Reviewed, UniProtKB/Swiss-Prot P30307 (MPIP3_HUMAN)

Names and origin

Protein names

Recommended name:
    M-phase inducer phosphatase 3
    EC=3.1.3.48
Alternative name(s):
    Dual specificity phosphatase Cdc25C

Gene names

Name:

CDC25C

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	473 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Functions as a dosage-dependent inducer in mitotic control. It is a tyrosine protein phosphatase required for progression of the cell cycle. It directly dephosphorylates CDC2 and activate its kinase activity.
Catalytic activity	Protein tyrosine phosphate + H(2)O = protein tyrosine + phosphate.
Subunit structure	Interacts with HIV-1 Vpr, thereby inactivating CDC25C phosphatase activity.
Subcellular location	Nucleus.
Developmental stage	Expressed predominantly in G2 phase.
Post-translational modification	Phosphorylated by CHK1 on Ser-216. This phosphorylation creates a binding site for 14-3-3 protein and inhibits the phosphatase.
Sequence similarities	Belongs to the MPI phosphatase family. Contains 1 rhodanese domain.

Ontologies

Keywords
Biological process	Cell cycle Cell division Host-virus interaction Mitosis
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Hydrolase Protein phosphatase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA replication Inferred from Experiment. Source: Reactome cell proliferation Ref.5 Traceable author statement. Source: UniProtKB regulation of cyclin-dependent protein kinase activity Ref.5 Traceable author statement. Source: UniProtKB regulation of mitosis Traceable author statement. Source: ProtInc traversing start control point of mitotic cell cycle Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	protein binding Inferred from physical interaction. Source: IntAct protein tyrosine phosphatase activity Ref.2 Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDC2	P06493	1	EBI-974439,EBI-444308
CHEK1	O14757	1	EBI-974439,EBI-974488
LZTS1	Q9Y250	1	EBI-974439,EBI-1216080
PPP2R5D	Q14738	1	EBI-974439,EBI-396563

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P30307-1)

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.

Isoform 2 (identifier: P30307-2)

Also known as: CDC25C2;

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

Isoform 3 (identifier: P30307-5)

Also known as: CDC25C3;

The sequence of this isoform is not available.

Isoform 4 (identifier: P30307-3)

Also known as: CDC25C4;

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

Isoform 5 (identifier: P30307-4)

Also known as: CDC25C5; Cdc25Cdm;

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

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 473

473

M-phase inducer phosphatase 3

Regions

Domain

321 – 428

108

Rhodanese

Region

334 – 379

46

HIV-1 Vpr binding site

Sites

Active site

377

1

By similarity

Amino acid modifications

Modified residue

168

1

Phosphoserine

Modified residue

216

1

Phosphoserine; by CHK1, CHK2 and BRSK1

Natural variations

Alternative sequence

66 – 123

58

GTPKR…MKCSP → SPGFFRTSGSAFSWD in isoform 4 and isoform 5.

Alternative sequence

124 – 153

30

Missing in isoform 2 and isoform 5.

Natural variant

14

1

S → N: dbSNP rs11567959.

Natural variant

70

1

R → C: dbSNP rs3734166.

Natural variant

78

1

S → N: dbSNP rs11567962.

Natural variant

297

1

G → R: dbSNP rs11567997.

Experimental info

Mutagenesis

352

1

E → K: Partial loss of HIV-1 Vpr binding

Mutagenesis

359

1

K → E: No effect on HIV-1 Vpr binding

Secondary structure

1

.

.

.

473

Helix Strand Turn

Details...

