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Q9UM73

- ALK_HUMAN

UniProt

Q9UM73 - ALK_HUMAN

Protein

ALK tyrosine kinase receptor

Gene

ALK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 149 (01 Oct 2014)
      Sequence version 3 (18 May 2010)
      Previous versions | rss
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    Functioni

    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.11 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.PROSITE-ProRule annotation

    Enzyme regulationi

    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.3 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei1124 – 11241ATP; via carbonyl oxygen
    Binding sitei1150 – 11501ATPPROSITE-ProRule annotation
    Binding sitei1150 – 11501Inhibitor2 Publications
    Binding sitei1199 – 11991Inhibitor; via amide nitrogen2 Publications
    Binding sitei1203 – 12031Inhibitor2 Publications
    Binding sitei1210 – 12101Inhibitor2 Publications
    Active sitei1249 – 12491Proton acceptorPROSITE-ProRule annotation
    Binding sitei1270 – 12701ATP

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi1197 – 11993ATP

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. NF-kappaB-inducing kinase activity Source: UniProtKB
    3. protein binding Source: IntAct
    4. protein tyrosine kinase activity Source: MGI
    5. transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

    GO - Biological processi

    1. activation of MAPK activity Source: UniProtKB
    2. cell proliferation Source: UniProtKB
    3. neuron development Source: UniProtKB
    4. NIK/NF-kappaB signaling Source: GOC
    5. peptidyl-tyrosine phosphorylation Source: GOC
    6. phosphorylation Source: UniProtKB
    7. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    8. protein autophosphorylation Source: UniProtKB
    9. regulation of apoptotic process Source: UniProtKB
    10. signal transduction Source: UniProtKB
    11. transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro

    Keywords - Molecular functioni

    Kinase, Receptor, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.1. 2681.
    SignaLinkiQ9UM73.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    ALK tyrosine kinase receptor (EC:2.7.10.1)
    Alternative name(s):
    Anaplastic lymphoma kinase
    CD_antigen: CD246
    Gene namesi
    Name:ALK
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:427. ALK.

    Subcellular locationi

    Cell membrane 2 Publications; Single-pass type I membrane protein 2 Publications
    Note: Membrane attachment was crucial for promotion of neuron-like differentiation and cell proliferation arrest through specific activation of the MAP kinase pathway.

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt
    2. integral component of plasma membrane Source: UniProtKB
    3. protein complex Source: MGI

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.
    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.
    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.3 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti1091 – 10911D → N in NBLST3; somatic mutation. 1 Publication
    VAR_063850
    Natural varianti1128 – 11281G → A in NBLST3. 1 Publication
    VAR_063851
    Natural varianti1151 – 11511T → M in NBLST3. 1 Publication
    VAR_063852
    Natural varianti1166 – 11661M → R in NBLST3; somatic mutation. 1 Publication
    VAR_063853
    Natural varianti1171 – 11711I → N in NBLST3; somatic mutation. 1 Publication
    VAR_063854
    Natural varianti1174 – 11741F → C in NBLST3. 1 Publication
    VAR_063855
    Natural varianti1174 – 11741F → I in NBLST3; somatic mutation. 1 Publication
    VAR_063856
    Natural varianti1174 – 11741F → L in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 2 Publications
    VAR_063857
    Natural varianti1174 – 11741F → V in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 1 Publication
    VAR_063858
    Natural varianti1192 – 11921R → P in NBLST3. 2 Publications
    VAR_063859
    Natural varianti1234 – 12341A → T in NBLST3; somatic mutation. 1 Publication
    VAR_063860
    Natural varianti1245 – 12451F → C in NBLST3; somatic mutation. 2 Publications
    VAR_063861
    Natural varianti1245 – 12451F → V in NBLST3; somatic mutation.
    VAR_063862
    Natural varianti1250 – 12501I → T in NBLST3; somatic mutation. 1 Publication
    VAR_063863
    Natural varianti1275 – 12751R → Q in NBLST3; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 3 Publications
    VAR_063865
    Natural varianti1278 – 12781Y → S in NBLST3; somatic mutation. 1 Publication
    VAR_063866
    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.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1507 – 15071Y → F: Impairs interaction with SHC1. 1 Publication

