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ALK Gene

protein-coding   GIFtS: 69
GCID: GC02M029327

Anaplastic Lymphoma Receptor Tyrosine Kinase

(Previous name: anaplastic lymphoma kinase (Ki-1))
  See related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Anaplastic Lymphoma Receptor Tyrosine Kinase1 2     CD2462
CD246 Antigen2 3     ALK Tyrosine Kinase Receptor2
EC 2.7.10.13 8     Mutant Anaplastic Lymphoma Kinase2
NBLST32 5     Anaplastic Lymphoma Kinase3
Anaplastic Lymphoma Kinase (Ki-1)1     

External Ids:    HGNC: 4271   Entrez Gene: 2382   Ensembl: ENSG000001710947   OMIM: 1055905   UniProtKB: Q9UM733   

Export aliases for ALK gene to outside databases

Previous GC identifers: GC02M029337 GC02M029508 GC02M029390 GC02M029269 GC02M029156


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for ALK Gene:
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)

GeneCards Summary for ALK Gene:
ALK (anaplastic lymphoma receptor tyrosine kinase) is a protein-coding gene. Diseases associated with ALK include alk-positive large b-cell lymphoma, and anaplastic large cell lymphoma. GO annotations related to this gene include NF-kappaB-inducing kinase activity and protein tyrosine kinase activity. An important paralog of this gene is ROR1.

UniProtKB/Swiss-Prot: ALK_HUMAN, Q9UM73
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

Gene Wiki entry for ALK (Anaplastic lymphoma kinase) Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:
NC_000002.12  NC_018913.2  NT_022184.16  
Regulatory elements:
   Regulatory transcription factor binding sites in the ALK gene promoter:
         p53   AP-1   ATF-2   Nkx2-5   CUTL1   AREB6   STAT3   c-Jun   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): ALK promoter sequence
   Search Chromatin IP Primers for ALK

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat ALK


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2p23   Ensembl cytogenetic band:  2p23.1   HGNC cytogenetic band: 2p23

ALK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
ALK gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M029327:  view genomic region     (about GC identifiers)

Start:
29,415,640 bp from pter      End:
30,144,477 bp from pter
Size:
728,838 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: ALK_HUMAN, Q9UM73 (See protein sequence)
Recommended Name: ALK tyrosine kinase receptor precursor  
Size: 1620 amino acids; 176442 Da
Subunit: Homodimer. Homodimerizes when bound to ligand. Interacts with FRS2, IRS1, MDK, PTN and SHC1. Interacts
with CBL, PIK3R1 and PLCG1 (By similarity)
Sequence caution: Sequence=BAD92714.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Selected PDB 3D structures from and Proteopedia for ALK (see all 30):
2KUP (3D)        2KUQ (3D)        2XB7 (3D)        2XBA (3D)        2XP2 (3D)        2YFX (3D)    
Secondary accessions: Q4ZFX9 Q53QQ6 Q53RZ4 Q59FI3 Q9Y4K6

Explore the universe of human proteins at neXtProt for ALK: NX_Q9UM73

Explore proteomics data for ALK at MOPED

Post-translational modifications: 

  • Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity. In cells not stimulated by
    a ligand, receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) dephosphorylates ALK at the
    sites in ALK that are undergoing autophosphorylation through autoactivation1
  • N-glycosylated1
  • Glycosylation2 at Asn169, Asn244, Asn285, Asn324, Asn411, Asn424, Asn445, Asn563, Asn571, Asn627,
                                 Asn709, Asn808, Asn863, Asn864, Asn886, Asn986
  • Modification sites at PhosphoSitePlus
  • Selected DME Specific Peptides for ALK (Q9UM73) (see all 5)
     WEIFSLG  YILVGQQG  KIGDFGMARDIY  CPGPVYRIMTQCWQH 


    See ALK Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_004295.2  
    ENSEMBL proteins: 
     ENSP00000373700   ENSP00000387488   ENSP00000414027  

