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Protein

ALK tyrosine kinase receptor

Gene

ALK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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

Activity 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)DescriptionActionsGraphical viewLength
Binding sitei1124ATP; via carbonyl oxygen1
Binding sitei1150ATPPROSITE-ProRule annotation1
Binding sitei1150Inhibitor2 Publications1
Binding sitei1199Inhibitor; via amide nitrogen2 Publications1
Binding sitei1203Inhibitor2 Publications1
Binding sitei1210Inhibitor2 Publications1
Active sitei1249Proton acceptorPROSITE-ProRule annotation1
Binding sitei1270ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi1197 – 1199ATP3

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • identical protein binding Source: IntAct
  • NF-kappaB-inducing kinase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: MGI
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB
  • transmembrane signaling receptor activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionKinase, Receptor, Transferase, Tyrosine-protein kinase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
SignaLinkiQ9UM73
SIGNORiQ9UM73

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
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000171094.15
HGNCiHGNC:427 ALK
MIMi105590 gene
neXtProtiNX_Q9UM73

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini19 – 1038ExtracellularSequence analysisAdd BLAST1020
Transmembranei1039 – 1059HelicalSequence analysisAdd BLAST21
Topological domaini1060 – 1620CytoplasmicSequence analysisAdd BLAST561

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)4 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:613014
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0638501091D → N in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs864309584EnsemblClinVar.1
Natural variantiVAR_0638511128G → A in NBLST3. 1 PublicationCorresponds to variant dbSNP:rs113994088EnsemblClinVar.1
Natural variantiVAR_0638521151T → M in NBLST3. 1 PublicationCorresponds to variant dbSNP:rs113994091EnsemblClinVar.1
Natural variantiVAR_0638531166M → R in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1057520019Ensembl.1
Natural variantiVAR_0638541171I → N in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1057519698Ensembl.1
Natural variantiVAR_0638551174F → C in NBLST3. 1 PublicationCorresponds to variant dbSNP:rs1057519697Ensembl.1
Natural variantiVAR_0638561174F → I in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs281864719EnsemblClinVar.1
Natural variantiVAR_0638571174F → L in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 3 PublicationsCorresponds to variant dbSNP:rs863225281EnsemblClinVar.1
Natural variantiVAR_0638581174F → V in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 2 PublicationsCorresponds to variant dbSNP:rs281864719EnsemblClinVar.1
Natural variantiVAR_0638591192R → P in NBLST3. 2 PublicationsCorresponds to variant dbSNP:rs113994089EnsemblClinVar.1
Natural variantiVAR_0638601234A → T in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638611245F → C in NBLST3; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs863225283EnsemblClinVar.1
Natural variantiVAR_0638621245F → V in NBLST3; somatic mutation. Corresponds to variant dbSNP:rs281864720EnsemblClinVar.1
Natural variantiVAR_0638631250I → T in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs113994092EnsemblClinVar.1
Natural variantiVAR_0638651275R → Q in NBLST3; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 4 PublicationsCorresponds to variant dbSNP:rs113994087EnsemblClinVar.1
Natural variantiVAR_0638661278Y → S in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs863225285EnsemblClinVar.1
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.
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.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi1507Y → F: Impairs interaction with SHC1. 1 Publication1

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi238
GeneReviewsiALK
MalaCardsiALK
MIMi613014 phenotype
OpenTargetsiENSG00000171094
Orphaneti300895 ALK-positive anaplastic large cell lymphoma
364043 ALK-positive large B-cell lymphoma
146 Differentiated thyroid carcinoma
178342 Inflammatory myofibroblastic tumor
635 Neuroblastoma
357191 Selection of therapeutic option in non-small cell lung carcinoma
PharmGKBiPA24719

Chemistry databases

ChEMBLiCHEMBL4247
DrugBankiDB00171 Adenosine triphosphate
DB11363 Alectinib
DB09063 Ceritinib
DB08865 Crizotinib
GuidetoPHARMACOLOGYi1839

Polymorphism and mutation databases

BioMutaiALK
DMDMi296439447

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000001674019 – 1620ALK tyrosine kinase receptorAdd BLAST1602

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi169N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi244N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi285N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi324N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi411N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi424N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi445N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi563N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi571N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi627N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi709N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi808N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi863N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi864N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi886N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi986N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei1078PhosphotyrosineCombined sources1
Modified residuei1092PhosphotyrosineBy similarity1
Modified residuei1096PhosphotyrosineCombined sources1 Publication1
Modified residuei1131PhosphotyrosineCombined sources1
Modified residuei1278Phosphotyrosine1 Publication1
Modified residuei1507Phosphotyrosine1 Publication1
Modified residuei1604PhosphotyrosineCombined sources1

