Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

ALK tyrosine kinase receptor

Gene

ALK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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)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
  • NF-kappaB-inducing kinase activity Source: UniProtKB
  • protein tyrosine kinase activity Source: MGI
  • transmembrane receptor protein tyrosine kinase activity Source: UniProtKB

GO - Biological processi

  • activation of MAPK activity Source: UniProtKB
  • cell proliferation Source: UniProtKB
  • neuron development Source: UniProtKB
  • phosphorylation Source: UniProtKB
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • regulation of apoptotic process Source: UniProtKB
  • signal transduction Source: UniProtKB
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Receptor, Transferase, Tyrosine-protein kinase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS10239-MONOMER.
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

HGNCiHGNC:427. ALK.

Subcellular locationi

Topology

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

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • intracellular Source: GOC
  • protein complex Source: MGI
Complete GO annotation...

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)3 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 Publication1
Natural variantiVAR_0638511128G → A in NBLST3. 1 PublicationCorresponds to variant rs113994088dbSNPEnsembl.1
Natural variantiVAR_0638521151T → M in NBLST3. 1 PublicationCorresponds to variant rs113994091dbSNPEnsembl.1
Natural variantiVAR_0638531166M → R in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638541171I → N in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638551174F → C in NBLST3. 1 Publication1
Natural variantiVAR_0638561174F → I in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638571174F → L in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 3 Publications1
Natural variantiVAR_0638581174F → V in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 2 PublicationsCorresponds to variant rs281864719dbSNPEnsembl.1
Natural variantiVAR_0638591192R → P in NBLST3. 2 PublicationsCorresponds to variant rs113994089dbSNPEnsembl.1
Natural variantiVAR_0638601234A → T in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638611245F → C in NBLST3; somatic mutation. 2 Publications1
Natural variantiVAR_0638621245F → V in NBLST3; somatic mutation. Corresponds to variant rs281864720dbSNPEnsembl.1
Natural variantiVAR_0638631250I → T in NBLST3; somatic mutation. 1 PublicationCorresponds to variant rs113994092dbSNPEnsembl.1
Natural variantiVAR_0638651275R → Q in NBLST3; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 4 PublicationsCorresponds to variant rs113994087dbSNPEnsembl.1
Natural variantiVAR_0638661278Y → S in NBLST3; somatic mutation. 1 Publication1

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.

Mutagenesis

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

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi238.
MalaCardsiALK.
MIMi613014. phenotype.
OpenTargetsiENSG00000171094.
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.

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...)Sequence analysis1
Glycosylationi244N-linked (GlcNAc...)Sequence analysis1
Glycosylationi285N-linked (GlcNAc...)Sequence analysis1
Glycosylationi324N-linked (GlcNAc...)Sequence analysis1
Glycosylationi411N-linked (GlcNAc...)Sequence analysis1
Glycosylationi424N-linked (GlcNAc...)Sequence analysis1
Glycosylationi445N-linked (GlcNAc...)Sequence analysis1
Glycosylationi563N-linked (GlcNAc...)Sequence analysis1
Glycosylationi571N-linked (GlcNAc...)Sequence analysis1
Glycosylationi627N-linked (GlcNAc...)Sequence analysis1
Glycosylationi709N-linked (GlcNAc...)Sequence analysis1
Glycosylationi808N-linked (GlcNAc...)Sequence analysis1
Glycosylationi863N-linked (GlcNAc...)Sequence analysis1
Glycosylationi864N-linked (GlcNAc...)Sequence analysis1
Glycosylationi886N-linked (GlcNAc...)Sequence analysis1
Glycosylationi986N-linked (GlcNAc...)Sequence 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

PaxDbiQ9UM73.
PeptideAtlasiQ9UM73.
PRIDEiQ9UM73.

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.
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

WithEntry#Exp.IntActNotes
itself10EBI-357361,EBI-357361
FAM150AQ6UXT87EBI-357361,EBI-11691642
FAM150BQ6UX465EBI-357361,EBI-11691780
HSP90AB1P082382EBI-357361,EBI-352572
PTPRZ1P234712EBI-357361,EBI-2263175

Protein-protein interaction databases

BioGridi106739. 62 interactors.
DIPiDIP-5954N.
IntActiQ9UM73. 10 interactors.
MINTiMINT-1133857.
STRINGi9606.ENSP00000373700.

Chemistry databases

BindingDBiQ9UM73.

Structurei

Secondary structure

11620
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi1087 – 1092Combined sources6
Beta strandi1096 – 1098Combined sources3
Beta strandi1101 – 1103Combined sources3
Helixi1105 – 1107Combined sources3
Helixi1113 – 1115Combined sources3
Beta strandi1116 – 1124Combined sources9
Beta strandi1126 – 1135Combined sources10
Beta strandi1137 – 1140Combined sources4
Beta strandi1145 – 1152Combined sources8
Beta strandi1154 – 1156Combined sources3
Helixi1158 – 1173Combined sources16
Beta strandi1182 – 1186Combined sources5
Beta strandi1188 – 1197Combined sources10
Helixi1204 – 1211Combined sources8
Beta strandi1215 – 1217Combined sources3
Helixi1223 – 1242Combined sources20
Helixi1252 – 1254Combined sources3
Beta strandi1255 – 1258Combined sources4
Beta strandi1260 – 1263Combined sources4
Beta strandi1266 – 1268Combined sources3
Helixi1272 – 1280Combined sources9
Helixi1288 – 1290Combined sources3
Helixi1293 – 1295Combined sources3
Helixi1298 – 1303Combined sources6
Helixi1308 – 1323Combined sources16
Helixi1335 – 1343Combined sources9
Helixi1356 – 1365Combined sources10
Helixi1370 – 1372Combined sources3
Helixi1376 – 1388Combined sources13
Helixi1390 – 1393Combined sources4
Beta strandi1574 – 1576Combined sources3
Beta strandi1582 – 1584Combined sources3

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[»]
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
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

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

Family and domain databases

CDDicd06263. MAM. 2 hits.
Gene3Di4.10.400.10. 1 hit.
InterProiIPR026830. ALK.
IPR013320. ConA-like_dom.
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

