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Protein

Protein Mdm4

Gene

Mdm4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Inhibits p53/TP53- and TP73/p73-mediated cell cycle arrest and apoptosis by binding its transcriptional activation domain. Inhibits degradation of MDM2. Can reverse MDM2-targeted degradation of TP53 while maintaining suppression of TP53 transactivation and apoptotic functions. The short isoform is a more potent inhibitor of TP53 activity than the long isoform.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri299 – 328RanBP2-typePROSITE-ProRule annotationAdd BLAST30
Zinc fingeri436 – 477RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

GO - Biological processi

Keywordsi

LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-2559580 Oxidative Stress Induced Senescence
R-MMU-2559585 Oncogene Induced Senescence
R-MMU-5689880 Ub-specific processing proteases
R-MMU-6804756 Regulation of TP53 Activity through Phosphorylation
R-MMU-6804757 Regulation of TP53 Degradation
R-MMU-6804760 Regulation of TP53 Activity through Methylation
R-MMU-69541 Stabilization of p53

Names & Taxonomyi

Protein namesi
Recommended name:
Protein Mdm4
Alternative name(s):
Double minute 4 protein
Mdm2-like p53-binding protein
Protein Mdmx
p53-binding protein Mdm4
Gene namesi
Name:Mdm4
Synonyms:Mdmx
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:107934 Mdm4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001573371 – 489Protein Mdm4Add BLAST489

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei179PhosphoserineBy similarity1
Modified residuei341Phosphoserine; by CHEK2By similarity1
Modified residuei367Phosphoserine; by CHEK1 and CHEK2By similarity1

Post-translational modificationi

Phosphorylated. Phosphorylation at Ser-367 promotes interaction with YWHAG and subsequent ubiquitination and degradation. Phosphorylation at Ser-341 also induces ubiquitination and degradation but to a lower extent (By similarity).By similarity
Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO35618
PaxDbiO35618
PRIDEiO35618

PTM databases

iPTMnetiO35618
PhosphoSitePlusiO35618

Expressioni

Tissue specificityi

In all tissues tested. The short isoform is expressed in a variety of transformed cell lines.

Gene expression databases

BgeeiENSMUSG00000054387 Expressed in 269 organ(s), highest expression level in primary oocyte
CleanExiMM_MDM4
ExpressionAtlasiO35618 baseline and differential
GenevisibleiO35618 MM

Interactioni

Subunit structurei

Found in a trimeric complex with USP2, MDM2 and MDM4. Interacts with USP2. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53 (By similarity). Interacts with MDM2, TP53 and TP73.By similarity

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201373, 9 interactors
DIPiDIP-24201N
IntActiO35618, 5 interactors
STRINGi10090.ENSMUSP00000070411

Structurei

3D structure databases

ProteinModelPortaliO35618
SMRiO35618
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 106SWIBAdd BLAST81

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni246 – 331Region IIAdd BLAST86
Regioni392 – 489Necessary for interaction with USP2By similarityAdd BLAST98

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi441 – 444Nuclear localization signalSequence analysis4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi233 – 301Asp/Glu-rich (acidic)Add BLAST69

Domaini

Region I is sufficient for binding TP53 and inhibiting its G1 arrest and apoptosis functions. It also binds TP73. Region II contains most of a central acidic region and a putative C4-type zinc finger. The RING finger domain which coordinates two molecules of zinc mediates the heterooligomerization with MDM2.

Sequence similaritiesi

Belongs to the MDM2/MDM4 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri299 – 328RanBP2-typePROSITE-ProRule annotationAdd BLAST30
Zinc fingeri436 – 477RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IE9V Eukaryota
ENOG410XSWN LUCA
GeneTreeiENSGT00530000063539
HOGENOMiHOG000293341
HOVERGENiHBG013472
InParanoidiO35618
KOiK10127