    ALK Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant ALK Protein
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    OriGene Protein Over-expression Lysate for ALK
    OriGene MassSpec for ALK
    OriGene Custom Protein Services for ALK
    GenScript Custom Purified and Recombinant Proteins Services for ALK
    Novus Biologicals ALK Proteins
    Novus Biologicals ALK Lysate
    Browse Sino Biological Recombinant Proteins
    Browse Sino Biological Cell Lysates
    ProSpec Recombinant Protein for ALK
    Cloud-Clone Corp. Proteins for ALK

    ALK Antibody Products:

    Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
    R&D Systems Antibodies for ALK (ALK/CD246)
    Cell Signaling Technology (CST) Antibodies for ALK 
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    OriGene Custom Antibody Services for ALK
    Novus Biologicals ALK Antibodies
    Abcam antibodies for ALK
    Cloud-Clone Corp. Antibodies for ALK
    ThermoFisher Antibody for ALK
    Search LSBio for Antibodies for ALK

    ALK Assay Products:

    Browse Kits and Assays available from EMD Millipore
    OriGene Custom Assay Services for ALK
    R&D Systems Proteome Profiler Antibody Arrays for ALK (ALK/CD246)
    GenScript Custom Assay Services for ALK
    Cell Signaling Technology (CST) Sandwich ELISA Kits for ALK
    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for ALK
    Cloud-Clone Corp. CLIAs for ALK


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CD: CD molecules

    IUPHAR Guide to PHARMACOLOGY protein family classification: anaplastic lymphoma receptor tyrosine kinase
    Alk family
    Leukocyte tyrosine kinase (LTK) receptor family

    Selected InterPro protein domains (see all 11):
     IPR017441 Protein_kinase_ATP_BS
     IPR011009 Kinase-like_dom
     IPR002011 Tyr_kinase_rcpt_2_CS
     IPR000719 Prot_kinase_dom
     IPR002172 LDrepeatLR_classA_rpt

    Graphical View of Domain Structure for InterPro Entry Q9UM73

    ProtoNet protein and cluster: Q9UM73

    3 Blocks protein domains:
    IPB002011 Receptor tyrosine kinase
    IPB002172 Low density lipoprotein-receptor
    IPB008266 Tyrosine protein kinase


    UniProtKB/Swiss-Prot: ALK_HUMAN, Q9UM73
    Similarity: Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily
    Similarity: Contains 1 LDL-receptor class A domain
    Similarity: Contains 2 MAM domains
    Similarity: Contains 1 protein kinase domain


    ALK for domains           About GeneDecksing


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: ALK_HUMAN, Q9UM73
    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
    Catalytic activity: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
    Enzyme regulation: Activated by ligand-binding and subsequent phosphorylation. Inactivated through
    dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no
    stimulation by a ligand. Staurosporine, crizotinib and CH5424802 act as inhibitors of ALK kinase activity

         Genatlas biochemistry entry for ALK:
    anaplastic (CD30 + large cell) lymphoma kinase playing an important role in brain development,involved in
    anaplastic nodal non Hodgkin lymphoma or Hodgkin disease with translocation t(2;5)(p23;q35) or inv2(23;q35),see
    NPM1

         Enzyme Number (IUBMB): EC 2.7.10.11 2

         Gene Ontology (GO): Selected molecular function terms (see all 7):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004672protein kinase activity ----
    GO:0004704NF-kappaB-inducing kinase activity TAS19459784
    GO:0004713protein tyrosine kinase activity IDA9174053
    GO:0004714transmembrane receptor protein tyrosine kinase activity TAS19459784
    GO:0005515protein binding IPI17681947
         
    ALK for ontologies           About GeneDecksing


    Phenotypes:
         1 GenomeRNAi human phenotype for ALK:
     Decreased substrate adherent c 

         1 MGI phenotypic allele for Alk (no phenotypes)

    ALK for phenotypes           About GeneDecksing

    Animal Models:
         MGI mouse knock-out Alktm1Lex for ALK

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for ALK
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for ALK

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for ALK
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for ALK

    miRNA
    Products:
        
    miRTarBase miRNAs that target ALK:
    hsa-mir-132-3p (MIRT021811)

    Block miRNA regulation of human, mouse, rat ALK using miScript Target Protectors
    2 qRT-PCR Assays for microRNAs that regulate ALK:
    hsa-miR-1271 hsa-miR-96
    SwitchGear 3'UTR luciferase reporter plasmidALK 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for ALK
    Predesigned siRNA for gene silencing in human, mouse, rat ALK

