UniProt functional annotation for P21796



	UniProt functional annotation for P21796

UniProt code: P21796.

Organism: Homo sapiens (Human).

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

Function: Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:11845315, PubMed:18755977, PubMed:20230784, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol (PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756). May mediate ATP export from cells (PubMed:30061676). {ECO:0000269|PubMed:11845315, ECO:0000269|PubMed:15033708, ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:20230784, ECO:0000269|PubMed:25296756, ECO:0000269|PubMed:30061676, ECO:0000269|PubMed:31015432, ECO:0000269|PubMed:32047033, ECO:0000269|PubMed:8420959}.

Activity regulation: Inhibited by nitric oxide. {ECO:0000269|PubMed:21156174}.

Subunit: Homodimer and homotrimer; in response to cyclic AMP or calcium (PubMed:30061676). Interacts with hexokinases including HK1 (PubMed:8420959, PubMed:22304920). The HK1-VDAC1 complex interacts with ATF2 (PubMed:22304920). Interacts with BCL2L1 (PubMed:18755977, PubMed:25296756). Interacts with BAK1 (PubMed:25296756). Interacts with RTL10/BOP (via BH3 domain) (PubMed:23055042). Interacts with amyloid- beta and APP; induces VDAC1 dephosphorylation (PubMed:25168729). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735). Interacts with SPG7, NIPSNAP2 and SLC25A30 (PubMed:26387735). Interacts with TMEM41B (PubMed:30352685). Interacts with BCAP31 (PubMed:31206022). {ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:22304920, ECO:0000269|PubMed:23055042, ECO:0000269|PubMed:25168729, ECO:0000269|PubMed:25296756, ECO:0000269|PubMed:26387735, ECO:0000269|PubMed:30061676, ECO:0000269|PubMed:30352685, ECO:0000269|PubMed:31206022, ECO:0000269|PubMed:8420959}.

Subunit: (Microbial infection) Interacts with influenza A virus PB1-F2 protein. {ECO:0000269|PubMed:16201016}.

Subcellular location: Mitochondrion outer membrane {ECO:0000269|PubMed:31015432, ECO:0000269|PubMed:31206022, ECO:0000269|PubMed:7539795}; Multi-pass membrane protein {ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:18832158, ECO:0000269|PubMed:27641616}. Cell membrane {ECO:0000269|PubMed:25168729, ECO:0000269|PubMed:25296756}; Multi-pass membrane protein {ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:18832158}. Membrane raft {ECO:0000269|PubMed:25168729}; Multi-pass membrane protein {ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:18832158}.

Tissue specificity: Expressed in erythrocytes (at protein level) (PubMed:27641616). Expressed in heart, liver and skeletal muscle (PubMed:8420959). {ECO:0000269|PubMed:27641616, ECO:0000269|PubMed:8420959}.

Domain: Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands (PubMed:18832158, PubMed:18755977). The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity (PubMed:18832158, PubMed:18755977). {ECO:0000269|PubMed:18755977, ECO:0000269|PubMed:18832158}.

Ptm: Phosphorylation at Ser-193 by NEK1 promotes the open conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury. Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation. {ECO:0000269|PubMed:20230784}.

Ptm: Ubiquitinated (PubMed:25621951, PubMed:32047033). Undergoes monoubiquitination and polyubiquitination by PRKN; monoubiquitination at Lys-274 inhibits apoptosis, whereas polyubiquitination leads to its degradation and promotes mitophagy (PubMed:25621951, PubMed:32047033). Deubiquitinated by USP30 (PubMed:25621951). {ECO:0000269|PubMed:25621951, ECO:0000269|PubMed:32047033}.

Similarity: Belongs to the eukaryotic mitochondrial porin 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:		Forms a channel through the mitochondrial outer membrane and also the plasma membrane. The channel at the outer mitochondrial membrane allows diffusion of small hydrophilic molecules; in the plasma membrane it is involved in cell volume regulation and apoptosis. It adopts an open conformation at low or zero membrane potential and a closed conformation at potentials above 30-40 mV. The open state has a weak anion selectivity whereas the closed state is cation-selective (PubMed:11845315, PubMed:18755977, PubMed:20230784, PubMed:8420959). Binds various signaling molecules, including the sphingolipid ceramide, the phospholipid phosphatidylcholine, and the sterol cholesterol (PubMed:31015432). In depolarized mitochondria, acts downstream of PRKN and PINK1 to promote mitophagy or prevent apoptosis; polyubiquitination by PRKN promotes mitophagy, while monoubiquitination by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). May participate in the formation of the permeability transition pore complex (PTPC) responsible for the release of mitochondrial products that triggers apoptosis (PubMed:15033708, PubMed:25296756). May mediate ATP export from cells (PubMed:30061676). {ECO:0000269\|PubMed:11845315, ECO:0000269\|PubMed:15033708, ECO:0000269\|PubMed:18755977, ECO:0000269\|PubMed:20230784, ECO:0000269\|PubMed:25296756, ECO:0000269\|PubMed:30061676, ECO:0000269\|PubMed:31015432, ECO:0000269\|PubMed:32047033, ECO:0000269\|PubMed:8420959}.