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.5 Publications
N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ9UM73
PaxDbiQ9UM73
PeptideAtlasiQ9UM73
PRIDEiQ9UM73
ProteomicsDBi85185

PTM databases

iPTMnetiQ9UM73
PhosphoSitePlusiQ9UM73

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

BgeeiENSG00000171094 Expressed in 144 organ(s), highest expression level in sperm
CleanExiHS_ALK
ExpressionAtlasiQ9UM73 baseline and differential
GenevisibleiQ9UM73 HS

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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106739, 65 interactors
DIPiDIP-5954N
IntActiQ9UM73, 10 interactors
MINTiQ9UM73
STRINGi9606.ENSP00000373700

Chemistry databases

BindingDBiQ9UM73

Structurei

Secondary structure

11620
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9UM73
SMRiQ9UM73
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UM73

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini264 – 427MAM 1PROSITE-ProRule annotationAdd BLAST164
Domaini437 – 473LDL-receptor class AAdd BLAST37
Domaini478 – 636MAM 2PROSITE-ProRule annotationAdd BLAST159
Domaini1116 – 1392Protein kinasePROSITE-ProRule annotationAdd BLAST277

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1197 – 1199Inhibitor binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi816 – 940Gly-richAdd BLAST125

Sequence similaritiesi

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1095 Eukaryota
ENOG410XPVX LUCA
GeneTreeiENSGT00760000118818
HOGENOMiHOG000231766
HOVERGENiHBG018726
InParanoidiQ9UM73
KOiK05119
OMAiHKVQGSR
OrthoDBiEOG091G003T
PhylomeDBiQ9UM73
TreeFamiTF351636

Family and domain databases

CDDicd00112 LDLa, 1 hit
cd06263 MAM, 2 hits
InterProiView protein in InterPro
IPR026830 ALK
IPR013320 ConA-like_dom_sf
IPR011009 Kinase-like_dom_sf
IPR036055 LDL_receptor-like_sf
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
PANTHERiPTHR24416:SF276 PTHR24416:SF276, 1 hit
PfamiView protein in Pfam
PF00629 MAM, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00192 LDLa, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF49899 SSF49899, 2 hits
SSF56112 SSF56112, 1 hit
SSF57424 SSF57424, 1 hit
PROSITEiView protein in PROSITE
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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

