Free for academic non-profit institutions. Other users need a Commercial license
This gene encodes a receptor tyrosine kinase, which belongs to the insulin receptor superfamily. This protein comprises an extracellular domain, an hydrophobic stretch corresponding to a single pass transmembrane region, and an intracellular kinase domain. It plays an important role in the development of the brain and exerts its effects on specific neurons in the nervous system. This gene has been found to be rearranged, mutated, or amplified in a series of tumours including anaplastic large cell lymphomas, neuroblastoma, and non-small cell lung cancer. The chromosomal rearrangements are the most common genetic alterations in this gene, which result in creation of multiple fusion genes in tumourigenesis, including ALK (chromosome 2)/EML4 (chromosome 2), ALK/RANBP2 (chromosome 2), ALK/ATIC (chromosome 2), ALK/TFG (chromosome 3), ALK/NPM1 (chromosome 5), ALK/SQSTM1 (chromosome 5), ALK/KIF5B (chromosome 10), ALK/CLTC (chromosome 17), ALK/TPM4 (chromosome 19), and ALK/MSN (chromosome X).[provided by RefSeq, Jan 2011]
ALK amplifications, fusions and mutations have been shown to be driving events in non-small cell lung cancer. While crizontinib has demonstrated efficacy in treating the amplification, mutations in ALK have been shown to confer resistance to current tyrosine kinase inhibitors. Second-generation TKI's have seen varied success in treating these resistant cases, and the HSP90 inhibitor 17-AAG has been shown to be cytostatic in ALK-altered cell lines.
ALK (ALK Receptor Tyrosine Kinase) is a Protein Coding gene. Diseases associated with ALK include Neuroblastoma 3 and Neuroblastoma. Among its related pathways are Activation of cAMP-Dependent PKA and Actin Nucleation by ARP-WASP Complex. Gene Ontology (GO) annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is LTK.
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that was first identified in anaplastic large cell lymphoma (ALCL) as part of the fusion protein NPM-ALK. ALK has been implicated in the pathogenesis of many types of cancer.
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000166 | nucleotide binding | IEA | -- |
GO:0004672 | protein kinase activity | IEA | -- |
GO:0004704 | NF-kappaB-inducing kinase activity | TAS | 19459784 |
GO:0004713 | protein tyrosine kinase activity | IEA,IDA | 9174053 |
GO:0004714 | transmembrane receptor protein tyrosine kinase activity | IEA,TAS | 19459784 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005886 | plasma membrane | IEA,IDA | -- |
GO:0005887 | integral component of plasma membrane | IBA,TAS | 19459784 |
GO:0016020 | membrane | IEA | -- |
GO:0016021 | integral component of membrane | IEA | -- |
GO:0032991 | protein-containing complex | IDA | 23382219 |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | GPCR Pathway |
Paxillin Interactions
.73
Ras Pathway
.73
GPCR Pathway
.62
Pancreatic Adenocarcinoma
.59
|
Breast Cancer Regulation by Stathmin1
.58
NFAT in Immune Response
.58
Estrogen Pathway
.55
P2Y Receptor Signaling
.38
|
2 | ERK Signaling |
ERK Signaling
.61
Rho Family GTPases
.61
MAPK Signaling
.58
|
Molecular Mechanisms of Cancer
.51
ILK Signaling
.49
|
3 | Nanog in Mammalian ESC Pluripotency |
GSK3 Signaling
.62
Nanog in Mammalian ESC Pluripotency
.62
|
14-3-3 Induced Intracellular Signaling
.59
eNOS Signaling
.48
|
4 | Actin Nucleation by ARP-WASP Complex |
Actin Nucleation and Branching
.66
Actin Nucleation by ARP-WASP Complex
.66
|
CDC42 Pathway
.41
|
5 | Activation of cAMP-Dependent PKA |
Activation of cAMP-Dependent PKA
.77
|
Activation of PKA through GPCR
.71
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000187 | activation of MAPK activity | IEA,TAS | 19459784 |
GO:0006468 | protein phosphorylation | IEA | -- |
GO:0007165 | signal transduction | IEA,TAS | 19459784 |
GO:0007169 | transmembrane receptor protein tyrosine kinase signaling pathway | IEA,IBA | 21873635 |
