Protein detail

ALK

ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246)

Entry name ALK	UniProt ID Q9UM73	EVMP confidence score 0.50
Supporting publications (n) 1	Transmembrane count 1	Protein classification Cancer-related genesCD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

ALK tyrosine kinase receptor (EC 2.7.10.1) (Anaplastic lymphoma kinase) (CD antigen CD246)

Protein Class (9)

Cancer-related genesCD markersDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPlasma proteinsPredicted intracellular proteinsPredicted membrane proteins

Protein Function (11)

Human disease related genes:Cancers:Cancers of the lung and pleura
Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
Predicted intracellular proteins
ENZYME proteins:Transferases
Cancer-related genes:Mutated cancer genes
CD markers
Enzymes
Human disease related genes:Cancers:Cancers of haematopoietic and lymphoid tissues
Kinases:Tyr protein kinases
Disease related genes

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Transmembrane

1039..1059; Helical

Transmembrane Count

Ensembl

ENSG00000171094

Entrez Gene Symbol

ALK

Gene Synonym (2)

ALK1CD246

Gene Description

ALK receptor tyrosine kinase

Chromosome

Position

29192774-29921586

Supporting publications (n)

EVMP confidence score

0.50

Fluorescence & Localization3

Tissue Specificbone marrowCell SpecificEsophageal apical cells

Function & Pathway6

Protein Function (11)

Human disease related genes:Cancers:Cancers of the lung and pleura
Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
Predicted intracellular proteins
ENZYME proteins:Transferases
Cancer-related genes:Mutated cancer genes
CD markers
Enzymes
Human disease related genes:Cancers:Cancers of haematopoietic and lymphoid tissues
Kinases:Tyr protein kinases
Disease related genes

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Cellular Component (4)

Molecular Function (7)

KEGG (3)

Reactome (5)

Mediation Categories (2)

Clinical-translation mediationReceptor-signaling mediation

Relations & Evidence109

Enzyme-Mediated Modification (3)

3 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database	References
ALK	HCK	P08631	Y	1,507	phosphorylation	KEA	KEA:17570479
ALK	IGF1R	P08069	Y	1,278	phosphorylation	KEA	KEA:17570479
ALK	IGF1R	P08069	Y	1,327	phosphorylation	KEA	KEA:17570479

Ligand-Receptor Signaling (49)

49 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
plasma_membrane	plasma_membrane	OmniPath	No	No	No	Yes	No
plasma_membrane_transmembrane	plasma_membrane_transmembrane	Membranome	No	No	No	Yes	No
plasma_membrane_transmembrane	plasma_membrane_transmembrane	HPMR	No	No	No	Yes	No
plasma_membrane_transmembrane	plasma_membrane_transmembrane	OmniPath	No	No	No	Yes	No
cell_surface	cell_surface	Surfaceome	No	No	No	Yes	No
cell_surface	cell_surface	connectomeDB2020	No	No	No	Yes	No
cell_surface	cell_surface	OmniPath	No	No	No	Yes	No
receptor	receptor	talklr	No	Yes	No	Yes	No
receptor	receptor	Cellinker	No	Yes	No	Yes	No
receptor	receptor	scConnect	No	Yes	No	Yes	No

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Regulatory Interaction Network (17)

