UniProt functional annotation for O15350



	UniProt functional annotation for O15350

UniProt code: O15350.

Organism: Homo sapiens (Human).

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

Function: Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. {ECO:0000269|PubMed:10203277, ECO:0000269|PubMed:11753569, ECO:0000269|PubMed:18174154}.

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};

Subunit: Found in a complex with p53/TP53 and CABLES1. The C-terminal oligomerization domain binds to the ABL1 tyrosine kinase SH3 domain. Interacts with HECW2. Isoform Beta interacts homotypically and with p53/TP53, whereas isoform Alpha does not. Isoform Gamma interacts homotypically and with all p73 isoforms. Isoform Delta interacts with isoform Gamma, isoform Alpha, and homotypically. Isoforms Alpha and Beta interact with HIPK2. Isoform Alpha interacts with RANBP9. Isoform Beta interacts with WWOX. Interacts (via SAM domain) with FBXO45 (via B30.2/SPRY domain). Interacts with YAP1 (phosphorylated form). Interacts with HCK (via SH3 domain); this inhibits TP73 activity and degradation. {ECO:0000269|PubMed:10391251, ECO:0000269|PubMed:11706030, ECO:0000269|PubMed:11925430, ECO:0000269|PubMed:12890487, ECO:0000269|PubMed:15070730, ECO:0000269|PubMed:15558019, ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:18280240, ECO:0000269|PubMed:19581926}.

Subunit: (Microbial infection) Interacts with Epstein-Barr virus protein EBNA6; this interaction inhibits TP73-mediated apoptotic pathway. {ECO:0000269|PubMed:24314664}.

Subcellular location: Nucleus {ECO:0000269|PubMed:24314664}. Cytoplasm. Note=Accumulates in the nucleus in response to DNA damage.

Tissue specificity: Expressed in striatal neurons of patients with Huntington disease (at protein level). Brain, kidney, placenta, colon, heart, liver, spleen, skeletal muscle, prostate, thymus and pancreas. Highly expressed in fetal tissue. {ECO:0000269|PubMed:11753569, ECO:0000269|PubMed:16461361}.

Induction: Not induced by DNA damage. Isoforms lacking the transactivation domain block gene induction. {ECO:0000269|PubMed:11753569}.

Domain: Possesses an acidic transactivation domain, a central DNA binding domain and a C-terminal oligomerization domain that binds to the ABL1 tyrosine kinase SH3 domain. {ECO:0000269|PubMed:15070730}.

Domain: The PPxY motif mediates interaction with WWOX. {ECO:0000269|PubMed:15070730}.

Ptm: Isoform alpha (but not isoform beta) is sumoylated on Lys-627, which potentiates proteasomal degradation but does not affect transcriptional activity. Phosphorylation by PLK1 and PLK3 inhibits the transcription regulator activity and pro-apoptotic function. {ECO:0000269|PubMed:10961991}.

Ptm: Higher levels of phosphorylation seen in the brain from patients with Huntington disease.

Ptm: Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by the proteasome. {ECO:0000269|PubMed:19581926, ECO:0000269|PubMed:21994467}.

Miscellaneous: Maps to a chromosome region frequently mutated in diverse cell lines of human cancer. Appears not to be frequently mutated in human cancers, in contrast to p53/TP53. Hemizygosity is observed in neuroblastoma and oligodendroglioma.

Miscellaneous: Activated and stabilized by interaction with RANBP9.

Miscellaneous: [Isoform Beta]: Produced by alternative splicing of isoform Alpha. {ECO:0000305}.

Miscellaneous: [Isoform Gamma]: Produced by alternative splicing of isoform Alpha. The splicing of exon 11 results in a frameshift from the original reading frame. {ECO:0000305}.

Miscellaneous: [Isoform Delta]: Produced by alternative splicing of isoform Alpha. {ECO:0000305}.

Miscellaneous: [Isoform Epsilon]: Produced by alternative splicing of isoform Alpha. The splicing of exon 11 results in a frameshift from the original reading frame. The splicing of exon 13 reverts the reading frame to the sequence of isoform Alpha. {ECO:0000305}.

Miscellaneous: [Isoform Zeta]: Produced by alternative splicing of isoform Alpha. {ECO:0000305}.

Miscellaneous: [Isoform dN-Alpha]: Produced by alternative promoter usage. {ECO:0000305}.

Miscellaneous: [Isoform dN-Beta]: Produced by alternative splicing of isoform dN-Alpha. {ECO:0000305}.

Miscellaneous: [Isoform dN-Gamma]: Produced by alternative splicing of isoform dN-Alpha. {ECO:0000305}.

Similarity: Belongs to the p53 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:		Participates in the apoptotic response to DNA damage. Isoforms containing the transactivation domain are pro-apoptotic, isoforms lacking the domain are anti-apoptotic and block the function of p53 and transactivating p73 isoforms. May be a tumor suppressor protein. {ECO:0000269\|PubMed:10203277, ECO:0000269\|PubMed:11753569, ECO:0000269\|PubMed:18174154}.


Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; Note=Binds 1 zinc ion per subunit. {ECO:0000250};
Subunit:		Found in a complex with p53/TP53 and CABLES1. The C-terminal oligomerization domain binds to the ABL1 tyrosine kinase SH3 domain. Interacts with HECW2. Isoform Beta interacts homotypically and with p53/TP53, whereas isoform Alpha does not. Isoform Gamma interacts homotypically and with all p73 isoforms. Isoform Delta interacts with isoform Gamma, isoform Alpha, and homotypically. Isoforms Alpha and Beta interact with HIPK2. Isoform Alpha interacts with RANBP9. Isoform Beta interacts with WWOX. Interacts (via SAM domain) with FBXO45 (via B30.2/SPRY domain). Interacts with YAP1 (phosphorylated form). Interacts with HCK (via SH3 domain); this inhibits TP73 activity and degradation. {ECO:0000269\|PubMed:10391251, ECO:0000269\|PubMed:11706030, ECO:0000269\|PubMed:11925430, ECO:0000269\|PubMed:12890487, ECO:0000269\|PubMed:15070730, ECO:0000269\|PubMed:15558019, ECO:0000269\|PubMed:17535448, ECO:0000269\|PubMed:18280240, ECO:0000269\|PubMed:19581926}.
Subunit:		(Microbial infection) Interacts with Epstein-Barr virus protein EBNA6; this interaction inhibits TP73-mediated apoptotic pathway. {ECO:0000269\|PubMed:24314664}.
Subcellular location:		Nucleus {ECO:0000269\|PubMed:24314664}. Cytoplasm. Note=Accumulates in the nucleus in response to DNA damage.
Tissue specificity:		Expressed in striatal neurons of patients with Huntington disease (at protein level). Brain, kidney, placenta, colon, heart, liver, spleen, skeletal muscle, prostate, thymus and pancreas. Highly expressed in fetal tissue. {ECO:0000269\|PubMed:11753569, ECO:0000269\|PubMed:16461361}.
Induction:		Not induced by DNA damage. Isoforms lacking the transactivation domain block gene induction. {ECO:0000269\|PubMed:11753569}.
Domain:		Possesses an acidic transactivation domain, a central DNA binding domain and a C-terminal oligomerization domain that binds to the ABL1 tyrosine kinase SH3 domain. {ECO:0000269\|PubMed:15070730}.
Domain:		The PPxY motif mediates interaction with WWOX. {ECO:0000269\|PubMed:15070730}.
Ptm:		Isoform alpha (but not isoform beta) is sumoylated on Lys-627, which potentiates proteasomal degradation but does not affect transcriptional activity. Phosphorylation by PLK1 and PLK3 inhibits the transcription regulator activity and pro-apoptotic function. {ECO:0000269\|PubMed:10961991}.
Ptm:		Higher levels of phosphorylation seen in the brain from patients with Huntington disease.
Ptm:		Polyubiquitinated by RCHY1/PIRH2; leading to its degradation by the proteasome. {ECO:0000269\|PubMed:19581926, ECO:0000269\|PubMed:21994467}.
Miscellaneous:		Maps to a chromosome region frequently mutated in diverse cell lines of human cancer. Appears not to be frequently mutated in human cancers, in contrast to p53/TP53. Hemizygosity is observed in neuroblastoma and oligodendroglioma.
Miscellaneous:		Activated and stabilized by interaction with RANBP9.
Miscellaneous:		[Isoform Beta]: Produced by alternative splicing of isoform Alpha. {ECO:0000305}.
Miscellaneous:		[Isoform Gamma]: Produced by alternative splicing of isoform Alpha. The splicing of exon 11 results in a frameshift from the original reading frame. {ECO:0000305}.
Miscellaneous:		[Isoform Delta]: Produced by alternative splicing of isoform Alpha. {ECO:0000305}.
Miscellaneous:		[Isoform Epsilon]: Produced by alternative splicing of isoform Alpha. The splicing of exon 11 results in a frameshift from the original reading frame. The splicing of exon 13 reverts the reading frame to the sequence of isoform Alpha. {ECO:0000305}.
Miscellaneous:		[Isoform Zeta]: Produced by alternative splicing of isoform Alpha. {ECO:0000305}.
Miscellaneous:		[Isoform dN-Alpha]: Produced by alternative promoter usage. {ECO:0000305}.
Miscellaneous:		[Isoform dN-Beta]: Produced by alternative splicing of isoform dN-Alpha. {ECO:0000305}.
Miscellaneous:		[Isoform dN-Gamma]: Produced by alternative splicing of isoform dN-Alpha. {ECO:0000305}.
Similarity:		Belongs to the p53 family. {ECO:0000305}.