Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P56950

- MDM2_CANFA

UniProt

P56950 - MDM2_CANFA

Protein

E3 ubiquitin-protein ligase Mdm2

Gene

MDM2

Organism
Canis familiaris (Dog) (Canis lupus familiaris)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 117 (01 Oct 2014)
      Sequence version 1 (30 May 2000)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    E3 ubiquitin-protein ligase that mediates ubiquitination of p53/TP53, leading to its degradation by the proteasome. Inhibits p53/TP53- and p73/TP73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Also acts as a ubiquitin ligase E3 toward itself and ARRB1. Permits the nuclear export of p53/TP53. Promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma RB1 protein. Inhibits DAXX-mediated apoptosis by inducing its ubiquitination and degradation. Component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in stabilizing p53/TP53. Also component of the TRIM28/KAP1-ERBB4-MDM2 complex which links growth factor and DNA damage response pathways. Mediates ubiquitination and subsequent proteasome degradation of DYRK2 in nucleus. Ubiquitinates IGF1R and SNAI1 and promotes them to proteasomal degradation By similarity.By similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri299 – 32830RanBP2-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri434 – 47542RING-typePROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. ligase activity Source: UniProtKB-KW
    2. zinc ion binding Source: InterPro

    GO - Biological processi

    1. negative regulation of apoptotic process Source: InterPro
    2. negative regulation of cell cycle arrest Source: InterPro
    3. negative regulation of transcription from RNA polymerase II promoter Source: InterPro
    4. protein ubiquitination Source: UniProtKB

    Keywords - Molecular functioni

    Ligase

    Keywords - Biological processi

    Ubl conjugation pathway

    Keywords - Ligandi

    Metal-binding, Zinc

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    E3 ubiquitin-protein ligase Mdm2 (EC:6.3.2.-)
    Alternative name(s):
    Double minute 2 protein
    Short name:
    Cdm2
    p53-binding protein Mdm2
    Gene namesi
    Name:MDM2
    OrganismiCanis familiaris (Dog) (Canis lupus familiaris)
    Taxonomic identifieri9615 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
    ProteomesiUP000002254: Unplaced

    Subcellular locationi

    Nucleusnucleoplasm By similarity. Cytoplasm By similarity. Nucleusnucleolus By similarity
    Note: Expressed predominantly in the nucleoplasm. Interaction with ARF(P14) results in the localization of both proteins to the nucleolus. The nucleolar localization signals in both ARF(P14) and MDM2 may be necessary to allow efficient nucleolar localization of both proteins. Colocalizes with RASSF1 isoform A in the nucleus By similarity.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB-SubCell
    2. nucleolus Source: UniProtKB
    3. nucleoplasm Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 487487E3 ubiquitin-protein ligase Mdm2PRO_0000157329Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei166 – 1661Phosphoserine; by SGK1By similarity
    Modified residuei240 – 2401PhosphoserineBy similarity
    Modified residuei242 – 2421PhosphoserineBy similarity
    Modified residuei246 – 2461PhosphoserineBy similarity
    Modified residuei260 – 2601PhosphoserineBy similarity
    Modified residuei262 – 2621PhosphoserineBy similarity
    Modified residuei382 – 3821Phosphoserine; by ATMBy similarity
    Modified residuei391 – 3911Phosphoserine; by ATMBy similarity
    Modified residuei403 – 4031Phosphoserine; by ATMBy similarity
    Modified residuei415 – 4151Phosphothreonine; by ATMBy similarity
    Modified residuei425 – 4251Phosphoserine; by ATMBy similarity

    Post-translational modificationi

    Phosphorylation on Ser-166 by SGK1 activates ubiquitination of p53/TP53. Phosphorylated at multiple sites near the RING domain by ATM upon DNA damage; this prevents oligomerization and E3 ligase processivity and impedes constitutive p53/TP53 degradation By similarity.By similarity
    Autoubiquitination leads to proteasomal degradation; resulting in p53/TP53 activation it may be regulated by SFN. Also ubiquitinated by TRIM13. Deubiquitinated by USP2 leads to its accumulation and increases deubiquitination and degradation of p53/TP53. Deubiquitinated by USP7 leading to its stabilization.

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Expressioni

    Tissue specificityi

    Isoform Mdm2-alpha is present in lymphoid and testicular tissues.