    Keywords - Diseasei

    Disease mutation, Proto-oncogene

    Organism-specific databases

    MIMi613014. phenotype.
    Orphaneti300895. ALK-positive anaplastic large cell lymphoma.
    364043. ALK-positive large B-cell lymphoma.
    178342. Inflammatory myofibroblastic tumor.
    635. Neuroblastoma.
    357191. Selection of therapeutic option in non-small cell lung carcinoma.
    PharmGKBiPA24719.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1818Sequence AnalysisAdd
    BLAST
    Chaini19 – 16201602ALK tyrosine kinase receptorPRO_0000016740Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi169 – 1691N-linked (GlcNAc...)Sequence Analysis
    Modified residuei211 – 2111Phosphoserine
    Glycosylationi244 – 2441N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi285 – 2851N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi324 – 3241N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi411 – 4111N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi424 – 4241N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi445 – 4451N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi563 – 5631N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi571 – 5711N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi627 – 6271N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi709 – 7091N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi808 – 8081N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi863 – 8631N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi864 – 8641N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi886 – 8861N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi986 – 9861N-linked (GlcNAc...)Sequence Analysis
    Modified residuei1078 – 10781Phosphotyrosine1 Publication
    Modified residuei1092 – 10921Phosphotyrosine
    Modified residuei1096 – 10961Phosphotyrosine2 Publications
    Modified residuei1131 – 11311Phosphotyrosine1 Publication
    Modified residuei1278 – 12781Phosphotyrosine1 Publication
    Modified residuei1282 – 12821Phosphotyrosine; by autocatalysis
    Modified residuei1283 – 12831Phosphotyrosine
    Modified residuei1359 – 13591Phosphotyrosine
    Modified residuei1507 – 15071Phosphotyrosine1 Publication
    Modified residuei1584 – 15841Phosphotyrosine
    Modified residuei1604 – 16041Phosphotyrosine1 Publication

    Post-translational modificationi

    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 autoactivation. Phosphorylation at Tyr-1507 is critical for SHC1 association.6 Publications
    N-glycosylated.1 Publication

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    PaxDbiQ9UM73.
    PRIDEiQ9UM73.

    PTM databases

    PhosphoSiteiQ9UM73.

    Expressioni

    Tissue specificityi

    Expressed in brain and CNS. Also expressed in the small intestine and testis, but not in normal lymphoid cells.1 Publication

    Gene expression databases

    ArrayExpressiQ9UM73.
    BgeeiQ9UM73.
    CleanExiHS_ALK.
    GenevestigatoriQ9UM73.

    Organism-specific databases

    HPAiHPA010694.

    Interactioni

    Subunit structurei

    Homodimer. Homodimerizes when bound to ligand. Interacts with FRS2, IRS1, MDK, PTN and SHC1. Interacts with CBL, PIK3R1 and PLCG1 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    HSP90AB1P082382EBI-357361,EBI-352572
    PTPRZ1P234712EBI-357361,EBI-2263175

    Protein-protein interaction databases

    BioGridi106739. 46 interactions.
    DIPiDIP-5954N.
    IntActiQ9UM73. 7 interactions.
    MINTiMINT-1133857.
    STRINGi9606.ENSP00000373700.

    Structurei

    Secondary structure

    1
    1620
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi1087 – 10926
    Beta strandi1096 – 10983
    Beta strandi1101 – 11033
    Helixi1105 – 11073
    Helixi1113 – 11153
    Beta strandi1117 – 11215
    Beta strandi1126 – 11283
    Beta strandi1130 – 11345
    Beta strandi1137 – 11404
    Beta strandi1146 – 11516
    Helixi1158 – 117316
    Beta strandi1182 – 11865
    Beta strandi1188 – 11914
    Beta strandi1193 – 11975
    Helixi1204 – 12107
    Beta strandi1215 – 12173
    Helixi1223 – 124220
    Helixi1252 – 12543
    Beta strandi1255 – 12584
    Beta strandi1260 – 12634
    Beta strandi1266 – 12683
    Helixi1272 – 12787
    Beta strandi1280 – 12823
    Helixi1288 – 12903
    Helixi1293 – 12953
    Helixi1298 – 13036
    Helixi1308 – 132316
    Helixi1335 – 13439
    Helixi1356 – 136510
    Helixi1370 – 13723
    Helixi1376 – 138813
    Helixi1390 – 13934
    Beta strandi1574 – 15763
    Beta strandi1582 – 15843

