F1QVU0
SS
Gene name |
ltk |
Protein name |
Tyrosine-protein kinase receptor |
Names |
EC 2.7.10.1 , Anaplastic lymphoma kinase 1 , alk-1 , Protein moonstone , mne , Protein shady , shd |
Species |
Danio rerio (Zebrafish) (Brachydanio rerio) |
KEGG Pathway |
dre:564470 |
EC number |
2.7.10.1: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
ALK is a receptor tyrosine kinase involved in the development of several human cancers. Its autoinhibition is mediated by an intramolecular interaction between β-sheet (β1' and β2') and DFG helix in an activation loop, which occludes the substrate binding site. The activation loop contains phosphorylation sites, which need to be phosphorylated for ALK activation.
Autoinhibitory domains (AIDs)
Target domain |
935-1211 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
1088-1113 (Activation loop from InterPro)
Target domain |
935-1211 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- Bossi RT et al. (2010) "Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitors", Biochemistry, 49, 6813-25
- Donella-Deana A et al. (2005) "Unique substrate specificity of anaplastic lymphoma kinase (ALK): development of phosphoacceptor peptides for the assay of ALK activity", Biochemistry, 44, 8533-42
- Craddock BP et al. (2007) "Autoinhibition of the insulin-like growth factor I receptor by the juxtamembrane region", FEBS letters, 581, 3235-40
- Tu CH et al. (2016) "Pyrazolylamine Derivatives Reveal the Conformational Switching between Type I and Type II Binding Modes of Anaplastic Lymphoma Kinase (ALK)", Journal of medicinal chemistry, 59, 3906-19
- 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,
- 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 F1QVU0
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-F1QVU0-F1 | Predicted | AlphaFoldDB |
No variants for F1QVU0
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for F1QVU0 | |||||
No associated diseases with F1QVU0
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 | |
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| 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. |
2 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| 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 |
12 GO annotations of biological process
| Name | Definition |
|---|---|
| developmental pigmentation | The developmental process that results in the deposition of coloring matter in an organism, tissue or cell. |
| iridophore differentiation | The process in which a relatively unspecialized cell acquires the specialized features of an iridophore. Iridophores are pigment cells derived from the neural crest. They contain guanidine or other purine crystals deposited in stacks called reflecting platets or iridisomes. This gives them a silver, gold, or iridescent appearance. |
| maintenance of cell number | Any process by which the numbers of cells of a particular type or in a tissue are maintained. |
| melanocyte differentiation | The process in which a relatively unspecialized cell acquires specialized features of a melanocyte. |
| melanocyte migration | The orderly movement of melanocytes from one site to another, often during the development of a multicellular organism. A melanocyte is a pigment cell derived from the neural crest. It contains melanin-filled pigment granules, which give a brown to black appearance. |
| 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. |
| pigment cell development | The process whose specific outcome is the progression of a pigment cell over time, from its formation to the mature structure. Cell development does not include the steps involved in committing a cell to a pigment cell fate. |
