Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Protein Mdm4

Gene

MDM4

Organism
Homo sapiens (Human)
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.2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri300 – 329RanBP2-typePROSITE-ProRule annotationAdd BLAST30
Zinc fingeri437 – 478RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • ubiquitin protein ligase activity Source: Reactome
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • cell proliferation Source: UniProtKB
  • cellular response to hypoxia Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
  • G0 to G1 transition Source: UniProtKB
  • negative regulation of apoptotic process Source: InterPro
  • negative regulation of cell cycle arrest Source: InterPro
  • negative regulation of cell proliferation Source: ProtInc
  • negative regulation of protein catabolic process Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • protein-containing complex assembly Source: UniProtKB
  • protein deubiquitination Source: Reactome
  • protein stabilization Source: UniProtKB
  • regulation of signal transduction by p53 class mediator Source: Reactome

Keywordsi

LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-5689880 Ub-specific processing proteases
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757 Regulation of TP53 Degradation
R-HSA-6804760 Regulation of TP53 Activity through Methylation
R-HSA-69541 Stabilization of p53
SIGNORiO15151

Protein family/group databases

MoonDBiO15151 Predicted

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000198625.12
HGNCiHGNC:6974 MDM4
MIMi602704 gene
neXtProtiNX_O15151

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

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi437C → G: Fails to interact with MDM2. 1 Publication1

Organism-specific databases

DisGeNETi4194
OpenTargetsiENSG00000198625
PharmGKBiPA30719

Chemistry databases

ChEMBLiCHEMBL1255126

Polymorphism and mutation databases

BioMutaiMDM4

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001573361 – 490Protein Mdm4Add BLAST490

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei342Phosphoserine; by CHEK2Combined sources1 Publication1
Modified residuei367Phosphoserine; by CHEK1 and CHEK2Combined sources2 Publications1

Post-translational modificationi

Phosphorylated. Phosphorylation at Ser-367 promotes interaction with YWHAG and subsequent ubiquitination and degradation. Phosphorylation at Ser-342 also induces ubiquitination and degradation but to a lower extent.3 Publications
Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO15151
MaxQBiO15151
PaxDbiO15151
PeptideAtlasiO15151
PRIDEiO15151
ProteomicsDBi48474
48475 [O15151-2]
48476 [O15151-3]
48477 [O15151-4]
48478 [O15151-5]

PTM databases

iPTMnetiO15151
PhosphoSitePlusiO15151

Miscellaneous databases

PMAP-CutDBiO15151

Expressioni

Tissue specificityi

Expressed in all tissues tested with high levels in thymus.

Inductioni

Down-regulated by cisplatin (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000198625
CleanExiHS_MDM4
ExpressionAtlasiO15151 baseline and differential
GenevisibleiO15151 HS

Organism-specific databases

HPAiHPA018919
HPA048821

Interactioni

Subunit structurei

Interacts with MDM2, TP53, TP73 and USP2. Found in a trimeric complex with USP2, MDM2 and MDM4. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53.3 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110359, 72 interactors
DIPiDIP-24199N
IntActiO15151, 38 interactors
MINTiO15151
STRINGi9606.ENSP00000356150

Chemistry databases

BindingDBiO15151

Structurei

Secondary structure

1490
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 29Combined sources3
Helixi31 – 39Combined sources9
Helixi49 – 62Combined sources14
Beta strandi70 – 75Combined sources6
Helixi76 – 78Combined sources3
Helixi80 – 85Combined sources6
Beta strandi88 – 91Combined sources4
Helixi96 – 105Combined sources10
Beta strandi106 – 109Combined sources4
Beta strandi307 – 309Combined sources3
Turni321 – 323Combined sources3
Helixi429 – 434Combined sources6
Turni438 – 440Combined sources3
Beta strandi442 – 445Combined sources4
Beta strandi447 – 451Combined sources5
Beta strandi454 – 459Combined sources6
Helixi461 – 469Combined sources9
Turni475 – 477Combined sources3
Beta strandi483 – 489Combined sources7

3D structure databases

ProteinModelPortaliO15151
SMRiO15151
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15151

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni246 – 332Region IIAdd BLAST87
Regioni393 – 490Necessary for interaction with USP21 PublicationAdd BLAST98

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi442 – 445Nuclear localization signalSequence analysis4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi243 – 308Asp/Glu-rich (acidic)Add BLAST66

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 fingeri300 – 329RanBP2-typePROSITE-ProRule annotationAdd BLAST30
Zinc fingeri437 – 478RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiENOG410IE9V Eukaryota
ENOG410XSWN LUCA
GeneTreeiENSGT00530000063539
HOGENOMiHOG000293341
HOVERGENiHBG013472
InParanoidiO15151
KOiK10127
OMAiTENMEDC
OrthoDBiEOG091G0FYK
PhylomeDBiO15151
TreeFamiTF105306

