MPIP1_MOUSE
ID MPIP1_MOUSE Reviewed; 514 AA.
AC P48964; E9PVD0;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2013, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=M-phase inducer phosphatase 1;
DE EC=3.1.3.48;
DE AltName: Full=Dual specificity phosphatase Cdc25A;
GN Name=Cdc25a; Synonyms=Cdc25m3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=7635051; DOI=10.1242/dev.121.7.2047;
RA Wickramasinghe D., Becker S., Ernst M.K., Resnick J.L., Centanni J.M.,
RA Tessarollo L., Grabel L.B., Donovan P.J.;
RT "Two CDC25 homologues are differentially expressed during mouse
RT development.";
RL Development 121:2047-2056(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
CC -!- FUNCTION: Tyrosine protein phosphatase which functions as a dosage-
CC dependent inducer of mitotic progression. Directly dephosphorylates
CC CDK1 and stimulates its kinase activity. Also dephosphorylates CDK2 in
CC complex with cyclin E, in vitro (By similarity). Phosphorylation by
CC PIM1 leads to an increase in phosphatase activity (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + O-phospho-L-tyrosyl-[protein] = L-tyrosyl-[protein] +
CC phosphate; Xref=Rhea:RHEA:10684, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15377, ChEBI:CHEBI:43474, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620; EC=3.1.3.48;
CC -!- ACTIVITY REGULATION: Stimulated by B-type cyclins. Stimulated by PIM1-
CC mediated phosphorylation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with CCNB1/cyclin B1. Interacts with YWHAE/14-3-3
CC epsilon when phosphorylated. Interacts with CUL1 specifically when CUL1
CC is neddylated and active. Interacts with BTRC/BTRCP1 and FBXW11/BTRCP2.
CC Interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage.
CC Interacts with PIM1. Interacts with CHEK2; mediates CDC25A
CC phosphorylation and degradation in response to infrared-induced DNA
CC damages (By similarity). Interacts with HSP90AB1; prevents heat shock-
CC mediated CDC25A degradation and contributes to cell cycle progression
CC (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:P30304}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed in most developing tissue.
CC High levels in the testis and lower levels in the ovary, particularly
CC in germ cells. Lower levels also in kidney, liver, heart and muscle.
CC {ECO:0000269|PubMed:7635051}.
CC -!- DEVELOPMENTAL STAGE: First detected at the blastocyst stage.
CC {ECO:0000269|PubMed:7635051}.
CC -!- DOMAIN: The phosphodegron motif mediates interaction with specific F-
CC box proteins when phosphorylated. Putative phosphorylation sites at
CC Ser-78 and Ser-81 appear to be essential for this interaction (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated by CHEK1 on Ser-75, Ser-123, Ser-172, Ser-271, Ser-
CC 284 and Thr-497 during checkpoint mediated cell cycle arrest. Also
CC phosphorylated by CHEK2 on Ser-123, Ser-271, and Ser-284 during
CC checkpoint mediated cell cycle arrest. Phosphorylation on Ser-172 and
CC Thr-497 creates binding sites for YWHAE/14-3-3 epsilon which inhibits
CC CDC25A. Phosphorylation on Ser-75, Ser-123, Ser-172, Ser-271 and Ser-
CC 284 may also promote ubiquitin-dependent proteolysis of CDC25A by the
CC SCF complex. Phosphorylation of CDC25A at Ser-75 by CHEK1 primes it for
CC subsequent phosphorylation at Ser-75, Ser-81 and Ser-87 by NEK11.
CC Phosphorylation by NEK11 is required for BTRC-mediated
CC polyubiquitination and degradation. Phosphorylation by PIM1 leads to an
CC increase in phosphatase activity. Phosphorylated by PLK3 following DNA
CC damage, leading to promote its ubiquitination and degradation (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C)
CC ubiquitin ligase complex that contains FZR1/CDH1 during G1 phase
CC leading to its degradation by the proteasome. Ubiquitinated by a SCF
CC complex containing BTRC and FBXW11 during S phase leading to its
CC degradation by the proteasome. Deubiquitination by USP17L2/DUB3 leads
CC to its stabilization (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the MPI phosphatase family. {ECO:0000305}.
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DR EMBL; U27323; AAA85580.1; -; mRNA.
DR EMBL; CT573087; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS23559.1; -.
DR RefSeq; NP_031684.3; NM_007658.3.
DR AlphaFoldDB; P48964; -.
DR SMR; P48964; -.
DR STRING; 10090.ENSMUSP00000091882; -.
DR iPTMnet; P48964; -.
DR PhosphoSitePlus; P48964; -.
DR PaxDb; P48964; -.
DR PRIDE; P48964; -.
DR ProteomicsDB; 295583; -.
DR Antibodypedia; 1619; 1755 antibodies from 47 providers.
DR DNASU; 12530; -.
DR Ensembl; ENSMUST00000094324; ENSMUSP00000091882; ENSMUSG00000032477.
DR GeneID; 12530; -.
DR KEGG; mmu:12530; -.
DR UCSC; uc009rsw.1; mouse.
DR CTD; 993; -.
DR MGI; MGI:103198; Cdc25a.
DR VEuPathDB; HostDB:ENSMUSG00000032477; -.
DR eggNOG; KOG3772; Eukaryota.
DR GeneTree; ENSGT00940000160737; -.
