UniProt functional annotation for P07174



	UniProt functional annotation for P07174

UniProt code: P07174.

Organism: Rattus norvegicus (Rat).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.

Function: Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4 (PubMed:3027580, PubMed:15131306, PubMed:18596692). Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF, BDNF and NTF3 with high affinity, and has much lower affinity for mature NGF and BDNF (PubMed:24908487, PubMed:22155786). In response to proNGF binding, the heterodimeric receptor with SORCS2 activates a signaling cascade that leads to decreased Rac activity, reorganization of the actin cytoskeleton and neuronal growth cone collapse (PubMed:22155786). Plays an important role in differentiation and survival of specific neuronal populations during development (By similarity). Can mediate cell survival as well as cell death of neural cells (PubMed:10514511, PubMed:10985348, PubMed:24908487). Plays a role in the inactivation of RHOA (By similarity). Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Necessary for the circadian oscillation of the clock genes ARNTL/BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver (By similarity). {ECO:0000250|UniProtKB:P08138, ECO:0000250|UniProtKB:Q9Z0W1, ECO:0000269|PubMed:10514511, ECO:0000269|PubMed:10985348, ECO:0000269|PubMed:15131306, ECO:0000269|PubMed:18596692, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:3027580}.

Subunit: Homodimer; disulfide-linked (PubMed:27056327). Heterodimer with SORCS2 (PubMed:27457814, PubMed:22155786, PubMed:24908487). The extracellular domains of the heterodimer bind NGF (PubMed:22155786, PubMed:24908487). The cytoplasmic region of the heterodimer binds TRIO. NGF binding mediates dissociation of TRIO from the receptor complex (PubMed:22155786). Interacts with RTN4R (By similarity). Interacts with TRAF2, TRAF4 and TRAF6 (PubMed:10514511). Interacts with PTPN13 and RANBP9. Interacts through TRAF6 with SQSTM1 which bridges NGFR to NTRK1 (By similarity). Interacts with BEX1 (PubMed:16498402). Interacts with BEX3 (By similarity). Interacts with KIDINS220 and NTRK1. Can form a ternary complex with NTRK1 and KIDINS220 and this complex is affected by the expression levels of KIDINS220. An increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1 (PubMed:11150334, PubMed:15378608). Interacts (via death domain) with RAB31 (By similarity). Interacts with NTRK2; may regulate the ligand specificity of the NTRK2 receptor (PubMed:9927421). Interacts with LINGO1 (By similarity). Interacts with NRADD (PubMed:12095158). Interacts with MAGED1; the interaction antagonizes the association NGFR:NTRK1 (PubMed:10985348). Interacts (via death domain) with ARHGDIA and RIPK2 (By similarity). {ECO:0000250|UniProtKB:P08138, ECO:0000250|UniProtKB:Q9Z0W1, ECO:0000269|PubMed:10514511, ECO:0000269|PubMed:10985348, ECO:0000269|PubMed:11150334, ECO:0000269|PubMed:12095158, ECO:0000269|PubMed:15378608, ECO:0000269|PubMed:16498402, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:27056327, ECO:0000269|PubMed:27457814, ECO:0000269|PubMed:9927421}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:20036257, ECO:0000269|PubMed:22155786, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:3027580}; Single-pass type I membrane protein {ECO:0000305}. Perikaryon {ECO:0000269|PubMed:22155786}. Cell projection, growth cone {ECO:0000269|PubMed:22155786}. Cell projection, dendritic spine {ECO:0000250|UniProtKB:Q9Z0W1}.

Domain: Death domain is responsible for interaction with RANBP9. It also mediates interaction with ARHGDIA and RIPK2 (By similarity). {ECO:0000250|UniProtKB:P08138, ECO:0000269|PubMed:15378608}.

Domain: The extracellular domain is responsible for interaction with NTRK1. {ECO:0000269|PubMed:15378608}.

Ptm: Subject to intramembrane proteolytic cleavage by the gamma- secretase complex, giving rise to an intracellular fragment that is rapidly degraded via the proteasome. {ECO:0000269|PubMed:27056327}.

Ptm: N- and O-glycosylated. {ECO:0000269|PubMed:20036257}.

Ptm: Phosphorylated on serine residues.

Annotations taken from UniProtKB at the EBI.


Organism:		Rattus norvegicus (Rat).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus.