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2KUPNMR-B1571-1589[»]
    2KUQNMR-A1571-1589[»]
    2XB7X-ray2.50A1094-1407[»]
    2XBAX-ray1.95A1094-1407[»]
    2XP2X-ray1.90A1093-1411[»]
    2YFXX-ray1.70A1093-1411[»]
    2YHVX-ray1.90A1093-1411[»]
    2YJRX-ray1.90A1093-1411[»]
    2YJSX-ray1.90A1093-1411[»]
    2YS5NMR-B1571-1589[»]
    2YT2NMR-A1571-1589[»]
    3AOXX-ray1.75A1069-1411[»]
    3L9PX-ray1.80A1072-1410[»]
    3LCSX-ray1.95A1072-1410[»]
    3LCTX-ray2.10A1072-1410[»]
    4ANLX-ray1.70A1093-1411[»]
    4ANQX-ray1.76A1093-1411[»]
    4ANSX-ray1.85A1093-1411[»]
    4CCBX-ray2.03A1093-1411[»]
    4CCUX-ray2.00A1093-1411[»]
    4CD0X-ray2.23A1093-1411[»]
    4CLIX-ray2.05A1093-1411[»]
    4CLJX-ray1.66A1093-1411[»]
    4CMOX-ray1.83A1093-1411[»]
    4CMTX-ray1.73A1093-1411[»]
    4CMUX-ray1.80A1093-1411[»]
    4CNHX-ray1.90A/B1093-1411[»]
    4CTBX-ray1.79A1093-1411[»]
    4CTCX-ray2.03A1093-1411[»]
    4DCEX-ray2.03A/B1078-1410[»]
    4FNWX-ray1.75A1084-1410[»]
    4FNXX-ray1.70A1084-1410[»]
    4FNYX-ray2.45A1084-1410[»]
    4FNZX-ray2.60A1084-1410[»]
    4FOBX-ray1.90A1058-1410[»]
    4FOCX-ray1.70A1058-1410[»]
    4FODX-ray2.00A1078-1410[»]
    4JOAX-ray2.70A1072-1410[»]
    4MKCX-ray2.01A1072-1410[»]
    ProteinModelPortaliQ9UM73.
    SMRiQ9UM73. Positions 1096-1480.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ9UM73.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini19 – 10381020ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1060 – 1620561CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1039 – 105921HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini264 – 427164MAM 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini437 – 47337LDL-receptor class AAdd
    BLAST
    Domaini478 – 636159MAM 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini1116 – 1392277Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1197 – 11993Inhibitor binding

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi816 – 940125Gly-richAdd
    BLAST

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation
    Contains 1 LDL-receptor class A domain.Curated
    Contains 2 MAM domains.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000231766.
    HOVERGENiHBG018726.
    InParanoidiQ9UM73.
    KOiK05119.
    OMAiLIQKVCI.
    OrthoDBiEOG7GN2KT.
    PhylomeDBiQ9UM73.
    TreeFamiTF351636.

    Family and domain databases

    Gene3Di4.10.400.10. 1 hit.
    InterProiIPR026830. ALK.
    IPR008985. ConA-like_lec_gl_sf.
    IPR011009. Kinase-like_dom.
    IPR002172. LDrepeatLR_classA_rpt.
    IPR000998. MAM_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR002011. Tyr_kinase_rcpt_2_CS.
    [Graphical view]