DR HOGENOM; CLU_014464_0_1_1; -.
DR InParanoid; P48964; -.
DR OMA; ECEQPLE; -.
DR OrthoDB; 1423329at2759; -.
DR PhylomeDB; P48964; -.
DR TreeFam; TF101056; -.
DR Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR Reactome; R-MMU-5689880; Ub-specific processing proteases.
DR Reactome; R-MMU-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-MMU-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-MMU-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
DR Reactome; R-MMU-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR BioGRID-ORCS; 12530; 5 hits in 75 CRISPR screens.
DR ChiTaRS; Cdc25a; mouse.
DR PRO; PR:P48964; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; P48964; protein.
DR Bgee; ENSMUSG00000032477; Expressed in otic placode and 232 other tissues.
DR ExpressionAtlas; P48964; baseline and differential.
DR Genevisible; P48964; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0051087; F:chaperone binding; ISO:MGI.
DR GO; GO:0004721; F:phosphoprotein phosphatase activity; ISO:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0034644; P:cellular response to UV; ISO:MGI.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:1904056; P:positive regulation of cholangiocyte proliferation; ISO:MGI.
DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; IBA:GO_Central.
DR GO; GO:0110032; P:positive regulation of G2/MI transition of meiotic cell cycle; IBA:GO_Central.
DR GO; GO:0006470; P:protein dephosphorylation; IEA:InterPro.
DR GO; GO:0009314; P:response to radiation; ISS:UniProtKB.
DR CDD; cd01530; Cdc25; 1.
DR Gene3D; 3.40.250.10; -; 1.
DR InterPro; IPR000751; MPI_Phosphatase.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR Pfam; PF06617; M-inducer_phosp; 1.
DR Pfam; PF00581; Rhodanese; 1.
DR PRINTS; PR00716; MPIPHPHTASE.
DR SMART; SM00450; RHOD; 1.
DR SUPFAM; SSF52821; SSF52821; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
PE 2: Evidence at transcript level;
KW Cell cycle; Cell division; Hydrolase; Mitosis; Phosphoprotein;
KW Protein phosphatase; Reference proteome; Ubl conjugation.
FT CHAIN 1..514
FT /note="M-phase inducer phosphatase 1"
FT /id="PRO_0000198642"
FT DOMAIN 366..472
FT /note="Rhodanese"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT REGION 256..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 73..83
FT /note="Phosphodegron"
FT MOTIF 140..142
FT /note="KEN box"
FT COMPBIAS 265..281
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 421
FT /evidence="ECO:0000250"
FT MOD_RES 75
FT /note="Phosphoserine; by CHEK1"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 78
FT /note="Phosphoserine; by NEK11"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 81
FT /note="Phosphoserine; by NEK11"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 87
FT /note="Phosphoserine; by NEK11"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 123
FT /note="Phosphoserine; by CHEK1 and CHEK2"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 172
FT /note="Phosphoserine; by CHEK1"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 271
FT /note="Phosphoserine; by CHEK1 and CHEK2"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 284
FT /note="Phosphoserine; by CHEK1 and CHEK2"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 497
FT /note="Phosphothreonine; by CHEK1"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 503
FT /note="Phosphoserine; by PLK3"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT MOD_RES 509
FT /note="Phosphoserine; by PLK3"
FT /evidence="ECO:0000250|UniProtKB:P30304"
FT CONFLICT 6
FT /note="E -> S (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 9..10
FT /note="HR -> P (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 23
FT /note="P -> S (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="H -> Q (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 138
FT /note="E -> K (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 147..160
FT /note="FKKPIRPASRHIYE -> PKKQYDLHLSSHLQ (in Ref. 1;
FT AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 165..168
FT /note="PFTH -> LYTQ (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 174..176
FT /note="PAR -> QLG (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="I -> T (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 218
FT /note="M -> L (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 226..229
FT /note="SCMA -> TSMV (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 248
FT /note="C -> LR (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="G -> S (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
FT CONFLICT 503
FT /note="S -> R (in Ref. 1; AAA85580)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 514 AA; 57806 MW; 7D7AD1CB4C39ACF6 CRC64;
MELGPEPPHR RRLFFACSPT PAPQPTGKML FGASAAGGLS PVTNLTVTMD QLEGLGSDCE
KMEVRNNSSL QRMGSSESTD SGFCLDSPGP LDSKENLEIS LTRINSLPQK LLGCSPALKR
SHSDSLDHDT FHLIDQDENK ENEAFEFKKP IRPASRHIYE ESKDPFTHRQ NSAPARMLSS
NESESGNFSP LFIPQSPVKA TLSDEDDGFI DLLDGENMKN DEETPSCMAS LWTAPLVMRR
PANLADRCGL FDSPSPCGSS TRAVLKRADR SHEEPPRGTK RRKSVPSPVK AKADVPEPAQ
LPSQSLSLMS SPKGTIENIL DSDPRDLIGD FSKGYLFNTV SGKHQDLKYI SPEIMASVLN
GKFAGLIKEF VIIDCRYPYE YEGGHIKGAV NLHMEEEVED FLLKNPIVPT DGKRVIVVFH
CEFSSERGPR MCRYVRERDR LGNEYPKLHY PELYVLKGGY KEFFLKCQSH CEPPSYRPMH
HEDFKEDLKK FRTKSRTWAG EKSKREMYSR LKKL
