UniProt functional annotation for P23560



	UniProt functional annotation for P23560

UniProt code: P23560.

Organism: Homo sapiens (Human).

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

Function: Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability. {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:12553913, ECO:0000269|PubMed:29909994}.

Function: [BDNF precursor form]: Important signaling molecule that activates signaling cascades downstream of NTRK2. Activates signaling cascades via the heterodimeric receptor formed by NGFR and SORCS2 (PubMed:24908487, PubMed:29909994). Signaling via NGFR and SORCS2 plays a role in synaptic plasticity and long-term depression (LTD). Binding to NGFR and SORCS2 promotes neuronal apoptosis. Promotes neuronal growth cone collapse (By similarity). {ECO:0000250|UniProtKB:P21237, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:29909994}.

Subunit: Monomers and homodimers. Binds to NTRK2/TRKB (PubMed:8527932, PubMed:11152678). Can form heterodimers with other neurotrophin family members, such as NTF3 and NTF4 (in vitro), but the physiological relevance of this is not clear (PubMed:7703225, PubMed:10631974). BDNF precursor form: interacts with the heterodimer formed by NGFR and SORCS2 (PubMed:24908487). {ECO:0000269|PubMed:10631974, ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:24908487, ECO:0000269|PubMed:7703225, ECO:0000269|PubMed:8527932}.

Subcellular location: Secreted {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:19467646, ECO:0000269|PubMed:8527932}.

Subcellular location: [BDNF precursor form]: Secreted {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:19467646}. Note=A proportion of BDNF is secreted as immature precursor (proBDNF). {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:19467646}.

Tissue specificity: Detected in blood plasma and in saliva (at protein level) (PubMed:11152678, PubMed:19467646). Brain. Highly expressed in hippocampus, amygdala, cerebral cortex and cerebellum. Also expressed in heart, lung, skeletal muscle, testis, prostate and placenta. {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:17629449, ECO:0000269|PubMed:19467646, ECO:0000269|PubMed:2236018}.

Ptm: [BDNF precursor form]: N-glycosylated and glycosulfated, contrary to mature BDNF. {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:19467646}.

Ptm: Mature BDNF is produced by proteolytic removal of the propeptide, catalyzed by a FURIN family member. In addition, the precursor form is proteolytically cleaved within the propeptide, but this is not an obligatory intermediate for the production of mature BDNF (PubMed:11152678). Can be converted into mature BDNF by plasmin (PLG) (PubMed:19467646). {ECO:0000269|PubMed:11152678, ECO:0000269|PubMed:19467646}.

Disease: Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. {ECO:0000269|PubMed:11840487}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the NGF-beta 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:		Important signaling molecule that activates signaling cascades downstream of NTRK2 (PubMed:11152678). During development, promotes the survival and differentiation of selected neuronal populations of the peripheral and central nervous systems. Participates in axonal growth, pathfinding and in the modulation of dendritic growth and morphology. Major regulator of synaptic transmission and plasticity at adult synapses in many regions of the CNS. The versatility of BDNF is emphasized by its contribution to a range of adaptive neuronal responses including long-term potentiation (LTP), long-term depression (LTD), certain forms of short-term synaptic plasticity, as well as homeostatic regulation of intrinsic neuronal excitability. {ECO:0000269\|PubMed:11152678, ECO:0000269\|PubMed:12553913, ECO:0000269\|PubMed:29909994}.



Function:		[BDNF precursor form]: Important signaling molecule that activates signaling cascades downstream of NTRK2. Activates signaling cascades via the heterodimeric receptor formed by NGFR and SORCS2 (PubMed:24908487, PubMed:29909994). Signaling via NGFR and SORCS2 plays a role in synaptic plasticity and long-term depression (LTD). Binding to NGFR and SORCS2 promotes neuronal apoptosis. Promotes neuronal growth cone collapse (By similarity). {ECO:0000250\|UniProtKB:P21237, ECO:0000269\|PubMed:24908487, ECO:0000269\|PubMed:29909994}.


Subunit:		Monomers and homodimers. Binds to NTRK2/TRKB (PubMed:8527932, PubMed:11152678). Can form heterodimers with other neurotrophin family members, such as NTF3 and NTF4 (in vitro), but the physiological relevance of this is not clear (PubMed:7703225, PubMed:10631974). BDNF precursor form: interacts with the heterodimer formed by NGFR and SORCS2 (PubMed:24908487). {ECO:0000269\|PubMed:10631974, ECO:0000269\|PubMed:11152678, ECO:0000269\|PubMed:24908487, ECO:0000269\|PubMed:7703225, ECO:0000269\|PubMed:8527932}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:11152678, ECO:0000269\|PubMed:19467646, ECO:0000269\|PubMed:8527932}.
Subcellular location:		[BDNF precursor form]: Secreted {ECO:0000269\|PubMed:11152678, ECO:0000269\|PubMed:19467646}. Note=A proportion of BDNF is secreted as immature precursor (proBDNF). {ECO:0000269\|PubMed:11152678, ECO:0000269\|PubMed:19467646}.
Tissue specificity:		Detected in blood plasma and in saliva (at protein level) (PubMed:11152678, PubMed:19467646). Brain. Highly expressed in hippocampus, amygdala, cerebral cortex and cerebellum. Also expressed in heart, lung, skeletal muscle, testis, prostate and placenta. {ECO:0000269\|PubMed:11152678, ECO:0000269\|PubMed:17629449, ECO:0000269\|PubMed:19467646, ECO:0000269\|PubMed:2236018}.
Ptm:		[BDNF precursor form]: N-glycosylated and glycosulfated, contrary to mature BDNF. {ECO:0000269\|PubMed:11152678, ECO:0000269\|PubMed:19467646}.
Ptm:		Mature BDNF is produced by proteolytic removal of the propeptide, catalyzed by a FURIN family member. In addition, the precursor form is proteolytically cleaved within the propeptide, but this is not an obligatory intermediate for the production of mature BDNF (PubMed:11152678). Can be converted into mature BDNF by plasmin (PLG) (PubMed:19467646). {ECO:0000269\|PubMed:11152678, ECO:0000269\|PubMed:19467646}.
Disease:		Congenital central hypoventilation syndrome (CCHS) [MIM:209880]: Rare disorder characterized by abnormal control of respiration in the absence of neuromuscular or lung disease, or an identifiable brain stem lesion. A deficiency in autonomic control of respiration results in inadequate or negligible ventilatory and arousal responses to hypercapnia and hypoxemia. {ECO:0000269\|PubMed:11840487}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the NGF-beta family. {ECO:0000305}.