sources1

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

PaxDbiP30307.
PeptideAtlasiP30307.
PRIDEiP30307.

PTM databases

DEPODiP30307.
iPTMnetiP30307.
PhosphoSitePlusiP30307.

Expressioni

Developmental stagei

Expressed predominantly in G2 phase.

Gene expression databases

BgeeiENSG00000158402.
CleanExiHS_CDC25C.
ExpressionAtlasiP30307. baseline and differential.
GenevisibleiP30307. HS.

Organism-specific databases

HPAiCAB003800.

Interactioni

Subunit structurei

Interacts with HIV-1 Vpr, thereby inactivating CDC25C phosphatase activity. Interacts with MAPK14 and 14-3-3 proteins. When phosphorylated on Ser-129 and/or Thr-130, interacts with PLK1.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CDK1P064932EBI-974439,EBI-444308
CHEK1O147572EBI-974439,EBI-974488
LZTS1Q9Y2502EBI-974439,EBI-1216080

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB
  • WW domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107430. 36 interactors.
DIPiDIP-24183N.
IntActiP30307. 9 interactors.
MINTiMINT-86355.
STRINGi9606.ENSP00000321656.

Chemistry databases

BindingDBiP30307.

Structurei

Secondary structure

1473
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi127 – 129Combined sources3
Beta strandi286 – 289Combined sources4
Beta strandi300 – 305Combined sources6
Helixi307 – 314Combined sources8
Turni315 – 321Combined sources7
Beta strandi322 – 329Combined sources8
Helixi333 – 337Combined sources5
Beta strandi339 – 341Combined sources3
Helixi350 – 357Combined sources8
Beta strandi369 – 376Combined sources8
Helixi384 – 397Combined sources14
Beta strandi409 – 412Combined sources4
Helixi415 – 419Combined sources5
Turni420 – 422Combined sources3
Helixi424 – 426Combined sources3
Beta strandi427 – 430Combined sources4
Beta strandi438 – 440Combined sources3

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[»]
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
Contains 1 rhodanese domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3772. Eukaryota.
COG5105. LUCA.
GeneTreeiENSGT00390000018747.
HOVERGENiHBG052501.
InParanoidiP30307.
KOiK05867.
OMAiTVSLCDI.
OrthoDBiEOG091G0H0D.
PhylomeDBiP30307.
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 (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

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02792214S → N.Corresponds to variant rs11567959dbSNPEnsembl.1
Natural variantiVAR_02792370R → C.3 PublicationsCorresponds to variant rs3734166dbSNPEnsembl.1
Natural variantiVAR_02792478S → N.Corresponds to variant rs11567962dbSNPEnsembl.1
Natural variantiVAR_020146297G → R.Corresponds to variant rs11567997dbSNPEnsembl.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

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[»]
ProteinModelPortaliP30307.
SMRiP30307.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107430. 36 interactors.
DIPiDIP-24183N.
IntActiP30307. 9 interactors.
MINTiMINT-86355.
STRINGi9606.ENSP00000321656.

Chemistry databases

BindingDBiP30307.
ChEMBLiCHEMBL2378.

PTM databases

DEPODiP30307.
iPTMnetiP30307.
PhosphoSitePlusiP30307.

Polymorphism and mutation databases

BioMutaiCDC25C.
DMDMi116242631.

Proteomic databases

PaxDbiP30307.
PeptideAtlasiP30307.
PRIDEiP30307.

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.
GeneCardsiCDC25C.
HGNCiHGNC:1727. CDC25C.
HPAiCAB003800.
MIMi157680. gene.
neXtProtiNX_P30307.
OpenTargetsiENSG00000158402.
PharmGKBiPA100.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3772. Eukaryota.
COG5105. LUCA.
GeneTreeiENSGT00390000018747.
HOVERGENiHBG052501.
InParanoidiP30307.
KOiK05867.
OMAiTVSLCDI.
OrthoDBiEOG091G0H0D.
PhylomeDBiP30307.
TreeFamiTF101056.

Enzyme and pathway databases

BioCyciZFISH:HS08286-MONOMER.
BRENDAi3.1.3.48. 2681.
ReactomeiR-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-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 associated events during G2/M transition.
R-HSA-75035. Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
SIGNORiP30307.

Miscellaneous databases

ChiTaRSiCDC25C. human.
EvolutionaryTraceiP30307.
GeneWikiiCDC25C.
GenomeRNAii995.
PROiP30307.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000158402.
CleanExiHS_CDC25C.
ExpressionAtlasiP30307. baseline and differential.
GenevisibleiP30307. 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 nameiMPIP3_HUMAN
AccessioniPrimary (citable) accession number: P30307
Secondary accession number(s): D3DQB8
, Q96PL3, Q9H168, Q9H2E8, Q9H2E9, Q9H2F1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: October 17, 2006
Last modified: November 2, 2016
This is version 175 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 5
    Human chromosome 5: 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.