UniProt Accession

 ALK_HUMAN; Q9UM73; Q4ZFX9; Q53QQ6; Q53RZ4; Q59FI3; Q9Y4K6 

Genbank Protein ID

 U62540; U66559; AB209477; AC106870; AC093756; AC074096 

Genbank Nucleotide ID

 AAB71619.1; AAC51104.1; BAD92714.1; AAX93126.1; AAX88892.1; AAY15027.1 

Protein Name

 ALK tyrosine kinase receptor 

Protein Synonyms/Alias

 Anaplastic lymphoma kinase; CD246 

Gene Name

 ALK 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
831	ATYVFKMKDGVPVPL	ubiquitination	[1]
1498	KVHGSRNKPTSLWNP	ubiquitination	[1]
1514	YGSWFTEKPTKKNNP	ubiquitination	[1]
1517	WFTEKPTKKNNPIAK	ubiquitination	[1]

Reference

 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661] 

Functional Description

 Neuronal orphan 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. 

Sequence Annotation

 DOMAIN 264 427 MAM 1.
 DOMAIN 437 473 LDL-receptor class A.
 DOMAIN 478 636 MAM 2.
 DOMAIN 1116 1392 Protein kinase.
 NP_BIND 1197 1199 ATP.
 REGION 1197 1199 Inhibitor binding.
 ACT_SITE 1249 1249 Proton acceptor (By similarity).
 BINDING 1124 1124 ATP; via carbonyl oxygen.
 BINDING 1150 1150 ATP (By similarity).
 BINDING 1150 1150 Inhibitor.
 BINDING 1199 1199 Inhibitor; via amide nitrogen.
 BINDING 1203 1203 Inhibitor.
 BINDING 1210 1210 Inhibitor.
 BINDING 1270 1270 ATP.
 MOD_RES 211 211 Phosphoserine.
 MOD_RES 1078 1078 Phosphotyrosine.
 MOD_RES 1092 1092 Phosphotyrosine.
 MOD_RES 1096 1096 Phosphotyrosine.
 MOD_RES 1131 1131 Phosphotyrosine.
 MOD_RES 1278 1278 Phosphotyrosine.
 MOD_RES 1282 1282 Phosphotyrosine; by autocatalysis.
 MOD_RES 1283 1283 Phosphotyrosine.
 MOD_RES 1359 1359 Phosphotyrosine.
 MOD_RES 1507 1507 Phosphotyrosine.
 MOD_RES 1584 1584 Phosphotyrosine.
 MOD_RES 1604 1604 Phosphotyrosine.
 CARBOHYD 169 169 N-linked (GlcNAc...) (Potential).
 CARBOHYD 244 244 N-linked (GlcNAc...) (Potential).
 CARBOHYD 285 285 N-linked (GlcNAc...) (Potential).
 CARBOHYD 324 324 N-linked (GlcNAc...) (Potential).
 CARBOHYD 411 411 N-linked (GlcNAc...) (Potential).
 CARBOHYD 424 424 N-linked (GlcNAc...) (Potential).
 CARBOHYD 445 445 N-linked (GlcNAc...) (Potential).
 CARBOHYD 563 563 N-linked (GlcNAc...) (Potential).
 CARBOHYD 571 571 N-linked (GlcNAc...) (Potential).
 CARBOHYD 627 627 N-linked (GlcNAc...) (Potential).
 CARBOHYD 709 709 N-linked (GlcNAc...) (Potential).
 CARBOHYD 808 808 N-linked (GlcNAc...) (Potential).
 CARBOHYD 863 863 N-linked (GlcNAc...) (Potential).
 CARBOHYD 864 864 N-linked (GlcNAc...) (Potential).
 CARBOHYD 886 886 N-linked (GlcNAc...) (Potential).
 CARBOHYD 986 986 N-linked (GlcNAc...) (Potential).  

Keyword

 3D-structure; ATP-binding; Cell membrane; Chromosomal rearrangement; Complete proteome; Disease mutation; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Proto-oncogene; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 1620 AA 

Protein Sequence

Gene Ontology

 GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004704; F:NF-kappaB-inducing kinase activity; TAS:UniProtKB.
 GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IDA:UniProtKB.
 GO:0000187; P:activation of MAPK activity; TAS:UniProtKB.
 GO:0008283; P:cell proliferation; TAS:UniProtKB.
 GO:0048666; P:neuron development; TAS:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
 GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IEA:InterPro. 

Interpro

 IPR026830; ALK.
 IPR008985; ConA-like_lec_gl_sf.
 IPR011009; Kinase-like_dom.
 IPR002172; LDrepeatLR_classA_rpt.
 IPR000998; MAM_dom.
 IPR000719; Prot_kinase_cat_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. 

Pfam

 PF00629; MAM
 PF07714; Pkinase_Tyr 

SMART

 SM00192; LDLa
 SM00219; TyrKc 

PROSITE

 PS01209; LDLRA_1
 PS50068; LDLRA_2
 PS00740; MAM_1
 PS50060; MAM_2
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS00239; RECEPTOR_TYR_KIN_II 

PRINTS

 PR00109; TYRKINASE.