    PANTHERiPTHR24416:SF276. PTHR24416:SF276. 1 hit.
    PfamiPF00629. MAM. 2 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view]
    PRINTSiPR00109. TYRKINASE.
    SMARTiSM00192. LDLa. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF49899. SSF49899. 2 hits.
    SSF56112. SSF56112. 1 hit.
    SSF57424. SSF57424. 1 hit.
    PROSITEiPS50060. MAM_2. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q9UM73-1 [UniParc]FASTAAdd to Basket

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    MGAIGLLWLL PLLLSTAAVG SGMGTGQRAG SPAAGPPLQP REPLSYSRLQ     50
    RKSLAVDFVV PSLFRVYARD LLLPPSSSEL KAGRPEARGS LALDCAPLLR 100
    LLGPAPGVSW TAGSPAPAEA RTLSRVLKGG SVRKLRRAKQ LVLELGEEAI 150
    LEGCVGPPGE AAVGLLQFNL SELFSWWIRQ GEGRLRIRLM PEKKASEVGR 200
    EGRLSAAIRA SQPRLLFQIF GTGHSSLESP TNMPSPSPDY FTWNLTWIMK 250
    DSFPFLSHRS RYGLECSFDF PCELEYSPPL HDLRNQSWSW RRIPSEEASQ 300
    MDLLDGPGAE RSKEMPRGSF LLLNTSADSK HTILSPWMRS SSEHCTLAVS 350
    VHRHLQPSGR YIAQLLPHNE AAREILLMPT PGKHGWTVLQ GRIGRPDNPF 400
    RVALEYISSG NRSLSAVDFF ALKNCSEGTS PGSKMALQSS FTCWNGTVLQ 450
    LGQACDFHQD CAQGEDESQM CRKLPVGFYC NFEDGFCGWT QGTLSPHTPQ 500
    WQVRTLKDAR FQDHQDHALL LSTTDVPASE SATVTSATFP APIKSSPCEL 550
    RMSWLIRGVL RGNVSLVLVE NKTGKEQGRM VWHVAAYEGL SLWQWMVLPL 600
    LDVSDRFWLQ MVAWWGQGSR AIVAFDNISI SLDCYLTISG EDKILQNTAP 650
    KSRNLFERNP NKELKPGENS PRQTPIFDPT VHWLFTTCGA SGPHGPTQAQ 700
    CNNAYQNSNL SVEVGSEGPL KGIQIWKVPA TDTYSISGYG AAGGKGGKNT 750
    MMRSHGVSVL GIFNLEKDDM LYILVGQQGE DACPSTNQLI QKVCIGENNV 800
    IEEEIRVNRS VHEWAGGGGG GGGATYVFKM KDGVPVPLII AAGGGGRAYG 850
    AKTDTFHPER LENNSSVLGL NGNSGAAGGG GGWNDNTSLL WAGKSLQEGA 900
    TGGHSCPQAM KKWGWETRGG FGGGGGGCSS GGGGGGYIGG NAASNNDPEM 950
    DGEDGVSFIS PLGILYTPAL KVMEGHGEVN IKHYLNCSHC EVDECHMDPE 1000
    SHKVICFCDH GTVLAEDGVS CIVSPTPEPH LPLSLILSVV TSALVAALVL 1050
    AFSGIMIVYR RKHQELQAMQ MELQSPEYKL SKLRTSTIMT DYNPNYCFAG 1100
    KTSSISDLKE VPRKNITLIR GLGHGAFGEV YEGQVSGMPN DPSPLQVAVK 1150
    TLPEVCSEQD ELDFLMEALI ISKFNHQNIV RCIGVSLQSL PRFILLELMA 1200
    GGDLKSFLRE TRPRPSQPSS LAMLDLLHVA RDIACGCQYL EENHFIHRDI 1250
    AARNCLLTCP GPGRVAKIGD FGMARDIYRA SYYRKGGCAM LPVKWMPPEA 1300
    FMEGIFTSKT DTWSFGVLLW EIFSLGYMPY PSKSNQEVLE FVTSGGRMDP 1350
    PKNCPGPVYR IMTQCWQHQP EDRPNFAIIL ERIEYCTQDP DVINTALPIE 1400
    YGPLVEEEEK VPVRPKDPEG VPPLLVSQQA KREEERSPAA PPPLPTTSSG 1450
    KAAKKPTAAE ISVRVPRGPA VEGGHVNMAF SQSNPPSELH KVHGSRNKPT 1500
    SLWNPTYGSW FTEKPTKKNN PIAKKEPHDR GNLGLEGSCT VPPNVATGRL 1550
    PGASLLLEPS SLTANMKEVP LFRLRHFPCG NVNYGYQQQG LPLEAATAPG 1600
    AGHYEDTILK SKNSMNQPGP 1620
    Length:1,620
    Mass (Da):176,442
    Last modified:May 18, 2010 - v3
    Checksum:i0733D6C4FD212F41
    GO