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for ALK

    Clone
    Products:
         
    OriGene clones in human, mouse for ALK (see all 7)
    OriGene ORF clones in mouse, rat for ALK
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector: ALK (NM_004304)
    Browse Sino Biological Human cDNA Clones
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for ALK
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat ALK

    Cell Line
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    Browse ESI BIO Cell Lines and PureStem Progenitors for ALK 
    In Situ Assay
    Products:
       

     
    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for ALK


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    ALK_HUMAN, Q9UM73: Cell membrane; Single-pass type I membrane protein. Note=Membrane attachment was crucial for
    promotion of neuron-like differentiation and cell proliferation arrest through specific activation of the MAP
    kinase pathway
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytoskeleton2
    extracellular2
    nucleus2
    endoplasmic reticulum1

    Gene Ontology (GO): 4 cellular component terms:    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005887integral component of plasma membrane TAS19459784
    GO:0016020membrane ----
    GO:0043234protein complex IDA--
    GO:0070062extracellular vesicular exosome IDA19056867

    ALK for ontologies           About GeneDecksing


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for ALK About   (see all 12)                                                                                              See pathways by source

    SuperPathContained pathways About
    1GPCR Pathway
    Ras Pathway0.73
    Breast Cancer Regulation by Stathmin10.58
    Paxillin Interactions0.73
    NFAT in Immune Response0.58
    GPCR Pathway0.62
    Estrogen Pathway0.55
    Pancreatic Adenocarcinoma0.59
    P2Y Receptor Signaling0.38
    2ERK Signaling
    Rho Family GTPases0.61
    Molecular Mechanisms of Cancer0.51
    ERK Signaling0.61
    ILK Signaling0.49
    MAPK Signaling0.58
    3Nanog in Mammalian ESC Pluripotency
    Nanog in Mammalian ESC Pluripotency0.61
    14-3-3 Induced Intracellular Signaling0.59
    GSK3 Signaling0.61
    eNOS Signaling0.48
    4Actin Nucleation by ARP-WASP Complex
    Actin Nucleation and Branching0.66
    CDC42 Pathway0.41
    Actin Nucleation by ARP-WASP Complex0.66
    5Activation of cAMP-Dependent PKA
    Activation of cAMP-Dependent PKA0.77
    Activation of PKA through GPCR0.71

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for ALK (see all 29)
        MAPK Signaling
    Paxillin Interactions
    Endothelin-1 Signaling Pathway
    Molecular Mechanisms of Cancer
    Intracellular Calcium Signaling

    1 Cell Signaling Technology (CST) Pathway for ALK
        Tyrosine Kinases / Adaptors


    1 Kegg Pathway  (Kegg details for ALK):
        Non-small cell lung cancer


    ALK for pathways           About GeneDecksing

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ALK: 
              Neurogenesis in human mouse rat
              Lymphoma in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for ALK

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for ALK (Q9UM731, 2, 3 ENSP000003737004) via UniProtKB, MINT, STRING, and/or I2D (see all 61)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    VAV3Q9UKW42, 3, ENSP000003590734MINT-8030831 I2D: score=1 STRING: ENSP00000359073
    MAP3K3Q997592, 3MINT-48477 I2D: score=2 
    PTPRZ1P234711, 2, 3, ENSP000003770474EBI-357361,EBI-2263175 MINT-8238486 MINT-8238512 I2D: score=2 STRING: ENSP00000377047
    PLCG1P191743, ENSP000002440074I2D: score=2 STRING: ENSP00000244007
    PTNP212463, ENSP000003411704I2D: score=2 STRING: ENSP00000341170
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 13):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000187activation of MAPK activity TAS19459784
    GO:0006468protein phosphorylation ----
    GO:0007165signal transduction TAS19459784
    GO:0007169transmembrane receptor protein tyrosine kinase signaling pathway IEA--
    GO:0007399nervous system development ----