| pigmentation | The accumulation of pigment in an organism, tissue or cell, either by increased deposition or by increased number of cells. |
| regulation of cell population proliferation | Any process that modulates the frequency, rate or extent of cell proliferation. |
| regulation of developmental pigmentation | Any process that modulates the frequency, rate or extent of the developmental process that results in the deposition of coloring matter in an organism. |
| regulation of neuron differentiation | Any process that modulates the frequency, rate or extent of neuron differentiation. |
| 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. |
34 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q769I5 | MET | Hepatocyte growth factor receptor | Bos taurus (Bovine) | PR |
| A0M8S8 | MET | Hepatocyte growth factor receptor | Felis catus (Cat) (Felis silvestris catus) | PR |
| Q04912 | MST1R | Macrophage-stimulating protein receptor | Homo sapiens (Human) | EV |
| P08581 | MET | Hepatocyte growth factor receptor | Homo sapiens (Human) | EV |
| P14616 | INSRR | Insulin receptor-related protein | Homo sapiens (Human) | SS |
| P08922 | ROS1 | Proto-oncogene tyrosine-protein kinase ROS | Homo sapiens (Human) | SS |
| Q9UM73 | ALK | ALK tyrosine kinase receptor | Homo sapiens (Human) | EV |
| P29376 | LTK | Leukocyte tyrosine kinase receptor | Homo sapiens (Human) | SS |
| Q9WTL4 | Insrr | Insulin receptor-related protein | Mus musculus (Mouse) | SS |
| Q62190 | Mst1r | Macrophage-stimulating protein receptor | Mus musculus (Mouse) | SS |
| P16056 | Met | Hepatocyte growth factor receptor | Mus musculus (Mouse) | PR |
| P97793 | Alk | ALK tyrosine kinase receptor | Mus musculus (Mouse) | SS |
| P97523 | Met | Hepatocyte growth factor receptor | Rattus norvegicus (Rat) | PR |
| Q64716 | Insrr | Insulin receptor-related protein | Rattus norvegicus (Rat) | SS |
| Q8I7I5 | rol-3 | Protein roller-3 | Caenorhabditis elegans | PR |
| Q19238 | F09A5.2 | Putative tyrosine-protein kinase F09A5.2 | Caenorhabditis elegans | SS |
| H2KZU7 | svh-2 | Tyrosine-protein kinase receptor svh-2 | Caenorhabditis elegans | SS |
| F8W3R9 | alk | ALK tyrosine kinase receptor | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| O73878 | ephb4b | Ephrin type-B receptor 4b | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| E7F3X9 | ddr1 | receptor protein-tyrosine kinase | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q8AXB3 | kdrl | Vascular endothelial growth factor receptor kdr-like | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q5GIT4 | kdr | Vascular endothelial growth factor receptor 2 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| O13146 | epha3 | Ephrin type-A receptor 3 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q90Z00 | fgfr1a | Fibroblast growth factor receptor 1-A | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q90413 | fgfr4 | Fibroblast growth factor receptor 4 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| O73791 | tek | Angiopoietin-1 receptor | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q8JFR5 | kita | Mast/stem cell growth factor receptor kita | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q9I8N6 | csf1r | Macrophage colony-stimulating factor 1 receptor | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q9DE49 | pdgfra | Platelet-derived growth factor receptor alpha | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| O13147 | ephb3 | Ephrin type-B receptor 3 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q9YI66 | tyro3 | Tyrosine-protein kinase receptor TYRO3 | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| Q5MD89 | flt4 | Vascular endothelial growth factor receptor 3 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q8JG38 | fgfr2 | Fibroblast growth factor receptor 2 | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q9I8X3 | fgfr3 | Fibroblast growth factor receptor 3 | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MDYITRQTFV | KLALFIFTVL | RSSCALLEKA | AEDPVHPNPL | QSSPAEDSDV | SFCDFESPCS |
| 70 | 80 | 90 | 100 | 110 | 120 |
| WTLSSHSTGG | DWFITSAQQH | RSSRRDTQPI | RDYSTGKSEG | HFLLLKPSSS | HLSAGRCSFH |
| 130 | 140 | 150 | 160 | 170 | 180 |
| MTSPVVLSSG | PFCHLQLARF | QPEPHAGNIS | AFVKHTDSTD | IKPIDLTIKE | QESDSSQWEV |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LEAVIGQLNE | PFQVTVQYSA | CSSHEVGFLA | FDSLELKNCV | MGDDYVDLGS | DCEKYSSLQC |
| 250 | 260 | 270 | 280 | 290 | 300 |
| HSGGCIEKQR | VCDFHTDCPE | GEDEGLICST | LPLGSYCSFE | LGSCGWLAAD | TQSSWRLVSG |
| 310 | 320 | 330 | 340 | 350 | 360 |
| QQLIEDTHLL | GTTLKNTQGH | FLFLKVRGHG | DEREALVQSP | ALPSTISNQD | CQLQFSLYRY |
| 370 | 380 | 390 | 400 | 410 | 420 |
| GDFNGTVLLS | VVESGASAPA | LIWERSGHWK | DAWQEITLPI | TEILNGFHLK | VQAFWTSGSK |
| 430 | 440 | 450 | 460 | 470 | 480 |
| ADIALDDISL | SAACFDTELN | ELLHEGLPHD | LDFSPLPEPS | ASEASPITWW | FTSCGASGPF |
| 490 | 500 | 510 | 520 | 530 | 540 |
| GPTQAQCDSA | YRNTNVSVVV | GKEGPLRGVQ | MWKVPATNTY | KISAYGAAGG | KGAKNHNKRS |
| 550 | 560 | 570 | 580 | 590 | 600 |
| HGVFISATFP | LEKGDILYIL | IGHQGEDACP | GRNPQTHKIC | LGESSVIEDG | FDSDGSALKW |
| 610 | 620 | 630 | 640 | 650 | 660 |
| AGGGGGGGGA | TYIYRMENGQ | PLPLLIAAGG | GGKAYLEDPE | SSQDQSFREQ | YENDTTVSGV |
| 670 | 680 | 690 | 700 | 710 | 720 |
| SGRSGAAGGG | GGWSDVSSLS | WAGKSLVEGG | QGGSSCPEAL | SVLGWATFGG | FGGGGGACSA |
| 730 | 740 | 750 | 760 | 770 | 780 |
| GGGGGGYRGG | DAPLLDDISA | DGQDGLSFVH | PMGKIFLQPL | AAMESHGEAE | IVVYLNCSHC |
| 790 | 800 | 810 | 820 | 830 | 840 |
| KTQSCKRDED | TKLILCLCDS | DEVLAPDNVT | CAGTKHSLCQ | FINKHLQHNS | SPLVCPPLVV |
| 850 | 860 | 870 | 880 | 890 | 900 |
| PMGSLADGPP | SLVFIMAVIV | STVVTGVVLT | CASLTLIYYR | KKNHLHAVRI | RLQSPEYKLS |
| 910 | 920 | 930 | 940 | 950 | 960 |
| KIRSSTIMTD | YNPNYGYFGK | AASLSELKEV | PRKNITLLRA | LGHGAFGEVY | EGQVLGMNGE |
| 970 | 980 | 990 | 1000 | 1010 | 1020 |
| NTAMQVAIKT | LPEICSEQDE | MDFLMEALIM | SKFSHQNIVR | CIGVSLQILP | RFILLELMTG |
| 1030 | 1040 | 1050 | 1060 | 1070 | 1080 |
| GDMKSFLRLN | RPRTNHSSSL | SMLELLHMAR | DIALGCRYLE | ENHFIHRDIA | ARNCLLTCPG |
| 1090 | 1100 | 1110 | 1120 | 1130 | 1140 |
| PDRVAKIGDF | GMARDIYRAS | YYRKGGRAML | PVKWMPPEAF | LEGIFTCKTD | TWSFGVLLWE |
| 1150 | 1160 | 1170 | 1180 | 1190 | 1200 |
| IFSLGYMPYP | CKTNQEVLEF | VTGGGRMDPP | KSCPGPVYRI | MTQCWQHCPE | HRPNFTTILE |
| 1210 | 1220 | 1230 | 1240 | 1250 | 1260 |
| RINYCTQDPD | VINTPLPVEC | GPPVEEEGGT | VIRPDGSGSM | TPLLVARSLS | QDASPRASIT |
| 1270 | 1280 | 1290 | 1300 | 1310 | 1320 |
| SVTPQALKPR | LQLQRPVHLT | QEVGTYRETL | EPCWAEPVPA | SGVCPGPWLQ | VPEHRPCSRS |
| 1330 | 1340 | 1350 | 1360 | 1370 | 1380 |
| SSSSGSQKLK | NKTKNLWNPT | YGSWVLESFG | RGKSALCHTQ | SMPLSCNPTS | VSAPSSTSEH |
| 1390 | 1400 | 1410 | 1420 | 1430 | 1440 |
| TDPVVEVNAN | VSASPPPSAA | PSQTTLTPTA | APSRKSPTGA | AGVSLATVMD | LAKLQSFPCG |
| 1450 | 1460 | 1470 | 1480 | 1490 | 1500 |
| NVNYAYDEQS | YETESLPVVV | SKSLEPSTSS | AATSSLVALS | QPGSFTHKPL | VKRHASYGHE |
| 1510 | 1520 | ||||
| DVRRYTQPEK | PTRDRDSGFS | LSEDLSVTPV |