    Sequence cautioni

    The sequence BAD92714.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti36 – 361P → S in AAB71619. (PubMed:9174053)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti90 – 901S → L.1 Publication
    Corresponds to variant rs34617074 [ dbSNP | Ensembl ].
    VAR_041477
    Natural varianti163 – 1631V → L.1 Publication
    Corresponds to variant rs55697431 [ dbSNP | Ensembl ].
    VAR_041478
    Natural varianti296 – 2961E → Q.1 Publication
    Corresponds to variant rs56077855 [ dbSNP | Ensembl ].
    VAR_041479
    Natural varianti476 – 4761V → A.1 Publication
    Corresponds to variant rs35093491 [ dbSNP | Ensembl ].
    VAR_041480
    Natural varianti560 – 5601L → F in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication
    VAR_041481
    Natural varianti680 – 6801T → I.1 Publication
    Corresponds to variant rs35228363 [ dbSNP | Ensembl ].
    VAR_041482
    Natural varianti704 – 7041A → T.1 Publication
    Corresponds to variant rs34829159 [ dbSNP | Ensembl ].
    VAR_041483
    Natural varianti868 – 8681L → Q.
    Corresponds to variant rs55941323 [ dbSNP | Ensembl ].
    VAR_061288
    Natural varianti877 – 8771A → S in an ovarian serous carcinoma sample; somatic mutation. 1 Publication
    VAR_041484
    Natural varianti1012 – 10121T → M.1 Publication
    Corresponds to variant rs35073634 [ dbSNP | Ensembl ].
    VAR_041485
    Natural varianti1091 – 10911D → N in NBLST3; somatic mutation. 1 Publication
    VAR_063850
    Natural varianti1121 – 11211G → D.1 Publication
    Corresponds to variant rs55760835 [ dbSNP | Ensembl ].
    VAR_041486
    Natural varianti1128 – 11281G → A in NBLST3. 1 Publication
    VAR_063851
    Natural varianti1151 – 11511T → M in NBLST3. 1 Publication
    VAR_063852
    Natural varianti1166 – 11661M → R in NBLST3; somatic mutation. 1 Publication
    VAR_063853
    Natural varianti1171 – 11711I → N in NBLST3; somatic mutation. 1 Publication
    VAR_063854
    Natural varianti1174 – 11741F → C in NBLST3. 1 Publication
    VAR_063855
    Natural varianti1174 – 11741F → I in NBLST3; somatic mutation. 1 Publication
    VAR_063856
    Natural varianti1174 – 11741F → L in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 2 Publications
    VAR_063857
    Natural varianti1174 – 11741F → V in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 1 Publication
    VAR_063858
    Natural varianti1192 – 11921R → P in NBLST3. 2 Publications
    VAR_063859
    Natural varianti1234 – 12341A → T in NBLST3; somatic mutation. 1 Publication
    VAR_063860
    Natural varianti1245 – 12451F → C in NBLST3; somatic mutation. 2 Publications
    VAR_063861
    Natural varianti1245 – 12451F → V in NBLST3; somatic mutation.
    VAR_063862
    Natural varianti1250 – 12501I → T in NBLST3; somatic mutation. 1 Publication
    VAR_063863
    Natural varianti1274 – 12741A → T.1 Publication
    Corresponds to variant rs45502292 [ dbSNP | Ensembl ].
    VAR_041487
    Natural varianti1275 – 12751R → L Observed in neuroblastoma. 1 Publication
    VAR_063864
    Natural varianti1275 – 12751R → Q in NBLST3; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 3 Publications
    VAR_063865
    Natural varianti1278 – 12781Y → S in NBLST3; somatic mutation. 1 Publication
    VAR_063866
    Natural varianti1328 – 13281M → L.1 Publication
    Corresponds to variant rs56160491 [ dbSNP | Ensembl ].
    VAR_041488
    Natural varianti1376 – 13761F → S.
    Corresponds to variant rs17694720 [ dbSNP | Ensembl ].
    VAR_055987
    Natural varianti1416 – 14161K → N.1 Publication
    Corresponds to variant rs55782189 [ dbSNP | Ensembl ].
    VAR_041489
    Natural varianti1419 – 14191E → K.1 Publication
    Corresponds to variant rs56181542 [ dbSNP | Ensembl ].
    VAR_041490
    Natural varianti1429 – 14291Q → R.1 Publication
    Corresponds to variant rs55906201 [ dbSNP | Ensembl ].
    VAR_041491
    Natural varianti1461 – 14611I → V.4 Publications
    Corresponds to variant rs1670283 [ dbSNP | Ensembl ].
    VAR_031042
    Natural varianti1491 – 14911K → R.3 Publications
    Corresponds to variant rs1881420 [ dbSNP | Ensembl ].
    VAR_031043
    Natural varianti1529 – 15291D → E.3 Publications
    Corresponds to variant rs1881421 [ dbSNP | Ensembl ].
    VAR_031044
    Natural varianti1599 – 15991P → H.
    Corresponds to variant rs1881423 [ dbSNP | Ensembl ].
    VAR_055988