    Interactioni

    Subunit structurei

    Binds p53/TP53, TP73/p73, ARF/P14, PML, RBL5 and RP11 and specifically to RNA. Can interact also with RB1, E1A-associated protein EP300 and the E2F1 transcription factor. Forms a ternary complex with p53/TP53 and WWOX. Interacts with CDKN2AIP, MTBP, RFWD3, TBRG1, USP7, PYHIN1, UBXN6, and RBBP6. Isoform Mdm2-F does not interact with p53/TP53. Interacts with ARRB1 and ARRB2. Interacts (isoform 2) with PSMA3. Found in a trimeric complex with MDM2, MDM4 and UPB2. Interacts with USP2 (via N-terminus and C-terminus). Interacts with MDM4. Part of a complex with MDM2, DAXX, RASSF1 and USP7. Part of a complex with DAXX, MDM2 and USP7. Interacts directly with DAXX and USP7. Interacts (via C-terminus) with RASSF1 isoform A (via N-terminus); the interaction is independent of TP53. Interacts with APEX1; the interaction leads to its ubiquitination and degradation. Interacts with RYBP; this inhibits ubiquitination of TP53. Identified in a complex with RYBP and p53/TP53. Also component of the TRIM28/KAP1-MDM2-p53/TP53 complex involved in regulating p53/TP53 stabilization and activity. Binds directly both p53/TP53 and TRIM28. Component of the TRIM28/KAP1-ERBB4-MDM2 complex involved in connecting growth factor responses with DNA damage. Interacts directly with both TRIM28 and ERBB4 in the complex. Interacts with DYRK2. Interacts with IGF1R. Interacts with TRIM13; the interaction ubiquitinates MDM2 leading to its proteasomal degradation. Interacts with SNAI1; this interaction promotes SNAI1 ubiquitination. Interacts with NOTCH1 (via intracellular domain). Interacts with FHIT. Interacts with RFFL. Interacts with MTA1 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliP56950.
    SMRiP56950. Positions 1-118, 290-335, 428-487.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini27 – 10781SWIBAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni150 – 23081Interaction with PYHIN1 and necessary for interaction with RFFLBy similarityAdd
    BLAST
    Regioni170 – 306137Interaction with MTBPBy similarityAdd
    BLAST
    Regioni210 – 30495ARF-bindingAdd
    BLAST
    Regioni223 – 23210Interaction with USP7By similarity
    Regioni242 – 33190Region IIAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi179 – 1857Nuclear localization signalSequence Analysis
    Motifi190 – 20213Nuclear export signalAdd
    BLAST
    Motifi462 – 4698Nucleolar localization signalSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi210 – 2156Poly-Ser
    Compositional biasi243 – 30159Asp/Glu-rich (acidic)Add
    BLAST

    Domaini

    Region I is sufficient for binding p53 and inhibiting its G1 arrest and apoptosis functions. It also binds p73 and E2F1. Region II contains most of a central acidic region required for interaction with ribosomal protein L5 and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc interacts specifically with RNA whether or not zinc is present and mediates the heterooligomerization with MDM4. It is also essential for its ubiquitin ligase E3 activity toward p53 and itself By similarity. Interacts with IGF1R By similarity.By similarity

    Sequence similaritiesi

    Belongs to the MDM2/MDM4 family.Curated
    Contains 1 RanBP2-type zinc finger.PROSITE-ProRule annotation
    Contains 1 RING-type zinc finger.PROSITE-ProRule annotation
    Contains 1 SWIB domain.Curated

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri299 – 32830RanBP2-typePROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri434 – 47542RING-typePROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Zinc-finger

    Phylogenomic databases

    eggNOGiNOG46328.
    HOGENOMiHOG000293341.
    HOVERGENiHBG013472.
    InParanoidiP56950.
    KOiK06643.

    Family and domain databases

    Gene3Di1.10.245.10. 1 hit.
    3.30.40.10. 1 hit.
    InterProiIPR028340. Mdm2.
    IPR015459. MDM2_E3_ligase.
    IPR016495. p53_neg-reg_MDM_2/4.
    IPR003121. SWIB_MDM2_domain.
    IPR001876. Znf_RanBP2.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    [Graphical view]
    PANTHERiPTHR10360:SF11. PTHR10360:SF11. 1 hit.
    PfamiPF02201. SWIB. 1 hit.
    PF00641. zf-RanBP. 1 hit.
    [Graphical view]
    PIRSFiPIRSF500700. MDM2. 1 hit.
    PIRSF006748. p53_MDM_2/4. 1 hit.
    SMARTiSM00184. RING. 1 hit.
    [Graphical view]
    SUPFAMiSSF47592. SSF47592. 2 hits.
    PROSITEiPS01358. ZF_RANBP2_1. 1 hit.
    PS50199. ZF_RANBP2_2. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform Mdm2 (identifier: P56950-1) [UniParc]FASTAAdd to Basket

    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.

