UniProt functional annotation for O43521



	UniProt functional annotation for O43521

UniProt code: O43521.

Organism: Homo sapiens (Human).

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

Function: Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase- mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis. {ECO:0000269|PubMed:11997495, ECO:0000269|PubMed:15486195, ECO:0000269|PubMed:9430630}.

Subunit: Forms heterodimers with a number of antiapoptotic Bcl-2 proteins, including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1, BHRF1, and BCL2L2/BCLW (PubMed:11997495, PubMed:27013495, PubMed:18812174). Isoform BimS and isoform Bim-alpha3 interact with BAX; this interaction may lead to BAX activation through conformational change (PubMed:11997495). Does not heterodimerize with proapoptotic proteins such as BAD, BOK or BAK. Identified in a complex containing BCL2L11, DYNLL1 and BCL2L1 isoform Bcl-X(L); BH3 integrity is required for BCL2L1-binding. Interacts with YWHAZ. When phosphorylated, interacts with TRIM2; this interaction is associated with ubiquitination and degradation (PubMed:21478148). Interacts with MCL1; may sequester BCL2L11 to prevent its pro-apoptotic activity (PubMed:27013495, PubMed:17389404). When phosphorylated, isoform BimEL interacts with USP27X; this interaction leads to BCL2L11 deubiquitination and stabilization (PubMed:27013495). Interacts with GIMAP5 (PubMed:16509771). {ECO:0000269|PubMed:11997495, ECO:0000269|PubMed:16509771, ECO:0000269|PubMed:17389404, ECO:0000269|PubMed:18812174, ECO:0000269|PubMed:21478148, ECO:0000269|PubMed:27013495}.

Subcellular location: Endomembrane system {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=Associated with intracytoplasmic membranes. {ECO:0000250}.

Subcellular location: [Isoform BimEL]: Mitochondrion. Note=Translocates from microtubules to mitochondria on loss of cell adherence.

Subcellular location: [Isoform BimL]: Mitochondrion.

Subcellular location: [Isoform BimS]: Mitochondrion.

Subcellular location: [Isoform Bim-alpha1]: Mitochondrion.

Tissue specificity: Isoform BimEL, isoform BimL and isoform BimS are the predominant isoforms and are widely expressed with tissue-specific variation. Isoform Bim-gamma is most abundantly expressed in small intestine and colon, and in lower levels in spleen, prostate, testis, heart, liver and kidney. {ECO:0000269|PubMed:12019181}.

Induction: By ER stress in a DDIT3/CHOP-dependent manner. {ECO:0000269|PubMed:22761832}.

Domain: The BH3 motif is required for interaction with Bcl-2 proteins and cytotoxicity. {ECO:0000250|UniProtKB:O54918}.

Ptm: Phosphorylation at Ser-69 by MAPK1/MAPK3 leads to interaction with TRIM2 and polyubiquitination, followed by proteasomal degradation (PubMed:15486195, PubMed:21478148). Deubiquitination catalyzed by USP27X stabilizes the protein (By similarity). {ECO:0000250|UniProtKB:O54918, ECO:0000269|PubMed:15486195, ECO:0000269|PubMed:21478148}.

Ptm: Ubiquitination by TRIM2 following phosphorylation by MAPK1/MAPK3 leads to proteasomal degradation. Conversely, deubiquitination catalyzed by USP27X stabilizes the protein. {ECO:0000250|UniProtKB:O54918}.

Similarity: Belongs to the Bcl-2 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:		Induces apoptosis and anoikis. Isoform BimL is more potent than isoform BimEL. Isoform Bim-alpha1, isoform Bim-alpha2 and isoform Bim-alpha3 induce apoptosis, although less potent than isoform BimEL, isoform BimL and isoform BimS. Isoform Bim-gamma induces apoptosis. Isoform Bim-alpha3 induces apoptosis possibly through a caspase- mediated pathway. Isoform BimAC and isoform BimABC lack the ability to induce apoptosis. {ECO:0000269\|PubMed:11997495, ECO:0000269\|PubMed:15486195, ECO:0000269\|PubMed:9430630}.


Subunit:		Forms heterodimers with a number of antiapoptotic Bcl-2 proteins, including MCL1, BCL2, BCL2L1 isoform Bcl-X(L), BCL2A1/BFL-1, BHRF1, and BCL2L2/BCLW (PubMed:11997495, PubMed:27013495, PubMed:18812174). Isoform BimS and isoform Bim-alpha3 interact with BAX; this interaction may lead to BAX activation through conformational change (PubMed:11997495). Does not heterodimerize with proapoptotic proteins such as BAD, BOK or BAK. Identified in a complex containing BCL2L11, DYNLL1 and BCL2L1 isoform Bcl-X(L); BH3 integrity is required for BCL2L1-binding. Interacts with YWHAZ. When phosphorylated, interacts with TRIM2; this interaction is associated with ubiquitination and degradation (PubMed:21478148). Interacts with MCL1; may sequester BCL2L11 to prevent its pro-apoptotic activity (PubMed:27013495, PubMed:17389404). When phosphorylated, isoform BimEL interacts with USP27X; this interaction leads to BCL2L11 deubiquitination and stabilization (PubMed:27013495). Interacts with GIMAP5 (PubMed:16509771). {ECO:0000269\|PubMed:11997495, ECO:0000269\|PubMed:16509771, ECO:0000269\|PubMed:17389404, ECO:0000269\|PubMed:18812174, ECO:0000269\|PubMed:21478148, ECO:0000269\|PubMed:27013495}.
Subcellular location:		Endomembrane system {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Note=Associated with intracytoplasmic membranes. {ECO:0000250}.
Subcellular location:		[Isoform BimEL]: Mitochondrion. Note=Translocates from microtubules to mitochondria on loss of cell adherence.
Subcellular location:		[Isoform BimL]: Mitochondrion.
Subcellular location:		[Isoform BimS]: Mitochondrion.
Subcellular location:		[Isoform Bim-alpha1]: Mitochondrion.
Tissue specificity:		Isoform BimEL, isoform BimL and isoform BimS are the predominant isoforms and are widely expressed with tissue-specific variation. Isoform Bim-gamma is most abundantly expressed in small intestine and colon, and in lower levels in spleen, prostate, testis, heart, liver and kidney. {ECO:0000269\|PubMed:12019181}.
Induction:		By ER stress in a DDIT3/CHOP-dependent manner. {ECO:0000269\|PubMed:22761832}.
Domain:		The BH3 motif is required for interaction with Bcl-2 proteins and cytotoxicity. {ECO:0000250\|UniProtKB:O54918}.
Ptm:		Phosphorylation at Ser-69 by MAPK1/MAPK3 leads to interaction with TRIM2 and polyubiquitination, followed by proteasomal degradation (PubMed:15486195, PubMed:21478148). Deubiquitination catalyzed by USP27X stabilizes the protein (By similarity). {ECO:0000250\|UniProtKB:O54918, ECO:0000269\|PubMed:15486195, ECO:0000269\|PubMed:21478148}.
Ptm:		Ubiquitination by TRIM2 following phosphorylation by MAPK1/MAPK3 leads to proteasomal degradation. Conversely, deubiquitination catalyzed by USP27X stabilizes the protein. {ECO:0000250\|UniProtKB:O54918}.
Similarity:		Belongs to the Bcl-2 family. {ECO:0000305}.