Top ALK
Localization (UniProt annotation) Cell membrane Note=Membrane attachment was crucial for promotion of neuron-likedifferentiation and cell proliferation arrest through specificactivation of the MAP kinase pathway Function (UniProt annotation) Neuronal receptor tyrosine kinase that is essentiallyand transiently expressed in specific regions of the central andperipheral nervous systems and plays an important role in thegenesis and differentiation of the nervous system Transducessignals from ligands at the cell surface, through specificactivation of the mitogen-activated protein kinase (MAPK) pathwayPhosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif Following activation by ligand, ALK inducestyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well asof the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 Acts as a receptorfor ligands pleiotrophin (PTN), a secreted growth factor, andmidkine (MDK), a PTN-related factor, thus participating in PTN andMDK signal transduction PTN-binding induces MAPK pathwayactivation, which is important for the anti-apoptotic signaling ofPTN and regulation of cell proliferation MDK-binding inducesphosphorylation of the ALK target insulin receptor substrate(IRS1), activates mitogen-activated protein kinases (MAPKs) andPI3-kinase, resulting also in cell proliferation induction DrivesNF-kappa-B activation, probably through IRS1 and the activation ofthe AKT serine/threonine kinase Recruitment of IRS1 to activatedALK and the activation of NF-kappa-B are essential for theautocrine growth and survival signaling of MDK Catalytic Activity (UniProt annotation) ATP + a [protein]-L-tyrosine = ADP + a[protein]-L-tyrosine phosphate Protein Sequence MGAIGLLWLLPLLLSTAAVGSGMGTGQRAGSPAAGPPLQPREPLSYSRLQRKSLAVDFVVPSLFRVYARDLLLPPSSSEL
KAGRPEARGSLALDCAPLLRLLGPAPGVSWTAGSPAPAEARTLSRVLKGGSVRKLRRAKQLVLELGEEAILEGCVGPPGE
AAVGLLQFNLSELFSWWIRQGEGRLRIRLMPEKKASEVGREGRLSAAIRASQPRLLFQIFGTGHSSLESPTNMPSPSPDY
FTWNLTWIMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHDLRNQSWSWRRIPSEEASQMDLLDGPGAERSKEMPRGSF
LLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGRYIAQLLPHNEAAREILLMPTPGKHGWTVLQGRIGRPDNPF
RVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDESQMCRKLPVGFYC
NFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSATFPAPIKSSPCELRMSWLIRGVL
RGNVSLVLVENKTGKEQGRMVWHVAAYEGLSLWQWMVLPLLDVSDRFWLQMVAWWGQGSRAIVAFDNISISLDCYLTISG
EDKILQNTAPKSRNLFERNPNKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSEGPL
KGIQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKDDMLYILVGQQGEDACPSTNQLIQKVCIGENNV
IEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLIIAAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGG
GGWNDNTSLLWAGKSLQEGATGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFIS
PLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGVSCIVSPTPEPHLPLSLILSVV
TSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIR
GLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMA
GGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRA
SYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYR
IMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAA
PPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNN
PIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVNYGYQQQGLPLEAATAPG
AGHYEDTILKSKNSMNQPGP
ELM Motif Motif Instance Description Motif Regex NA NA NA NA
ALK is dephosphorylated by following phosphatases:
Pathway ID Pathway Name Pathway Description (KEGG) hsa05200 Pathways in cancer hsa05223 Non-small cell lung cancer Lung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heterogeneous group of cancers, consisting mainly of squamous cell (SCC), adeno (AC) and large-cell carcinoma. Molecular mechanisms altered in NSCLC include activation of oncogenes, such as K-RAS, EGFR and EML4-ALK, and inactivation of tumorsuppressor genes, such as p53, p16INK4a, RAR-beta, and RASSF1. Point mutations within the K-RAS gene inactivate GTPase activity and the p21-RAS protein continuously transmits growth signals to the nucleus. Mutations or overexpression of EGFR leads to a proliferative advantage. EML4-ALK fusion leads to constitutive ALK activation, which causes cell proliferation, invasion, and inhibition of apoptosis. Inactivating mutation of p53 can lead to more rapid proliferation and reduced apoptosis. The protein encoded by the p16INK4a inhibits formation of CDK-cyclin-D complexes by competitive binding of CDK4 and CDK6. Loss of p16INK4a expression is a common feature of NSCLC. RAR-beta is a nuclear receptor that bears vitamin-A-dependent transcriptional activity. RASSF1A is able to form heterodimers with Nore-1, an RAS effector.Therefore loss of RASSF1A might shift the balance of RAS activity towards a growth-promoting effect.