Function:		Low affinity receptor which can bind to NGF, BDNF, NTF3, and NTF4 (PubMed:3027580, PubMed:15131306, PubMed:18596692). Forms a heterodimeric receptor with SORCS2 that binds the precursor forms of NGF, BDNF and NTF3 with high affinity, and has much lower affinity for mature NGF and BDNF (PubMed:24908487, PubMed:22155786). In response to proNGF binding, the heterodimeric receptor with SORCS2 activates a signaling cascade that leads to decreased Rac activity, reorganization of the actin cytoskeleton and neuronal growth cone collapse (PubMed:22155786). Plays an important role in differentiation and survival of specific neuronal populations during development (By similarity). Can mediate cell survival as well as cell death of neural cells (PubMed:10514511, PubMed:10985348, PubMed:24908487). Plays a role in the inactivation of RHOA (By similarity). Plays a role in the regulation of the translocation of GLUT4 to the cell surface in adipocytes and skeletal muscle cells in response to insulin, probably by regulating RAB31 activity, and thereby contributes to the regulation of insulin-dependent glucose uptake (By similarity). Necessary for the circadian oscillation of the clock genes ARNTL/BMAL1, PER1, PER2 and NR1D1 in the suprachiasmatic nucleus (SCN) of the brain and in liver and of the genes involved in glucose and lipid metabolism in the liver (By similarity). {ECO:0000250\|UniProtKB:P08138, ECO:0000250\|UniProtKB:Q9Z0W1, ECO:0000269\|PubMed:10514511, ECO:0000269\|PubMed:10985348, ECO:0000269\|PubMed:15131306, ECO:0000269\|PubMed:18596692, ECO:0000269\|PubMed:22155786, ECO:0000269\|PubMed:24908487, ECO:0000269\|PubMed:3027580}.


Subunit:		Homodimer; disulfide-linked (PubMed:27056327). Heterodimer with SORCS2 (PubMed:27457814, PubMed:22155786, PubMed:24908487). The extracellular domains of the heterodimer bind NGF (PubMed:22155786, PubMed:24908487). The cytoplasmic region of the heterodimer binds TRIO. NGF binding mediates dissociation of TRIO from the receptor complex (PubMed:22155786). Interacts with RTN4R (By similarity). Interacts with TRAF2, TRAF4 and TRAF6 (PubMed:10514511). Interacts with PTPN13 and RANBP9. Interacts through TRAF6 with SQSTM1 which bridges NGFR to NTRK1 (By similarity). Interacts with BEX1 (PubMed:16498402). Interacts with BEX3 (By similarity). Interacts with KIDINS220 and NTRK1. Can form a ternary complex with NTRK1 and KIDINS220 and this complex is affected by the expression levels of KIDINS220. An increase in KIDINS220 expression leads to a decreased association of NGFR and NTRK1 (PubMed:11150334, PubMed:15378608). Interacts (via death domain) with RAB31 (By similarity). Interacts with NTRK2; may regulate the ligand specificity of the NTRK2 receptor (PubMed:9927421). Interacts with LINGO1 (By similarity). Interacts with NRADD (PubMed:12095158). Interacts with MAGED1; the interaction antagonizes the association NGFR:NTRK1 (PubMed:10985348). Interacts (via death domain) with ARHGDIA and RIPK2 (By similarity). {ECO:0000250\|UniProtKB:P08138, ECO:0000250\|UniProtKB:Q9Z0W1, ECO:0000269\|PubMed:10514511, ECO:0000269\|PubMed:10985348, ECO:0000269\|PubMed:11150334, ECO:0000269\|PubMed:12095158, ECO:0000269\|PubMed:15378608, ECO:0000269\|PubMed:16498402, ECO:0000269\|PubMed:22155786, ECO:0000269\|PubMed:24908487, ECO:0000269\|PubMed:27056327, ECO:0000269\|PubMed:27457814, ECO:0000269\|PubMed:9927421}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:20036257, ECO:0000269\|PubMed:22155786, ECO:0000269\|PubMed:24908487, ECO:0000269\|PubMed:3027580}; Single-pass type I membrane protein {ECO:0000305}. Perikaryon {ECO:0000269\|PubMed:22155786}. Cell projection, growth cone {ECO:0000269\|PubMed:22155786}. Cell projection, dendritic spine {ECO:0000250\|UniProtKB:Q9Z0W1}.
Domain:		Death domain is responsible for interaction with RANBP9. It also mediates interaction with ARHGDIA and RIPK2 (By similarity). {ECO:0000250\|UniProtKB:P08138, ECO:0000269\|PubMed:15378608}.
Domain:		The extracellular domain is responsible for interaction with NTRK1. {ECO:0000269\|PubMed:15378608}.
Ptm:		Subject to intramembrane proteolytic cleavage by the gamma- secretase complex, giving rise to an intracellular fragment that is rapidly degraded via the proteasome. {ECO:0000269\|PubMed:27056327}.
Ptm:		N- and O-glycosylated. {ECO:0000269\|PubMed:20036257}.
Ptm:		Phosphorylated on serine residues.