    ALK for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
    Selected ApexBio Compounds for ALK (see all 11)     About this table
    CompoundAction CAS #
    (R)-Crizotinibselective, ATP-competitive, small molecule tyrosine kinase inhibitor of c-Met and ALK[877399-52-5]
    AP26113orally available inhibitor of receptor tyrosine kinases ALK[1197958-12-5]
    ASP3026a novel and selective inhibitor for the ALK kinase[1097917-15-1]
    AZD-3463ALK/IGF1R inhibitor[1356962-20-3]
    CH5424802ATP-competitive inhibitor for ALK and L1196M[1256580-46-7]
    GSK1838705AATP-competitive inhibitor of IGF-IR and IR[1116235-97-2]
    LDK378Potent ALK inhibitor[1032900-25-6]
    LDK378 dihydrochloridePotent ALK inhibitor[1380575-43-8]
    LDN193189 HydrochloridePotent and selective ALK inhibitor[1062368-62-0]
    SB525334Highly selective and ATP-competitive TGF-betaR1 (ALK5) inhibitor[356559-20-1]

    Browse Tocris compounds for ALK

    2 HMDB Compounds for ALK    About this table
    CompoundSynonyms CAS #PubMed Ids
    ADPadenosindiphosphorsaeure (see all 8)58-64-0--
    Adenosine triphosphate5'-(tetrahydrogen triphosphate) Adenosine (see all 24)56-65-5--

    Selected Novoseek inferred chemical compound relationships for ALK gene (see all 13)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    [alcl] 97.9 273 18549625 (6), 15713979 (5), 16114011 (5), 15291103 (4) (see all 86)
    cltc 90.3 15 17656252 (3), 12920229 (2), 12800156 (1), 11485898 (1) (see all 7)
    tyrosine 67.9 167 17681947 (4), 15226403 (4), 15938644 (3), 9174053 (3) (see all 82)
    n-ipa 59.5 5 12748172 (3), 16009132 (1), 16258267 (1)
    17-(allylamino)-17-demethoxygeldanamycin 35.9 4 17157164 (2), 11888936 (1)
    paraffin 24.3 5 19147828 (1), 12594387 (1), 14626344 (1)
    phosphatidylinositol 10.9 1 11278720 (1)
    doxorubicin 10.3 2 14657946 (1), 17157164 (1)
    phosphotyrosine 7.79 4 18083107 (1), 14626344 (1), 17274988 (1)
    alanine 0 3 1354511 (1), 16249437 (1), 18421281 (1)

    1 PharmGKB related drug/compound annotation for ALK gene    About this table
    Drug/compound PharmGKB Annotation
    crizotinib



    ALK for compounds           About GeneDecksing



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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    REFSEQ mRNAs for ALK gene: 
    NM_004304.4  

    Unigene Cluster for ALK:

    Anaplastic lymphoma receptor tyrosine kinase
    Hs.654469  [show with all ESTs]
    Unigene Representative Sequence: NM_004304
    4 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000389048(uc010ymo.2 uc002rmy.3) ENST00000453137 ENST00000498037
    ENST00000431873
    miRNA
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    2 qRT-PCR Assays for microRNAs that regulate ALK:
    hsa-miR-1271 hsa-miR-96
    SwitchGear 3'UTR luciferase reporter plasmidALK 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector: ALK (NM_004304)
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    Primer
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      QuantiTect SYBR Green Assays in human, mouse, rat ALK
      QuantiFast Probe-based Assays in human, mouse, rat ALK

    Additional mRNA sequence: 

    AB209477.4 AB600939.1 AB663645.1 AB795401.1 AK296218.1 BX648960.1 FJ838786.1 FJ838787.1 
    GU797894.1 HQ993071.1 JQ828841.1 U62540.1 U66559.1 

    3 DOTS entries:

    DT.87014966  DT.101966450  DT.120998959 

    12 AceView cDNA sequences:

    BG211498 BV183407 BE206076 BQ448051 BX283500 AA309216 BE019506 BF306767 
    U66559 U62540 NM_004304 AF362886 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    ALK expression in normal human tissues (normalized intensities)      ALK embryonic expression: see
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: --
    ALK Expression
    About this image


    ALK expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 5) fully expand
     
     Gut Tube (Gastrointestinal Tract)    fully expand to see all 2 entries
             Foregut
     
