UniProt functional annotation for A0FGR8



	UniProt functional annotation for A0FGR8

UniProt code: A0FGR8.

Organism: Homo sapiens (Human).

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

Function: Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP- 2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24847877, ECO:0000269|PubMed:27044890}.

Subunit: Homodimer. Interacts with ESYT1 and ESYT3. Interacts with FGFR1 that has been activated by FGF1 binding. Interacts with the AP-2 complex; identified in a complex with the AP-2 complex and FGFR1. {ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24373768, ECO:0000269|PubMed:24847877}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:20833364, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:29469807}; Peripheral membrane protein {ECO:0000269|PubMed:17360437}. Endoplasmic reticulum membrane {ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:29469807}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes to endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:29469807, PubMed:23791178, PubMed:30220461, PubMed:27044890). Recruited to the cell membrane via the third C2 domain (PubMed:17360437). {ECO:0000269|PubMed:17360437, ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:29469807, ECO:0000269|PubMed:30220461}.

Tissue specificity: Widely expressed with high level in cerebellum. {ECO:0000269|PubMed:17360437}.

Domain: Anchored to the endoplasmic reticulum membrane by a transmembrane hairpin structure; both N-terminus and C-terminus are cytoplasmic. {ECO:0000269|PubMed:23791178}.

Domain: The C2 domains mediate lipid and calcium binding. The N- terminal C2 domain binds calcium ions and is important for calcium- dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium (PubMed:24373768). The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for location at the cell membrane (PubMed:23791178). {ECO:0000269|PubMed:23791178, ECO:0000269|PubMed:24373768}.

Domain: The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior; can bind two lipid molecules simultaneously. Binds a variety of lipids, including phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol (PubMed:24847877). {ECO:0000269|PubMed:24847877}.

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

Sequence caution: Sequence=BAA91539.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAC85769.1; 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:		Tethers the endoplasmic reticulum to the cell membrane and promotes the formation of appositions between the endoplasmic reticulum and the cell membrane. Binds glycerophospholipids in a barrel-like domain and may play a role in cellular lipid transport. Plays a role in FGF signaling via its role in the rapid internalization of FGFR1 that has been activated by FGF1 binding; this occurs most likely via the AP- 2 complex. Promotes the localization of SACM1L at endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:27044890). {ECO:0000269\|PubMed:17360437, ECO:0000269\|PubMed:20833364, ECO:0000269\|PubMed:23791178, ECO:0000269\|PubMed:24847877, ECO:0000269\|PubMed:27044890}.


Subunit:		Homodimer. Interacts with ESYT1 and ESYT3. Interacts with FGFR1 that has been activated by FGF1 binding. Interacts with the AP-2 complex; identified in a complex with the AP-2 complex and FGFR1. {ECO:0000269\|PubMed:20833364, ECO:0000269\|PubMed:23791178, ECO:0000269\|PubMed:24373768, ECO:0000269\|PubMed:24847877}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:17360437, ECO:0000269\|PubMed:20833364, ECO:0000269\|PubMed:23791178, ECO:0000269\|PubMed:29469807}; Peripheral membrane protein {ECO:0000269\|PubMed:17360437}. Endoplasmic reticulum membrane {ECO:0000269\|PubMed:23791178, ECO:0000269\|PubMed:29469807}; Multi-pass membrane protein {ECO:0000255}. Note=Localizes to endoplasmic reticulum-plasma membrane contact sites (EPCS) (PubMed:29469807, PubMed:23791178, PubMed:30220461, PubMed:27044890). Recruited to the cell membrane via the third C2 domain (PubMed:17360437). {ECO:0000269\|PubMed:17360437, ECO:0000269\|PubMed:23791178, ECO:0000269\|PubMed:29469807, ECO:0000269\|PubMed:30220461}.
Tissue specificity:		Widely expressed with high level in cerebellum. {ECO:0000269\|PubMed:17360437}.
Domain:		Anchored to the endoplasmic reticulum membrane by a transmembrane hairpin structure; both N-terminus and C-terminus are cytoplasmic. {ECO:0000269\|PubMed:23791178}.
Domain:		The C2 domains mediate lipid and calcium binding. The N- terminal C2 domain binds calcium ions and is important for calcium- dependent lipid binding and interaction with membranes. Two calcium ions are bound at a high-affinity site and a third calcium ion is bound with lower affinity. May bind up to four calcium ions. In contrast, the second C2 domain apparently does not bind calcium (PubMed:24373768). The third C2 domain mediates interaction with membranes enriched in phosphatidylinositol 4,5-bisphosphate and is required for location at the cell membrane (PubMed:23791178). {ECO:0000269\|PubMed:23791178, ECO:0000269\|PubMed:24373768}.
Domain:		The SMP-LTD domain is a barrel-like domain that binds glycerophospholipids in its interior; can bind two lipid molecules simultaneously. Binds a variety of lipids, including phosphatidylethanolamine, phosphatidylcholine and phosphatidylinositol (PubMed:24847877). {ECO:0000269\|PubMed:24847877}.
Similarity:		Belongs to the extended synaptotagmin family. {ECO:0000305}.
Sequence caution:		Sequence=BAA91539.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=BAC85769.1; Type=Frameshift; Evidence={ECO:0000305};