ALK

Protein identityUniProt · HPA

UniProt accession

Q9UM73

Gene

ALK

Ensembl

ENSG00000171094

Chromosome

2

Canonical length

1620 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

1620 residues, UniProt reviewed canonical sequence.

>Q9UM73|ALK
     1  MGAIGLLWLL PLLLSTAAVG SGMGTGQRAG SPAAGPPLQP REPLSYSRLQ RKSLAVDFVV
    61  PSLFRVYARD LLLPPSSSEL KAGRPEARGS LALDCAPLLR LLGPAPGVSW TAGSPAPAEA
   121  RTLSRVLKGG SVRKLRRAKQ LVLELGEEAI LEGCVGPPGE AAVGLLQFNL SELFSWWIRQ
   181  GEGRLRIRLM PEKKASEVGR EGRLSAAIRA SQPRLLFQIF GTGHSSLESP TNMPSPSPDY
   241  FTWNLTWIMK DSFPFLSHRS RYGLECSFDF PCELEYSPPL HDLRNQSWSW RRIPSEEASQ
   301  MDLLDGPGAE RSKEMPRGSF LLLNTSADSK HTILSPWMRS SSEHCTLAVS VHRHLQPSGR
   361  YIAQLLPHNE AAREILLMPT PGKHGWTVLQ GRIGRPDNPF RVALEYISSG NRSLSAVDFF
   421  ALKNCSEGTS PGSKMALQSS FTCWNGTVLQ LGQACDFHQD CAQGEDESQM CRKLPVGFYC
   481  NFEDGFCGWT QGTLSPHTPQ WQVRTLKDAR FQDHQDHALL LSTTDVPASE SATVTSATFP
   541  APIKSSPCEL RMSWLIRGVL RGNVSLVLVE NKTGKEQGRM VWHVAAYEGL SLWQWMVLPL
   601  LDVSDRFWLQ MVAWWGQGSR AIVAFDNISI SLDCYLTISG EDKILQNTAP KSRNLFERNP
   661  NKELKPGENS PRQTPIFDPT VHWLFTTCGA SGPHGPTQAQ CNNAYQNSNL SVEVGSEGPL
   721  KGIQIWKVPA TDTYSISGYG AAGGKGGKNT MMRSHGVSVL GIFNLEKDDM LYILVGQQGE
   781  DACPSTNQLI QKVCIGENNV IEEEIRVNRS VHEWAGGGGG GGGATYVFKM KDGVPVPLII
   841  AAGGGGRAYG AKTDTFHPER LENNSSVLGL NGNSGAAGGG GGWNDNTSLL WAGKSLQEGA
   901  TGGHSCPQAM KKWGWETRGG FGGGGGGCSS GGGGGGYIGG NAASNNDPEM DGEDGVSFIS
   961  PLGILYTPAL KVMEGHGEVN IKHYLNCSHC EVDECHMDPE SHKVICFCDH GTVLAEDGVS
  1021  CIVSPTPEPH LPLSLILSVV TSALVAALVL AFSGIMIVYR RKHQELQAMQ MELQSPEYKL
  1081  SKLRTSTIMT DYNPNYCFAG KTSSISDLKE VPRKNITLIR GLGHGAFGEV YEGQVSGMPN
  1141  DPSPLQVAVK TLPEVCSEQD ELDFLMEALI ISKFNHQNIV RCIGVSLQSL PRFILLELMA
  1201  GGDLKSFLRE TRPRPSQPSS LAMLDLLHVA RDIACGCQYL EENHFIHRDI AARNCLLTCP
  1261  GPGRVAKIGD FGMARDIYRA SYYRKGGCAM LPVKWMPPEA FMEGIFTSKT DTWSFGVLLW
  1321  EIFSLGYMPY PSKSNQEVLE FVTSGGRMDP PKNCPGPVYR IMTQCWQHQP EDRPNFAIIL
  1381  ERIEYCTQDP DVINTALPIE YGPLVEEEEK VPVRPKDPEG VPPLLVSQQA KREEERSPAA
  1441  PPPLPTTSSG KAAKKPTAAE ISVRVPRGPA VEGGHVNMAF SQSNPPSELH KVHGSRNKPT
  1501  SLWNPTYGSW FTEKPTKKNN PIAKKEPHDR GNLGLEGSCT VPPNVATGRL PGASLLLEPS
  1561  SLTANMKEVP LFRLRHFPCG NVNYGYQQQG LPLEAATAPG AGHYEDTILK SKNSMNQPGP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ALK can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

2.4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ALK.

Disease | AllUniProt

Conditions ALK is implicated in, by any mechanism.

• Neuroblastoma 3 (NBLST3) MIM:613014

Disease | GeneticClinVar

19 pathogenic / likely-pathogenic of 6,396 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neuroblastoma, susceptibility to, 3
• Neuroblastoma
• Lung cancer
• Hereditary cancer-predisposing syndrome
• Neoplasm

Disease | ImmuneIEDB

Conditions an epitope on ALK was assayed in.

• lung non-small cell carcinoma B cell
• lymphoma T cell

ReferencesPubMed · IEDB

Publications for ALK from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.45

gnomAD pLI

0

gnomAD missense Z

0.01

DepMap mean gene effect

-0.05

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adult behavior
• cell surface receptor protein tyrosine kinase signaling pathway
• energy homeostasis
• hippocampus development
• negative regulation of lipid catabolic process
• neuron development
• peptidyl-tyrosine autophosphorylation
• phosphorylation
• positive regulation of dendrite development
• positive regulation of NF-kappaB transcription factor activity
• protein autophosphorylation
• regulation of apoptotic process
• regulation of cell population proliferation
• regulation of dopamine receptor signaling pathway
• regulation of neuron differentiation
• response to environmental enrichment
• response to stress
• signal transduction
• swimming behavior

Molecular functions

• ATP binding
• heparin binding
• identical protein binding
• protein tyrosine kinase activity
• receptor signaling protein tyrosine kinase activator activity
• transmembrane receptor protein tyrosine kinase activity

Cellular components

• extracellular exosome
• plasma membrane
• protein-containing complex
• receptor complex

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• MAM domain
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Tyrosine-protein kinase, receptor class II, conserved site
• Low-density lipoprotein (LDL) receptor class A repeat
• Tyrosine-protein kinase, active site
• Protein kinase-like domain superfamily
• Concanavalin A-like lectin/glucanase domain superfamily
• Protein kinase, ATP binding site
• Tyrosine-protein kinase, catalytic domain
• LDL receptor-like superfamily
• Receptor Tyrosine Kinase
• ALK/LTK-like, glycine-rich domain
• MAM domain, meprin/A5/mu
• Protein tyrosine and serine/threonine kinase
• ALK/LTK, Glycine-rich domain

KeywordsUniProt

• ATP-binding
• Cell membrane
• Chromosomal rearrangement
• Disulfide bond
• Glycoprotein
• Kinase
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Proto-oncogene
• Receptor
• Repeat
• Signal
• Transferase
• Transmembrane
• Transmembrane helix
• Tyrosine-protein kinase

InteractionsUniProt · HPA

Protein binding partners of ALK in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CBL
• FRS2
• IRS1
• MDK
• PIK3R1
• PLCG1
• PTN
• SHC1
• RET