ALK
entrez
238
canonical
uniprot
Q9UM73
canonical
ensembl
ENSG00000171094
resolver
ensp
ENSP00000373700
resolver
ensp
ENSP00000493203
resolver
enst
ENST00000389048
resolver
enst
ENST00000642122
resolver
genesymbol
ALK
resolver
hgnc
HGNC:427
resolver
uniprot
A0A0K2YUJ3
resolver
uniprot
A0A286YF68
resolver
uniprot
A6P4T4
resolver
uniprot
A6P4V4
resolver
uniprot
B6D4Y2
resolver
uniprot
Q4ZFX9
resolver
uniprot
Q53QQ6
resolver
uniprot
Q53RZ4
resolver
uniprot
Q59FI3
resolver
uniprot
Q9Y4K6
resolver
uniprot_entry
A0A0K2YUJ3_HUMAN
resolver
uniprot_entry
A0A286YF68_HUMAN
resolver
uniprot_entry
ALK_HUMAN
resolver
uniprot_entry
B6D4Y2_HUMAN
resolver
uniprot_sec
A6P4T4
resolver
uniprot_sec
A6P4V4
resolver
uniprot_sec
Q4ZFX9
resolver
uniprot_sec
Q53QQ6
resolver
uniprot_sec
Q53RZ4
resolver
uniprot_sec
Q59FI3
resolver
uniprot_sec
Q9Y4K6
resolver
activity_regulation
ACTIVITY REGULATION: Activated upon ALKAL2 ligand-binding (PubMed:34646012, PubMed:34819673). ALKAL2-driven activation is coupled with heparin-binding (PubMed:25605972, PubMed:34646012). Following ligand-binding, homodimerizes and autophosphorylates, activating its kinase activity (PubMed:16317043, PubMed:17681947, PubMed:34646012, PubMed:34819673). Inactivated through dephosphorylation by receptor protein tyrosine phosphatase beta and zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand (PubMed:17681947). Staurosporine, crizotinib and CH5424802 act as inhibitors of ALK kinase activity (PubMed:21575866). {ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:17681947, ECO:0000269|PubMed:21575866, ECO:0000269|PubMed:25605972, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}.
uniprot
proteins
amino_acid_sequence
MGAIGLLWLLPLLLSTAAVGSGMGTGQRAGSPAAGPPLQPREPLSYSRLQRKSLAVDFVVPSLFRVYARDLLLPPSSSELKAGRPEARGSLALDCAPLLRLLGPAPGVSWTAGSPAPAEARTLSRVLKGGSVRKLRRAKQLVLELGEEAILEGCVGPPGEAAVGLLQFNLSELFSWWIRQGEGRLRIRLMPEKKASEVGREGRLSAAIRASQPRLLFQIFGTGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHDLRNQSWSWRRIPSEEASQMDLLDGPGAERSKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGRYIAQLLPHNEAAREILLMPTPGKHGWTVLQGRIGRPDNPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDESQMCRKLPVGFYCNFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSATFPAPIKSSPCELRMSWLIRGVLRGNVSLVLVENKTGKEQGRMVWHVAAYEGLSLWQWMVLPLLDVSDRFWLQMVAWWGQGSRAIVAFDNISISLDCYLTISGEDKILQNTAPKSRNLFERNPNKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSEGPLKGIQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKDDMLYILVGQQGEDACPSTNQLIQKVCIGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLIIAAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLQEGATGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGVSCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVNYGYQQQGLPLEAATAPGAGHYEDTILKSKNSMNQPGP
uniprot
proteins
disease_involvement
DISEASE: 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. {ECO:0000269|PubMed:15938644}.; DISEASE: 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. {ECO:0000269|PubMed:12112524, ECO:0000269|PubMed:16161041}.; DISEASE: Note=A chromosomal aberration involving ALK is associated with anaplastic large-cell lymphoma (ALCL). Translocation t(2;17)(p23;q25) with ALO17. {ECO:0000269|PubMed:12112524}.; DISEASE: 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. {ECO:0000269|PubMed:18724359, ECO:0000269|PubMed:18923523, ECO:0000269|PubMed:18923525, ECO:0000269|PubMed:21242967, ECO:0000269|PubMed:22932897}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:15908427}.; DISEASE: Note=A chromosomal aberration involving ALK is found in one subject with colorectal cancer. Translocation t(2;2)(p23.1;p23.3). A 5 million base pair tandem duplication generates an in-frame WDCP-ALK gene fusion. {ECO:0000269|PubMed:22327622}.; DISEASE: Note=A chromosomal aberration involving ALK has been identified in a subset of patients with non-small-cell lung carcinoma. This aberration leads to the production of a fusion protein between the N-terminus of EML4 et the C-terminus of ALK. It is unclear whether the fusion protein is caused by a simple inversion within 2p (inv(2)(p21p23)) or whether the chromosome translocation involving 2p is more complex. When tested in a heterologous system, the fusion protein EML4-ALK possesses transforming activity that is dependent on ALK catalytic activity, possibly due to spontaneous dimerization mediated by the EML4 moiety, leading to ALK kinase activation. {ECO:0000269|PubMed:17625570}.