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source ACTN4 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID BCAR1 Affinity Capture-MS, Affinity Capture-Western physical 16105984 , (Europe PMC )NA BioGRID BICD2 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID CDK13 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID CDK9 Negative Genetic genetic 28319113 , (Europe PMC )NA BioGRID CENPF Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID CORO1C Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID DUSP19 Two-hybrid physical 28065597 , (Europe PMC )NA BioGRID EIF4B Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID EPHA1 Affinity Capture-MS, Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID EPHB2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID ERRFI1 Affinity Capture-Western physical 19815557 , (Europe PMC )NA BioGRID FLII Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID GAK Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID GRB2 Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex physical 14968112 , 16105984 , 9819383 , (Europe PMC )NA BioGRID HSP90AA1 Affinity Capture-Luminescence, Affinity Capture-Western physical 22939624 , (Europe PMC )NA BioGRID HSPD1 Affinity Capture-MS, Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID IKBKG Reconstituted Complex physical 20098747 , (Europe PMC )NA BioGRID IRF7 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID IRS1 Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID IRS4 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID JAK2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID JAK3 Affinity Capture-MS, Affinity Capture-Western physical 11850821 , 14968112 , (Europe PMC )NA BioGRID KRT18 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID KRT74 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAP2K7 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAP3K1 Affinity Capture-MS, Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID MAP3K4 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAP3K5 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAPK1 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAPK8IP3 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MEP1B Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MTIF2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MYBPC2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MYH10 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID MYH9 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID MYLK Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MYO6 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID PDLIM3 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID PDX1 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID PIK3CB Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID PIK3R1 Reconstituted Complex physical 16135792 , (Europe PMC )NA BioGRID PLCB2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID PLCG1 Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex physical 11888936 , 14968112 , 9819383 , (Europe PMC )NA BioGRID PPM1A Two-hybrid physical 28065597 , (Europe PMC )NA BioGRID PRKCQ Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID PTN Reconstituted Complex physical 11278720 , (Europe PMC )NA BioGRID PXN Affinity Capture-Western physical 16105984 , (Europe PMC )NA BioGRID RAB35 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID RACK1 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID RAD17 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID SHC1 Affinity Capture-Western physical 11888936 , (Europe PMC )NA BioGRID SHC3 Affinity Capture-Western physical 12185581 , (Europe PMC )NA BioGRID SMC6 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID SOCS1 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID SOCS5 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID SRC Affinity Capture-Western physical 16105984 , (Europe PMC )NA BioGRID STAT3 Affinity Capture-MS, Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID TNK2 Affinity Capture-Western physical 19815557 , (Europe PMC )NA BioGRID TUBB4B Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID TUBGCP2 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID UBASH3A Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID VIM Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID ZC3HC1 Affinity Capture-Western, Biochemical Activity, Reconstituted Complex physical 12748172 , (Europe PMC )NA BioGRID
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source ALKAL1 anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, enzyme linked immunosorbent assay, fluorescence microscopy, surface plasmon resonance colocalization, direct interaction, physical association 26418745 , (Europe PMC )0.66 IntAct ALKAL2 anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, fluorescence microscopy colocalization, physical association 26418745 , (Europe PMC )0.56 IntAct EBI-1108795 anti bait coimmunoprecipitation association 14968112 , (Europe PMC )0.35 IntAct HSP90AB1 anti tag coimmunoprecipitation, luminescence based mammalian interactome mapping physical association 22939624 , (Europe PMC )0.52 IntAct LTK anti tag coimmunoprecipitation association 26418745 , (Europe PMC )0.35 IntAct MAP3K3 tandem affinity purification physical association 14743216 , (Europe PMC )0.40 IntAct PKM protein kinase assay phosphorylation reaction 24606918 , (Europe PMC )0.44 IntAct PTPRB phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PTPRG phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PTPRJ phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PTPRZ1 phosphatase assay, pull down dephosphorylation reaction, physical association 17681947 , (Europe PMC )0.54 IntAct, MINT VAV3 coimmunoprecipitation association 17998938 , (Europe PMC )0.35 IntAct, MINT