« 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

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 → L.1 PublicationCorresponds to variant rs34617074dbSNPEnsembl.1
Natural variantiVAR_041478163V → L.1 PublicationCorresponds to variant rs55697431dbSNPEnsembl.1
Natural variantiVAR_041479296E → Q.1 PublicationCorresponds to variant rs56077855dbSNPEnsembl.1
Natural variantiVAR_041480476V → A.1 PublicationCorresponds to variant rs35093491dbSNPEnsembl.1
Natural variantiVAR_041481560L → F in a breast pleomorphic lobular carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_041482680T → I.1 PublicationCorresponds to variant rs35228363dbSNPEnsembl.1
Natural variantiVAR_041483704A → T.1 PublicationCorresponds to variant rs34829159dbSNPEnsembl.1
Natural variantiVAR_061288868L → Q.Corresponds to variant rs55941323dbSNPEnsembl.1
Natural variantiVAR_041484877A → S in an ovarian serous carcinoma sample; somatic mutation. 1 PublicationCorresponds to variant rs746442213dbSNPEnsembl.1
Natural variantiVAR_0414851012T → M.1 PublicationCorresponds to variant rs35073634dbSNPEnsembl.1
Natural variantiVAR_0638501091D → N in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0414861121G → D.1 PublicationCorresponds to variant rs55760835dbSNPEnsembl.1
Natural variantiVAR_0638511128G → A in NBLST3. 1 PublicationCorresponds to variant rs113994088dbSNPEnsembl.1
Natural variantiVAR_0638521151T → M in NBLST3. 1 PublicationCorresponds to variant rs113994091dbSNPEnsembl.1
Natural variantiVAR_0638531166M → R in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638541171I → N in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638551174F → C in NBLST3. 1 Publication1
Natural variantiVAR_0638561174F → I in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638571174F → L in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 3 Publications1
Natural variantiVAR_0638581174F → V in NBLST3; somatic mutation; constitutively activated; retained in the endoplasmic reticulum and Golgi compartments. 2 PublicationsCorresponds to variant rs281864719dbSNPEnsembl.1
Natural variantiVAR_0638591192R → P in NBLST3. 2 PublicationsCorresponds to variant rs113994089dbSNPEnsembl.1
Natural variantiVAR_0638601234A → T in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0638611245F → C in NBLST3; somatic mutation. 2 Publications1
Natural variantiVAR_0638621245F → V in NBLST3; somatic mutation. Corresponds to variant rs281864720dbSNPEnsembl.1
Natural variantiVAR_0638631250I → T in NBLST3; somatic mutation. 1 PublicationCorresponds to variant rs113994092dbSNPEnsembl.1
Natural variantiVAR_0414871274A → T.1 PublicationCorresponds to variant rs45502292dbSNPEnsembl.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 rs113994087dbSNPEnsembl.1
Natural variantiVAR_0638661278Y → S in NBLST3; somatic mutation. 1 Publication1
Natural variantiVAR_0414881328M → L.1 PublicationCorresponds to variant rs56160491dbSNPEnsembl.1
Natural variantiVAR_0559871376F → S.Corresponds to variant rs17694720dbSNPEnsembl.1
Natural variantiVAR_0414891416K → N.1 PublicationCorresponds to variant rs55782189dbSNPEnsembl.1
Natural variantiVAR_0414901419E → K.1 PublicationCorresponds to variant rs56181542dbSNPEnsembl.1
Natural variantiVAR_0414911429Q → R.1 PublicationCorresponds to variant rs55906201dbSNPEnsembl.1
Natural variantiVAR_0310421461I → V.4 PublicationsCorresponds to variant rs1670283dbSNPEnsembl.1
Natural variantiVAR_0310431491K → R.3 PublicationsCorresponds to variant rs1881420dbSNPEnsembl.1
Natural variantiVAR_0310441529D → E.3 PublicationsCorresponds to variant rs1881421dbSNPEnsembl.1
Natural variantiVAR_0559881599P → H.Corresponds to variant rs1881423dbSNPEnsembl.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

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[»]
ProteinModelPortaliQ9UM73.
SMRiQ9UM73.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106739. 62 interactors.
DIPiDIP-5954N.
IntActiQ9UM73. 10 interactors.
MINTiMINT-1133857.
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

PaxDbiQ9UM73.
PeptideAtlasiQ9UM73.
PRIDEiQ9UM73.

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.
GeneCardsiALK.
GeneReviewsiALK.
H-InvDBHIX0024259.
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.
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.
OMAiNAIMLSK.
OrthoDBiEOG091G003T.
PhylomeDBiQ9UM73.
TreeFamiTF351636.

Enzyme and pathway databases

BioCyciZFISH:HS10239-MONOMER.
BRENDAi2.7.10.1. 2681.
SignaLinkiQ9UM73.
SIGNORiQ9UM73.

Miscellaneous databases

ChiTaRSiALK. human.
EvolutionaryTraceiQ9UM73.
GeneWikiiAnaplastic_lymphoma_kinase.
GenomeRNAii238.
PROiQ9UM73.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000171094.
CleanExiHS_ALK.
ExpressionAtlasiQ9UM73. baseline and differential.
GenevisibleiQ9UM73. HS.

Family and domain databases

CDDicd06263. MAM. 2 hits.
Gene3Di4.10.400.10. 1 hit.
InterProiIPR026830. ALK.
IPR013320. ConA-like_dom.
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]
ProtoNetiSearch...

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: November 2, 2016
This is version 171 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.