Human Gene MDM4 (ENST00000367182.8_4) from GENCODE V47lift37
  Description: MDM4 regulator of p53, transcript variant 1 (from RefSeq NM_002393.5)
Gencode Transcript: ENST00000367182.8_4
Gencode Gene: ENSG00000198625.14_10
Transcript (Including UTRs)
   Position: hg19 chr1:204,485,534-204,527,248 Size: 41,715 Total Exon Count: 11 Strand: +
Coding Region
   Position: hg19 chr1:204,494,647-204,518,810 Size: 24,164 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr1:204,485,534-204,527,248)mRNA (may differ from genome)Protein (490 aa)
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-  Comments and Description Text from UniProtKB
  ID: MDM4_HUMAN
DESCRIPTION: RecName: Full=Protein Mdm4; AltName: Full=Double minute 4 protein; AltName: Full=Mdm2-like p53-binding protein; AltName: Full=Protein Mdmx; AltName: Full=p53-binding protein Mdm4;
FUNCTION: 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.
SUBUNIT: Interacts with MDM2, TP53, TP73 and USP2. Found in a trimeric complex with UPB2, MDM2 and MDM4. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53.
INTERACTION: Q00987:MDM2; NbExp=6; IntAct=EBI-398437, EBI-389668; Q13064:MKRN3; NbExp=2; IntAct=EBI-398437, EBI-2340269; P04637:TP53; NbExp=4; IntAct=EBI-398437, EBI-366083; P62837:UBE2D2; NbExp=2; IntAct=EBI-398437, EBI-347677;
SUBCELLULAR LOCATION: Nucleus.
TISSUE SPECIFICITY: Expressed in all tissues tested with high levels in thymus.
INDUCTION: Down-regulated by cisplatin (at protein level).
DOMAIN: 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.
PTM: 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.
PTM: Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein.
MASS SPECTROMETRY: Mass=54863.3; Method=MALDI; Range=1-490; Source=PubMed:11840567;
SIMILARITY: Belongs to the MDM2/MDM4 family.
SIMILARITY: Contains 1 RanBP2-type zinc finger.
SIMILARITY: Contains 1 RING-type zinc finger.
SIMILARITY: Contains 1 SWIB domain.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mdm4/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: MDM4
Diseases sorted by gene-association score: intraocular retinoblastoma (8), familial retinoblastoma (6)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 11.61 RPKM in Spleen
Total median expression: 300.63 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -38.80139-0.279 Picture PostScript Text
3' UTR -3151.978438-0.374 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR015458 - MDM4
IPR016495 - p53_neg-reg_MDM_2/4
IPR003121 - SWIB_MDM2_domain
IPR001876 - Znf_RanBP2
IPR001841 - Znf_RING

Pfam Domains:
PF00641 - Zn-finger in Ran binding protein and others
PF02201 - SWIB/MDM2 domain
PF13920 - Zinc finger, C3HC4 type (RING finger)

SCOP Domains:
47592 - SWIB/MDM2 domain
90209 - Ran binding protein zinc finger-like
57850 - RING/U-box

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2CR8 - NMR MuPIT 2VJE - X-ray MuPIT 2VJF - X-ray MuPIT 2VYR - X-ray MuPIT 3DAB - X-ray MuPIT 3EQY - X-ray 3FDO - X-ray MuPIT 3FE7 - X-ray MuPIT 3FEA - X-ray MuPIT 3JZO - X-ray MuPIT 3JZP - X-ray MuPIT 3JZQ - X-ray MuPIT 3LBJ - X-ray MuPIT 3U15 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on O15151
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0019899 enzyme binding
GO:0046872 metal ion binding
GO:0061630 ubiquitin protein ligase activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0006977 DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
GO:0008283 cell proliferation
GO:0008285 negative regulation of cell proliferation
GO:0016567 protein ubiquitination
GO:0016579 protein deubiquitination
GO:0030330 DNA damage response, signal transduction by p53 class mediator
GO:0042177 negative regulation of protein catabolic process
GO:0043066 negative regulation of apoptotic process
GO:0045023 G0 to G1 transition
GO:0050821 protein stabilization
GO:0065003 macromolecular complex assembly
GO:0071157 negative regulation of cell cycle arrest
GO:0071456 cellular response to hypoxia
GO:1901796 regulation of signal transduction by p53 class mediator