Beta strand

127 – 129

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (CDC25C1) [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 0658A1F1B9B8996A	FASTA	473	53,365
	10 20 30 40 50 60 MSTELFSSTR EEGSSGSGPS FRSNQRKMLN LLLERDTSFT VCPDVPRTPV GKFLGDSANL 70 80 90 100 110 120 SILSGGTPKR CLDLSNLSSG EITATQLTTS ADLDETGHLD SSGLQEVHLA GMNHDQHLMK 130 140 150 160 170 180 CSPAQLLCST PNGLDRGHRK RDAMCSSSAN KENDNGNLVD SEMKYLGSPI TTVPKLDKNP 190 200 210 220 230 240 NLGEDQAEEI SDELMEFSLK DQEAKVSRSG LYRSPSMPEN LNRPRLKQVE KFKDNTIPDK 250 260 270 280 290 300 VKKKYFSGQG KLRKGLCLKK TVSLCDITIT QMLEEDSNQG HLIGDFSKVC ALPTVSGKHQ 310 320 330 340 350 360 DLKYVNPETV AALLSGKFQG LIEKFYVIDC RYPYEYLGGH IQGALNLYSQ EELFNFFLKK 370 380 390 400 410 420 PIVPLDTQKR IIIVFHCEFS SERGPRMCRC LREEDRSLNQ YPALYYPELY ILKGGYRDFF 430 440 450 460 470 PEYMELCEPQ SYCPMHHQDH KTELLRCRSQ SKVQEGERQL REQIALLVKD MSP
	Isoform 2 (CDC25C2) [UniParc]. Checksum: 11480DF49B3F04DD		443	50,122
	10 20 30 40 50 60 MSTELFSSTR EEGSSGSGPS FRSNQRKMLN LLLERDTSFT VCPDVPRTPV GKFLGDSANL 70 80 90 100 110 120 SILSGGTPKR CLDLSNLSSG EITATQLTTS ADLDETGHLD SSGLQEVHLA GMNHDQHLMK 130 140 150 160 170 180 CSPDNGNLVD SEMKYLGSPI TTVPKLDKNP NLGEDQAEEI SDELMEFSLK DQEAKVSRSG 190 200 210 220 230 240 LYRSPSMPEN LNRPRLKQVE KFKDNTIPDK VKKKYFSGQG KLRKGLCLKK TVSLCDITIT 250 260 270 280 290 300 QMLEEDSNQG HLIGDFSKVC ALPTVSGKHQ DLKYVNPETV AALLSGKFQG LIEKFYVIDC 310 320 330 340 350 360 RYPYEYLGGH IQGALNLYSQ EELFNFFLKK PIVPLDTQKR IIIVFHCEFS SERGPRMCRC 370 380 390 400 410 420 LREEDRSLNQ YPALYYPELY ILKGGYRDFF PEYMELCEPQ SYCPMHHQDH KTELLRCRSQ 430 440 SKVQEGERQL REQIALLVKD MSP
	Isoform 3 (CDC25C3) (Sequence not available).		–	–
	Isoform 4 (CDC25C4) [UniParc]. Checksum: F2DDF9DB1653BCEE		430	48,851
	10 20 30 40 50 60 MSTELFSSTR EEGSSGSGPS FRSNQRKMLN LLLERDTSFT VCPDVPRTPV GKFLGDSANL 70 80 90 100 110 120 SILSGSPGFF RTSGSAFSWD AQLLCSTPNG LDRGHRKRDA MCSSSANKEN DNGNLVDSEM 130 140 150 160 170 180 KYLGSPITTV PKLDKNPNLG EDQAEEISDE LMEFSLKDQE AKVSRSGLYR SPSMPENLNR 190 200 210 220 230 240 PRLKQVEKFK DNTIPDKVKK KYFSGQGKLR KGLCLKKTVS LCDITITQML EEDSNQGHLI 250 260 270 280 290 300 GDFSKVCALP TVSGKHQDLK YVNPETVAAL LSGKFQGLIE KFYVIDCRYP YEYLGGHIQG 310 320 330 340 350 360 ALNLYSQEEL FNFFLKKPIV PLDTQKRIII VFHCEFSSER GPRMCRCLRE EDRSLNQYPA 370 380 390 400 410 420 LYYPELYILK GGYRDFFPEY MELCEPQSYC PMHHQDHKTE LLRCRSQSKV QEGERQLREQ 430 IALLVKDMSP
	Isoform 5 (CDC25C5) (Cdc25Cdm) [UniParc]. Checksum: 212EA5FD75672289		400	45,608
	10 20 30 40 50 60 MSTELFSSTR EEGSSGSGPS FRSNQRKMLN LLLERDTSFT VCPDVPRTPV GKFLGDSANL 70 80 90 100 110 120 SILSGSPGFF RTSGSAFSWD DNGNLVDSEM KYLGSPITTV PKLDKNPNLG EDQAEEISDE 130 140 150 160 170 180 LMEFSLKDQE AKVSRSGLYR SPSMPENLNR PRLKQVEKFK DNTIPDKVKK KYFSGQGKLR 190 200 210 220 230 240 KGLCLKKTVS LCDITITQML EEDSNQGHLI GDFSKVCALP TVSGKHQDLK YVNPETVAAL 250 260 270 280 290 300 LSGKFQGLIE KFYVIDCRYP YEYLGGHIQG ALNLYSQEEL FNFFLKKPIV PLDTQKRIII 310 320 330 340 350 360 VFHCEFSSER GPRMCRCLRE EDRSLNQYPA LYYPELYILK GGYRDFFPEY MELCEPQSYC 370 380 390 400 PMHHQDHKTE LLRCRSQSKV QEGERQLREQ IALLVKDMSP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human homolog of fission yeast cdc25 mitotic inducer is predominantly expressed in G2." Sadhu K., Reed B.I., Richardson H., Russell P. Proc. Natl. Acad. Sci. U.S.A. 87:5139-5143(1990) [PubMed: 2195549] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CYS-70.
[2]	"An additional transcript of the cdc25C gene from A431 cells encodes a functional protein." Bureik M., Rief N., Drescher R., Jungbluth A., Montenarh M., Wagner P. Int. J. Oncol. 17:1251-1258(2000) [PubMed: 11078813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[3]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A. Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT CYS-70. Tissue: Skin.
[5]	"Alternative splicing in the regulatory region of the human phosphatases CDC25A and CDC25C." Wegener S., Hampe W., Herrmann D., Schaller H.C. Eur. J. Cell Biol. 79:810-815(2000) [PubMed: 11139144] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 32-210 (ISOFORMS 2; 4 AND 5), VARIANT CYS-70.
[6]	"Differential expression of cdc25 cell-cycle-activating phosphatases in human colorectal carcinoma." Hernandez S., Bessa X., Bea S., Hernandez L., Nadal A., Mallofre C., Muntane J., Castells A., Fernandez P.L., Cardesa A., Campo E. Lab. Invest. 81:465-473(2001) [PubMed: 11304565] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5). Tissue: Colon carcinoma.
[7]	"Human SAD1 kinase is involved in UV-induced DNA damage checkpoint function." Lu R., Niida H., Nakanishi M. J. Biol. Chem. 279:31164-31170(2004) [PubMed: 15150265] [Abstract] Cited for: PHOSPHORYLATION AT SER-216. Tissue: Testis.
[8]	"The human immunodeficiency virus Vpr protein binds Cdc25C: implications for G2 arrest." Goh W.C., Manel N., Emerman M. Virology 318:337-349(2004) [PubMed: 14972559] [Abstract] Cited for: INTERACTION WITH HIV-1 VPR, MUTAGENESIS OF GLU-352 AND LYS-359.
[9]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-168, MASS SPECTROMETRY. Tissue: Epithelium.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M34065 mRNA. Translation: AAA35666.1.
AJ304504 mRNA. Translation: CAC19192.1.
AY497474 Genomic DNA. Translation: AAR32098.1.
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.

