UniProt functional annotation for O43581



	UniProt functional annotation for O43581

UniProt code: O43581.

Organism: Homo sapiens (Human).

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

Function: Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain (By similarity). Ca(2+) induces binding of the C2- domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis (By similarity). SYT7 binds Ca(2+) with high affinity and slow kinetics compared to other synaptotagmins (By similarity). Involved in Ca(2+)-triggered lysosomal exocytosis, a major component of the plasma membrane repair (PubMed:11342594). Ca(2+)-regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (By similarity). Ca(2+)-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (By similarity). In case of infection, involved in participates cell invasion by Trypanosoma cruzi via Ca(2+)- triggered lysosomal exocytosis (PubMed:11342594, PubMed:15811535). Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5- bisphosphate on peroxisomal membranes (By similarity). Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca(2+) into the axon terminal after spike generation, increasing the release probability of neurotransmitters (By similarity). Probably mediates synaptic facilitation by directly increasing the probability of release (By similarity). May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca(2+) and by forming a complex with calmodulin (By similarity). Also acts as a regulator of Ca(2+)- dependent insulin and glucagon secretion in beta-cells (By similarity). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (By similarity). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity). {ECO:0000250|UniProtKB:Q62747, ECO:0000250|UniProtKB:Q9R0N7, ECO:0000269|PubMed:11342594, ECO:0000269|PubMed:15811535}.

Cofactor: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255|PROSITE-ProRule:PRU00041}; Note=Binds 3 Ca(2+) ions per C2 domain. {ECO:0000255|PROSITE- ProRule:PRU00041};

Subunit: Homodimer. Can also form heterodimers with SYT6, SYT9 and SYT10. Interacts with calmodulin (CALM1, CALM2 or CALM3). Interacts with CD63; required for localization to lysosomes. Interacts with APP (By similarity). {ECO:0000250|UniProtKB:Q9R0N7}.

Subcellular location: Cell membrane {ECO:0000250|UniProtKB:Q62747}; Single-pass membrane protein {ECO:0000255}. Cell junction, synapse, presynaptic cell membrane {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Peroxisome membrane {ECO:0000250|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250|UniProtKB:Q62747}; Single-pass membrane protein {ECO:0000255}. Note=Localization to lysosomes is dependent on N-terminal palmitoylation and interaction with CD63. {ECO:0000250|UniProtKB:Q9R0N7}.

Tissue specificity: Expressed in a variety of adult and fetal tissues.

Domain: The C2 domains bind Ca(2+) and membranes. Binding to membranes involves Ca(2+)-dependent phospholipid binding. Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca(2+) concentrations that are lower than those required for other synaptotagmins (PubMed:22966849). The two C2 domains bind independently to planar membranes, without interdomain cooperativity (PubMed:25437758). Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins (PubMed:26322740, PubMed:26333120). {ECO:0000269|PubMed:22966849, ECO:0000269|PubMed:25437758, ECO:0000269|PubMed:26322740, ECO:0000269|PubMed:26333120}.

Ptm: Palmitoylated at its vesicular N-terminus; palmitoylation is required for localization to lysosome and phagocytosis in macrophages. {ECO:0000250|UniProtKB:Q9R0N7}.

Miscellaneous: [Isoform 1]: Major isoform. {ECO:0000269|PubMed:12071850}.

Similarity: Belongs to the synaptotagmin family. {ECO:0000305}.