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U62540 mRNA. Translation: AAB71619.1.
    U66559 mRNA. Translation: AAC51104.1.
    AB209477 mRNA. Translation: BAD92714.1. Different initiation.
    AC106870 Genomic DNA. Translation: AAX93126.1.
    AC093756 Genomic DNA. Translation: AAX88892.1.
    AC074096 Genomic DNA. Translation: AAY15027.1.
    CCDSiCCDS33172.1.
    RefSeqiNP_004295.2. NM_004304.4.
    UniGeneiHs.654469.

    Genome annotation databases

    EnsembliENST00000389048; ENSP00000373700; ENSG00000171094.
    GeneIDi238.
    KEGGihsa:238.
    UCSCiuc002rmy.3. human.

    Polymorphism databases

    DMDMi296439447.

    Keywords - Coding sequence diversityi

    Chromosomal rearrangement, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U62540 mRNA. Translation: AAB71619.1 .
    U66559 mRNA. Translation: AAC51104.1 .
    AB209477 mRNA. Translation: BAD92714.1 . Different initiation.
    AC106870 Genomic DNA. Translation: AAX93126.1 .
    AC093756 Genomic DNA. Translation: AAX88892.1 .
    AC074096 Genomic DNA. Translation: AAY15027.1 .
    CCDSi CCDS33172.1.
    RefSeqi NP_004295.2. NM_004304.4.
    UniGenei Hs.654469.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2KUP NMR - B 1571-1589 [» ]
    2KUQ NMR - A 1571-1589 [» ]
    2XB7 X-ray 2.50 A 1094-1407 [» ]
    2XBA X-ray 1.95 A 1094-1407 [» ]
    2XP2 X-ray 1.90 A 1093-1411 [» ]
    2YFX X-ray 1.70 A 1093-1411 [» ]
    2YHV X-ray 1.90 A 1093-1411 [» ]
    2YJR X-ray 1.90 A 1093-1411 [» ]
    2YJS X-ray 1.90 A 1093-1411 [» ]
    2YS5 NMR - B 1571-1589 [» ]
    2YT2 NMR - A 1571-1589 [» ]
    3AOX X-ray 1.75 A 1069-1411 [» ]
    3L9P X-ray 1.80 A 1072-1410 [» ]
    3LCS X-ray 1.95 A 1072-1410 [» ]
    3LCT X-ray 2.10 A 1072-1410 [» ]
    4ANL X-ray 1.70 A 1093-1411 [» ]
    4ANQ X-ray 1.76 A 1093-1411 [» ]
    4ANS X-ray 1.85 A 1093-1411 [» ]
    4CCB X-ray 2.03 A 1093-1411 [» ]
    4CCU X-ray 2.00 A 1093-1411 [» ]
    4CD0 X-ray 2.23 A 1093-1411 [» ]
    4CLI X-ray 2.05 A 1093-1411 [» ]
    4CLJ X-ray 1.66 A 1093-1411 [» ]
    4CMO X-ray 1.83 A 1093-1411 [» ]
    4CMT X-ray 1.73 A 1093-1411 [» ]
    4CMU X-ray 1.80 A 1093-1411 [» ]
    4CNH X-ray 1.90 A/B 1093-1411 [» ]
    4CTB X-ray 1.79 A 1093-1411 [» ]
    4CTC X-ray 2.03 A 1093-1411 [» ]
    4DCE X-ray 2.03 A/B 1078-1410 [» ]
    4FNW X-ray 1.75 A 1084-1410 [» ]
    4FNX X-ray 1.70 A 1084-1410 [» ]
    4FNY X-ray 2.45 A 1084-1410 [» ]
    4FNZ X-ray 2.60 A 1084-1410 [» ]
    4FOB X-ray 1.90 A 1058-1410 [» ]
    4FOC X-ray 1.70 A 1058-1410 [» ]
    4FOD X-ray 2.00 A 1078-1410 [» ]
    4JOA X-ray 2.70 A 1072-1410 [» ]
    4MKC X-ray 2.01 A 1072-1410 [» ]
    ProteinModelPortali Q9UM73.
    SMRi Q9UM73. Positions 1096-1480.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106739. 46 interactions.
    DIPi DIP-5954N.
    IntActi Q9UM73. 7 interactions.
    MINTi MINT-1133857.
    STRINGi 9606.ENSP00000373700.

    Chemistry

    BindingDBi Q9UM73.
    ChEMBLi CHEMBL4247.
    DrugBanki DB00171. Adenosine triphosphate.
    GuidetoPHARMACOLOGYi 1839.

    PTM databases

    PhosphoSitei Q9UM73.

    Polymorphism databases

    DMDMi 296439447.

    Proteomic databases

    PaxDbi Q9UM73.
    PRIDEi Q9UM73.

    Protocols and materials databases

    DNASUi 238.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000389048 ; ENSP00000373700 ; ENSG00000171094 .
    GeneIDi 238.
    KEGGi hsa:238.
    UCSCi uc002rmy.3. human.

    Organism-specific databases

    CTDi 238.
    GeneCardsi GC02M029327.
    GeneReviewsi ALK.
    H-InvDB HIX0024259.
    HIX0030037.
    HGNCi HGNC:427. ALK.
    HPAi HPA010694.
    MIMi 105590. gene.
    613014. phenotype.
    neXtProti NX_Q9UM73.
    Orphaneti 300895. ALK-positive anaplastic large cell lymphoma.
    364043. ALK-positive large B-cell lymphoma.
    178342. Inflammatory myofibroblastic tumor.
    635. Neuroblastoma.
    357191. Selection of therapeutic option in non-small cell lung carcinoma.
    PharmGKBi PA24719.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000231766.
    HOVERGENi HBG018726.
    InParanoidi Q9UM73.
    KOi K05119.
    OMAi LIQKVCI.
    OrthoDBi EOG7GN2KT.
    PhylomeDBi Q9UM73.
    TreeFami TF351636.

    Enzyme and pathway databases

    BRENDAi 2.7.10.1. 2681.
    SignaLinki Q9UM73.

    Miscellaneous databases

    ChiTaRSi ALK. human.
    EvolutionaryTracei Q9UM73.
    GeneWikii Anaplastic_lymphoma_kinase.
    GenomeRNAii 238.
    NextBioi 948.
    PROi Q9UM73.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9UM73.
    Bgeei Q9UM73.
    CleanExi HS_ALK.
    Genevestigatori Q9UM73.