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm


-  Descriptions from all associated GenBank mRNAs
  AF007111 - Homo sapiens MDM2-like p53-binding protein (MDMX) mRNA, complete cds.
BC025993 - Homo sapiens cDNA clone IMAGE:4825555, containing frame-shift errors.
CR749470 - Homo sapiens mRNA; cDNA DKFZp781B1423 (from clone DKFZp781B1423).
BC067299 - Homo sapiens Mdm4 p53 binding protein homolog (mouse), mRNA (cDNA clone MGC:75489 IMAGE:30390159), complete cds.
AK310903 - Homo sapiens cDNA, FLJ17945.
AK304698 - Homo sapiens cDNA FLJ56709 complete cds, highly similar to Mdm4 protein.
BX640923 - Homo sapiens mRNA; cDNA DKFZp686B01123 (from clone DKFZp686B01123).
AK303626 - Homo sapiens cDNA FLJ51436 complete cds, highly similar to Mdm4 protein.
AK223228 - Homo sapiens mRNA for mouse double minute 4 homolog, clone: STM03146.
BC143431 - Homo sapiens cDNA clone IMAGE:9051939.
BC105106 - Homo sapiens Mdm4 p53 binding protein homolog (mouse), mRNA (cDNA clone MGC:132766 IMAGE:8144109), complete cds.
BC143432 - Homo sapiens cDNA clone IMAGE:9051940.
AY923176 - Homo sapiens double minute 4 variant (MDM4) mRNA, complete cds, alternatively spliced.
AK310607 - Homo sapiens cDNA, FLJ17649.
KC479043 - Homo sapiens Mdm4 p53 binding protein transcript variant B (MDM4) mRNA, partial cds, alternatively spliced.
CU688282 - Synthetic construct Homo sapiens gateway clone IMAGE:100022864 5' read MDM4 mRNA.
KF435149 - Homo sapiens MDM4 protein variant G (MDM4) mRNA, complete cds.
KF435150 - Homo sapiens MDM4 protein variant Y (MDM4) mRNA, complete cds, alternatively spliced.
KJ891599 - Synthetic construct Homo sapiens clone ccsbBroadEn_00993 MDM4 gene, encodes complete protein.
AY949028 - Homo sapiens MDM4-related protein 1 mRNA, complete cds, alternatively spliced.
AB209383 - Homo sapiens mRNA for mouse double minute 4 homolog variant protein.
JD183353 - Sequence 164377 from Patent EP1572962.
JD078874 - Sequence 59898 from Patent EP1572962.
JD283096 - Sequence 264120 from Patent EP1572962.
JD085197 - Sequence 66221 from Patent EP1572962.
JD250120 - Sequence 231144 from Patent EP1572962.
JD274533 - Sequence 255557 from Patent EP1572962.
JD367646 - Sequence 348670 from Patent EP1572962.
JD459753 - Sequence 440777 from Patent EP1572962.
JD022622 - Sequence 3646 from Patent EP1572962.
AK097188 - Homo sapiens cDNA FLJ39869 fis, clone SPLEN2015433.
JD395738 - Sequence 376762 from Patent EP1572962.
JD284120 - Sequence 265144 from Patent EP1572962.
JD289632 - Sequence 270656 from Patent EP1572962.
JD319339 - Sequence 300363 from Patent EP1572962.
JD105364 - Sequence 86388 from Patent EP1572962.
JD409325 - Sequence 390349 from Patent EP1572962.
JD374586 - Sequence 355610 from Patent EP1572962.
JD489390 - Sequence 470414 from Patent EP1572962.
JD489391 - Sequence 470415 from Patent EP1572962.
JD070036 - Sequence 51060 from Patent EP1572962.
JD397401 - Sequence 378425 from Patent EP1572962.
JD525375 - Sequence 506399 from Patent EP1572962.
JD119297 - Sequence 100321 from Patent EP1572962.
JD480080 - Sequence 461104 from Patent EP1572962.
JD519103 - Sequence 500127 from Patent EP1572962.
DQ592853 - Homo sapiens piRNA piR-59965, complete sequence.
JD026224 - Sequence 7248 from Patent EP1572962.
JD033625 - Sequence 14649 from Patent EP1572962.
JD196144 - Sequence 177168 from Patent EP1572962.
JD140161 - Sequence 121185 from Patent EP1572962.
JD100945 - Sequence 81969 from Patent EP1572962.
JD498437 - Sequence 479461 from Patent EP1572962.
JD545831 - Sequence 526855 from Patent EP1572962.
JD487495 - Sequence 468519 from Patent EP1572962.
JD117533 - Sequence 98557 from Patent EP1572962.
JD447233 - Sequence 428257 from Patent EP1572962.
JD447232 - Sequence 428256 from Patent EP1572962.
JD233963 - Sequence 214987 from Patent EP1572962.
JD431525 - Sequence 412549 from Patent EP1572962.
JD274489 - Sequence 255513 from Patent EP1572962.
JD265905 - Sequence 246929 from Patent EP1572962.
JD063901 - Sequence 44925 from Patent EP1572962.
JD463035 - Sequence 444059 from Patent EP1572962.
JD371245 - Sequence 352269 from Patent EP1572962.
JD337525 - Sequence 318549 from Patent EP1572962.
JD463036 - Sequence 444060 from Patent EP1572962.
JD254677 - Sequence 235701 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein O15151 (Reactome details) participates in the following event(s):