GO:0007275 | multicellular organism development | IBA | 21873635 |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Crizotinib | Approved | Pharma | Target, inhibitor, Inhibition, Biomarker | C-MET/ALK inhibitor,potent and ATP-competitve, Potent c-MET/ALK inhibitor, cMET Inhibitors, Kinase Inhibitors, Anaplastic lymphoma kinase (ALK) inhibitor | 140 | |
Ceritinib | Approved | Pharma | Target, antagonist | 47 | ||
alectinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
brigatinib | Approved, Investigational | Pharma | Target, inhibitor | 0 | ||
lorlatinib | Approved, Investigational | Pharma | Target, inhibitor | 0 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs | |
---|---|---|---|---|---|---|
ADP |
|
Agonist, Full agonist, Partial agonist, Gating inhibitor, Antagonist | 58-64-0 |
|
Compound | Action | Cas Number |
---|---|---|
ASP 3026 | Potent anaplastic lymphoma kinase (ALK) inhibitor; also potent ACK inhibitor | 1097917-15-1 |
Crizotinib | Potent c-MET/ALK inhibitor | 877399-52-5 |
KRCA 0008 | Potent Ack1 and ALK dual inhibitor; orally bioavailable | 1472795-20-2 |
Compound | Action | Cas Number |
---|---|---|
ALK inhibitor 2 | ALK inhibitor, novel and selective | 761438-38-4 |
AP26113 | Anaplastic lymphoma kinase (ALK) inhibitor | 1197958-12-5 |
ASP3026 | ALK inhibitor,potent and selective | 1097917-15-1 |
AZD-3463 | ALK/IGF1R inhibitor | 1356962-20-3 |
CEP-37440 | FAK/ALK inhibitor,potent and selective | 1391712-60-9 |
CH5424802 | ALK inhibitor,potent and ATP-competitive | 1256580-46-7 |
Crizotinib hydrochloride | 1415560-69-8 | |
Dovitinib (TKI-258, CHIR-258) | Multitargeted RTK inhibitor | 405169-16-6 |
Entrectinib | Orally active inhibitor of ALK kinase | 1108743-60-7 |
GSK1838705A | IGF-IR/IR/ALK inhibitor, ATP-competitive | 1116235-97-2 |
K02288 | ALK inhibitor | 1431985-92-0 |
KRCA 0008 | 1472795-20-2 | |
LDK378 | Potent ALK inhibitor | 1032900-25-6 |
LDK378 dihydrochloride | ALK inhibitor | 1380575-43-8 |
LDN-193189 | ALK inhibitor,potent and selective | 1062368-24-4 |
LDN193189 Hydrochloride | ALK inhibitor,potent and selective | 1062368-62-0 |
LDN-214117 | 1627503-67-6 | |
PF-06463922 | 1454846-35-5 | |
SB 431542 | ALK inhibitor | 301836-41-9 |
TAE684 (NVP-TAE684) | ALK inhibitor,potent and selective | 761439-42-3 |
This gene was present in the common ancestor of animals.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | ALK 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | ALK 31 |
|
OneToOne | |
LOC536642 30 |
|
||||
Dog (Canis familiaris) |
Mammalia | ALK 30 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | Alk 30 |
|
||
Mouse (Mus musculus) |
Mammalia | Alk 30 17 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | ALK 31 |
|
OneToOne | |
Platypus (Ornithorhynchus anatinus) |
Mammalia | ALK 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | ALK 30 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | ALK 31 |
|
OneToOne | |
Tropical Clawed Frog (Silurana tropicalis) |
Amphibia | LOC100495071 30 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.30258 30 |
|
||
Zebrafish (Danio rerio) |
Actinopterygii | alk 30 31 |
|
OneToOne | |
Fruit Fly (Drosophila melanogaster) |
Insecta | Alk 31 32 |
|
OneToMany | |
Worm (Caenorhabditis elegans) |
Secernentea | F09A5.2 32 |
|
|
|
T25B9.5 32 |
|
|
|||
scd-2 31 32 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 02 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
638883 | Uncertain Significance: Neuroblastoma 3 | 29,717,621(-) | T/C | MISSENSE_VARIANT | |
638944 | Uncertain Significance: Neuroblastoma 3 | 29,193,817(-) | G/C | MISSENSE_VARIANT | |
639134 | Uncertain Significance: Neuroblastoma 3 | 29,207,165(-) | A/AC | INTRON_VARIANT | |
639161 | Uncertain Significance: Neuroblastoma 3 | 29,207,225(-) | C/T | NONSENSE | |
639239 | Uncertain Significance: Neuroblastoma 3 | 29,920,529(-) | A/C | MISSENSE_VARIANT |
Disorder | Aliases | PubMed IDs |
---|---|---|
neuroblastoma 3 |
|
|
neuroblastoma |
|
|
rhabdomyosarcoma |
|
|
inflammatory myofibroblastic tumor |
|
|
alk-positive anaplastic large cell lymphoma |
|
|