    Family and domain databases

    Gene3Di 4.10.400.10. 1 hit.
    InterProi IPR026830. ALK.
    IPR008985. ConA-like_lec_gl_sf.
    IPR011009. Kinase-like_dom.
    IPR002172. LDrepeatLR_classA_rpt.
    IPR000998. MAM_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    IPR002011. Tyr_kinase_rcpt_2_CS.
    [Graphical view ]
    PANTHERi PTHR24416:SF276. PTHR24416:SF276. 1 hit.
    Pfami PF00629. MAM. 2 hits.
    PF07714. Pkinase_Tyr. 1 hit.
    [Graphical view ]
    PRINTSi PR00109. TYRKINASE.
    SMARTi SM00192. LDLa. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF49899. SSF49899. 2 hits.
    SSF56112. SSF56112. 1 hit.
    SSF57424. SSF57424. 1 hit.
    PROSITEi PS50060. MAM_2. 2 hits.
    PS00107. PROTEIN_KINASE_ATP. 1 hit.
    PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00109. PROTEIN_KINASE_TYR. 1 hit.
    PS00239. RECEPTOR_TYR_KIN_II. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK)."
      Morris S.W., Naeve C.W., Mathew P., James P.L., Kirstein M.N., Cui X., Witte D.P.
      Oncogene 14:2175-2188(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, GLYCOSYLATION, VARIANT VAL-1461.
    2. Erratum
      Morris S.W., Naeve C.W., Mathew P., James P.L., Kirstein M.N., Cui X., Witte D.P.
      Oncogene 15:2883-2883(1997)
    3. "Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system."
      Iwahara T., Fujimoto J., Wen D., Cupples R., Bucay N., Arakawa T., Mori S., Ratzkin B., Yamamoto T.
      Oncogene 14:439-449(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS VAL-1461; ARG-1491 AND GLU-1529.
    4. Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
      Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS VAL-1461; ARG-1491 AND GLU-1529.
      Tissue: Brain.
    5. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma."
      Morris S.W., Kirstein M.N., Valentine M.B., Dittmer K.G., Shapiro D.N., Saltman D.L., Look A.T.
      Science 263:1281-1284(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH NPM1, VARIANT VAL-1461.
    7. "The cytoplasmic truncated receptor tyrosine kinase ALK homodimer immortalizes and cooperates with ras in cellular transformation."
      Simonitsch I., Polgar D., Hajek M., Duchek P., Skrzypek B., Fassl S., Lamprecht A., Schmidt G., Krupitza G., Cerni C.
      FASEB J. 15:1416-1418(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS AN ONCOGENE.
    8. "Activation of anaplastic lymphoma kinase receptor tyrosine kinase induces neuronal differentiation through the mitogen-activated protein kinase pathway."
      Souttou B., Carvalho N.B., Raulais D., Vigny M.
      J. Biol. Chem. 276:9526-9531(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, FUNCTION.
    9. "Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin."
      Stoica G.E., Kuo A., Aigner A., Sunitha I., Souttou B., Malerczyk C., Caughey D.J., Wen D., Karavanov A., Riegel A.T., Wellstein A.
      J. Biol. Chem. 276:16772-16779(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PTN, FUNCTION.
    10. "Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor."
      Cools J., Wlodarska I., Somers R., Mentens N., Pedeutour F., Maes B., De Wolf-Peeters C., Pauwels P., Hagemeijer A., Marynen P.
      Genes Chromosomes Cancer 34:354-362(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHROMOSOMAL TRANSLOCATION WITH ALO17 AND CARS.
    11. "Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth."
      Powers C., Aigner A., Stoica G.E., McDonnell K., Wellstein A.
      J. Biol. Chem. 277:14153-14158(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    12. "Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase."
      Bowden E.T., Stoica G.E., Wellstein A.
      J. Biol. Chem. 277:35862-35868(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    13. "Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types."
      Stoica G.E., Kuo A., Powers C., Bowden E.T., Sale E.B., Riegel A.T., Wellstein A.
      J. Biol. Chem. 277:35990-35998(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MDK, FUNCTION.
    14. "ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth."
      Motegi A., Fujimoto J., Kotani M., Sakuraba H., Yamamoto T.
      J. Cell Sci. 117:3319-3329(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CBL; IRS1; PIK3R1; PLCG1 AND SHC1, FUNCTION IN PHOSPHORYLATION OF CBL; IRS1 AND SHC1.
    15. "Unique substrate specificity of anaplastic lymphoma kinase (ALK): development of phosphoacceptor peptides for the assay of ALK activity."
      Donella-Deana A., Marin O., Cesaro L., Gunby R.H., Ferrarese A., Coluccia A.M., Tartari C.J., Mologni L., Scapozza L., Gambacorti-Passerini C., Pinna L.A.
      Biochemistry 44:8533-8542(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBSTRATE SPECIFICITY, PHOSPHORYLATION AT TYR-1278.
    16. "Differential induction of glioblastoma migration and growth by two forms of pleiotrophin."
      Lu K.V., Jong K.A., Kim G.Y., Singh J., Dia E.Q., Yoshimoto K., Wang M.Y., Cloughesy T.F., Nelson S.F., Mischel P.S.
      J. Biol. Chem. 280:26953-26964(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: ROLE IN GLIOBLASTOMA.
    17. "Role of the subcellular localization of ALK tyrosine kinase domain in neuronal differentiation of PC12 cells."