17 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
ALK	Q9UM73	PUR9	P31939	Yes	Yes	No	Sparser_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefSIGNORiPTMnetProtMapperREACH_ProtMapperPhosphoSite_ProtMapper	ProtMapper:33520699 SIGNOR:18845790
ALK	Q9UM73	CDK9	P50750	Yes	Yes	No	SIGNOR	SIGNOR:36253486
ALK	Q9UM73	P55G	Q92569	Yes	Yes	No	SIGNOR	SIGNOR:27322022
ALK	Q9UM73	PTN11	Q06124	Yes	Yes	No	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPPhosphoSite_norefProtMapperKEAKinexus_KEAWangPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:18320059 PhosphoSite:17483340 PhosphoSite:34692535 PhosphoSite:19223540 PhosphoSite:11684012 PhosphoSite:12721296 PhosphoSite:8041791 PhosphoSite:32076487 PhosphoSite:12531430 PhosphoSite:34301842 PhosphoSite:15710330 KEA:12522270
ALK	Q9UM73	ELP3	Q9H9T3	Yes	No	No	PhosphoSitePhosphoSite_ProtMapperProtMapper	PhosphoSite:31341009
ALK	Q9UM73	VASP	P50552	Yes	No	No	phosphoELM_MIMPPhosphoSite_MIMPMIMPHPRD_MIMPiPTMnetProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:18845790
ALK	Q9UM73	SRCN1	Q9C0H9	Yes	No	No	MIMPiPTMnetPhosphoSitePhosphoSite_MIMP	PhosphoSite:23383002

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Protein Complex Composition (39)

39 records.

Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs
CTBP1 GALK1 LCOR LCORL PRDM2 RREB1 ZBTB18 ZNF516	P51570 Q13029 Q13363 Q8N3X6 Q92618 Q92766 Q96JN0 Q99592	0:0:0:0:0:0:0:0	hu.MAP
ACSS2 CYCS GALK2 MVD	P53602 P99999 Q01415 Q9NR19	0:0:0:0	hu.MAP
GALK2 GALM PABPC3 ZC3H3	Q01415 Q8IXZ2 Q96C23 Q9H361	0:0:0:0	hu.MAP2
GALK2 GALM	Q01415 Q96C23	0:0	hu.MAP2
GALK2 GALM PABPC3	Q01415 Q96C23 Q9H361	0:0:0	hu.MAP2
GALK2 PABPC3	Q01415 Q9H361	0:0	hu.MAP2
ALKBH1	Q13686	8	PDB	PDB:6ie2
ALKBH3 ASCC1 ASCC2 ASCC3 TRIP4	Q15650 Q8N3C0 Q8N9N2 Q96Q83 Q9H1I8	0:0:0:0:0	hu.MAP2
ALKBH6 ARB2A EFL1 FAM98B	Q3KRA9 Q52LJ0 Q7Z2Z2 Q8WUF8	0:0:0:0	hu.MAP2
ALKBH6 ARB2A	Q3KRA9 Q8WUF8	0:0	hu.MAP2

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Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationSize Exclusion Chromatography	Mass spectrometry	1	30875722

Sequence, Structure & Domains13

Sequences

Length

1,620

Mass

176,442

Sequence

MGAIGLLWLLPLLLSTAAVGSGMGTGQRAGSPAAGPPLQPREPLSYSRLQRKSLAVDFVVPSLFRVYARDLLLPPSSSELKAGRPEARGSLALDCAPLLRLLGPAPGVSWTAGSPAPAEARTLSRVLKGGSVRKLRRAKQLVLELGEEAILEGCVGPPGEAAVGLLQFNLSELFSWWIRQGEGRLRIRLMPEKKASEVGREGRLSAAIRASQPRLLFQIFGTGHSSLESPTNMPSPSPDYFTWNLTWIMKDSFPFLSHRSRYGLECSFDFPCELEYSPPLHDLRNQSWSWRRIPSEEASQMDLLDGPGAERSKEMPRGSFLLLNTSADSKHTILSPWMRSSSEHCTLAVSVHRHLQPSGRYIAQLLPHNEAAREILLMPTPGKHGWTVLQGRIGRPDNPFRVALEYISSGNRSLSAVDFFALKNCSEGTSPGSKMALQSSFTCWNGTVLQLGQACDFHQDCAQGEDESQMCRKLPVGFYCNFEDGFCGWTQGTLSPHTPQWQVRTLKDARFQDHQDHALLLSTTDVPASESATVTSATFPAPIKSSPCELRMSWLIRGVLRGNVSLVLVENKTGKEQGRMVWHVAAYEGLSLWQWMVLPLLDVSDRFWLQMVAWWGQGSRAIVAFDNISISLDCYLTISGEDKILQNTAPKSRNLFERNPNKELKPGENSPRQTPIFDPTVHWLFTTCGASGPHGPTQAQCNNAYQNSNLSVEVGSEGPLKGIQIWKVPATDTYSISGYGAAGGKGGKNTMMRSHGVSVLGIFNLEKDDMLYILVGQQGEDACPSTNQLIQKVCIGENNVIEEEIRVNRSVHEWAGGGGGGGGATYVFKMKDGVPVPLIIAAGGGGRAYGAKTDTFHPERLENNSSVLGLNGNSGAAGGGGGWNDNTSLLWAGKSLQEGATGGHSCPQAMKKWGWETRGGFGGGGGGCSSGGGGGGYIGGNAASNNDPEMDGEDGVSFISPLGILYTPALKVMEGHGEVNIKHYLNCSHCEVDECHMDPESHKVICFCDHGTVLAEDGVSCIVSPTPEPHLPLSLILSVVTSALVAALVLAFSGIMIVYRRKHQELQAMQMELQSPEYKLSKLRTSTIMTDYNPNYCFAGKTSSISDLKEVPRKNITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFNHQNIVRCIGVSLQSLPRFILLELMAGGDLKSFLRETRPRPSQPSSLAMLDLLHVARDIACGCQYLEENHFIHRDIAARNCLLTCPGPGRVAKIGDFGMARDIYRASYYRKGGCAMLPVKWMPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCPGPVYRIMTQCWQHQPEDRPNFAIILERIEYCTQDPDVINTALPIEYGPLVEEEEKVPVRPKDPEGVPPLLVSQQAKREEERSPAAPPPLPTTSSGKAAKKPTAAEISVRVPRGPAVEGGHVNMAFSQSNPPSELHKVHGSRNKPTSLWNPTYGSWFTEKPTKKNNPIAKKEPHDRGNLGLEGSCTVPPNVATGRLPGASLLLEPSSLTANMKEVPLFRLRHFPCGNVNYGYQQQGLPLEAATAPGAGHYEDTILKSKNSMNQPGP

3D Structural Models

Turn

705..707; 921..923; 999..1001

Helix

698..704; 718..720; 788..794; 800..807; 896..898; 907..913; 987..989; 1087..1092; 1105..1107; 1113..1115; 1158..1173; 1204..1211; 1223..1242; 1252..1254; 1272..1280; 1288..1290; 1293..1295; 1298..1303; 1308..1323; 1335..1343; 1356..1365; 1370..1372; 1376..1388; 1390..1393

Beta Strand

675..677; 680..685; 692..694; 713..715; 724..727; 730..739; 747..751; 757..765; 770..774; 782..784; 808..810; 812..814; 825..831; 834..841; 860..862; 865..867; 875..877; 890..892; 928..930; 936..938; 956..959; 963..965; 970..975; 978..984; 990..993; 995..997; 1004..1006; 1012..1014; 1016..1022; 1096..1098; 1101..1103; 1116..1124; 1126..1135; 1137..1140; 1145..1152; 1154..1156; 1182..1186; 1188..1197; 1215..1217; 1255..1258; 1260..1263; 1266..1268; 1284..1286; 1574..1576; 1582..1584

3D Structure

Electron microscopy (2); NMR spectroscopy (5); X-ray crystallography (72)

Domain & Motif Annotations

Compositional Bias

654..666; Basic and acidic residues; 1410..1419; Basic and acidic residues

Domain (CC)

The EGF-like region drives the cytokine specificity for ALKAL2..; DOMAIN: The heparin-binding region binds heparin glycosaminoglycan (PubMed:25605972, PubMed:34646012). Heparin-binding is required for ALKAL2-driven activation (PubMed:34646012).

Domain (FT)

264..427; MAM 1; 437..473; LDL-receptor class A; 478..636; MAM 2; 1116..1392; Protein kinase

Region

48..70; Heparin-binding region; 650..674; Disordered; 987..1025; EGF-like; 1408..1463; Disordered; 1514..1540; Disordered

Protein Families (3)

Protein kinase superfamily
Tyr protein kinase family
Insulin receptor subfamily

Sequence Similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. Insulin receptor subfamily.