     Neurons
             Glycinergic Amacrine Cells Inner Nuclear Layer
     
     Eye (Sensory Organs)
             Glycinergic Amacrine Cells Inner Nuclear Layer
     
     Brain (Nervous System)
             Fourth Ventricle
     
     Spinal Cord (Nervous System)
    ALK Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    ALK Protein Expression

    Genevestigator expression for ALK

    SOURCE GeneReport for Unigene cluster: Hs.654469

    UniProtKB/Swiss-Prot: ALK_HUMAN, Q9UM73
    Tissue specificity: Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in
    normal lymphoid cells

        Pathway & Disease-focused RT2 Profiler PCR Arrays including ALK: 
              Neurogenesis in human mouse rat
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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for ALK gene from Selected species (see all 14)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Alk1 , 5 anaplastic lymphoma kinase1, 5 84.79(n)1
    88.38(a)1
      17 (43.77 cM)5
    116821  NM_007439.21  NP_031465.21 
     718694425 
    chicken
    (Gallus gallus)
    Aves ALK1 anaplastic lymphoma receptor tyrosine kinase 72.08(n)
    74.25(a)
      421297  XM_004940187.1  XP_004940244.1 
    lizard
    (Anolis carolinensis)
    Reptilia ALK6
    anaplastic lymphoma receptor tyrosine kinase
    72(a)
    1 ↔ 1
    1(248598424-248757216)
    African clawed frog
    (Xenopus laevis)
    Amphibia Xl.302582 Xenopus laevis transcribed sequence with weak similarity more 75.6(n)    BG345730.1 
    zebrafish
    (Danio rerio)
    Actinopterygii alk1 anaplastic lymphoma kinase (Ki-1) 61.65(n)
    60.57(a)
      563509  XM_686872.5  XP_691964.5 
    fruit fly
    (Drosophila melanogaster)
    Insecta Alk3 protein amino acid phosphorylation
    protein tyrosine more
    33(a)   53C10   --
    worm
    (Caenorhabditis elegans)
    Secernentea scd-23 protein kinase 41(a)
    (best of 3)
      V(6635869-6642021)   --


    ENSEMBL Gene Tree for ALK (if available)
    TreeFam Gene Tree for ALK (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for ALK gene
    ROR12  INSR2  ROS12  NTRK22  LTK2  IGF1R2  DDR12  NTRK32  
    INSRR2  ROR22  DDR22  MUSK2  NTRK12  
    Selected SIMAP similar genes for ALK using alignment to 30 protein entries:     ALK_HUMAN (see all proteins) (see all similar genes):
    DCTN1/ALK fusion    EML4-ALK variant 7    KIF5B-ALK    A20    EML4-ALK    PPFIBP1-ALK
    SQSTM1-ALK    EML4/ALK fusion    TFG/ALK fusion    EML4-ALK variant 6    EPHA4    tec
    BTK    LTK    FLT4    MET    ABL1    BTK kinase deficient isoform 6

    ALK for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for ALK (see all 16610)    About this table    
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    VAR_0638624
    Neuroblastoma 3 (NBLST3)4--see VAR_0638622 F V mis40--------
    VAR_0638604
    Neuroblastoma 3 (NBLST3)4--see VAR_0638602 A T mis40--------
    VAR_0638544
    Neuroblastoma 3 (NBLST3)4--see VAR_0638542 I N mis40--------
    VAR_0414844
    An ovarian serous carcinoma sample4--see VAR_0414842 A S mis40--------
    VAR_0638524
    Neuroblastoma 3 (NBLST3)4--see VAR_0638522 T M mis40--------
    VAR_0638534
    Neuroblastoma 3 (NBLST3)4--see VAR_0638532 M R mis40--------
    VAR_0638594
    Neuroblastoma 3 (NBLST3)4--see VAR_0638592 R P mis40--------
    VAR_0638564
    Neuroblastoma 3 (NBLST3)4--see VAR_0638562 F I mis40--------
    VAR_0638514
    Neuroblastoma 3 (NBLST3)4--see VAR_0638512 G A mis40--------
    VAR_0638584
    Neuroblastoma 3 (NBLST3)4--see VAR_0638582 F V mis40--------