Family and domain databases

Gene3Di1.10.245.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR015458 MDM4
IPR016495 p53_neg-reg_MDM_2/4
IPR036885 SWIB_MDM2_dom_sf
IPR003121 SWIB_MDM2_domain
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR13844:SF20 PTHR13844:SF20, 1 hit
PfamiView protein in Pfam
PF02201 SWIB, 1 hit
PF00641 zf-RanBP, 1 hit
PIRSFiPIRSF500699 MDM4, 1 hit
PIRSF006748 p53_MDM_2/4, 1 hit
SUPFAMiSSF47592 SSF47592, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

Isoform Long (identifier: O35618-1) [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
        10         20         30         40         50
MTSHSTSAQC SASDSACRIS SEQISQVRPK LQLLKILHAA GAQGEVFTMK
60 70 80 90 100
EVMHYLGQYI MVKQLYDQQE QHMVYCGGDL LGDLLGCQSF SVKDPSPLYD
110 120 130 140 150
MLRKNLVTSA SINTDAAQTL ALAQDHTMDF PSQDRLKHGA TEYSNPRKRT
160 170 180 190 200
EEEDTHTLPT SRHKCRDSRA DEDLIEHLSQ DETSRLDLDF EEWDVAGLPW
210 220 230 240 250
WFLGNLRNNC IPKSNGSTDL QTNQDIGTAI VSDTTDDLWF LNETVSEQLG
260 270 280 290 300
VGIKVEAANS EQTSEVGKTS NKKTVEVGKD DDLEDSRSLS DDTDVELTSE
310 320 330 340 350
DEWQCTECKK FNSPSKRYCF RCWALRKDWY SDCSKLTHSL STSNITAIPE
360 370 380 390 400
KKDNEGIDVP DCRRTISAPV VRPKDGYLKE EKPRFDPCNS VGFLDLAHSS
410 420 430 440 450
ESQEIISSAR EQTDIFSEQK AETESMEDFQ NVLKPCSLCE KRPRDGNIIH
460 470 480
GKTSHLTTCF HCARRLKKSG ASCPACKKEI QLVIKVFIA
Length:489
Mass (Da):54,963
Last modified:July 27, 2011 - v2
Checksum:i85A7602AA9AAFD52
GO
Isoform Short (identifier: O35618-2) [UniParc]FASTAAdd to basket
Also known as: MdmX-S

The sequence of this isoform differs from the canonical sequence as follows:
     115-127: DAAQTLALAQDHT → ARCNRILQSQKKN
     128-489: Missing.

Show »
Length:127
Mass (Da):14,143
Checksum:i2581190A9586E17E
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q3UTC9Q3UTC9_MOUSE
Protein Mdm4
Mdm4 mCG_12581
490Annotation score:
A0A087WQP2A0A087WQP2_MOUSE
Protein Mdm4
Mdm4
110Annotation score:
A0A087WQ90A0A087WQ90_MOUSE
Protein Mdm4
Mdm4
141Annotation score:
A0A087WQ20A0A087WQ20_MOUSE
Protein Mdm4
Mdm4
128Annotation score:
A0A087WRX7A0A087WRX7_MOUSE
Protein Mdm4
Mdm4
318Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti112I → N in AAB62927 (PubMed:8895579).Curated1
Sequence conflicti475A → V in AAB62927 (PubMed:8895579).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003216115 – 127DAAQT…AQDHT → ARCNRILQSQKKN in isoform Short. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_003217128 – 489Missing in isoform Short. 1 PublicationAdd BLAST362

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF007110 mRNA Translation: AAB62927.1
EU568360 mRNA Translation: ACB69756.1
AK017719 mRNA Translation: BAB30893.1
AK083349 mRNA Translation: BAC38879.1
CH466520 Genomic DNA Translation: EDL39660.1
CH466520 Genomic DNA Translation: EDL39662.1
CCDSiCCDS15290.1 [O35618-1]
PIRiS71955
RefSeqiNP_001289730.1, NM_001302801.1
NP_001289731.1, NM_001302802.1
NP_001289732.1, NM_001302803.1 [O35618-1]
NP_001289733.1, NM_001302804.1
NP_032601.2, NM_008575.4 [O35618-1]
UniGeneiMm.426531
Mm.476028

