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A7MBD1

- MPIP1_BOVIN

UniProt

A7MBD1 - MPIP1_BOVIN

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Protein
M-phase inducer phosphatase 1
Gene
CDC25A
Organism
Bos taurus (Bovine)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at transcript leveli

Functioni

Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Directly dephosphorylates CDK1 and stimulates its kinase activity. Also dephosphorylates CDK2 in complex with cyclin E, in vitro By similarity.

Catalytic activityi

Protein tyrosine phosphate + H2O = protein tyrosine + phosphate.

Enzyme regulationi

Stimulated by B-type cyclins By similarity. Stimulated by PIM1-mediated phosphorylation By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei432 – 4321 By similarity

GO - Molecular functioni

  1. protein tyrosine phosphatase activity Source: UniProtKB-EC

GO - Biological processi

  1. cellular response to UV Source: Ensembl
  2. mitotic nuclear division Source: UniProtKB-KW
  3. response to radiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protein phosphatase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Enzyme and pathway databases

ReactomeiREACT_203965. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
REACT_206864. Cyclin A:Cdk2-associated events at S phase entry.
REACT_215433. Cyclin B2 mediated events.
REACT_222889. E2F-enabled inhibition of pre-replication complex formation.
REACT_224007. Cyclin A/B1 associated events during G2/M transition.
REACT_226948. G0 and Early G1.
REACT_227227. p53-Independent DNA Damage Response.
REACT_227740. Activation of ATR in response to replication stress.

Names & Taxonomyi

Protein namesi
Recommended name:
M-phase inducer phosphatase 1 (EC:3.1.3.48)
Alternative name(s):
Dual specificity phosphatase Cdc25A
Gene namesi
Name:CDC25A
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
ProteomesiUP000009136: Chromosome 22

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. nucleus Source: Ensembl
Complete GO annotation...

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 525525M-phase inducer phosphatase 1
PRO_0000365161Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei75 – 751Phosphoserine; by CHEK1 By similarity
Modified residuei78 – 781Phosphoserine; by NEK11 By similarity
Modified residuei81 – 811Phosphoserine; by NEK11 By similarity
Modified residuei87 – 871Phosphoserine; by NEK11 By similarity
Modified residuei123 – 1231Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residuei177 – 1771Phosphoserine; by CHEK1 By similarity
Modified residuei279 – 2791Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residuei293 – 2931Phosphoserine; by CHEK1 and CHEK2 By similarity
Modified residuei508 – 5081Phosphothreonine; by CHEK1 By similarity
Modified residuei514 – 5141Phosphoserine; by PLK3 By similarity
Modified residuei520 – 5201Phosphoserine; by PLK3 By similarity

Post-translational modificationi

Phosphorylated by CHEK1 on Ser-75, Ser-123, Ser-177, Ser-279, Ser-293 and Thr-508 during checkpoint mediated cell cycle arrest. Also phosphorylated by CHEK2 on Ser-123, Ser-279, and Ser-293 during checkpoint mediated cell cycle arrest. Phosphorylation on Ser-177 and Thr-508 creates binding sites for YWHAE/14-3-3 epsilon which inhibits CDC25A. Phosphorylation on Ser-75, Ser-123, Ser-177, Ser-279 and Ser-293 may also promote ubiquitin-dependent proteolysis of CDC25A by the SCF complex. Phosphorylation of CDC25A at Ser-75 by CHEK1 primes it for subsequent phosphorylation at Ser-78, Ser-81 and Ser-87 by NEK11. Phosphorylation by NEK11 is required for BTRC-mediated polyubiquitination and degradation. Phosphorylation by PIM1 leads to an increase in phosphatase activity. Phosphorylated by PLK3 following DNA damage, leading to promote its ubiquitination and degradation By similarity.
Ubiquitinated by the anaphase promoting complex/cyclosome (APC/C) ubiquitin ligase complex that contains FZR1/CDH1 during G1 phase leading to its degradation by the proteasome. Ubiquitinated by a SCF complex containing BTRC and FBXW11 during S phase leading to its degradation by the proteasome. Deubiquitination by USP17L2/DUB3 leads to its stabilization By similarity.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiA7MBD1.

Interactioni

Subunit structurei

Interacts with CCNB1/cyclin B1. Interacts with YWHAE/14-3-3 epsilon when phosphorylated. Interacts with CUL1 specifically when CUL1 is neddylated and active. Interacts with BTRC/BTRCP1 and FBXW11/BTRCP2. Interactions with CUL1, BTRC and FBXW11 are enhanced upon DNA damage By similarity. Interacts with PIM1 By similarity.

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000012611.

Structurei

3D structure databases

ProteinModelPortaliA7MBD1.
SMRiA7MBD1. Positions 338-497.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini377 – 483107Rhodanese
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi73 – 8311Phosphodegron
Add
BLAST
Motifi140 – 1423KEN box

Domaini

The phosphodegron motif mediates interaction with specific F-box proteins when phosphorylated. Putative phosphorylation sites at Ser-78 and Ser-81 appear to be essential for this interaction By similarity.