PIR

A38874. I59168.

RefSeq

NP_001781.2.
NP_073720.1.

UniGene

Hs.656

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3BZI	X-ray	2.10	E	126-134	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:24183N.

IntAct

P30307.

PTM databases

PhosphoSite

P30307.

Polymorphism databases

NIEHS-SNPs

Search...

Genome annotation databases

Ensembl

ENSG00000158402. Homo sapiens. [Contig view]

GeneID

995.

KEGG

hsa:995.

Organism-specific databases

H-InvDB

HIX0005209.

HGNC

HGNC:1727. CDC25C.

HPA

CAB003800.

MIM

157680. gene.

PharmGKB

PA100.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P30307.

HOVERGEN

P30307.

Enzyme and pathway databases

Reactome

REACT_152. Cell Cycle, Mitotic.
REACT_1538. Cell Cycle Checkpoints.

Gene expression databases

ArrayExpress

P30307.

CleanEx

HS_CDC25C.

GermOnline

ENSG00000158402. Homo sapiens.

Family and domain databases

InterPro

IPR000751. MPI_Phosphatase.
IPR001763. Rhodanese-like.
[Graphical view]

Gene3D

G3DSA:3.40.250.10. Rhodanese-like. 1 hit.

PANTHER

PTHR10828. MPI_Phosphatase. 1 hit.

Pfam

PF06617. M-inducer_phosp. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view]

PRINTS

PR00716. MPIPHPHTASE.

SMART

SM00450. RHOD. 1 hit.
[Graphical view]

PROSITE

PS50206. RHODANESE_3. 1 hit.
[Graphical view]

BLOCKS

Search...

Other Resources

SOURCE

Search...

ProtoNet

Search...

Entry information

Entry name

MPIP3_HUMAN

Accession

Primary (citable) accession number: P30307
Secondary accession number(s): Q96PL3 , Q9H168, Q9H2E8, Q9H2E9, Q9H2F1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	October 17, 2006
Last modified:	October 14, 2008
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)