Target name

Q9UM73: ALK tyrosine kinase receptor


  Protein function

Neuronal orphan 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.

  Database links

Uniprot primary ID Q9UM73
PDB ID 2YS5 3L9P 3AOX 4CCU 2XBA 4FOD 4TT7 2XP2 4FNX 4CTB 4FNZ 2YT2 2YJS 2YJR 4CTC 4MKC 4CNH 2YHV 4CLI 4CD0 4CMT 4ANL 4FOC 4FOB 2XB7 4JOA 2KUP 2KUQ 4ANS 2YFX 4ANQ 4DCE 4CMU 4CCB 3LCS 3LCT 4CLJ 4FNW 4CMO 4FNY
DrugBank ID DB08865 DB00171 DB09063
BioGrid ID 106739
GuidetoPHARMACOLOGY ID 1839
PharmGKB ID PA24719
KEGG ID hsa:238
DIP ID DIP-5954N
STRING ID 9606.ENSP00000373700
IntAct ID Q9UM73
DMDM 296439447
BRENDA 2.7.10.1
Reactome
SignaLink Q9UM73
BioCyc
Entrez Gene (Gene ID) 238
BindingDB Q9UM73

  Model Performance Metrics

Fingerprint type Sensitivity SEN_std Specificity SPE_std Accuracy ACC_std F1-score F1-score_std AUC AUC_std MCC MCC_std Download model
FP2 fingerprints 0.850 0.007 0.942 0.005 0.896 0.005 0.891 0.006 0.950 0.000 0.795 0.007 Download
Estate fingerprints 0.804 0.007 0.742 0.007 0.773 0.008 0.777 0.007 0.847 0.005 0.547 0.013 Download
MACCS fingerprints 0.890 0.008 0.754 0.009 0.822 0.006 0.835 0.005 0.900 0.000 0.653 0.013 Download
Daylight fingerprints 0.858 0.006 0.836 0.007 0.847 0.005 0.850 0.000 0.881 0.003 0.697 0.005 Download
ECFP2 fingerprints 0.899 0.006 0.935 0.004 0.917 0.005 0.915 0.005 0.970 0.000 0.834 0.007 Download
ECFP4 fingerprints 0.865 0.007 0.975 0.004 0.920 0.005 0.915 0.005 0.968 0.004 0.844 0.008 Download
ECFP6 fingerprints 0.841 0.007 0.987 0.000 0.914 0.005 0.907 0.007 0.960 0.000 0.837 0.007 Download

  Download datasets

Positive dataset Negative dataset


Copyright @ 2012-2014 Computational Biology & Drug Design Group,
School of Pharmaceutical Sciences, Central South University. All rights reserved.

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