UniProt functional annotation for O15151



	UniProt functional annotation for O15151

UniProt code: O15151.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Along with MDM2, contributes to TP53 regulation (PubMed:32300648). 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. {ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:32300648}.

Subunit: Interacts with MDM2 (PubMed:16163388, PubMed:19838211, PubMed:32300648). 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. {ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:19838211, ECO:0000269|PubMed:32300648}.

Subcellular location: Nucleus.

Tissue specificity: Expressed in all tissues tested with high levels in thymus.

Induction: Down-regulated by cisplatin (at protein level). {ECO:0000269|PubMed:19838211}.

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. {ECO:0000269|PubMed:16163388, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:19838211}.

Ptm: Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein. {ECO:0000269|PubMed:19838211}.

Mass spectrometry: Mass=54863.3; Method=MALDI; Evidence={ECO:0000269|PubMed:11840567};

Disease: Bone marrow failure syndrome 6 (BMFS6) [MIM:618849]: A 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. {ECO:0000269|PubMed:32300648}. Note=The disease is caused by variants affecting the gene represented in this entry.

Miscellaneous: [Isoform HDMX211]: Cancer-specific isoform, may counteract MDM2/MDM4-mediated p53 degradation. {ECO:0000305}.

Similarity: Belongs to the MDM2/MDM4 family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Along with MDM2, contributes to TP53 regulation (PubMed:32300648). 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. {ECO:0000269\|PubMed:16163388, ECO:0000269\|PubMed:16511572, ECO:0000269\|PubMed:32300648}.


Subunit:		Interacts with MDM2 (PubMed:16163388, PubMed:19838211, PubMed:32300648). 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. {ECO:0000269\|PubMed:16163388, ECO:0000269\|PubMed:16511572, ECO:0000269\|PubMed:19838211, ECO:0000269\|PubMed:32300648}.
Subcellular location:		Nucleus.
Tissue specificity:		Expressed in all tissues tested with high levels in thymus.
Induction:		Down-regulated by cisplatin (at protein level). {ECO:0000269\|PubMed:19838211}.
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. {ECO:0000269\|PubMed:16163388, ECO:0000269\|PubMed:16511572, ECO:0000269\|PubMed:19838211}.
Ptm:		Ubiquitinated and degraded by MDM2. Deubiquitination by USP2 on the other hand stabilizes the MDM4 protein. {ECO:0000269\|PubMed:19838211}.
Mass spectrometry:		Mass=54863.3; Method=MALDI; Evidence={ECO:0000269\|PubMed:11840567};
Disease:		Bone marrow failure syndrome 6 (BMFS6) [MIM:618849]: A 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. {ECO:0000269\|PubMed:32300648}. Note=The disease is caused by variants affecting the gene represented in this entry.
Miscellaneous:		[Isoform HDMX211]: Cancer-specific isoform, may counteract MDM2/MDM4-mediated p53 degradation. {ECO:0000305}.
Similarity:		Belongs to the MDM2/MDM4 family. {ECO:0000305}.