MPIP1_RAT
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 03-AUG-2022, entry version 130.
DE RecName: Full=M-phase inducer phosphatase 1;
DE EC=3.1.3.48;
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 INTERACTION WITH PIM1, 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. 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. {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 CHEK2; mediates CDC25A phosphorylation and degradation
CC in response to infrared-induced DNA damages (By similarity). Interacts
CC with PIM1. Interacts with HSP90AB1; prevents heat shock-mediated CDC25A
CC degradation and contributes to cell cycle progression (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:P30304,
CC ECO:0000269|PubMed:10373478}.
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}.
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. Also
CC phosphorylated by CHEK2 on Ser-124, Ser-283, and Ser-296 during
CC checkpoint mediated cell cycle arrest. Phosphorylation on Ser-178 and
CC Thr-508 creates binding sites for YWHAE/14-3-3 epsilon which inhibits
CC CDC25A. Phosphorylation on Ser-76, Ser-124, Ser-178, Ser-283 and Ser-
CC 296 may also promote ubiquitin-dependent proteolysis of CDC25A by the
CC SCF complex. Phosphorylation of CDC25A at Ser-76 by CHEK1 primes it for
CC subsequent phosphorylation at Ser-79, Ser-82 and Ser-88 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; 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; P48965; -.
DR PRIDE; P48965; -.
DR GeneID; 171102; -.
DR KEGG; rno:171102; -.
DR UCSC; RGD:621498; rat.
DR CTD; 993; -.
DR RGD; 621498; Cdc25a.
DR eggNOG; KOG3772; Eukaryota.
DR InParanoid; P48965; -.
DR OrthoDB; 1423329at2759; -.
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; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0051087; F:chaperone binding; 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: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; 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 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"
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