Clinical Relevance9

Disease Involvement (4)

Cancer-related genesDisease variantFDA approved drug targetsProto-oncogene

Related Diseases (10)

Adrenal cancer Breast cancer Colorectal cancer Diffuse large B-cell lymphoma Lung cancer Lymphoma Mature T-cell lymphoma Metastatic tumour Non-small-cell lung cancer Solid tumour/cancer

Biomarker

Phase 1; Phase 2; Approved; Investigative; Patented

Drug Targets

FDA approved drug targets

Drugs (116)

CERITINIB X-396 CRIZOTINIB IL-10 RETASPIMYCIN HYDROCHLORIDE NIVOLUMAB NULL ALECTINIB ENTRECTINIB CENISERTIB AFATINIB PEMBROLIZUMAB DOXORUBICIN HYDROCHLORIDE ENSARTINIB CHEMBL:CHEMBL379975 TEPOTINIB CEMIPLIMAB-RWLC ZOLEDRONIC ACID ANHYDROUS APG-2449 LORLATINIB VANDETANIB RIBOCICLIB VINCRISTINE SULFATE IDASANUTLIN DACTOLISIB GEFITINIB DABRAFENIB NAVITOCLAX ATEZOLIZUMAB ALK INHIBITOR ASP3026 BRIGATINIB ALK INHIBITOR TAE684 AZD3463 TOPOTECAN HYDROCHLORIDE ERLOTINIB FORITINIB SUCCINATE GW441756X DINACICLIB TALETRECTINIB IPILIMUMAB CARBOPLATIN IFOSFAMIDE TPX-0131 TRAMETINIB DIMETHYL SULFOXIDE DOVITINIB TAK-715 TEMOZOLOMIDE PLB1003 BELIZATINIB GILTERITINIB EG5 KINESIN-RELATED MOTOR PROTEIN INHIBITOR 4SC-205 RAMUCIRUMAB JAK3 INHIBITOR II DALANTERCEPT ETOPOSIDE SELUMETINIB SHP2 INHIBITOR PF-07284892 LUMINESPIB DURVALUMAB BRENTUXIMAB VEDOTIN PAZOPANIB CISPLATIN IRINOTECAN HYDROCHLORIDE IRUPLINALKIB PD-0166285 CARBAMAZEPINE ALVOCIDIB GSK-1838705A CP-547632 PALBOCICLIB TOZASERTIB P53/HDM2 INTERACTION INHIBITOR CGM097 REPOTRECTINIB BATOPROTAFIB CYCLOPHOSPHAMIDE ANHYDROUS CONTELTINIB PEMETREXED DISODIUM JNJ-7706621 MTI-31 FULVESTRANT LINIFANIB METHOTREXATE FILGOTINIB DEXAMETHASONE MILADEMETAN RG-1530 CRENOLANIB ONALESPIB IXAZOMIB TAMATINIB ILORASERTIB HESPERADIN ALK/C-MET INHIBITOR TQ-B3139 ALK/TRK INHIBITOR TSR-011 OSIMERTINIB BEVACIZUMAB-AWWB CYTARABINE HJC0152 SARACATINIB ALECTINIB HYDROCHLORIDE ASP-3026 IMATINIB TREMELIMUMAB VENETOCLAX THZ1 CHEMBL:CHEMBL1997335 CHEMBL:CHEMBL546797 PF-562271 GANETESPIB ALK INHIBITOR NVL-655 CEDIRANIB FICONALKIB NVP-TAE 226 CEP-37440 OCTREOTIDE ACETATE SIROLIMUS

Antibody

HPA010694

Interaction Protein

ENSG00000165731

Interaction Count

Interaction Dataset

intact_biogrid

Supporting Publications1

PMID	Title	Abstract
35029059	Human neural cell type-specific extracellular vesicle proteome defines disease-related molecules associated with activated astrocytes in Alzheimer's disease brain.	No abstract available