Q9UM73-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGAIGLLWLL PLLLSTAAVG SGMGTGQRAG SPAAGPPLQP REPLSYSRLQ
60 70 80 90 100
RKSLAVDFVV PSLFRVYARD LLLPPSSSEL KAGRPEARGS LALDCAPLLR
110 120 130 140 150
LLGPAPGVSW TAGSPAPAEA RTLSRVLKGG SVRKLRRAKQ LVLELGEEAI
160 170 180 190 200
LEGCVGPPGE AAVGLLQFNL SELFSWWIRQ GEGRLRIRLM PEKKASEVGR
210 220 230 240 250
EGRLSAAIRA SQPRLLFQIF GTGHSSLESP TNMPSPSPDY FTWNLTWIMK
260 270 280 290 300
DSFPFLSHRS RYGLECSFDF PCELEYSPPL HDLRNQSWSW RRIPSEEASQ
310 320 330 340 350
MDLLDGPGAE RSKEMPRGSF LLLNTSADSK HTILSPWMRS SSEHCTLAVS
360 370 380 390 400
VHRHLQPSGR YIAQLLPHNE AAREILLMPT PGKHGWTVLQ GRIGRPDNPF
410 420 430 440 450
RVALEYISSG NRSLSAVDFF ALKNCSEGTS PGSKMALQSS FTCWNGTVLQ
460 470 480 490 500
LGQACDFHQD CAQGEDESQM CRKLPVGFYC NFEDGFCGWT QGTLSPHTPQ
510 520 530 540 550
WQVRTLKDAR FQDHQDHALL LSTTDVPASE SATVTSATFP APIKSSPCEL
560 570 580 590 600
RMSWLIRGVL RGNVSLVLVE NKTGKEQGRM VWHVAAYEGL SLWQWMVLPL
610 620 630 640 650
LDVSDRFWLQ MVAWWGQGSR AIVAFDNISI SLDCYLTISG EDKILQNTAP
660 670 680 690 700
KSRNLFERNP NKELKPGENS PRQTPIFDPT VHWLFTTCGA SGPHGPTQAQ
710 720 730 740 750
CNNAYQNSNL SVEVGSEGPL KGIQIWKVPA TDTYSISGYG AAGGKGGKNT
760 770 780 790 800
MMRSHGVSVL GIFNLEKDDM LYILVGQQGE DACPSTNQLI QKVCIGENNV
810 820 830 840 850
IEEEIRVNRS VHEWAGGGGG GGGATYVFKM KDGVPVPLII AAGGGGRAYG
860 870 880 890 900
AKTDTFHPER LENNSSVLGL NGNSGAAGGG GGWNDNTSLL WAGKSLQEGA
910 920 930 940 950
TGGHSCPQAM KKWGWETRGG FGGGGGGCSS GGGGGGYIGG NAASNNDPEM
960 970 980 990 1000
DGEDGVSFIS PLGILYTPAL KVMEGHGEVN IKHYLNCSHC EVDECHMDPE
1010 1020 1030 1040 1050
SHKVICFCDH GTVLAEDGVS CIVSPTPEPH LPLSLILSVV TSALVAALVL
1060 1070 1080 1090 1100
AFSGIMIVYR RKHQELQAMQ MELQSPEYKL SKLRTSTIMT DYNPNYCFAG
1110 1120 1130 1140 1150
KTSSISDLKE VPRKNITLIR GLGHGAFGEV YEGQVSGMPN DPSPLQVAVK
1160 1170 1180 1190 1200
TLPEVCSEQD ELDFLMEALI ISKFNHQNIV RCIGVSLQSL PRFILLELMA
1210 1220 1230 1240 1250
GGDLKSFLRE TRPRPSQPSS LAMLDLLHVA RDIACGCQYL EENHFIHRDI
1260 1270 1280 1290 1300
AARNCLLTCP GPGRVAKIGD FGMARDIYRA SYYRKGGCAM LPVKWMPPEA
1310 1320 1330 1340 1350
FMEGIFTSKT DTWSFGVLLW EIFSLGYMPY PSKSNQEVLE FVTSGGRMDP
1360 1370 1380 1390 1400
PKNCPGPVYR IMTQCWQHQP EDRPNFAIIL ERIEYCTQDP DVINTALPIE
1410 1420 1430 1440 1450
YGPLVEEEEK VPVRPKDPEG VPPLLVSQQA KREEERSPAA PPPLPTTSSG
1460 1470 1480 1490 1500
KAAKKPTAAE ISVRVPRGPA VEGGHVNMAF SQSNPPSELH KVHGSRNKPT
1510 1520 1530 1540 1550
SLWNPTYGSW FTEKPTKKNN PIAKKEPHDR GNLGLEGSCT VPPNVATGRL
1560 1570 1580 1590 1600
PGASLLLEPS SLTANMKEVP LFRLRHFPCG NVNYGYQQQG LPLEAATAPG
1610 1620
AGHYEDTILK SKNSMNQPGP
Length:1,620
Mass (Da):176,442
Last modified:May 18, 2010 - v3
Checksum:i0733D6C4FD212F41
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WZL3A0A087WZL3_HUMAN
Tyrosine-protein kinase receptor
ALK
1,243Annotation score:
A0A0K2YUJ3A0A0K2YUJ3_HUMAN
Tyrosine-protein kinase receptor
ALK
552Annotation score:
E7EPW7E7EPW7_HUMAN
ALK tyrosine kinase receptor
ALK
129Annotation score:
H7BZ33H7BZ33_HUMAN
ALK tyrosine kinase receptor
ALK
152Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti36P → S in AAB71619 (PubMed:9174053).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04147790S → L1 PublicationCorresponds to variant dbSNP:rs34617074Ensembl.1
Natural variantiVAR_041478163V → L1 PublicationCorresponds to variant dbSNP:rs55697431EnsemblClinVar.1
Natural variantiVAR_041479296E → Q1 PublicationCorresponds to variant dbSNP:rs56077855Ensembl.1
Natural variantiVAR_041480476V → A1 PublicationCorresponds to variant dbSNP:rs35093491EnsemblClinVar.1
Natural variantiVAR_041481560L → F in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041482680T → I1 PublicationCorresponds to variant dbSNP:rs35228363EnsemblClinVar.1