uniprot
proteins
ec_number
2.7.10.1
uniprot
proteins
function
FUNCTION: Neuronal 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 (PubMed:11121404, PubMed:11387242, PubMed:16317043, PubMed:17274988, PubMed:30061385, PubMed:34646012, PubMed:34819673). Also acts as a key thinness protein involved in the resistance to weight gain: in hypothalamic neurons, controls energy expenditure acting as a negative regulator of white adipose tissue lipolysis and sympathetic tone to fine-tune energy homeostasis (By similarity). Following activation by ALKAL2 ligand at the cell surface, transduces an extracellular signal into an intracellular response (PubMed:30061385, PubMed:33411331, PubMed:34646012, PubMed:34819673). In contrast, ALKAL1 is not a potent physiological ligand for ALK (PubMed:34646012). Ligand-binding to the extracellular domain induces tyrosine kinase activation, leading to activation of the mitogen-activated protein kinase (MAPK) pathway (PubMed:34819673). Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif (PubMed:15226403, PubMed:16878150). Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1 (PubMed:15226403, PubMed:16878150). ALK activation may also be regulated by pleiotrophin (PTN) and midkine (MDK) (PubMed:11278720, PubMed:11809760, PubMed:12107166, PubMed:12122009). PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation (PubMed:11278720, PubMed:11809760, PubMed:12107166). 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 (PubMed:12122009). Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase (PubMed:15226403, PubMed:16878150). Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK (PubMed:15226403, PubMed:16878150). May function as regulator of gastric epithelial differentiation (By similarity). {ECO:0000250|UniProtKB:P97793, ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:11278720, ECO:0000269|PubMed:11387242, ECO:0000269|PubMed:11809760, ECO:0000269|PubMed:12107166, ECO:0000269|PubMed:12122009, ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:30061385, ECO:0000269|PubMed:33411331, ECO:0000269|PubMed:34646012, ECO:0000269|PubMed:34819673}.
uniprot
proteins
mass_dalton
176442
uniprot
proteins
mutagenesis
MUTAGEN 48..52; /note="RLQRK->ELQEE: Abolished heparin-binding, leading to decreased ALK activation."; /evidence="ECO:0000269|PubMed:25605972"; MUTAGEN 859; /note="E->A: Slightly decreased autophosphorylation. Decreased autophosphorylation and subsequent activation; when associated with A-974."; /evidence="ECO:0000269|PubMed:34819673"; MUTAGEN 966; /note="Y->A: Slightly decreased autophosphorylation. Strongly reduced autophosphorylation and subsequent activation; when associated with A-994."; /evidence="ECO:0000269|PubMed:34819673"; MUTAGEN 974; /note="E->A: Slightly decreased autophosphorylation. Decreased autophosphorylation and subsequent activation; when associated with A-859."; /evidence="ECO:0000269|PubMed:34819673"; MUTAGEN 994; /note="E->A: SlStrongly reduced autophosphorylation and subsequent activation; when associated with A-966."; /evidence="ECO:0000269|PubMed:34819673"; MUTAGEN 1507; /note="Y->F: Impairs interaction with SHC1."; /evidence="ECO:0000269|PubMed:17274988
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity (PubMed:11121404, PubMed:15938644, PubMed:16878150, PubMed:34819673). 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 (PubMed:17681947). Phosphorylation at Tyr-1507 is critical for SHC1 association (PubMed:17274988). {ECO:0000269|PubMed:11121404, ECO:0000269|PubMed:15938644, ECO:0000269|PubMed:16878150, ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:17681947, ECO:0000269|PubMed:34819673}.; PTM: N-glycosylated. {ECO:0000269|PubMed:9174053}.
uniprot
proteins
protein_family
Insulin receptor subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
11121404
uniprot
proteins
pubmed
11278720
uniprot
proteins
pubmed
11387242
uniprot
proteins
pubmed
11809760
uniprot
proteins
pubmed
12107166
uniprot
proteins
pubmed
12112524
uniprot
proteins
pubmed
12122009
uniprot
proteins
pubmed
15226403
uniprot
proteins
pubmed
15592455
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
15908427
uniprot
proteins
pubmed
15938644
uniprot
proteins
pubmed
16161041
uniprot
proteins
pubmed
16317043
uniprot
proteins
pubmed
16878150
uniprot
proteins
pubmed
17274988
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17625570
uniprot
proteins
pubmed
17681947
uniprot
proteins
pubmed
18724359
uniprot
proteins
pubmed
18923523
uniprot
proteins
pubmed
18923525
uniprot
proteins
pubmed
19459784
uniprot
proteins
pubmed
20454865
uniprot
proteins
pubmed
20632993
uniprot
proteins
pubmed
20695522
uniprot
proteins
pubmed
21242967
uniprot
proteins
pubmed
21575866
uniprot
proteins
pubmed
22327622
uniprot
proteins
pubmed
22932897
uniprot
proteins
pubmed
25605972
uniprot
proteins
pubmed
30061385
uniprot
proteins
pubmed
33411331
uniprot
proteins
pubmed
34646012
uniprot
proteins
pubmed
34819673
uniprot
proteins
pubmed
8122112
uniprot
proteins
pubmed
9053841
uniprot
proteins
pubmed
9174053
uniprot
proteins
sequence_length
1620
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:34819673, ECO:0000269|PubMed:9174053}; Single-pass type I membrane protein {ECO:0000269|PubMed:16317043, ECO:0000269|PubMed:9174053}. Note=Membrane attachment is essential for promotion of neuron-like differentiation and cell proliferation arrest through specific activation of the MAP kinase pathway. {ECO:0000269|PubMed:16317043}.
uniprot
proteins
transmembrane_region
TRANSMEM 1039..1059; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins