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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 1. Among its related pathways are Actin Nucleation by ARP-WASP Complex and ERK Signaling. 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.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH02J030145 | Promoter/Enhancer | 2.4 | EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER | 750.1 | -226.3 | -226335 | 5.7 | SIN3A ZNF24 ZBTB40 SP1 CTCF FOXA1 POLR2A USF2 NR2F6 FOS | YPEL5 LOC101929418 NONHSAG027383.2 lnc-LBH-5 ALK LBH piR-58639 | |
GH02J029919 | Promoter/Enhancer | 1.4 | EPDnew Ensembl ENCODE | 750.6 | +0.4 | 410 | 2 | ZBTB6 GLIS2 REST ZBTB8A PATZ1 POLR2A SP2 NRF1 EHMT2 ZFHX2 | ALK ENSG00000197644 ENSG00000233862 | |
GH02J029918 | Promoter/Enhancer | 0.5 | FANTOM5 Ensembl | 60.9 | +2.5 | 2536 | 1.5 | ALK ENSG00000230737 ENSG00000197644 ENSG00000233862 | ||
GH02J029528 | Enhancer | 1 | FANTOM5 Ensembl ENCODE dbSUPER | 23.4 | +392.7 | 392698 | 2.2 | MAFK ZBTB17 FOS CREB1 POLR2A ZNF335 | ALK piR-37026-330 lnc-CLIP4-2 | |
GH02J029613 | Enhancer | 0.4 | FANTOM5 | 58.7 | +307.6 | 307585 | 0.2 | POLR2A RCOR1 | ALK ENSG00000197644 lnc-CLIP4-2 piR-37026-330 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
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 | TAS,IEA | 19459784 |
GO:0005515 | protein binding | IEA,IPI | 17681947 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005886 | plasma membrane | IDA,IEA | -- |
GO:0005887 | integral component of plasma membrane | TAS,IBA | 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
.61
Nanog in Mammalian ESC Pluripotency
.61
|
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 | TAS,IEA | 19459784 |
GO:0007169 | transmembrane receptor protein tyrosine kinase signaling pathway | IEA,IBA | 21873635 |
GO:0007399 | nervous system development | IEA | -- |
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 | 125 | |
Ceritinib | Approved | Pharma | Target, antagonist | 45 | ||
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 |
|
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor | 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 1 | ALK inhibitor, novel and selective | 761436-81-1 |
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 |
HG-14-10-04 | 1356962-34-9 | |
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 33 32 |
|
OneToOne | |
cow (Bos Taurus) |
Mammalia | ALK 33 |
|
OneToOne | |
LOC536642 32 |
|
||||
dog (Canis familiaris) |
Mammalia | ALK 33 32 |
|
OneToOne | |
rat (Rattus norvegicus) |
Mammalia | Alk 32 |
|
||
mouse (Mus musculus) |
Mammalia | Alk 17 33 32 |
|
||
oppossum (Monodelphis domestica) |
Mammalia | ALK 33 |
|
OneToOne | |
platypus (Ornithorhynchus anatinus) |
Mammalia | ALK 33 |
|
OneToOne | |
chicken (Gallus gallus) |
Aves | ALK 33 32 |
|
OneToOne | |
lizard (Anolis carolinensis) |
Reptilia | ALK 33 |
|
OneToOne | |
tropical clawed frog (Silurana tropicalis) |
Amphibia | LOC100495071 32 |
|
||
African clawed frog (Xenopus laevis) |
Amphibia | Xl.30258 32 |
|
||
zebrafish (Danio rerio) |
Actinopterygii | alk 33 32 |
|
OneToOne | |
fruit fly (Drosophila melanogaster) |
Insecta | Alk 33 34 |
|
OneToMany | |
worm (Caenorhabditis elegans) |
Secernentea | F09A5.2 34 |
|
|
|
T25B9.5 34 |
|
|
|||
scd-2 33 34 |
|
OneToMany |
SNP ID | Clin | Chr 02 pos | Variation | AA Info | Type |
---|---|---|---|---|---|
rs1010580453 | uncertain-significance, Neuroblastoma 3 | 29,296,980(-) | C/G | coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, non_coding_transcript_variant | |
rs1023682229 | uncertain-significance, Neuroblastoma 3 | 29,920,317(-) | G/A/C | coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, non_coding_transcript_variant | |
rs1026192345 | uncertain-significance, Neuroblastoma 3 | 29,920,569(-) | A/C | coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, non_coding_transcript_variant | |
rs1031317995 | uncertain-significance, Hereditary cancer-predisposing syndrome | 29,920,662(-) | C/G/T | 5_prime_UTR_variant, genic_upstream_transcript_variant, non_coding_transcript_variant | |
rs1034835558 | uncertain-significance, Neuroblastoma 3 | 29,220,809(-) | C/G/T | coding_sequence_variant, genic_downstream_transcript_variant, missense_variant |
Disorder | Aliases | PubMed IDs |
---|---|---|
neuroblastoma 3 |
|
|
neuroblastoma 1 |
|
|
rhabdomyosarcoma |
|
|
inflammatory myofibroblastic tumor |
|
|
alk-positive anaplastic large cell lymphoma |
|
|