Natural variantiVAR_041483704A → T1 PublicationCorresponds to variant dbSNP:rs34829159Ensembl.1
Natural variantiVAR_061288868L → Q. Corresponds to variant dbSNP:rs55941323EnsemblClinVar.1
Natural variantiVAR_041484877A → S in an ovarian serous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs746442213Ensembl.1
Natural variantiVAR_0414851012T → M1 PublicationCorresponds to variant dbSNP:rs35073634EnsemblClinVar.1
Natural variantiVAR_0638501091D → N in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs864309584EnsemblClinVar.1
Natural variantiVAR_0414861121G → D1 PublicationCorresponds to variant dbSNP:rs55760835EnsemblClinVar.1
Natural variantiVAR_0638511128G → A in NBLST3. 1 PublicationCorresponds to variant dbSNP:rs113994088EnsemblClinVar.1
Natural variantiVAR_0638521151T → M in NBLST3. 1 PublicationCorresponds to variant dbSNP:rs113994091EnsemblClinVar.1
Natural variantiVAR_0638531166M → R in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1057520019Ensembl.1
Natural variantiVAR_0638541171I → N in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs1057519698Ensembl.1
Natural variantiVAR_0638551174F → C in NBLST3. 1 PublicationCorresponds to variant dbSNP:rs1057519697Ensembl.1
Natural variantiVAR_0638561174F → I in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs281864719EnsemblClinVar.1
Natural variantiVAR_0638571174F → L in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 3 PublicationsCorresponds to variant dbSNP:rs863225281EnsemblClinVar.1
Natural variantiVAR_0638581174F → V in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 2 PublicationsCorresponds to variant dbSNP:rs281864719EnsemblClinVar.1
Natural variantiVAR_0638591192R → P in NBLST3. 2 PublicationsCorresponds to variant dbSNP:rs113994089EnsemblClinVar.1
Natural variantiVAR_0638601234A → T in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638611245F → C in NBLST3; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs863225283EnsemblClinVar.1
Natural variantiVAR_0638621245F → V in NBLST3; somatic mutation. Corresponds to variant dbSNP:rs281864720EnsemblClinVar.1
Natural variantiVAR_0638631250I → T in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs113994092EnsemblClinVar.1
Natural variantiVAR_0414871274A → T1 PublicationCorresponds to variant dbSNP:rs45502292EnsemblClinVar.1
Natural variantiVAR_0638641275R → L Observed in neuroblastoma. 1 Publication1
Natural variantiVAR_0638651275R → Q in NBLST3; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 4 PublicationsCorresponds to variant dbSNP:rs113994087EnsemblClinVar.1
Natural variantiVAR_0638661278Y → S in NBLST3; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs863225285EnsemblClinVar.1
Natural variantiVAR_0414881328M → L1 PublicationCorresponds to variant dbSNP:rs56160491Ensembl.1
Natural variantiVAR_0559871376F → S. Corresponds to variant dbSNP:rs17694720Ensembl.1
Natural variantiVAR_0414891416K → N1 PublicationCorresponds to variant dbSNP:rs55782189Ensembl.1
Natural variantiVAR_0414901419E → K1 PublicationCorresponds to variant dbSNP:rs56181542EnsemblClinVar.1
Natural variantiVAR_0414911429Q → R1 PublicationCorresponds to variant dbSNP:rs55906201Ensembl.1
Natural variantiVAR_0310421461I → V4 PublicationsCorresponds to variant dbSNP:rs1670283EnsemblClinVar.1
Natural variantiVAR_0310431491K → R3 PublicationsCorresponds to variant dbSNP:rs1881420EnsemblClinVar.1
Natural variantiVAR_0310441529D → E3 PublicationsCorresponds to variant dbSNP:rs1881421EnsemblClinVar.1
Natural variantiVAR_0559881599P → H. Corresponds to variant dbSNP:rs1881423EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.4 human