      Gouzi J.Y., Moog-Lutz C., Vigny M., Brunet-de Carvalho N.
      J. Cell Sci. 118:5811-5823(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, SUBUNIT, ENZYME REGULATION, FUNCTION.
    18. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
      Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
      Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-1078; TYR-1096; TYR-1131 AND TYR-1604, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    19. "Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor."
      Panagopoulos I., Nilsson T., Domanski H.A., Isaksson M., Lindblom P., Mertens F., Mandahl N.
      Int. J. Cancer 118:1181-1186(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHROMOSOMAL TRANSLOCATION WITH SEC31A.
    20. "ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation."
      Degoutin J., Vigny M., Gouzi J.Y.
      FEBS Lett. 581:727-734(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FRS2 AND SHC1, PHOSPHORYLATION AT TYR-1507, MUTAGENESIS OF TYR-1507, FUNCTION IN PHOSPHORYLATION OF FRS2; MAPK1/ERK2; MAPK3/ERK1 AND SHC1.
    21. "Anaplastic lymphoma kinase is activated through the pleiotrophin/receptor protein-tyrosine phosphatase beta/zeta signaling pathway: an alternative mechanism of receptor tyrosine kinase activation."
      Perez-Pinera P., Zhang W., Chang Y., Vega J.A., Deuel T.F.
      J. Biol. Chem. 282:28683-28690(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, ENZYME REGULATION.
    22. "Recruitment of insulin receptor substrate-1 and activation of NF-kappaB essential for midkine growth signaling through anaplastic lymphoma kinase."
      Kuo A.H., Stoica G.E., Riegel A.T., Wellstein A.
      Oncogene 26:859-869(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS1 AND SHC, PHOSPHORYLATION AT TYR-1096, FUNCTION.
    23. "Anaplastic lymphoma kinase: signalling in development and disease."
      Palmer R.H., Vernersson E., Grabbe C., Hallberg B.
      Biochem. J. 420:345-361(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON FUNCTION.
    24. "Solution structure of the complex of the PTB domain of SNT-2 and 19-residue peptide (aa 1571-1589) of HALK."
      RIKEN structural genomics initiative (RSGI)
      Submitted (APR-2008) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 1571-1589.
    25. "Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain."
      Lee C.C., Jia Y., Li N., Sun X., Ng K., Ambing E., Gao M.Y., Hua S., Chen C., Kim S., Michellys P.Y., Lesley S.A., Harris J.L., Spraggon G.
      Biochem. J. 430:425-437(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 1072-1410.
    26. Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 1094-1407 IN COMPLEX WITH INHIBITOR.
    27. "Structural basis for the recognition of nucleophosmin-anaplastic lymphoma kinase oncoprotein by the phosphotyrosine binding domain of Suc1-associated neurotrophic factor-induced tyrosine-phosphorylated target-2."
      Koshiba S., Li H., Motoda Y., Tomizawa T., Kasai T., Tochio N., Yabuki T., Harada T., Watanabe S., Tanaka A., Shirouzu M., Kigawa T., Yamamoto T., Yokoyama S.
      J. Struct. Funct. Genomics 11:125-141(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1571-1589.
    28. "Structure of L1196M mutant anaplastic lymphoma kinase in complex with crizotinib."
      Mctigue M., Deng Y., Liu W., Brooun A.
      Submitted (MAY-2011) to the PDB data bank
      Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 1093-1411 IN COMPLEX WITH CRIZOTINIB.
    29. "CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant."
      Sakamoto H., Tsukaguchi T., Hiroshima S., Kodama T., Kobayashi T., Fukami T.A., Oikawa N., Tsukuda T., Ishii N., Aoki Y.
      Cancer Cell 19:679-690(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1069-1411 IN COMPLEX WITH INHIBITOR, ENZYME REGULATION.
    30. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-90; LEU-163; GLN-296; ALA-476; PHE-560; ILE-680; THR-704; SER-877; MET-1012; ASP-1121; THR-1274; LEU-1328; ASN-1416; LYS-1419; ARG-1429; ARG-1491 AND GLU-1529.
    31. Cited for: VARIANTS NBLST3 ASN-1091; ALA-1128; ARG-1166; ASN-1171; ILE-1174; PRO-1192; CYS-1245; VAL-1245 THR-1250 AND GLN-1275.
    32. Cited for: VARIANTS NBLST3 VAL-1174; LEU-1174; CYS-1174; PRO-1192; GLN-1275 AND SER-1278, VARIANT LEU-1275.
    33. Cited for: VARIANTS NBLST3 MET-1151; LEU-1174; THR-1234; CYS-1245 AND GLN-1275.
    34. "The constitutive activity of the ALK mutated at positions F1174 or R1275 impairs receptor trafficking."
      Mazot P., Cazes A., Boutterin M.C., Figueiredo A., Raynal V., Combaret V., Hallberg B., Palmer R.H., Delattre O., Janoueix-Lerosey I., Vigny M.
      Oncogene 30:2017-2025(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANTS NBLST3 LEU-1174; VAL-1174 AND GLN-1275.

    Entry informationi

    Entry nameiALK_HUMAN
    AccessioniPrimary (citable) accession number: Q9UM73
    Secondary accession number(s): Q4ZFX9
    , Q53QQ6, Q53RZ4, Q59FI3, Q9Y4K6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: March 27, 2002
    Last sequence update: May 18, 2010
    Last modified: October 1, 2014
    This is version 149 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    8. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3