Activity regulation:		Inhibited by nitric oxide. {ECO:0000269\|PubMed:21156174}.
Subunit:		Homodimer and homotrimer; in response to cyclic AMP or calcium (PubMed:30061676). Interacts with hexokinases including HK1 (PubMed:8420959, PubMed:22304920). The HK1-VDAC1 complex interacts with ATF2 (PubMed:22304920). Interacts with BCL2L1 (PubMed:18755977, PubMed:25296756). Interacts with BAK1 (PubMed:25296756). Interacts with RTL10/BOP (via BH3 domain) (PubMed:23055042). Interacts with amyloid- beta and APP; induces VDAC1 dephosphorylation (PubMed:25168729). Component of the mitochondrial permeability transition pore complex (mPTPC), at least composed of SPG7, VDAC1 and PPIF (PubMed:26387735). Interacts with SPG7, NIPSNAP2 and SLC25A30 (PubMed:26387735). Interacts with TMEM41B (PubMed:30352685). Interacts with BCAP31 (PubMed:31206022). {ECO:0000269\|PubMed:18755977, ECO:0000269\|PubMed:22304920, ECO:0000269\|PubMed:23055042, ECO:0000269\|PubMed:25168729, ECO:0000269\|PubMed:25296756, ECO:0000269\|PubMed:26387735, ECO:0000269\|PubMed:30061676, ECO:0000269\|PubMed:30352685, ECO:0000269\|PubMed:31206022, ECO:0000269\|PubMed:8420959}.
Subunit:		(Microbial infection) Interacts with influenza A virus PB1-F2 protein. {ECO:0000269\|PubMed:16201016}.
Subcellular location:		Mitochondrion outer membrane {ECO:0000269\|PubMed:31015432, ECO:0000269\|PubMed:31206022, ECO:0000269\|PubMed:7539795}; Multi-pass membrane protein {ECO:0000269\|PubMed:18755977, ECO:0000269\|PubMed:18832158, ECO:0000269\|PubMed:27641616}. Cell membrane {ECO:0000269\|PubMed:25168729, ECO:0000269\|PubMed:25296756}; Multi-pass membrane protein {ECO:0000269\|PubMed:18755977, ECO:0000269\|PubMed:18832158}. Membrane raft {ECO:0000269\|PubMed:25168729}; Multi-pass membrane protein {ECO:0000269\|PubMed:18755977, ECO:0000269\|PubMed:18832158}.
Tissue specificity:		Expressed in erythrocytes (at protein level) (PubMed:27641616). Expressed in heart, liver and skeletal muscle (PubMed:8420959). {ECO:0000269\|PubMed:27641616, ECO:0000269\|PubMed:8420959}.
Domain:		Consists mainly of a membrane-spanning beta-barrel formed by 19 beta-strands (PubMed:18832158, PubMed:18755977). The helical N-terminus folds back into the pore opening and plays a role in voltage-gated channel activity (PubMed:18832158, PubMed:18755977). {ECO:0000269\|PubMed:18755977, ECO:0000269\|PubMed:18832158}.
Ptm:		Phosphorylation at Ser-193 by NEK1 promotes the open conformational state preventing excessive mitochondrial membrane permeability and subsequent apoptotic cell death after injury. Phosphorylation by the AKT-GSK3B axis stabilizes the protein probably by preventing ubiquitin-mediated proteasomal degradation. {ECO:0000269\|PubMed:20230784}.
Ptm:		Ubiquitinated (PubMed:25621951, PubMed:32047033). Undergoes monoubiquitination and polyubiquitination by PRKN; monoubiquitination at Lys-274 inhibits apoptosis, whereas polyubiquitination leads to its degradation and promotes mitophagy (PubMed:25621951, PubMed:32047033). Deubiquitinated by USP30 (PubMed:25621951). {ECO:0000269\|PubMed:25621951, ECO:0000269\|PubMed:32047033}.
Similarity:		Belongs to the eukaryotic mitochondrial porin family. {ECO:0000305}.