UniProt functional annotation for O43464



	UniProt functional annotation for O43464

UniProt code: O43464.

Organism: Homo sapiens (Human).

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

Function: Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase- independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive. {ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:19502560}.

Catalytic activity: Reaction=Cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues.; EC=3.4.21.108;

Subunit: Homotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions. The mature protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with BIRC6/bruce. {ECO:0000269|PubMed:11583623, ECO:0000269|PubMed:11967569, ECO:0000269|PubMed:15200957, ECO:0000269|PubMed:19502560}.

Subcellular location: Mitochondrion intermembrane space. Mitochondrion membrane {ECO:0000305}; Single-pass membrane protein {ECO:0000305}. Note=Predominantly present in the intermembrane space. Released into the cytosol following apoptotic stimuli, such as UV treatment, and stimulation of mitochondria with caspase-8 truncated BID/tBID.

Tissue specificity: Isoform 1 is ubiquitous. Isoform 2 is expressed predominantly in the kidney, colon and thyroid.

Domain: The mature N-terminus is involved in the interaction with XIAP.

Domain: The PDZ domain mediates interaction with MXI2.

Ptm: Autoproteolytically activated.

Disease: 3-methylglutaconic aciduria 8 (MGCA8) [MIM:617248]: An autosomal recessive inborn error of metabolism resulting in early death. Clinical features include extreme hypertonia observed at birth, alternating with hypotonia, subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, and intractable seizures. Patients show lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, and progressive brain atrophy. {ECO:0000269|PubMed:27208207, ECO:0000269|PubMed:27696117}. Note=The disease is caused by variants affecting the gene represented in this entry.

Disease: Parkinson disease 13 (PARK13) [MIM:610297]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. {ECO:0000269|PubMed:15961413, ECO:0000269|PubMed:18401856}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase S1C 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:		Serine protease that shows proteolytic activity against a non-specific substrate beta-casein. Promotes or induces cell death either by direct binding to and inhibition of BIRC proteins (also called inhibitor of apoptosis proteins, IAPs), leading to an increase in caspase activity, or by a BIRC inhibition-independent, caspase- independent and serine protease activity-dependent mechanism. Cleaves THAP5 and promotes its degradation during apoptosis. Isoform 2 seems to be proteolytically inactive. {ECO:0000269\|PubMed:15200957, ECO:0000269\|PubMed:19502560}.


Catalytic activity:		Reaction=Cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues.; EC=3.4.21.108;
Subunit:		Homotrimer. Interacts with MXI2. Interacts with THAP5 under apoptotic conditions. The mature protein, but not the precursor, binds to BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Interacts with BIRC6/bruce. {ECO:0000269\|PubMed:11583623, ECO:0000269\|PubMed:11967569, ECO:0000269\|PubMed:15200957, ECO:0000269\|PubMed:19502560}.
Subcellular location:		Mitochondrion intermembrane space. Mitochondrion membrane {ECO:0000305}; Single-pass membrane protein {ECO:0000305}. Note=Predominantly present in the intermembrane space. Released into the cytosol following apoptotic stimuli, such as UV treatment, and stimulation of mitochondria with caspase-8 truncated BID/tBID.
Tissue specificity:		Isoform 1 is ubiquitous. Isoform 2 is expressed predominantly in the kidney, colon and thyroid.
Domain:		The mature N-terminus is involved in the interaction with XIAP.
Domain:		The PDZ domain mediates interaction with MXI2.
Ptm:		Autoproteolytically activated.
Disease:		3-methylglutaconic aciduria 8 (MGCA8) [MIM:617248]: An autosomal recessive inborn error of metabolism resulting in early death. Clinical features include extreme hypertonia observed at birth, alternating with hypotonia, subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, and intractable seizures. Patients show lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, and progressive brain atrophy. {ECO:0000269\|PubMed:27208207, ECO:0000269\|PubMed:27696117}. Note=The disease is caused by variants affecting the gene represented in this entry.
Disease:		Parkinson disease 13 (PARK13) [MIM:610297]: A complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. {ECO:0000269\|PubMed:15961413, ECO:0000269\|PubMed:18401856}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase S1C family. {ECO:0000305}.