Protein Domain : IPR020461

Type:  Family Name:  Tyrosine-protein kinase, neurotrophic receptor, type 1
Description:  Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyse the reverse process. Protein kinases fall into three broad classes, characterised with respect to substrate specificity []:Serine/threonine-protein kinasesTyrosine-protein kinasesDual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins)Protein kinase function is evolutionarily conserved from Escherichia coli to human []. Protein kinases play a role in a multitude of cellular processes, including division, proliferation, apoptosis, and differentiation []. Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. The catalytic subunits of protein kinases are highly conserved, and several structures have been solved [], leading to large screens to develop kinase-specific inhibitors for the treatments of a number of diseases [].Tyrosine-protein kinases can transfer a phosphate group from ATP to a tyrosine residue in a protein. These enzymes can be divided into two main groups []:Receptor tyrosine kinases (RTK), which are transmembrane proteins involved in signal transduction; they play key roles in growth, differentiation, metabolism, adhesion, motility, death and oncogenesis []. RTKs are composed of 3 domains: an extracellular domain (binds ligand), a transmembrane (TM) domain, and an intracellular catalytic domain (phosphorylates substrate). The TM domain plays an important role in the dimerisation process necessary for signal transduction []. Cytoplasmic / non-receptor tyrosine kinases, which act as regulatory proteins, playing key roles in cell differentiation, motility, proliferation, and survival. For example, the Src-family of protein-tyrosine kinases [].Neurotrophins are a family of secreted proteins that regulate development, maintenance and function of vertebrate nervous systems. They act via two different classes of receptor: p75NTR (a member of the TNF receptor superfamily), and neurotrophic tyrosine kinase receptors (NTRKs) - also known as tropomyosin-related kinases (Trks) []. NTRKs are multi-domain, transmembrane proteins - in addition to their cytoplasmic kinase domains, members of the family possess a number of extracellular leucine-rich repeat (LRR) and Ig-like C2-type regions. Ligand binding induces them to dimerise, resulting in activation of their cytoplasmic tyrosine kinase domains. The activated receptors couple to a variety of intracellular signalling cascades, including the Ras, phosphatidylinositol-3-kinase (PI-3 kinase), mitogen-activated protein (MAP) kinase, and phospholipase C (PLC)-gamma pathways []. NTRK1 (also termed TrkA) is a high-affinity receptor for nerve growth factor (NGF). The receptor is expressed in the dorsal root ganglia, trigeminal ganglia and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons []. It is also expressed in peripheral sites, such as scalp skin []. Whereas p75NTR activation by NGF induces apoptosis, NTRK1 mediates the growth factor's cell survival-promoting effects []. Short Name:  Tyr_kinase_neurotrophic_rcpt_1

0 Child Features

11 Contains

DB identifier Type Name
IPR000719 Domain Protein kinase domain
IPR011009 Domain Protein kinase-like domain
IPR020635 Domain Tyrosine-protein kinase, catalytic domain
IPR001245 Domain Serine-threonine/tyrosine-protein kinase catalytic domain
IPR013783 Domain Immunoglobulin-like fold
IPR007110 Domain Immunoglobulin-like domain
IPR000483 Domain Cysteine-rich flanking region, C-terminal
IPR003599 Domain Immunoglobulin subtype
IPR017441 Binding_site Protein kinase, ATP binding site
IPR008266 Active_site Tyrosine-protein kinase, active site
IPR002011 Conserved_site Tyrosine-protein kinase, receptor class II, conserved site

1 Cross References


0 Found In

5 GO Annotations

GO Term Gene Name Organism
GO:0004714 IPR020461
GO:0005030 IPR020461
GO:0006468 IPR020461
GO:0007169 IPR020461
GO:0005887 IPR020461

1 Parent Features

DB identifier Type Name
IPR020777 Family Tyrosine-protein kinase, neurotrophic receptor

0 Proteins

13 Publications

First Author Title Year Journal Volume Pages PubMed ID