Q9UM73

Background

Protein Name
ALK tyrosine kinase receptor
Gene Name
ALK
Organism
Homo sapiens

Annotations

Function
Neuronal receptor tyrosine kinase that is essentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.

Mapping Statistics

Site Maximum Consensus Site Population Minimum Consensus Site Population Median Consensus Site Population
MPP 16 2 8.0
AAS 6 4 5.0
MT3 25 2 9.0
ATP 21 2 8.0
DFG 20 2 4.5
CMP 22 2 12.5
PIF 21 2 18.0

Mapping Results

PDB ID Maximum Consensus Site Population
MPP site AAS site MT3 site LBP site ATP site DEF site DFG site CMP site PMP site EDI site DRS site PDIG site PIF site
Total Druggable Structures per Site 1 0 9 0 4 0 3 7 0 0 0 0 36
5IMX 8 0 3 0 21 0 2 13 0 0 0 0 5
5AA9 0 0 3 0 8 0 3 5 0 0 0 0 18
5AAC 0 0 0 0 7 0 4 10 0 0 0 0 5
2XB7 10 0 13 0 16 0 2 9 0 0 0 0 16
4FNW 0 0 0 0 0 0 3 0 0 0 0 0 20
4CLI 0 0 2 0 6 0 3 15 0 0 0 0 0
5J7H 0 0 14 0 11 0 0 0 0 0 0 0 14
3AOX 0 0 20 0 4 0 0 5 0 0 0 0 15
4TT7 0 0 13 0 13 0 0 14 0 0 0 0 17
2YHV 0 0 16 0 11 0 4 16 0 0 0 0 18
2YJS 0 0 0 0 0 0 0 15 0 0 0 0 0
5AAB 0 0 0 0 7 0 2 0 0 0 0 0 11
4CNH 0 0 0 0 7 0 10 15 0 0 0 0 17
5IUI 0 6 11 0 11 0 0 22 0 0 0 0 17
4FNZ 0 0 6 0 7 0 16 12 0 0 0 0 15
3L9P 0 0 0 0 4 0 3 0 0 0 0 0 20
4FNY 12 0 11 0 8 0 13 14 0 0 0 0 18
4JOA 16 6 9 0 12 0 0 7 0 0 0 0 0
4CMT 5 0 2 0 10 0 5 16 0 0 0 0 0
4Z55 0 0 3 0 3 0 8 0 0 0 0 0 16
5IUH 4 5 11 0 11 0 5 15 0 0 0 0 20
4CTC 0 0 0 0 4 0 8 22 0 0 0 0 0
4ANL 0 0 2 0 11 0 15 18 0 0 0 0 17
4CD0 0 0 0 0 9 0 14 15 0 0 0 0 19
4ANQ 0 0 3 0 14 0 10 0 0 0 0 0 19
4FOD 0 0 16 0 2 0 0 0 0 0 0 0 18
4ANS 0 0 0 0 12 0 10 0 0 0 0 0 19
4DCE 5 0 0 0 10 0 20 13 0 0 0 0 15
2YFX 0 0 10 0 0 0 0 5 0 0 0 0 19
3LCS 10 0 2 0 16 0 6 2 0 0 0 0 17
4CLJ 0 0 0 0 9 0 9 13 0 0 0 0 17
3LCT 0 0 0 0 6 0 2 3 0 0 0 0 21
4FNX 0 0 16 0 0 0 3 0 0 0 0 0 20
4CMU 0 0 0 0 15 0 4 15 0 0 0 0 19
5AA8 0 0 0 0 9 0 4 8 0 0 0 0 20
5A9U 0 0 0 0 9 0 3 11 0 0 0 0 19
2XBA 0 0 19 0 11 0 0 15 0 0 0 0 18
4CTB 0 0 2 0 8 0 4 9 0 0 0 0 18
2XP2 0 0 0 0 8 0 9 0 0 0 0 0 21
5FTQ 0 0 16 0 10 0 2 0 0 0 0 0 18
5FTO 0 0 19 0 10 0 2 16 0 0 0 0 18
5AAA 0 0 15 0 6 0 0 0 0 0 0 0 17
2YJR 0 4 8 0 0 0 0 14 0 0 0 0 16
4CCU 0 0 0 0 6 0 5 10 0 0 0 0 0
4MKC 8 0 7 0 16 0 3 9 0 0 0 0 19
5IUG 4 5 12 0 9 0 5 13 0 0 0 0 19
4CCB 0 0 2 0 7 0 11 15 0 0 0 0 0
4CMO 0 0 2 0 11 0 4 9 0 0 0 0 21
4FOC 0 0 20 0 6 0 0 0 0 0 0 0 18
4FOB 0 0 25 0 8 0 0 20 0 0 0 0 20
AFQ9UM73 0 0 0 0 0 0 18 0 0 0 0 0 0