Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

     From NCBI Gene: Obesity, hyperphagia, and developmental delayFrom UniProt: Obesity, hyperphagia, and developmental delay (OBHD): A disorder characterized by early-onset obesity, hyperphagia, and severe developmental delay in motor function, speech, and language. [MIM:613886]

     From NCBI Gene: This gene encodes a member of the neurotrophic tyrosine receptor kinase (NTRK) family. This kinase is a membrane-bound receptor that, upon neurotrophin binding, phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to cell differentiation. Mutations in this gene have been associated with obesity and mood disorders. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014] From UniProt: Receptor tyrosine kinase involved in the development and the maturation of the central and the peripheral nervous systems through regulation of neuron survival, proliferation, migration, differentiation, and synapse formation and plasticity. Receptor for BDNF/brain-derived neurotrophic factor and NTF4/neurotrophin-4. Alternatively can also bind NTF3/neurotrophin-3 which is less efficient in activating the receptor but regulates neuron survival through NTRK2. Upon ligand-binding, undergoes homodimerization, autophosphorylation and activation. Recruits, phosphorylates and/or activates several downstream effectors including SHC1, FRS2, SH2B1, SH2B2 and PLCG1 that regulate distinct overlapping signaling cascades. Through SHC1, FRS2, SH2B1, SH2B2 activates the GRB2-Ras-MAPK cascade that regulates for instance neuronal differentiation including neurite outgrowth. Through the same effectors controls the Ras-PI3 kinase-AKT1 signaling cascade that mainly regulates growth and survival. Through PLCG1 and the downstream protein kinase C-regulated pathways controls synaptic plasticity. Thereby, plays a role in learning and memory by regulating both short term synaptic function and long-term potentiation. PLCG1 also leads to NF-Kappa-B activation and the transcription of genes involved in cell survival. Hence, it is able to suppress anoikis, the apoptosis resulting from loss of cell-matrix interactions. May also play a role in neutrophin-dependent calcium signaling in glial cells and mediate communication between neurons and glia.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• CREB
• deltaCREB
• NF-kappaB
• NF-kappaB1
• c-Jun
• AP-1
• C/EBPbeta
• Sox9
• C/EBPalpha

Tissue specificity:

Isoform TrkB is expressed in the central and peripheral nervous system. In the central nervous system (CNS), expression is observed in the cerebral cortex, hippocampus, thalamus, choroid plexus, granular layer of the cerebellum, brain stem, and spinal cord. In the peripheral nervous system, it is expressed in many cranial ganglia, the ophthalmic nerve, the vestibular system, multiple facial structures, the submaxillary glands, and dorsal root ganglia. Isoform TrkB-T1 is mainly expressed in the brain but also detected in other tissues including pancreas, kidney and heart. Isoform TrkB-T-Shc is predominantly expressed in the brain.

Developmental stage:

Widely expressed in fetal brain.

Enzyme Regulation:

The neuronal activity and the influx of calcium positively regulate the kinase activity and the internalization of the receptor which are both important for active signaling. Regulated by NGFR that may control the internalization of the receptor. NGFR may also stimulate the activation by BDNF compared to NTF3 and NTF4. SH2D1A inhibits the autophosphorylation of the receptor, and alters the recruitment and activation of downstream effectors and signaling cascades. The formation of active receptors dimers able to fully transduce the ligand-mediated signal, may be negatively regulated by the formation of inactive heterodimers with the non-catalytic isoforms.

Molecular Function:

• Atp Binding
• Protein Homodimerization Activity
• Neurotrophin Binding
• Brain-Derived Neurotrophic Factor Binding
• Brain-Derived Neurotrophic Factor-Activated Receptor Activity

Biological Processes:

• Vasculogenesis
• Neuron Migration
• Positive Regulation Of Protein Phosphorylation
• Inflammatory Response
• Neuromuscular Junction Development
• Aging
• Learning
• Long-Term Memory
• Circadian Rhythm
• Feeding Behavior
• Positive Regulation Of Cell Proliferation
• Response To Light Stimulus
• Positive Regulation Of Gene Expression
• Positive Regulation Of Neuron Projection Development
• Response To Auditory Stimulus
• Glutamate Secretion
• Positive Regulation Of Phosphatidylinositol 3-Kinase Signaling
• Central Nervous System Neuron Development
• Cerebral Cortex Development
• Neuron Differentiation
• Brain-Derived Neurotrophic Factor Receptor Signaling Pathway
• Positive Regulation Of Peptidyl-Serine Phosphorylation
• Calcium-Mediated Signaling Using Intracellular Calcium Source
• Mechanoreceptor Differentiation
• Regulation Of Gtpase Activity
• Positive Regulation Of Mapk Cascade
• Negative Regulation Of Neuron Apoptotic Process
• Retinal Rod Cell Development
• Protein Autophosphorylation
• Regulation Of Neurotransmitter Secretion
• Oligodendrocyte Differentiation
• Peripheral Nervous System Neuron Development
• Positive Regulation Of Axonogenesis
• Regulation Of Dendrite Development
• Regulation Of Protein Kinase B Signaling
• Positive Regulation Of Synapse Assembly
• Positive Regulation Of Synaptic Transmission, Glutamatergic
• Retina Development In Camera-Type Eye
• Long-Term Synaptic Potentiation
• Cellular Response To Amino Acid Stimulus
• Cellular Response To Tumor Necrosis Factor
• Cellular Response To Brain-Derived Neurotrophic Factor Stimulus
• Negative Regulation Of Anoikis

Drug Bank:

• Amitriptyline

*synonyms