    « Hide

    MCNTNMSVST GGAVSTSQIP ASEQETLVRP KPLLLKLLKS VGAQKDTYTM    50
    KEVIFYLGQY IMTKRLYDEK QQHIVYCSND LLGDLFGVPS FSVKEHRKIY 100
    TMIYRNLVVV NQHEPSDSGT SVSENSCHRE GGSDQKDPVQ ELQEEKPSSS 150
    DLISRPSTSS RRRTISETEE HADDLPGERQ RKRHKSDSIS LSFDESLALC 200
    VIREICCERS SSSESTGTPS NPDLDAGVSE HSGDWLDQDS VSDQFSVEFE 250
    VESLDSEDYS LSEEGQELSD EDDEVYRVTV YQAGESDTDS FEEDPEISLA 300
    DYWKCTSCNE MNPPLPPHCN RCWALRENWL PEDKGKIPEK ATPENSTQVE 350
    EGFDVPDCKK AAASDSRESC AEEIDDKITQ ASHSQESEDY SQPSTSNSII 400
    YSSQEDVKEF EREETQDKEE IVESSFPLNA IEPCVICQGR PKNGCIVHGK 450
    TGHLMACFTC AKKLKKRNKP CPVCRQPIQM IVLTYFP 487
    Length:487
    Mass (Da):54,696
    Last modified:May 30, 2000 - v1
    Checksum:i60CDB470A32A8E69
    GO
    Isoform Mdm2-alpha (identifier: P56950-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-61: Missing.

    Show »
    Length:426
    Mass (Da):48,034
    Checksum:i43C0FFFB2004E4BF
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti11 – 111G → D in AAG42840. (PubMed:10597303)Curated
    Sequence conflicti238 – 2392QD → HH in AAG42840. (PubMed:10597303)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6161Missing in isoform Mdm2-alpha. 1 PublicationVSP_003206Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF100705 mRNA. Translation: AAF67833.1.
    AF322416 mRNA. Translation: AAG42840.1.
    RefSeqiNP_001003103.1. NM_001003103.2.
    UniGeneiCfa.702.

    Genome annotation databases

    GeneIDi403693.
    KEGGicfa:403693.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF100705 mRNA. Translation: AAF67833.1 .
    AF322416 mRNA. Translation: AAG42840.1 .
    RefSeqi NP_001003103.1. NM_001003103.2.
    UniGenei Cfa.702.

    3D structure databases

    ProteinModelPortali P56950.
    SMRi P56950. Positions 1-118, 290-335, 428-487.
    ModBasei Search...
    MobiDBi Search...

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 403693.
    KEGGi cfa:403693.

    Organism-specific databases

    CTDi 4193.

    Phylogenomic databases

    eggNOGi NOG46328.
    HOGENOMi HOG000293341.
    HOVERGENi HBG013472.
    InParanoidi P56950.
    KOi K06643.

    Miscellaneous databases

    NextBioi 20817197.

    Family and domain databases

    Gene3Di 1.10.245.10. 1 hit.
    3.30.40.10. 1 hit.
    InterProi IPR028340. Mdm2.
    IPR015459. MDM2_E3_ligase.
    IPR016495. p53_neg-reg_MDM_2/4.
    IPR003121. SWIB_MDM2_domain.
    IPR001876. Znf_RanBP2.
    IPR001841. Znf_RING.
    IPR013083. Znf_RING/FYVE/PHD.
    [Graphical view ]
    PANTHERi PTHR10360:SF11. PTHR10360:SF11. 1 hit.
    Pfami PF02201. SWIB. 1 hit.
    PF00641. zf-RanBP. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF500700. MDM2. 1 hit.
    PIRSF006748. p53_MDM_2/4. 1 hit.
    SMARTi SM00184. RING. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47592. SSF47592. 2 hits.
    PROSITEi PS01358. ZF_RANBP2_1. 1 hit.
    PS50199. ZF_RANBP2_2. 1 hit.
    PS50089. ZF_RING_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Cloning, sequence analysis and expression of the cDNAs encoding the canine and equine homologues of the mouse double minute 2 (mdm2) proto-oncogene."
      Nasir L., Burr P.D., McFarlane S.T., Gault E., Thompson H., Argyle D.J.
      Cancer Lett. 152:9-13(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-484.
    2. "A novel exon within the mdm2 gene modulates translation initiation in vitro and disrupts the p53-binding domain of mdm2 protein."
      Veldhoen N., Metcalfe S., Milner J.
      Oncogene 18:7026-7033(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MDM2 AND MDM2-ALPHA).

    Entry informationi

    Entry nameiMDM2_CANFA
    AccessioniPrimary (citable) accession number: P56950
    Secondary accession number(s): Q95KN5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: May 30, 2000
    Last modified: October 1, 2014
    This is version 117 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