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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-ray2.05A1093-1411[»]
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[»]
4TT7X-ray2.10A1095-1410[»]
4Z55X-ray1.55A1072-1410[»]
5A9UX-ray1.60A1093-1411[»]
5AA8X-ray1.86A1093-1411[»]
5AA9X-ray1.93A1093-1411[»]
5AAAX-ray1.73A1093-1411[»]
5AABX-ray2.20A1093-1411[»]
5AACX-ray1.70A1093-1411[»]
5FTOX-ray2.22A1094-1407[»]
5FTQX-ray1.70A1094-1407[»]
5IMXX-ray2.12A1093-1411[»]
5IUGX-ray1.93A1084-1410[»]
5IUHX-ray2.10A1084-1410[»]
5IUIX-ray1.88A1084-1410[»]
5J7HX-ray1.96A1093-1407[»]
5KZ0X-ray2.30A1093-1411[»]
6AT9X-ray2.95C1274-1283[»]
ProteinModelPortaliQ9UM73
SMRiQ9UM73
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106739, 65 interactors
DIPiDIP-5954N
IntActiQ9UM73, 10 interactors
MINTiQ9UM73
STRINGi9606.ENSP00000373700

Chemistry databases

BindingDBiQ9UM73
ChEMBLiCHEMBL4247
DrugBankiDB00171 Adenosine triphosphate
DB11363 Alectinib
DB09063 Ceritinib
DB08865 Crizotinib
GuidetoPHARMACOLOGYi1839

PTM databases

iPTMnetiQ9UM73
PhosphoSitePlusiQ9UM73

Polymorphism and mutation databases

BioMutaiALK
DMDMi296439447

Proteomic databases

EPDiQ9UM73
PaxDbiQ9UM73
PeptideAtlasiQ9UM73
PRIDEiQ9UM73
ProteomicsDBi85185

Protocols and materials databases

DNASUi238
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000389048; ENSP00000373700; ENSG00000171094
GeneIDi238
KEGGihsa:238
UCSCiuc002rmy.4 human

Organism-specific databases

CTDi238
DisGeNETi238
EuPathDBiHostDB:ENSG00000171094.15
GeneCardsiALK
GeneReviewsiALK
H-InvDBiHIX0024259
HIX0030037
HGNCiHGNC:427 ALK
HPAiHPA010694
MalaCardsiALK
MIMi105590 gene
613014 phenotype
neXtProtiNX_Q9UM73
OpenTargetsiENSG00000171094
Orphaneti300895 ALK-positive anaplastic large cell lymphoma
364043 ALK-positive large B-cell lymphoma
146 Differentiated thyroid carcinoma
178342 Inflammatory myofibroblastic tumor
635 Neuroblastoma
357191 Selection of therapeutic option in non-small cell lung carcinoma
PharmGKBiPA24719
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1095 Eukaryota
ENOG410XPVX LUCA
GeneTreeiENSGT00760000118818
HOGENOMiHOG000231766
HOVERGENiHBG018726
InParanoidiQ9UM73
KOiK05119
OMAiHKVQGSR
OrthoDBiEOG091G003T
PhylomeDBiQ9UM73
TreeFamiTF351636

Enzyme and pathway databases

BRENDAi2.7.10.1 2681
SignaLinkiQ9UM73
SIGNORiQ9UM73

Miscellaneous databases

ChiTaRSiALK human
EvolutionaryTraceiQ9UM73
GeneWikiiAnaplastic_lymphoma_kinase
GenomeRNAii238
PROiPR:Q9UM73
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171094 Expressed in 144 organ(s), highest expression level in sperm
CleanExiHS_ALK
ExpressionAtlasiQ9UM73 baseline and differential
GenevisibleiQ9UM73 HS

Family and domain databases

CDDicd00112 LDLa, 1 hit
cd06263 MAM, 2 hits
InterProiView protein in InterPro
IPR026830 ALK
IPR013320 ConA-like_dom_sf
IPR011009 Kinase-like_dom_sf
IPR036055 LDL_receptor-like_sf
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
PANTHERiPTHR24416:SF276 PTHR24416:SF276, 1 hit
PfamiView protein in Pfam
PF00629 MAM, 2 hits
PF07714 Pkinase_Tyr, 1 hit
PRINTSiPR00109 TYRKINASE
SMARTiView protein in SMART
SM00192 LDLa, 1 hit
SM00219 TyrKc, 1 hit
SUPFAMiSSF49899 SSF49899, 2 hits
SSF56112 SSF56112, 1 hit
SSF57424 SSF57424, 1 hit
PROSITEiView protein in PROSITE
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
ProtoNetiSearch...

Entry informationi

Entry nameiALK_HUMAN
AccessioniPrimary (citable) accession number: Q9UM73
Secondary accession number(s): Q4ZFX9
, Q53QQ6, Q53RZ4, Q59FI3, Q9Y4K6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 27, 2002
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 193 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
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Main funding by: National Institutes of Health

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