Sequence caution: Sequence=AAB92667.1; Type=Frameshift; Evidence={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:		Ca(2+) sensor involved in Ca(2+)-dependent exocytosis of secretory and synaptic vesicles through Ca(2+) and phospholipid binding to the C2 domain (By similarity). Ca(2+) induces binding of the C2- domains to phospholipid membranes and to assembled SNARE-complexes; both actions contribute to triggering exocytosis (By similarity). SYT7 binds Ca(2+) with high affinity and slow kinetics compared to other synaptotagmins (By similarity). Involved in Ca(2+)-triggered lysosomal exocytosis, a major component of the plasma membrane repair (PubMed:11342594). Ca(2+)-regulated delivery of lysosomal membranes to the cell surface is also involved in the phagocytic uptake of particles by macrophages (By similarity). Ca(2+)-triggered lysosomal exocytosis also plays a role in bone remodeling by regulating secretory pathways in osteoclasts and osteoblasts (By similarity). In case of infection, involved in participates cell invasion by Trypanosoma cruzi via Ca(2+)- triggered lysosomal exocytosis (PubMed:11342594, PubMed:15811535). Involved in cholesterol transport from lysosome to peroxisome by promoting membrane contacts between lysosomes and peroxisomes: probably acts by promoting vesicle fusion by binding phosphatidylinositol-4,5- bisphosphate on peroxisomal membranes (By similarity). Acts as a key mediator of synaptic facilitation, a process also named short-term synaptic potentiation: synaptic facilitation takes place at synapses with a low initial release probability and is caused by influx of Ca(2+) into the axon terminal after spike generation, increasing the release probability of neurotransmitters (By similarity). Probably mediates synaptic facilitation by directly increasing the probability of release (By similarity). May also contribute to synaptic facilitation by regulating synaptic vesicle replenishment, a process required to ensure that synaptic vesicles are ready for the arrival of the next action potential: SYT7 is required for synaptic vesicle replenishment by acting as a sensor for Ca(2+) and by forming a complex with calmodulin (By similarity). Also acts as a regulator of Ca(2+)- dependent insulin and glucagon secretion in beta-cells (By similarity). Triggers exocytosis by promoting fusion pore opening and fusion pore expansion in chromaffin cells (By similarity). Also regulates the secretion of some non-synaptic secretory granules of specialized cells (By similarity). {ECO:0000250\|UniProtKB:Q62747, ECO:0000250\|UniProtKB:Q9R0N7, ECO:0000269\|PubMed:11342594, ECO:0000269\|PubMed:15811535}.


Cofactor:		Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000255\|PROSITE-ProRule:PRU00041}; Note=Binds 3 Ca(2+) ions per C2 domain. {ECO:0000255\|PROSITE- ProRule:PRU00041};
Subunit:		Homodimer. Can also form heterodimers with SYT6, SYT9 and SYT10. Interacts with calmodulin (CALM1, CALM2 or CALM3). Interacts with CD63; required for localization to lysosomes. Interacts with APP (By similarity). {ECO:0000250\|UniProtKB:Q9R0N7}.
Subcellular location:		Cell membrane {ECO:0000250\|UniProtKB:Q62747}; Single-pass membrane protein {ECO:0000255}. Cell junction, synapse, presynaptic cell membrane {ECO:0000250\|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane {ECO:0000250\|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Lysosome membrane {ECO:0000250\|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, phagosome membrane {ECO:0000250\|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Peroxisome membrane {ECO:0000250\|UniProtKB:Q9R0N7}; Single-pass membrane protein {ECO:0000255}. Cytoplasmic vesicle, secretory vesicle membrane {ECO:0000250\|UniProtKB:Q62747}; Single-pass membrane protein {ECO:0000255}. Note=Localization to lysosomes is dependent on N-terminal palmitoylation and interaction with CD63. {ECO:0000250\|UniProtKB:Q9R0N7}.
Tissue specificity:		Expressed in a variety of adult and fetal tissues.
Domain:		The C2 domains bind Ca(2+) and membranes. Binding to membranes involves Ca(2+)-dependent phospholipid binding. Compared to other members of the family, the C2 domains of SYT7 dock and insert into cellular membranes in response to intracellular Ca(2+) concentrations that are lower than those required for other synaptotagmins (PubMed:22966849). The two C2 domains bind independently to planar membranes, without interdomain cooperativity (PubMed:25437758). Moreover, SYT7 C2 domains insert more deeply into membranes compared to other synaptotagmins (PubMed:26322740, PubMed:26333120). {ECO:0000269\|PubMed:22966849, ECO:0000269\|PubMed:25437758, ECO:0000269\|PubMed:26322740, ECO:0000269\|PubMed:26333120}.
Ptm:		Palmitoylated at its vesicular N-terminus; palmitoylation is required for localization to lysosome and phagocytosis in macrophages. {ECO:0000250\|UniProtKB:Q9R0N7}.
Miscellaneous:		[Isoform 1]: Major isoform. {ECO:0000269\|PubMed:12071850}.
Similarity:		Belongs to the synaptotagmin family. {ECO:0000305}.
Sequence caution:		Sequence=AAB92667.1; Type=Frameshift; Evidence={ECO:0000305};