Q5IS37
SS
Gene name |
NTRK3 |
Protein name |
NT-3 growth factor receptor |
Names |
EC 2.7.10.1 , Neurotrophic tyrosine kinase receptor type 3 |
Species |
Pan troglodytes (Chimpanzee) |
KEGG Pathway |
ptr:467751 |
EC number |
2.7.10.1: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
NTRK1 is a high-affinity nerve growth factor receptor and its ligand is nerve growth factor (NGF), which is involved in the survival, differentiation, development, and maturation of the central and peripheral nervous systems, particularly the sensory and sympathetic neurons. Studies have shown that deletion of the second Ig-like domain of NTRK1 results in spontaneous activation, so the second Ig-like domain is an autoinhibitory domain required to prevent spontaneous activation by receptor dimerization.
Autoinhibitory domains (AIDs)
Target domain |
538-810 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
696-721 (Activation loop from InterPro)
Target domain |
538-814 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Arevalo JC et al. (2000) "TrkA immunoglobulin-like ligand binding domains inhibit spontaneous activation of the receptor", Molecular and cellular biology, 20, 5908-16
- Artim SC et al. (2012) "Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family", The Biochemical journal, 448, 213-20
- Uchikawa E et al. (2019) "Activation mechanism of the insulin receptor revealed by cryo-EM structure of the fully liganded receptor-ligand complex", eLife, 8,
- Nielsen J et al. (2022) "Structural Investigations of Full-Length Insulin Receptor Dynamics and Signalling", Journal of molecular biology, 434, 167458
- Chen YS et al. (2021) "Insertion of a synthetic switch into insulin provides metabolite-dependent regulation of hormone-receptor activation", Proceedings of the National Academy of Sciences of the United States of America, 118,
- Craddock BP et al. (2007) "Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region", FEBS letters, 581, 3235-40
- Huang X et al. (2009) "Structural insights into the inhibited states of the Mer receptor tyrosine kinase", Journal of structural biology, 165, 88-96
Autoinhibited structure
Activated structure
1 structures for Q5IS37
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q5IS37-F1 | Predicted | AlphaFoldDB |
No variants for Q5IS37
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q5IS37 | |||||
No associated diseases with Q5IS37
14 regional properties for Q5IS37
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Leucine-rich repeat N-terminal domain | 31 - 63 | IPR000372 |
| domain | Cysteine-rich flanking region, C-terminal | 160 - 208 | IPR000483 |
| domain | Protein kinase domain | 538 - 814 | IPR000719 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 539 - 809 | IPR001245 |
| repeat | Leucine-rich repeat | 104 - 160 | IPR001611 |
| conserved_site | Tyrosine-protein kinase, receptor class II, conserved site | 703 - 711 | IPR002011 |
| domain | Immunoglobulin subtype | 216 - 302 | IPR003599 |
| domain | Immunoglobulin-like domain | 210 - 300 | IPR007110 |
| active_site | Tyrosine-protein kinase, active site | 675 - 687 | IPR008266 |
| domain | Immunoglobulin I-set | 323 - 391 | IPR013098 |
| domain | Immunoglobulin-like beta-sandwich domain | 218 - 296 | IPR013151 |
| binding_site | Protein kinase, ATP binding site | 544 - 572 | IPR017441 |
| domain | Tyrosine-protein kinase, catalytic domain | 538 - 810 | IPR020635 |
| domain | Growth factor receptor NTRK, leucine rich repeat C-terminal | 163 - 208 | IPR031635 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.10.1 | Protein-tyrosine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| axon | The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| receptor complex | Any protein complex that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. |
4 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| neurotrophin binding | Binding to a neurotrophin, any of a family of growth factors that prevent apoptosis in neurons and promote nerve growth. |
| neurotrophin receptor activity | Combining with a neurotrophin, any of a family of growth factors that prevent apoptosis in neurons and promote nerve growth, and transmitting the signal to initiate a change in cell activity. |
| transmembrane receptor protein tyrosine kinase activity | Combining with a signal and transmitting the signal from one side of the membrane to the other to initiate a change in cell activity by catalysis of the reaction |
8 GO annotations of biological process
| Name | Definition |
|---|---|
| cell differentiation | The cellular developmental process in which a relatively unspecialized cell, e.g. embryonic or regenerative cell, acquires specialized structural and/or functional features that characterize a specific cell. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| cellular response to nerve growth factor stimulus | A process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a nerve growth factor stimulus. |