Sequence similaritiesi

Belongs to the MPI phosphatase family.
Contains 1 rhodanese domain.

Phylogenomic databases

eggNOGiCOG5105.
GeneTreeiENSGT00390000018747.
HOGENOMiHOG000082672.
HOVERGENiHBG052501.
InParanoidiA7MBD1.
KOiK06645.
OMAiNLTVTMD.
OrthoDBiEOG7288R1.
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]

Sequencei

Sequence statusi: Complete.

A7MBD1-1 [UniParc]FASTAAdd to Basket

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MELGPEPPHR RRLLFACSPP PAPQPVVKAL FGTPAAGGLS PVTNLTVTMD    50
QLQGLGSEYE QPIEVKNSSL QRMGSSESTD SGFCLDSPGP LDSKENLENP 100
MRRINSLPQK LLGCSPALKR SHSDSLDHDV FQLIDQDENK ENQVFEFKKP 150
IRPASRGCLH VHGLEEGKDV FTQRQNSAPA RMLSSNERDG NEPGNSIPFM 200
PQSPVTPTLS DEDDGFMDLL DGENLKNDEE TPSCMASLWT APLVMRRTNN 250
LGNRCKLFDS PSASCSSTIR SMLKRPDRSL EESPGGSRKR RKSVAGASPE 300
EAASPEKPQE ILHHQSLSLA SSPKGTIENI LDNDPRDLIG DFSKGYLFHT 350
VAGKHQDLKY ISPEIITSVL NGKFANLIKE FVIIDCRYPY EYEGGHIKGA 400
VNLHMEEEVE EFLLKKPIVP TDGKRVIVVF HCEFSSERGP RMCRYVRERD 450
RLGNEYPKLH YPELYVLKGG YKEFFLKCQS HCEPPSYRPM HHEDFKEDLK 500
KFRTKSRTWA GEKSKREMYS RLKKL 525
Length:525
Mass (Da):59,142
Last modified:October 2, 2007 - v1
Checksum:i3608ED70EE8293BB
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC151493 mRNA. Translation: AAI51494.1.
RefSeqiNP_001094570.1. NM_001101100.2.
UniGeneiBt.62587.

Genome annotation databases

EnsembliENSBTAT00000012611; ENSBTAP00000012611; ENSBTAG00000009586.
GeneIDi520188.
KEGGibta:520188.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
BC151493 mRNA. Translation: AAI51494.1 .
RefSeqi NP_001094570.1. NM_001101100.2.
UniGenei Bt.62587.

3D structure databases

ProteinModelPortali A7MBD1.
SMRi A7MBD1. Positions 338-497.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9913.ENSBTAP00000012611.

Proteomic databases

PRIDEi A7MBD1.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSBTAT00000012611 ; ENSBTAP00000012611 ; ENSBTAG00000009586 .
GeneIDi 520188.
KEGGi bta:520188.

Organism-specific databases

CTDi 993.

Phylogenomic databases

eggNOGi COG5105.
GeneTreei ENSGT00390000018747.
HOGENOMi HOG000082672.
HOVERGENi HBG052501.
InParanoidi A7MBD1.
KOi K06645.
OMAi NLTVTMD.
OrthoDBi EOG7288R1.
TreeFami TF101056.

Enzyme and pathway databases

Reactomei REACT_203965. Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
REACT_206864. Cyclin A:Cdk2-associated events at S phase entry.
REACT_215433. Cyclin B2 mediated events.
REACT_222889. E2F-enabled inhibition of pre-replication complex formation.
REACT_224007. Cyclin A/B1 associated events during G2/M transition.
REACT_226948. G0 and Early G1.
REACT_227227. p53-Independent DNA Damage Response.
REACT_227740. Activation of ATR in response to replication stress.

Miscellaneous databases

NextBioi 20873047.

Family and domain databases

Gene3Di 3.40.250.10. 1 hit.
InterProi IPR000751. MPI_Phosphatase.
IPR001763. Rhodanese-like_dom.
[Graphical view ]
Pfami PF06617. M-inducer_phosp. 1 hit.
PF00581. Rhodanese. 1 hit.
[Graphical view ]
PRINTSi PR00716. MPIPHPHTASE.
SMARTi SM00450. RHOD. 1 hit.
[Graphical view ]
SUPFAMi SSF52821. SSF52821. 1 hit.
PROSITEi PS50206. RHODANESE_3. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. NIH - Mammalian Gene Collection (MGC) project
    Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: Hereford.
    Tissue: Fetal liver.

Entry informationi

Entry nameiMPIP1_BOVIN
AccessioniPrimary (citable) accession number: A7MBD1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 3, 2009
Last sequence update: October 2, 2007
Last modified: September 3, 2014
This is version 53 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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