UniProt functional annotation for P01138



	UniProt functional annotation for P01138

UniProt code: P01138.

Organism: Homo sapiens (Human).

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

Function: Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:14976160, PubMed:20978020). Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival (PubMed:20978020) (Probable). The immature NGF precursor (proNGF) functions as ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse. In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro) (By similarity). Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI (PubMed:20164177). Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer. The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form (By similarity). {ECO:0000250|UniProtKB:P01139, ECO:0000269|PubMed:14976160, ECO:0000269|PubMed:20164177, ECO:0000269|PubMed:20978020, ECO:0000305|PubMed:10490030, ECO:0000305|PubMed:15131306}.

Subunit: Homodimer (PubMed:10490030, PubMed:15131306, PubMed:17196528). The homodimer interacts with a single NTRK1 chain (PubMed:10490030, PubMed:17196528). The homodimer interacts with a single NGFR chain (PubMed:15131306). The NGF dimer interacts with a single SORCS2 chain (via extracellular domain) (By similarity). The NGF precursor (proNGF) binds to a receptor complex formed by SORT1 and NGFR, which leads to NGF endocytosis. Both mature NGF and the immature NGF precursor (proNGF) interact with SORCS2 and with the heterodimer formed by SORCS2 and NGFR (via extracellular domains) (By similarity). The NGF precursor (proNGF) has much higher affinity for SORCS2 than mature NGF. The NGF precursor (proNGF) has much higher affinity for SORT1 than mature NGF (By similarity). Interacts with ADAM10 in a divalent cation-dependent manner (PubMed:20164177). {ECO:0000250|UniProtKB:P01139, ECO:0000269|PubMed:10490030, ECO:0000269|PubMed:15131306, ECO:0000269|PubMed:17196528, ECO:0000269|PubMed:20164177}.

Subcellular location: Secreted {ECO:0000269|PubMed:20978020}. Endosome lumen {ECO:0000250|UniProtKB:P01139}. Note=ProNGF is endocytosed after binding to the cell surface receptor formed by SORT1 and NGFR. {ECO:0000250|UniProtKB:P01139}.

Disease: Neuropathy, hereditary sensory and autonomic, 5 (HSAN5) [MIM:608654]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable. {ECO:0000269|PubMed:14976160, ECO:0000269|PubMed:20978020, ECO:0000269|PubMed:22302274}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the NGF-beta family. {ECO:0000305}.

Sequence caution: Sequence=AAH32517.2; Type=Erroneous initiation; Note=Extended N-terminus.; 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:		Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems (PubMed:14976160, PubMed:20978020). Extracellular ligand for the NTRK1 and NGFR receptors, activates cellular signaling cascades to regulate neuronal proliferation, differentiation and survival (PubMed:20978020) (Probable). The immature NGF precursor (proNGF) functions as ligand for the heterodimeric receptor formed by SORCS2 and NGFR, and activates cellular signaling cascades that lead to inactivation of RAC1 and/or RAC2, reorganization of the actin cytoskeleton and neuronal growth cone collapse. In contrast to mature NGF, the precursor form (proNGF) promotes neuronal apoptosis (in vitro) (By similarity). Inhibits metalloproteinase-dependent proteolysis of platelet glycoprotein VI (PubMed:20164177). Binds lysophosphatidylinositol and lysophosphatidylserine between the two chains of the homodimer. The lipid-bound form promotes histamine relase from mast cells, contrary to the lipid-free form (By similarity). {ECO:0000250\|UniProtKB:P01139, ECO:0000269\|PubMed:14976160, ECO:0000269\|PubMed:20164177, ECO:0000269\|PubMed:20978020, ECO:0000305\|PubMed:10490030, ECO:0000305\|PubMed:15131306}.


Subunit:		Homodimer (PubMed:10490030, PubMed:15131306, PubMed:17196528). The homodimer interacts with a single NTRK1 chain (PubMed:10490030, PubMed:17196528). The homodimer interacts with a single NGFR chain (PubMed:15131306). The NGF dimer interacts with a single SORCS2 chain (via extracellular domain) (By similarity). The NGF precursor (proNGF) binds to a receptor complex formed by SORT1 and NGFR, which leads to NGF endocytosis. Both mature NGF and the immature NGF precursor (proNGF) interact with SORCS2 and with the heterodimer formed by SORCS2 and NGFR (via extracellular domains) (By similarity). The NGF precursor (proNGF) has much higher affinity for SORCS2 than mature NGF. The NGF precursor (proNGF) has much higher affinity for SORT1 than mature NGF (By similarity). Interacts with ADAM10 in a divalent cation-dependent manner (PubMed:20164177). {ECO:0000250\|UniProtKB:P01139, ECO:0000269\|PubMed:10490030, ECO:0000269\|PubMed:15131306, ECO:0000269\|PubMed:17196528, ECO:0000269\|PubMed:20164177}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:20978020}. Endosome lumen {ECO:0000250\|UniProtKB:P01139}. Note=ProNGF is endocytosed after binding to the cell surface receptor formed by SORT1 and NGFR. {ECO:0000250\|UniProtKB:P01139}.
Disease:		Neuropathy, hereditary sensory and autonomic, 5 (HSAN5) [MIM:608654]: A form of hereditary sensory and autonomic neuropathy, a genetically and clinically heterogeneous group of disorders characterized by degeneration of dorsal root and autonomic ganglion cells, and by sensory and/or autonomic abnormalities. HSAN5 patients manifest loss of pain perception and impaired temperature sensitivity, ulcers, and in some cases self-mutilation. The autonomic involvement is variable. {ECO:0000269\|PubMed:14976160, ECO:0000269\|PubMed:20978020, ECO:0000269\|PubMed:22302274}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the NGF-beta family. {ECO:0000305}.
Sequence caution:		Sequence=AAH32517.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};