    HapMap Linkage Disequilibrium report for ALK (29415640 - 29665640 bp, first 250kb of ALK)

    Structural Variations
         Database of Genomic Variants (DGV) Selected variations for ALK (see all 40):    About this table    
    Variant IDTypeSubtypePubMed ID
    esv2667588CNV Deletion23128226
    esv1273908CNV Deletion17803354
    esv4149CNV Deletion18987735
    esv2678336CNV Deletion23128226
    esv2421745CNV Deletion20811451
    esv2675184CNV Deletion23128226
    esv2671680CNV Deletion23128226
    esv2719856CNV Deletion23290073
    esv2663423CNV Deletion23128226
    esv2719857CNV Deletion23290073

    Human Gene Mutation Database (HGMD): ALK
    Selected Site Specific Mutation Identification with PCR Assays for ALK (see all 10):
    Cosmic IdAA Change
    28498p.I1171N
    28499p.F1245V
    28500p.F1245C
    28491p.F1174I
    28495p.T1211T
    5 Site Specific Cancer Mutation PCR Panels containing ALK:
    Tyrosine Kinases & Cell Signaling Pathways Panel 384HT
    Oncogene and Tumor Suppressor Panel 384HT
    Lung and Colon Cancers (Expanded Panel) 384HT
    Cancer Comprehensive Panel 384HT
    Oncogene Panel 384HT
    2 Copy Number PCR Panels containing ALK:
    Oncogenes & Tumor Suppressor Genes 384HC
    Kinases & Phosphatases
    SeqTarget long-range PCR primers for resequencing ALK
    DNA2.0 Custom Variant and Variant Library Synthesis for ALK

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 105590   
    OMIM disorders: 613014  
    UniProtKB/Swiss-Prot: ALK_HUMAN, Q9UM73
  • Note=A chromosomal aberration involving ALK is found in a form of non-Hodgkin lymphoma. Translocation
    t(2;5)(p23;q35) with NPM1. The resulting chimeric NPM1-ALK protein homodimerize and the kinase becomes
    constitutively activated. The constitutively active fusion proteins are responsible for 5-10% of non-Hodgkin
    lymphomas
  • Note=A chromosomal aberration involving ALK is associated with inflammatory myofibroblastic tumors
    (IMTs). Translocation t(2;11)(p23;p15) with CARS; translocation t(2;4)(p23;q21) with SEC31A
  • Note=A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL).
    Translocation t(2;17)(p23;q25) with ALO17
  • Neuroblastoma 3 (NBLST3) [MIM:613014]: A common neoplasm of early childhood arising from embryonic cells
    that form the primitive neural crest and give rise to the adrenal medulla and the sympathetic nervous system.
    Note=Disease susceptibility is associated with variations affecting the gene represented in this entry
  • Note=The ALK signaling pathway plays an important role in glioblastoma, the most common malignant brain
    tumor of adults and one of the most lethal cancers. It regulates both glioblastoma migration and growth

  • Selected diseases for ALK (see all 66):    About MalaCards
    alk-positive large b-cell lymphoma    anaplastic large cell lymphoma    alk-related neuroblastoma susceptibility    inflammatory myofibroblastic tumor
    alk-positive anaplastic large cell lymphoma    neuroblastoma 3    tracheal lymphoma    neuroblastoma
    alk+ histiocytosis    primary cutaneous anaplastic large cell lymphoma    neuroblastoma, susceptibility    alk-negative anaplastic large cell lymphoma
    kyasanur forest disease    lymphomatoid papulosis    reticulosarcoma    follicular dendritic cell tumor
    fibrous histiocytoma    lung cancer    histiocytoma    peripheral t-cell lymphoma

    5 diseases from the University of Copenhagen DISEASES database for ALK:
    Lymphoma     Reticulosarcoma     Lung cancer     Neuroblastoma
    Carcinoma

