ID MPIP1_RAT Reviewed; 525 AA. AC P48965; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 27-MAR-2024, entry version 136. DE RecName: Full=M-phase inducer phosphatase 1; DE EC=3.1.3.48 {ECO:0000269|PubMed:10373478}; DE AltName: Full=Dual specificity phosphatase Cdc25A; GN Name=Cdc25a; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=NRK49F; RX PubMed=8156993; DOI=10.1002/j.1460-2075.1994.tb06417.x; RA Jinno S., Suto K., Nagata A., Igarashi M., Kanaoka Y., Nojima H., RA Okayama H.; RT "Cdc25A is a novel phosphatase functioning early in the cell cycle."; RL EMBO J. 13:1549-1556(1994). RN [2] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PHOSPHORYLATION. RX PubMed=10373478; DOI=10.1074/jbc.274.26.18659; RA Mochizuki T., Kitanaka C., Noguchi K., Muramatsu T., Asai A., Kuchino Y.; RT "Physical and functional interactions between Pim-1 kinase and Cdc25A RT phosphatase. Implications for the Pim-1-mediated activation of the c-Myc RT signaling pathway."; RL J. Biol. Chem. 274:18659-18666(1999). CC -!- FUNCTION: Tyrosine protein phosphatase which functions as a dosage- CC dependent inducer of mitotic progression (PubMed:10373478). Directly CC dephosphorylates CDK1 and stimulates its kinase activity CC (PubMed:10373478). Also dephosphorylates CDK2 in complex with cyclin-E, CC in vitro (By similarity). {ECO:0000250|UniProtKB:P30304, CC ECO:0000269|PubMed:10373478}. 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 Evidence={ECO:0000269|PubMed:10373478}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10685; CC Evidence={ECO:0000269|PubMed:10373478}; CC -!- ACTIVITY REGULATION: Stimulated by B-type cyclins (By similarity). CC Stimulated by PIM1-mediated phosphorylation (PubMed:10373478). CC {ECO:0000250|UniProtKB:P30304, ECO:0000269|PubMed:10373478}. 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 CHEK2; mediates CDC25A phosphorylation and degradation CC in response to infrared-induced DNA damages (By similarity). Interacts CC with HSP90AB1; prevents heat shock-mediated CDC25A degradation and CC contributes to cell cycle progression (By similarity). CC {ECO:0000250|UniProtKB:P30304}. CC -!- DOMAIN: The phosphodegron motif mediates interaction with specific F- CC box proteins when phosphorylated. Putative phosphorylation sites at CC Ser-79 and Ser-82 appear to be essential for this interaction (By CC similarity). {ECO:0000250|UniProtKB:P30304}. CC -!- PTM: Phosphorylated by CHEK1 on Ser-76, Ser-124, Ser-178, Ser-283, Ser- CC 296 and Thr-508 during checkpoint mediated cell cycle arrest (By CC similarity). Also phosphorylated by CHEK2 on Ser-124, Ser-283, and Ser- CC 296 during checkpoint mediated cell cycle arrest (By similarity). CC Phosphorylation on Ser-178 and Thr-508 creates binding sites for CC YWHAE/14-3-3 epsilon which inhibits CDC25A (By similarity). CC Phosphorylation on Ser-76, Ser-124, Ser-178, Ser-283 and Ser-296 may CC also promote ubiquitin-dependent proteolysis of CDC25A by the SCF CC complex (By similarity). Phosphorylation of CDC25A at Ser-76 by CHEK1 CC primes it for subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 CC by NEK11 (By similarity). Phosphorylation by NEK11 is required for CC BTRC-mediated polyubiquitination and degradation (By similarity). CC Phosphorylation by PIM1 leads to an increase in phosphatase activity CC (PubMed:10373478). Phosphorylated by PLK3 following DNA damage, leading CC to promote its ubiquitination and degradation (By similarity). CC {ECO:0000250|UniProtKB:P30304, ECO:0000269|PubMed:10373478}. 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|UniProtKB:P30304}. CC -!