O15151 · MDM4_HUMAN
- ProteinProtein Mdm4
- GeneMDM4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids490 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Keywords
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameProtein Mdm4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO15151
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Bone marrow failure syndrome 6 (BMFS6)
- Note
- DescriptionA form of bone marrow failure syndrome, a heterogeneous group of life-threatening disorders characterized by hematopoietic defects in association with a range of variable extra-hematopoietic manifestations. BMFS6 is an autosomal dominant form characterized by intermittent neutropenia, lymphopenia, or anemia associated with hypocellular bone marrow, and increased susceptibility to cancer.
- See alsoMIM:618849
Natural variants in BMFS6
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_084553 | 454 | T>M | in BMFS6; altered capacity to interact with MDM2 RING domain in a yeast two-hybrid assay; no effect on ATP binding; expressed at lower levels than wild-type; when expressed in a mouse model, leads to increased TP53 activity, decreased telomerase length and ultimately to bone marrow failure; dbSNP:rs1270135772 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_017106 | 175 | in dbSNP:rs4252716 | |||
Sequence: I → T | ||||||
Natural variant | VAR_017107 | 406 | in dbSNP:rs4252741 | |||
Sequence: T → I | ||||||
Mutagenesis | 437 | Fails to interact with MDM2. | ||||
Sequence: C → G | ||||||
Natural variant | VAR_084553 | 454 | in BMFS6; altered capacity to interact with MDM2 RING domain in a yeast two-hybrid assay; no effect on ATP binding; expressed at lower levels than wild-type; when expressed in a mouse model, leads to increased TP53 activity, decreased telomerase length and ultimately to bone marrow failure; dbSNP:rs1270135772 | |||
Sequence: T → M |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 910 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000157336 | 1-490 | UniProt | Protein Mdm4 | |||
Sequence: MTSFSTSAQCSTSDSACRISPGQINQVRPKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKNLVTLATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA | |||||||
Modified residue (large scale data) | 20 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 161 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 342 | UniProt | Phosphoserine; by CHEK2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 342 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 343 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 344 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 365 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 367 | UniProt | Phosphoserine; by CHEK1 and CHEK2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 367 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with TP53, TP73 and USP2. Found in a trimeric complex with USP2, MDM2 and MDM4. Interacts (phosphorylated) with YWHAG; negatively regulates MDM4 activity toward TP53
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias, zinc finger, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 25-108 | SWIB/MDM2 | ||||
Sequence: NQVRPKLPLLKILHAAGAQGEMFTVKEVMHYLGQYIMVKQLYDQQEQHMVYCGGDLLGELLGRQSFSVKDPSPLYDMLRKNLVT | ||||||
Region | 129-160 | Disordered | ||||
Sequence: DIPSQDQLKQSAEESSTSRKRTTEDDIPTLPT | ||||||
Compositional bias | 141-160 | Basic and acidic residues | ||||
Sequence: EESSTSRKRTTEDDIPTLPT | ||||||
Region | 246-332 | Region II | ||||
Sequence: SEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYS | ||||||
Zinc finger | 300-329 | RanBP2-type | ||||
Sequence: SEDEWQCTECKKFNSPSKRYCFRCWALRKD | ||||||
Region | 393-490 | Necessary for interaction with USP2 | ||||
Sequence: EFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA | ||||||
Zinc finger | 437-478 | RING-type | ||||
Sequence: CSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICK | ||||||
Motif | 442-445 | Nuclear localization signal | ||||
Sequence: KRPR |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 5 isoforms produced by Alternative splicing. Additional isoforms seem to exist.
O15151-1
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.
- Name1
- NoteCancer-specific isoform, may counteract MDM2/MDM4-mediated p53 degradation.
- Length490
- Mass (Da)54,864
- Last updated2005-09-27 v2
- Checksum415E6FA5A0C69857
O15151-2
- Name2
- SynonymsMDMX-S
- NoteCancer-specific isoform, may counteract MDM2/MDM4-mediated p53 degradation.
- Differences from canonical
- 109-490: LATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA → SASNNTARCNRILQSQKKN
O15151-3
- Name3
- SynonymsMDMX
- Differences from canonical
- 109-490: LATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA → SASNNTDAAQTLALAQDHT
O15151-4
- NameHDMX211
- NoteCancer-specific isoform, may counteract MDM2/MDM4-mediated p53 degradation.
- Differences from canonical
- 27-352: Missing
O15151-5
- Name5
- Differences from canonical
- 225-274: Missing
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q5T0Y2 | Q5T0Y2_HUMAN | MDM4 | 213 | ||
Q5T0Y3 | Q5T0Y3_HUMAN | MDM4 | 171 | ||
Q5T0Y4 | Q5T0Y4_HUMAN | MDM4 | 131 | ||
Q68DC0 | Q68DC0_HUMAN | MDM4 | 140 | ||
A0A087WTR9 | A0A087WTR9_HUMAN | MDM4 | 267 | ||
A0A087WUE3 | A0A087WUE3_HUMAN | MDM4 | 116 | ||
A0A087WZ58 | A0A087WZ58_HUMAN | MDM4 | 392 |
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_042563 | 27-352 | in isoform HDMX211 | |||
Sequence: Missing | ||||||
Sequence conflict | 94 | in Ref. 1; AAB62928 | ||||
Sequence: D → N | ||||||
Alternative sequence | VSP_035669 | 109-490 | in isoform 2 | |||
Sequence: LATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA → SASNNTARCNRILQSQKKN | ||||||
Alternative sequence | VSP_035670 | 109-490 | in isoform 3 | |||
Sequence: LATATTDAAQTLALAQDHSMDIPSQDQLKQSAEESSTSRKRTTEDDIPTLPTSEHKCIHSREDEDLIENLAQDETSRLDLGFEEWDVAGLPWWFLGNLRSNYTPRSNGSTDLQTNQDVGTAIVSDTTDDLWFLNESVSEQLGVGIKVEAADTEQTSEEVGKVSDKKVIEVGKNDDLEDSKSLSDDTDVEVTSEDEWQCTECKKFNSPSKRYCFRCWALRKDWYSDCSKLTHSLSTSDITAIPEKENEGNDVPDCRRTISAPVVRPKDAYIKKENSKLFDPCNSVEFLDLAHSSESQETISSMGEQLDNLSEQRTDTENMEDCQNLLKPCSLCEKRPRDGNIIHGRTGHLVTCFHCARRLKKAGASCPICKKEIQLVIKVFIA → SASNNTDAAQTLALAQDHT | ||||||
Compositional bias | 141-160 | Basic and acidic residues | ||||
Sequence: EESSTSRKRTTEDDIPTLPT | ||||||
Alternative sequence | VSP_043145 | 225-274 | in isoform 5 | |||
Sequence: Missing |
Mass Spectrometry
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF007111 EMBL· GenBank· DDBJ | AAB62928.1 EMBL· GenBank· DDBJ | mRNA | ||
AY923176 EMBL· GenBank· DDBJ | AAY22054.1 EMBL· GenBank· DDBJ | mRNA | ||
AK223228 EMBL· GenBank· DDBJ | BAD96948.1 EMBL· GenBank· DDBJ | mRNA | ||
AY207458 EMBL· GenBank· DDBJ | AAO13494.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL512306 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC067299 EMBL· GenBank· DDBJ | AAH67299.1 EMBL· GenBank· DDBJ | mRNA | ||
BC105106 EMBL· GenBank· DDBJ | AAI05107.1 EMBL· GenBank· DDBJ | mRNA |