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 (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: O15151-1) [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
MTSFSTSAQC STSDSACRIS PGQINQVRPK LPLLKILHAA GAQGEMFTVK
60 70 80 90 100
EVMHYLGQYI MVKQLYDQQE QHMVYCGGDL LGELLGRQSF SVKDPSPLYD
110 120 130 140 150
MLRKNLVTLA TATTDAAQTL ALAQDHSMDI PSQDQLKQSA EESSTSRKRT
160 170 180 190 200
TEDDIPTLPT SEHKCIHSRE DEDLIENLAQ DETSRLDLGF EEWDVAGLPW
210 220 230 240 250
WFLGNLRSNY TPRSNGSTDL QTNQDVGTAI VSDTTDDLWF LNESVSEQLG
260 270 280 290 300
VGIKVEAADT EQTSEEVGKV SDKKVIEVGK NDDLEDSKSL SDDTDVEVTS
310 320 330 340 350
EDEWQCTECK KFNSPSKRYC FRCWALRKDW YSDCSKLTHS LSTSDITAIP
360 370 380 390 400
EKENEGNDVP DCRRTISAPV VRPKDAYIKK ENSKLFDPCN SVEFLDLAHS
410 420 430 440 450
SESQETISSM GEQLDNLSEQ RTDTENMEDC QNLLKPCSLC EKRPRDGNII
460 470 480 490
HGRTGHLVTC FHCARRLKKA GASCPICKKE IQLVIKVFIA
Length:490
Mass (Da):54,864
Last modified:September 27, 2005 - v2
Checksum:i415E6FA5A0C69857
GO
Isoform 2 (identifier: O15151-2) [UniParc]FASTAAdd to basket
Also known as: MDMX-S

The sequence of this isoform differs from the canonical sequence as follows:
     109-490: LATATTDAAQ...IQLVIKVFIA → SASNNTARCNRILQSQKKN

Note: No experimental confirmation available.
Show »
Length:127
Mass (Da):14,185
Checksum:i59649D26B113EFB4
GO
Isoform 3 (identifier: O15151-3) [UniParc]FASTAAdd to basket
Also known as: MDMX

The sequence of this isoform differs from the canonical sequence as follows:
     109-490: LATATTDAAQ...IQLVIKVFIA → SASNNTDAAQTLALAQDHT

Note: No experimental confirmation available.
Show »
Length:127
Mass (Da):13,981
Checksum:i0A00E52B32331543
GO
Isoform HDMX211 (identifier: O15151-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     27-352: Missing.

Note: Cancer-specific isoform, may counteract MDM2/MDM4-mediated p53 degradation.
Show »
Length:164
Mass (Da):18,195
Checksum:i1C39025CBD527C11
GO
Isoform 5 (identifier: O15151-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     225-274: Missing.

Note: No experimental confirmation available.
Show »
Length:440
Mass (Da):49,541
Checksum:iBB377C938A8C3D1C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti94D → N in AAB62928 (PubMed:9226370).Curated1

Mass spectrometryi

Molecular mass is 54863.3 Da from positions 1 - 490. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_017106175I → T1 PublicationCorresponds to variant dbSNP:rs4252716Ensembl.1
Natural variantiVAR_017107406T → I1 PublicationCorresponds to variant dbSNP:rs4252741Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04256327 – 352Missing in isoform HDMX211. 1 PublicationAdd BLAST326
Alternative sequenceiVSP_035669109 – 490LATAT…KVFIA → SASNNTARCNRILQSQKKN in isoform 2. CuratedAdd BLAST382
Alternative sequenceiVSP_035670109 – 490LATAT…KVFIA → SASNNTDAAQTLALAQDHT in isoform 3. CuratedAdd BLAST382
Alternative sequenceiVSP_043145225 – 274Missing in isoform 5. 1 PublicationAdd BLAST50

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF007111 mRNA Translation: AAB62928.1
AY923176 mRNA Translation: AAY22054.1
AK223228 mRNA Translation: BAD96948.1
AY207458 Genomic DNA Translation: AAO13494.1
AL512306 Genomic DNA No translation available.
BC067299 mRNA Translation: AAH67299.1
BC105106 mRNA Translation: AAI05107.1
CCDSiCCDS1447.1 [O15151-1]
CCDS55674.1 [O15151-5]
CCDS55675.1 [O15151-4]
RefSeqiNP_001191100.1, NM_001204171.1 [O15151-5]
NP_001191101.1, NM_001204172.1 [O15151-4]
NP_001265445.1, NM_001278516.1
NP_001265446.1, NM_001278517.1
NP_001265447.1, NM_001278518.1
NP_001265448.1, NM_001278519.1
NP_002384.2, NM_002393.4 [O15151-1]
UniGeneiHs.497492
Hs.715871

Genome annotation databases

EnsembliENST00000367182; ENSP00000356150; ENSG00000198625 [O15151-1]
ENST00000367183; ENSP00000356151; ENSG00000198625 [O15151-4]
ENST00000454264; ENSP00000396840; ENSG00000198625 [O15151-5]
GeneIDi4194
KEGGihsa:4194
UCSCiuc001hay.3 human [O15151-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMDM4_HUMAN
AccessioniPrimary (citable) accession number: O15151
Secondary accession number(s): Q2M2Y2
, Q32SL2, Q6GS18, Q8IV83
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: September 27, 2005
Last modified: July 18, 2018
This is version 188 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health