- SIMILARITY: Belongs to the MPI phosphatase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; D16236; BAA03761.1; -; mRNA. DR RefSeq; NP_598255.1; NM_133571.1. DR AlphaFoldDB; P48965; -. DR SMR; P48965; -. DR BioGRID; 251110; 2. DR STRING; 10116.ENSRNOP00000028141; -. DR iPTMnet; P48965; -. DR PhosphoSitePlus; P48965; -. DR PaxDb; 10116-ENSRNOP00000028141; -. DR GeneID; 171102; -. DR KEGG; rno:171102; -. DR UCSC; RGD:621498; rat. DR AGR; RGD:621498; -. DR CTD; 993; -. DR RGD; 621498; Cdc25a. DR eggNOG; KOG3772; Eukaryota. DR InParanoid; P48965; -. DR OrthoDB; 12481at2759; -. DR PhylomeDB; P48965; -. DR Reactome; R-RNO-176187; Activation of ATR in response to replication stress. DR Reactome; R-RNO-5689880; Ub-specific processing proteases. DR Reactome; R-RNO-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-RNO-69273; Cyclin A/B1/B2 associated events during G2/M transition. DR Reactome; R-RNO-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A. DR Reactome; R-RNO-69656; Cyclin A:Cdk2-associated events at S phase entry. DR PRO; PR:P48965; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0004721; F:phosphoprotein phosphatase activity; IDA:RGD. DR GO; GO:0019901; F:protein kinase binding; ISO:RGD. DR GO; GO:0004725; F:protein tyrosine phosphatase activity; IBA:GO_Central. DR GO; GO:0051087; F:protein-folding chaperone binding; ISO:RGD. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0034644; P:cellular response to UV; ISO:RGD. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:RGD. 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; IMP:RGD. DR GO; GO:0010971; P:positive regulation of G2/M transition of mitotic cell cycle; ISS:UniProtKB. DR GO; GO:0110032; P:positive regulation of G2/MI transition of meiotic cell cycle; IBA:GO_Central. DR GO; GO:0009314; P:response to radiation; ISS:UniProtKB. DR CDD; cd01530; Cdc25; 1. DR Gene3D; 3.40.250.10; Rhodanese-like domain; 1. DR InterPro; IPR000751; MPI_Phosphatase. DR InterPro; IPR001763; Rhodanese-like_dom. DR InterPro; IPR036873; Rhodanese-like_dom_sf. DR PANTHER; PTHR10828:SF46; M-PHASE INDUCER PHOSPHATASE 1; 1. DR PANTHER; PTHR10828; M-PHASE INDUCER PHOSPHATASE DUAL SPECIFICITY PHOSPHATASE CDC25; 1. DR Pfam; PF06617; M-inducer_phosp; 1. DR Pfam; PF00581; Rhodanese; 1. DR PRINTS; PR00716; MPIPHPHTASE. DR SMART; SM00450; RHOD; 1. DR SUPFAM; SSF52821; Rhodanese/Cell cycle control phosphatase; 1. DR PROSITE; PS50206; RHODANESE_3; 1. PE 1: Evidence at protein level; KW Cell cycle; Cell division; Hydrolase; Mitosis; Phosphoprotein; KW Protein phosphatase; Reference proteome; Ubl conjugation. FT CHAIN 1..525 FT /note="M-phase inducer phosphatase 1" FT /id="PRO_0000198643" FT DOMAIN 377..483 FT /note="Rhodanese" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173" FT REGION 1..42 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 260..318 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 74..84 FT /note="Phosphodegron" FT MOTIF 141..143 FT /note="KEN box" FT COMPBIAS 262..276 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 277..301 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 432 FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 76 FT /note="Phosphoserine; by CHEK1" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 79 FT /note="Phosphoserine; by NEK11" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 82 FT /note="Phosphoserine; by NEK11" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 88 FT /note="Phosphoserine; by NEK11" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 124 FT /note="Phosphoserine; by CHEK1 and CHEK2" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 178 FT /note="Phosphoserine; by CHEK1" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 283 FT /note="Phosphoserine; by CHEK1 and CHEK2" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 296 FT /note="Phosphoserine; by CHEK1 and CHEK2" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 508 FT /note="Phosphothreonine; by CHEK1" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 514 FT /note="Phosphoserine; by PLK3" FT /evidence="ECO:0000250|UniProtKB:P30304" FT MOD_RES 520 FT /note="Phosphoserine; by PLK3" FT /evidence="ECO:0000250|UniProtKB:P30304" SQ SEQUENCE 525 AA; 59218 MW; A60EC0AF46D63A9C CRC64; MELGPEPPHR RRLLFTCSPT PAPQPTGKVQ FGASRAGGLS PVTNLTVTMD QLEGLGSDYE KPMDVRNSSS LQRMGSSEST DSGFCLDSPG PLDSKENLEI SLRRINCLPQ KLLGCSPALK RSHSDSLDHD IFQLIDQDEN KENEAFEFKK PIRPASRGCL NAHVHEESKD PFTHRQNSAP ARMLSSNESD ISESGNFSPL FTPQSPVKAS LSDEDDGFID LLDGENLKND EETPSCMSSL WTAPLVMRRP TNLADRCGLF DSPSPCSSTS SCSTRAVKRA DRSHEESPRG TKRRKSSEAS PVKADVPEPT QLPHQSLSLT SFPKGTIENI FHSDPRDLIG DFSKGYLFHT VSGKHQDLKY ISPEIMASVL NGKFANLIKE FVIIDCRYPY EYEGGHIKGA VNLHMEEEVE EFLLKKPIVP ADGKRVIVVF HCEFSSERGP RMCRYVRERD RLGNEYPKLH YPELYVLKGG YKEFFLKCQS HCEPPSYRPM HHEDFKEDLK KFRTKSRTWA GEKSKREMYS RLKKL //