Genome annotation databases

EnsembliENSMUST00000067429; ENSMUSP00000070411; ENSMUSG00000054387 [O35618-1]
ENSMUST00000188090; ENSMUSP00000140609; ENSMUSG00000054387 [O35618-1]
GeneIDi17248
KEGGimmu:17248
UCSCiuc007cpk.2 mouse [O35618-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF007110 mRNA Translation: AAB62927.1
EU568360 mRNA Translation: ACB69756.1
AK017719 mRNA Translation: BAB30893.1
AK083349 mRNA Translation: BAC38879.1
CH466520 Genomic DNA Translation: EDL39660.1
CH466520 Genomic DNA Translation: EDL39662.1
CCDSiCCDS15290.1 [O35618-1]
PIRiS71955
RefSeqiNP_001289730.1, NM_001302801.1
NP_001289731.1, NM_001302802.1
NP_001289732.1, NM_001302803.1 [O35618-1]
NP_001289733.1, NM_001302804.1
NP_032601.2, NM_008575.4 [O35618-1]
UniGeneiMm.426531
Mm.476028

3D structure databases

ProteinModelPortaliO35618
SMRiO35618
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201373, 9 interactors
DIPiDIP-24201N
IntActiO35618, 5 interactors
STRINGi10090.ENSMUSP00000070411

PTM databases

iPTMnetiO35618
PhosphoSitePlusiO35618

Proteomic databases

MaxQBiO35618
PaxDbiO35618
PRIDEiO35618

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000067429; ENSMUSP00000070411; ENSMUSG00000054387 [O35618-1]
ENSMUST00000188090; ENSMUSP00000140609; ENSMUSG00000054387 [O35618-1]
GeneIDi17248
KEGGimmu:17248
UCSCiuc007cpk.2 mouse [O35618-1]

Organism-specific databases

CTDi4194
MGIiMGI:107934 Mdm4

Phylogenomic databases

eggNOGiENOG410IE9V Eukaryota
ENOG410XSWN LUCA
GeneTreeiENSGT00530000063539
HOGENOMiHOG000293341
HOVERGENiHBG013472
InParanoidiO35618
KOiK10127

Enzyme and pathway databases

ReactomeiR-MMU-2559580 Oxidative Stress Induced Senescence
R-MMU-2559585 Oncogene Induced Senescence
R-MMU-5689880 Ub-specific processing proteases
R-MMU-6804756 Regulation of TP53 Activity through Phosphorylation
R-MMU-6804757 Regulation of TP53 Degradation
R-MMU-6804760 Regulation of TP53 Activity through Methylation
R-MMU-69541 Stabilization of p53

Miscellaneous databases

PROiPR:O35618
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000054387 Expressed in 269 organ(s), highest expression level in primary oocyte
CleanExiMM_MDM4
ExpressionAtlasiO35618 baseline and differential
GenevisibleiO35618 MM

Family and domain databases

Gene3Di1.10.245.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR015458 MDM4
IPR016495 p53_neg-reg_MDM_2/4
IPR036885 SWIB_MDM2_dom_sf
IPR003121 SWIB_MDM2_domain
IPR001876 Znf_RanBP2
IPR036443 Znf_RanBP2_sf
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR13844:SF20 PTHR13844:SF20, 1 hit
PfamiView protein in Pfam
PF02201 SWIB, 1 hit
PF00641 zf-RanBP, 1 hit
PIRSFiPIRSF500699 MDM4, 1 hit
PIRSF006748 p53_MDM_2/4, 1 hit
SUPFAMiSSF47592 SSF47592, 1 hit
SSF90209 SSF90209, 1 hit
PROSITEiView protein in PROSITE
PS01358 ZF_RANBP2_1, 1 hit
PS50199 ZF_RANBP2_2, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMDM4_MOUSE
AccessioniPrimary (citable) accession number: O35618
Secondary accession number(s): Q9CYG1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: September 12, 2018
This is version 157 of the entry and version 2 of the sequence. See 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
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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