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Interacting partner Detection method Interaction type PubMed IDs Interaction Score Source ACTN4 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID ALK protein kinase assay phosphorylation reaction 25517749 , (Europe PMC )0.44 IntAct ALKAL1 anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, enzyme linked immunosorbent assay, fluorescence microscopy, surface plasmon resonance colocalization, direct interaction, physical association 26418745 , (Europe PMC )0.66 IntAct ALKAL2 anti bait coimmunoprecipitation, anti tag coimmunoprecipitation, fluorescence microscopy colocalization, physical association 26418745 , (Europe PMC )0.56 IntAct BCAR1 Affinity Capture-MS, Affinity Capture-Western physical 16105984 , (Europe PMC )NA BioGRID BICD2 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID CDK13 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID CDK9 Negative Genetic genetic 28319113 , (Europe PMC )NA BioGRID CENPF Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID CORO1C Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID DUSP19 Two-hybrid physical 28065597 , (Europe PMC )NA BioGRID EBI-1108795 anti bait coimmunoprecipitation association 14968112 , (Europe PMC )0.35 IntAct EIF4B Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID EPHA1 Affinity Capture-MS, Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID EPHB2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID ERRFI1 Affinity Capture-Western physical 19815557 , (Europe PMC )NA BioGRID FLII Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID GAK Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID GRB2 Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex physical 14968112 , 16105984 , 9819383 , (Europe PMC )NA BioGRID HSP90AA1 Affinity Capture-Luminescence, Affinity Capture-Western physical 22939624 , (Europe PMC )NA BioGRID HSP90AB1 anti tag coimmunoprecipitation, luminescence based mammalian interactome mapping physical association 22939624 , (Europe PMC )0.52 IntAct HSPD1 Affinity Capture-MS, Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID IKBKG Reconstituted Complex physical 20098747 , (Europe PMC )NA BioGRID IRF7 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID IRS1 Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID IRS4 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID JAK2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID JAK3 Affinity Capture-MS, Affinity Capture-Western physical 11850821 , 14968112 , (Europe PMC )NA BioGRID KRT18 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID KRT74 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID LTK anti tag coimmunoprecipitation association 26418745 , (Europe PMC )0.35 IntAct MAP2K7 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAP3K1 Affinity Capture-MS, Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID MAP3K3 tandem affinity purification physical association 14743216 , (Europe PMC )0.40 IntAct MAP3K4 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAP3K5 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAPK1 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MAPK8IP3 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MEP1B Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MTIF2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MYBPC2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MYH10 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID MYH9 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID MYLK Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID MYO6 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID PDLIM3 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID PDX1 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID PIK3CB Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID PIK3R1 Reconstituted Complex physical 16135792 , (Europe PMC )NA BioGRID PKM protein kinase assay phosphorylation reaction 24606918 , (Europe PMC )0.44 IntAct PLCB2 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID PLCG1 Affinity Capture-MS, Affinity Capture-Western, Reconstituted Complex physical 11888936 , 14968112 , 9819383 , (Europe PMC )NA BioGRID PPM1A Two-hybrid physical 28065597 , (Europe PMC )NA BioGRID PRKCQ Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID PTN Reconstituted Complex physical 11278720 , (Europe PMC )NA BioGRID PTPRB phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PTPRG phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PTPRJ phosphatase assay dephosphorylation reaction 19167335 , (Europe PMC )0.44 IntAct PTPRZ1 phosphatase assay, pull down dephosphorylation reaction, physical association 17681947 , (Europe PMC )0.54 IntAct, MINT PXN Affinity Capture-Western physical 16105984 , (Europe PMC )NA BioGRID RAB35 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID RACK1 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID RAD17 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID SHC1 Affinity Capture-Western physical 11888936 , (Europe PMC )NA BioGRID SHC3 Affinity Capture-Western physical 12185581 , (Europe PMC )NA BioGRID SMC6 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID SOCS1 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID SOCS5 Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID SRC Affinity Capture-Western physical 16105984 , (Europe PMC )NA BioGRID STAT3 Affinity Capture-MS, Affinity Capture-Western physical 14968112 , (Europe PMC )NA BioGRID TNK2 Affinity Capture-Western physical 19815557 , (Europe PMC )NA BioGRID TUBB4B Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID TUBGCP2 Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID UBASH3A Affinity Capture-MS physical 14968112 , (Europe PMC )NA BioGRID VAV3 coimmunoprecipitation association 17998938 , (Europe PMC )0.35 IntAct, MINT VIM Affinity Capture-MS physical 16105984 , (Europe PMC )NA BioGRID ZC3HC1 Affinity Capture-Western, Biochemical Activity, Reconstituted Complex physical 12748172 , (Europe PMC )NA BioGRID
Phosphorylating Kinases Phosphoresidues Detection Method PubMed IDs Source
Visualize a network of protein kinases and phosphatases phosphorylating and dephosphorylating this protein respectively
ALK Y1278_FGMARDIyRASYYRK , Y1282_RDIYRASyYRKGGCA , Y1283_DIYRASYyRKGGCAM , Y1604_TAPGAGHyEDTILKS , LTP, in vivo 11110708 , 9174053 , 9819383 ,(Europe PMC )HPRD, PhosphoELM , PhosphoSitePlus , Unknown S211_LSAAIRAsQPRLLFQ , S47_PREPLSYsRLQRKSL , Y1078_MELQSPEyKLSKLRT , Y1092_TSTIMTDyNPNYCFA , Y1096_MTDYNPNyCFAGKTS , Y1131_HGAFGEVyEGQVSGM , Y1278_FGMARDIyRASYYRK , Y1282_RDIYRASyYRKGGCA , Y1283_DIYRASYyRKGGCAM , Y1359_KNCPGPVyRIMTQCW , Y1507_TSLWNPTyGSWFTEK , Y1584_FPCGNVNyGYQQQGL , Y1604_TAPGAGHyEDTILKS , HTP, LTP, in vivo 11110708 , 15592455 , 15938644 , 16565220 , 18083107 , 19664994 , 9174053 , 9819383 ,(Europe PMC )HPRD, PhosphoELM ,
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