R-HSA-349455 Phosphorylation of MDM4 by ATM
R-HSA-6804741 MDM2 forms homo- or heterodimers
R-HSA-6804724 MDM2 ubiquitinates phosphorylated MDM4
R-HSA-349426 Phosphorylation of MDM4 by CHEK2
R-HSA-5689972 USP2 deubiquitinates MDM2,MDM4
R-HSA-6805022 USP2 binds the heterodimer of MDM2 and MDM4
R-HSA-5633460 MDM2 binds TP53
R-HSA-6804879 MDM2 ubiquitinates TP53
R-HSA-5689950 USP7 deubiquitinates TP53,MDM2,MDM4,FOXO4, PTEN
R-HSA-3215295 USP7 deubiquitinates MDM2
R-HSA-3222072 DAXX binds Ub-MDM2 and USP7
R-HSA-6804998 p14-ARF forms a ternary complex with MDM2 and TP53
R-HSA-6804996 p14-ARF sequesters MDM2
R-HSA-6798373 MDM2 ubiquitinates DYRK2
R-HSA-6804253 MDM2 ubiquitinates JMY
R-HSA-69541 Stabilization of p53
R-HSA-6804757 Regulation of TP53 Degradation
R-HSA-5689880 Ub-specific processing proteases
R-HSA-2559580 Oxidative Stress Induced Senescence
R-HSA-2559585 Oncogene Induced Senescence
R-HSA-69563 p53-Dependent G1 DNA Damage Response
R-HSA-6806003 Regulation of TP53 Expression and Degradation
R-HSA-5688426 Deubiquitination
R-HSA-2559583 Cellular Senescence
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-6804760 Regulation of TP53 Activity through Methylation
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint
R-HSA-5633007 Regulation of TP53 Activity
R-HSA-597592 Post-translational protein modification
R-HSA-2262752 Cellular responses to stress
R-HSA-69615 G1/S DNA Damage Checkpoints
R-HSA-3700989 Transcriptional Regulation by TP53
R-HSA-392499 Metabolism of proteins
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-69620 Cell Cycle Checkpoints
R-HSA-212436 Generic Transcription Pathway
R-HSA-1640170 Cell Cycle
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: ENST00000367182.1, ENST00000367182.2, ENST00000367182.3, ENST00000367182.4, ENST00000367182.5, ENST00000367182.6, ENST00000367182.7, MDM4_HUMAN, MDMX, NM_002393, O15151, Q2M2Y2, Q32SL2, Q6GS18, Q8IV83, uc318fsc.1, uc318fsc.2
UCSC ID: ENST00000367182.8_4
RefSeq Accession: NM_002393.5
Protein: O15151 (aka MDM4_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.