| heart development | The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood. |
| nervous system development | The process whose specific outcome is the progression of nervous tissue over time, from its formation to its mature state. |
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
| positive regulation of neuron projection development | Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites). |
| regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | Any process that modulates the frequency, rate or extent of protein kinase B signaling, a series of reactions mediated by the intracellular serine/threonine kinase protein kinase B. |
| transmembrane receptor protein tyrosine kinase signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription. |
27 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q91987 | NTRK2 | BDNF/NT-3 growth factors receptor | Gallus gallus (Chicken) | SS |
| Q91009 | NTRK1 | High affinity nerve growth factor receptor | Gallus gallus (Chicken) | SS |
| Q8AXY6 | MUSK | Muscle, skeletal receptor tyrosine protein kinase | Gallus gallus (Chicken) | SS |
| Q91044 | NTRK3 | NT-3 growth factor receptor | Gallus gallus (Chicken) | SS |
| Q7YR43 | DDR1 | Epithelial discoidin domain-containing receptor 1 | Pan troglodytes (Chimpanzee) | SS |
| Q24488 | Ror | Tyrosine-protein kinase transmembrane receptor Ror | Drosophila melanogaster (Fruit fly) | SS |
| Q9V6K3 | Nrk | Tyrosine-protein kinase transmembrane receptor Ror2 | Drosophila melanogaster (Fruit fly) | SS |
| Q16620 | NTRK2 | BDNF/NT-3 growth factors receptor | Homo sapiens (Human) | EV |
| Q01973 | ROR1 | Inactive tyrosine-protein kinase transmembrane receptor ROR1 | Homo sapiens (Human) | PR |
| O15146 | MUSK | Muscle, skeletal receptor tyrosine-protein kinase | Homo sapiens (Human) | EV |
| Q01974 | ROR2 | Tyrosine-protein kinase transmembrane receptor ROR2 | Homo sapiens (Human) | EV |
| P04629 | NTRK1 | High affinity nerve growth factor receptor | Homo sapiens (Human) | EV |
| Q16288 | NTRK3 | NT-3 growth factor receptor | Homo sapiens (Human) | SS |
| Q9Z138 | Ror2 | Tyrosine-protein kinase transmembrane receptor ROR2 | Mus musculus (Mouse) | SS |
| Q3UFB7 | Ntrk1 | High affinity nerve growth factor receptor | Mus musculus (Mouse) | SS |
| Q9Z139 | Ror1 | Inactive tyrosine-protein kinase transmembrane receptor ROR1 | Mus musculus (Mouse) | PR |
| P15209 | Ntrk2 | BDNF/NT-3 growth factors receptor | Mus musculus (Mouse) | SS |
| Q61006 | Musk | Muscle, skeletal receptor tyrosine-protein kinase | Mus musculus (Mouse) | SS |
| Q6VNS1 | Ntrk3 | NT-3 growth factor receptor | Mus musculus (Mouse) | SS |
| P24786 | NTRK3 | NT-3 growth factor receptor | Sus scrofa (Pig) | SS |
| P35739 | Ntrk1 | High affinity nerve growth factor receptor | Rattus norvegicus (Rat) | SS |
| Q62838 | Musk | Muscle, skeletal receptor tyrosine protein kinase | Rattus norvegicus (Rat) | SS |
| Q63604 | Ntrk2 | BDNF/NT-3 growth factors receptor | Rattus norvegicus (Rat) | SS |
| Q03351 | Ntrk3 | NT-3 growth factor receptor | Rattus norvegicus (Rat) | SS |
| G5EGK5 | cam-1 | Tyrosine-protein kinase receptor cam-1 | Caenorhabditis elegans | SS |
| P43298 | TMK1 | Receptor protein kinase TMK1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9LFG1 | At3g53590 | Putative leucine-rich repeat receptor-like serine/threonine-protein kinase At3g53590 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MDVSLCPAKC | SFWRIFLLGS | VWLDYVGSVL | ACPANCVCSK | TEINCRRPDD | GNLFPLLEGQ |
| 70 | 80 | 90 | 100 | 110 | 120 |
| DSGNSNGNAS | INITDISRNI | TSIHIENWRS | LHTLNAVDME | LYTGLQKLTI | KNSGLRSIQP |
| 130 | 140 | 150 | 160 | 170 | 180 |
| RAFAKNPHLR | YINLSSNRLT | TLSWQLFQTL | SLRELQLEQN | FFNCSCDIRW | MQLWQEQGEA |
| 190 | 200 | 210 | 220 | 230 | 240 |
| KLNSQNLYCI | NTDGSQLPLF | RMNISQCDLP | EISVSHVNLT | VREGDNAVIT | CNGSGSPLPD |
| 250 | 260 | 270 | 280 | 290 | 300 |
| VDWIVTGLQS | INTHQTNLNW | TNVHAINLTL | VNVTSEDNGF | TLTCIAENVV | GMSNASVALT |
| 310 | 320 | 330 | 340 | 350 | 360 |
| VYYPPRVVSL | EEPELRLEHC | IEFVVRGNPP | PTLHWLHNGQ | PLRESKIIHV | EYYQEGEISE |
| 370 | 380 | 390 | 400 | 410 | 420 |
| GCLLFNKPTH | YNNGNYTLIA | KNPLGTANQT | ISGHFLKEPF | PESTDNFILF | DEVSPTPPIT |
| 430 | 440 | 450 | 460 | 470 | 480 |
| VTHKPEEDTF | GVSIAVGLAA | FACVLLVVLF | VMINKYGRRS | KFGMKGPVAV | ISGEEDSASP |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LHHINHGITT | PSSLDAGPDT | VVIGMTRIPV | IENPQYFRQG | HNCHKPDTYV | QHIKRRDIVL |
| 550 | 560 | 570 | 580 | 590 | 600 |
| KRELGEGAFG | KVFLAECYNL | SPTKDKMLVA | VKALKDPTLA | ARKDFQREAE | LLTNLQHEHI |
| 610 | 620 | 630 | 640 | 650 | 660 |
| VKFYGVCGDG | DPLIMVFEYM | KHGDLNKFLR | AHGPDAMILV | DGQPRQAKGE | LGLSQMLHIA |
| 670 | 680 | 690 | 700 | 710 | 720 |
| SQIASGMVYL | ASQHFVHRDL | ATRNCLVGAN | LLVKIGDFGM | SRDVYSTDYY | RVGGHTMLPI |
| 730 | 740 | 750 | 760 | 770 | 780 |
| RWMPPESIMY | RKFTTESDVW | SFGVILWEIF | TYGKQPWFQL | SNTEVIECIT | QGRVLERPRV |
| 790 | 800 | 810 | 820 | ||
| CPKEVYDVML | GCWQREPQQR | LNIKEIYKIL | HALGKATPIY | LDILG |