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Protein

Protein Mdm4

Gene

Mdm4

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri299 – 32830RanBP2-typePROSITE-ProRule annotationAdd
BLAST
Zinc fingeri436 – 47742RING-typePROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • atrial septum development Source: MGI
  • atrioventricular valve morphogenesis Source: MGI
  • cell proliferation Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  • endocardial cushion morphogenesis Source: MGI
  • G0 to G1 transition Source: UniProtKB
  • heart valve development Source: MGI
  • negative regulation of apoptotic process Source: InterPro
  • negative regulation of cell cycle arrest Source: InterPro
  • negative regulation of protein catabolic process Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • positive regulation of cell proliferation Source: MGI
  • protein complex assembly Source: MGI
  • regulation of heart rate Source: MGI
  • ventricular septum development Source: MGI
Complete GO annotation...

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 1

Organism-specific databases

MGIiMGI:107934. Mdm4.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 489489Protein Mdm4PRO_0000157337Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei179 – 1791PhosphoserineBy similarity
Modified residuei341 – 3411Phosphoserine; by CHEK2By similarity
Modified residuei367 – 3671Phosphoserine; by CHEK1 and CHEK2By similarity

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.
PhosphoSiteiO35618.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000054387.
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

WithEntry#Exp.IntActNotes
Mdm2P23804-12EBI-2603376,EBI-3386476
Mdm2P23804-22EBI-2603376,EBI-3386480
USP7Q930094EBI-2603376,EBI-302474From a different organism.

GO - Molecular functioni

Protein-protein interaction databases

BioGridi201373. 10 interactions.
DIPiDIP-24201N.
IntActiO35618. 5 interactions.
STRINGi10090.ENSMUSP00000070411.

Structurei

3D structure databases

ProteinModelPortaliO35618.
SMRiO35618. Positions 26-108, 300-343, 430-489.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini26 – 10681SWIBAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni246 – 33186Region IIAdd
BLAST
Regioni392 – 48998Necessary for interaction with USP2By similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi441 – 4444Nuclear localization signalSequence analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi233 – 30169Asp/Glu-rich (acidic)Add
BLAST

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
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 fingeri436 – 47742RING-typePROSITE-ProRule annotationAdd
BLAST

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.
InterProiIPR015458. MDM4.
IPR016495. p53_neg-reg_MDM_2/4.
IPR003121. SWIB_MDM2_domain.
IPR001876. Znf_RanBP2.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02201. SWIB. 1 hit.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
PIRSFiPIRSF500699. MDM4. 1 hit.
PIRSF006748. p53_MDM_2/4. 1 hit.
SUPFAMiSSF47592. SSF47592. 1 hit.
SSF90209. SSF90209. 1 hit.
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. AlignAdd to basket

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti112 – 1121I → N in AAB62927 (PubMed:8895579).Curated
Sequence conflicti475 – 4751A → V in AAB62927 (PubMed:8895579).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei115 – 12713DAAQT…AQDHT → ARCNRILQSQKKN in isoform Short. 1 PublicationVSP_003216Add
BLAST
Alternative sequencei128 – 489362Missing in isoform Short. 1 PublicationVSP_003217Add
BLAST

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

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. Positions 26-108, 300-343, 430-489.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201373. 10 interactions.
DIPiDIP-24201N.
IntActiO35618. 5 interactions.
STRINGi10090.ENSMUSP00000070411.

PTM databases

iPTMnetiO35618.
PhosphoSiteiO35618.

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-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

PROiO35618.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000054387.
CleanExiMM_MDM4.
ExpressionAtlasiO35618. baseline and differential.
GenevisibleiO35618. MM.

Family and domain databases

Gene3Di1.10.245.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR015458. MDM4.
IPR016495. p53_neg-reg_MDM_2/4.
IPR003121. SWIB_MDM2_domain.
IPR001876. Znf_RanBP2.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02201. SWIB. 1 hit.
PF00641. zf-RanBP. 1 hit.
[Graphical view]
PIRSFiPIRSF500699. MDM4. 1 hit.
PIRSF006748. p53_MDM_2/4. 1 hit.
SUPFAMiSSF47592. SSF47592. 1 hit.
SSF90209. SSF90209. 1 hit.
PROSITEiPS01358. ZF_RANBP2_1. 1 hit.
PS50199. ZF_RANBP2_2. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMDM4_MOUSE
AccessioniPrimary (citable) accession number: O35618
Secondary accession number(s): Q9CYG1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: July 27, 2011
Last modified: September 7, 2016
This is version 144 of the entry and version 2 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.