UniProt functional annotation for O15344



	UniProt functional annotation for O15344

UniProt code: O15344.

Organism: Homo sapiens (Human).

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

Function: Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination. {ECO:0000269|PubMed:10400985, ECO:0000269|PubMed:11685209, ECO:0000269|PubMed:22613722}.

Catalytic activity: Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;

Subunit: Homodimer or heterodimer with MID2. Interacts with IGBP1. Interacts with TRIM16. {ECO:0000269|PubMed:11806752, ECO:0000269|PubMed:22613722, ECO:0000269|PubMed:22629402}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:10077590}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:10077590}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:10077590}. Note=Microtubule- associated. It is associated with microtubules throughout the cell cycle, co-localizing with cytoplasmic fibers in interphase and with the mitotic spindle and midbodies during mitosis and cytokinesis.

Tissue specificity: In the fetus, highest expression found in kidney, followed by brain and lung. Expressed at low levels in fetal liver. In the adult, most abundant in heart, placenta and brain.

Induction: A retroviral element acts as an alternative tissue-specific promoter for this gene. The LTR of an HERV-E element enhances the expression in placenta and embryonic kidney.

Ptm: Phosphorylated on serine and threonine residues. {ECO:0000269|PubMed:11806752}.

Disease: Opitz GBBB syndrome 1 (GBBB1) [MIM:300000]: A congenital midline malformation syndrome characterized by hypertelorism, genital- urinary defects such as hypospadias in males and splayed labia in females, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and congenital heart defects. {ECO:0000269|PubMed:11030761, ECO:0000269|PubMed:15558842, ECO:0000269|PubMed:9354791, ECO:0000269|PubMed:9718340}. Note=The disease is caused by variants affecting the gene represented in this entry. MID1 mutations produce proteins with a decreased affinity for microtubules.

Similarity: Belongs to the TRIM/RBCC 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:		Has E3 ubiquitin ligase activity towards IGBP1, promoting its monoubiquitination, which results in deprotection of the catalytic subunit of protein phosphatase PP2A, and its subsequent degradation by polyubiquitination. {ECO:0000269\|PubMed:10400985, ECO:0000269\|PubMed:11685209, ECO:0000269\|PubMed:22613722}.


Catalytic activity:		Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L- cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.; EC=2.3.2.27;
Subunit:		Homodimer or heterodimer with MID2. Interacts with IGBP1. Interacts with TRIM16. {ECO:0000269\|PubMed:11806752, ECO:0000269\|PubMed:22613722, ECO:0000269\|PubMed:22629402}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:10077590}. Cytoplasm, cytoskeleton {ECO:0000269\|PubMed:10077590}. Cytoplasm, cytoskeleton, spindle {ECO:0000269\|PubMed:10077590}. Note=Microtubule- associated. It is associated with microtubules throughout the cell cycle, co-localizing with cytoplasmic fibers in interphase and with the mitotic spindle and midbodies during mitosis and cytokinesis.
Tissue specificity:		In the fetus, highest expression found in kidney, followed by brain and lung. Expressed at low levels in fetal liver. In the adult, most abundant in heart, placenta and brain.
Induction:		A retroviral element acts as an alternative tissue-specific promoter for this gene. The LTR of an HERV-E element enhances the expression in placenta and embryonic kidney.
Ptm:		Phosphorylated on serine and threonine residues. {ECO:0000269\|PubMed:11806752}.
Disease:		Opitz GBBB syndrome 1 (GBBB1) [MIM:300000]: A congenital midline malformation syndrome characterized by hypertelorism, genital- urinary defects such as hypospadias in males and splayed labia in females, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and congenital heart defects. {ECO:0000269\|PubMed:11030761, ECO:0000269\|PubMed:15558842, ECO:0000269\|PubMed:9354791, ECO:0000269\|PubMed:9718340}. Note=The disease is caused by variants affecting the gene represented in this entry. MID1 mutations produce proteins with a decreased affinity for microtubules.
Similarity:		Belongs to the TRIM/RBCC family. {ECO:0000305}.