    ALK for disorders           About GeneDecksing

    Selected Novoseek inferred disease relationships for ALK gene (see all 49)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    anaplastic large cell lymphoma 97.8 225 8866227 (2), 11215285 (2), 16434370 (2), 19135051 (2) (see all 99)
    lymphoma large cell 90.5 73 10886208 (2), 20227918 (2), 17332315 (2), 16189272 (2) (see all 35)
    lymphoma 89.9 830 19386350 (9), 9415224 (7), 7655001 (5), 10994999 (4) (see all 99)
    lymphomatoid papulosis 84.4 10 9415224 (2), 9638979 (1), 9250148 (1), 17325487 (1) (see all 5)
    lymphoma t-cell peripheral 80.5 1 9736036 (1)
    hodgkin disease 72.3 14 20227918 (2), 11697652 (2), 9638979 (1), 9490693 (1) (see all 10)
    lymphoma non-hodgkins 71.2 22 9174053 (2), 15938644 (1), 9121481 (1), 17694547 (1) (see all 12)
    lymphoma b-cell 71 40 17509395 (2), 18220322 (2), 10886208 (2), 12750159 (2) (see all 19)
    pseudotumor inflammatory 65 4 11395553 (3)
    lymphoma t-cell 64.8 15 16170336 (2), 11781220 (1), 12213716 (1), 18670314 (1) (see all 10)

    Genatlas disease: ALK
    nodal and extranodal,CD30+,anaplastic large-cell non Hodgkin's lymphoma,Hodgkin disease with translocation
    t(2;5)(p23;q35),infalmmatory myofibroblastic tumors

    Genetic Association Database (GAD): ALK
    Human Genome Epidemiology (HuGE) Navigator: ALK (14 documents)
    Tumor Gene Database (TGDB): ALK

    Export disorders for ALK gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for ALK gene, integrated from 10 sources (see all 639):
    (articles sorted by number of sources associating them with ALK)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. (PubMed id 8122112)1, 2, 3, 9 Morris S.W.... Look A.T. (Science 1994)
    2. Anaplastic lymphoma kinase is activated through the pleiotrophin/receptor protein-tyrosine phosphatase beta/zeta signaling pathway: an alternative mechanism of receptor tyrosine kinase activation. (PubMed id 17681947)1, 2, 9 Perez-Pinera P.... Deuel T.F. (J. Biol. Chem. 2007)
    3. Unique substrate specificity of anaplastic lymphoma kinase (ALK): development of phosphoacceptor peptides for the assay of ALK activity. (PubMed id 15938644)1, 2, 9 Donella-Deana A.... Pinna L.A. (Biochemistry 2005)
    4. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. (PubMed id 9053841)1, 2, 9 Iwahara T.... Yamamoto T. (Oncogene 1997)
    5. Identification of ALK as a major familial neuroblastoma predisposition gene. (PubMed id 18724359)1, 2, 9 Mosse Y.P....Maris J.M. (Nature 2008)
    6. Activating mutations in ALK provide a therapeutic target in neuroblastoma. (PubMed id 18923525)1, 2, 9 George R.E.... Look A.T. (Nature 2008)
    7. Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor. (PubMed id 16161041)1, 2, 9 Panagopoulos I.... Mandahl N. (Int. J. Cancer 2006)
    8. Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types. (PubMed id 12122009)1, 2, 9 Stoica G.E....Wellstein A. (J. Biol. Chem. 2002)
    9. ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth. (PubMed id 15226403)1, 2, 9 Motegi A.... Yamamoto T. (J. Cell Sci. 2004)
    10. Pleiotrophin signaling through anaplastic lymphoma kinase is rate- limiting for glioblastoma growth. (PubMed id 11809760)1, 2, 9 Powers C.... Wellstein A. (J. Biol. Chem. 2002)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 238 HGNC: 427 AceView: ALK Ensembl:ENSG00000171094 euGenes: HUgn238
    ECgene: ALK Kegg: 238 H-InvDB: ALK

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for ALK Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for ALK Genetics and Cytogenetics in Oncology and Haematology
    GeneReviewshttp://www.ncbi.nlm.nih.gov/books/NBK1116/?term=ALK[genesymbol]

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for ALK gene:
    Search GeneIP for patents involving ALK

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



    (Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Cloud-Clone Corp., Thermo Fisher Scientific, LSBio, Gene Editing from DNA2.0. Clones from OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript, and ESI BIO, PCR Arrays from QIAGEN, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, Enzo Life Sciences, and/or ApexBio, In Situ Hybridization Assays from
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