ALK ALK receptor tyrosine kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: ALKprovided by HGNC
Official Full Name: ALK receptor tyrosine kinaseprovided by HGNC
Primary source: HGNC:HGNC:427
See related: Ensembl:ENSG00000171094 MIM:105590; AllianceGenome:HGNC:427
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ALK1; CD246; NBLST3
Summary: 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]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 2p23.2-p23.1

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (29192774..29921586, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (29236229..29965553, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (29415640..30144452, complement)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance.
Title: Oncogenic EML4-ALK assemblies suppress growth factor perception and modulate drug tolerance.
Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.
Title: Super-enhancer-driven IRF2BP2 enhances ALK activity and promotes neuroblastoma cell proliferation.
Spitz Melanoma With SLC20A1::ALK Fusion: A Novel Fusion Previously Undescribed in Spitz Melanocytic Neoplasm.
Title: Spitz Melanoma With SLC20A1::ALK Fusion: A Novel Fusion Previously Undescribed in Spitz Melanocytic Neoplasm.
Mucinous epidermoid carcinoma of the lung with ALK mutation: Case report and literature review.
Title: Mucinous epidermoid carcinoma of the lung with ALK mutation: Case report and literature review.
Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.
Title: Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth.
[ALK rearranged Spitz melanocytoma: a clinicopathological and molecular genetic analysis of two cases].
Title: [ALK rearranged Spitz melanocytoma: a clinicopathological and molecular genetic analysis of two cases].
ALK upregulates POSTN and WNT signaling to drive neuroblastoma.
Title: ALK upregulates POSTN and WNT signaling to drive neuroblastoma.
Dissecting the role of ALK double mutations in drug resistance to lorlatinib with in-depth theoretical modeling and analysis.
Title: Dissecting the role of ALK double mutations in drug resistance to lorlatinib with in-depth theoretical modeling and analysis.
Targeting ALK averts ribonuclease 1-induced immunosuppression and enhances antitumor immunity in hepatocellular carcinoma.
Title: Targeting ALK averts ribonuclease 1-induced immunosuppression and enhances antitumor immunity in hepatocellular carcinoma.
Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK).
Title: Melanoma in infants, caused by a gene fusion involving the anaplastic lymphoma kinase (ALK).

Submit: New GeneRIF Correction See all GeneRIFs (776)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Neuroblastoma, susceptibility to, 3 MedGen: C2751681 OMIM: 613014 GeneReviews: ALK-Related Neuroblastic Tumor Susceptibility	Compare labs

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2019-12-20) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2019-12-20) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 Nef and ALK show similar effects by increasing different cytokines/chemokines, such as IL-1beta, TNF-alpha, and RANTES, that may be relevant for HAD pathogenesis	PubMed
	nef	Overexpression of HIV-1 Nef and ALK effect gelatinase activation in astrocytic glioma cells	PubMed
	nef	HIV-1 Nef and ALK are capable of cumulatively influencing the MAP-K phosphorylation in astrocytic glioma cells	PubMed
	nef	HIV-1 Nef and anaplastic lymphoma kinase (ALK) do not physically interact but ALK expression is upregulated by Nef in astrocytic glioma cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

FB8C12 (e-PCR)
- UniSTS:9730

RH92401 (e-PCR)
- UniSTS:86276

SHGC-142979 (e-PCR)
- UniSTS:183309

G43539 (e-PCR)
- UniSTS:94994

RH119031 (e-PCR)
- UniSTS:138260

SHGC-143855 (e-PCR)
- UniSTS:172066

NoName (e-PCR)
- UniSTS:483881

SHGC-78963 (e-PCR)
- UniSTS:100909

SHGC-153445 (e-PCR)
- UniSTS:183367

RH70535 (e-PCR)
- UniSTS:22866

RH123131 (e-PCR)
- UniSTS:135512

D2S405 (e-PCR), detects polymorphism
- UniSTS:25448

NoName (e-PCR)
- UniSTS:481655

SHGC-155671 (e-PCR)
- UniSTS:185212

SHGC-79251 (e-PCR)
- UniSTS:102781

G29204 (e-PCR)
- UniSTS:40577

G62530 (e-PCR)
- UniSTS:139659

D2S390 (e-PCR), detects polymorphism
- UniSTS:27544

D2S146 (e-PCR), detects polymorphism
- UniSTS:66973

D2S146 (e-PCR), detects polymorphism
- UniSTS:65441

SHGC-83664 (e-PCR)
- UniSTS:95912

WI-13310 (e-PCR)
- UniSTS:56757

SHGC-148322 (e-PCR)
- UniSTS:176322

SHGC-82409 (e-PCR)
- UniSTS:104397

D2S390 (e-PCR), detects polymorphism
- UniSTS:31440

SHGC-144661 (e-PCR)
- UniSTS:174296

G19150 (e-PCR)
- UniSTS:1520

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables GPI-linked ephrin receptor activity	IEA Inferred from Electronic Annotation more info
enables boss receptor activity	IEA Inferred from Electronic Annotation more info
enables brain-derived neurotrophic factor receptor activity	IEA Inferred from Electronic Annotation more info
enables epidermal growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables fibroblast growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables heparin binding	IDA Inferred from Direct Assay more info	PubMed
enables hepatocyte growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables histone H2AXY142 kinase activity	IEA Inferred from Electronic Annotation more info
enables histone H3Y41 kinase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables insulin receptor activity	IEA Inferred from Electronic Annotation more info
enables insulin-like growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables macrophage colony-stimulating factor receptor activity	IEA Inferred from Electronic Annotation more info
enables placental growth factor receptor activity	IEA Inferred from Electronic Annotation more info
enables platelet-derived growth factor alpha-receptor activity	IEA Inferred from Electronic Annotation more info
enables platelet-derived growth factor beta-receptor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase activity	TAS Traceable Author Statement more info
enables protein tyrosine kinase collagen receptor activity	IEA Inferred from Electronic Annotation more info
enables receptor signaling protein tyrosine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables stem cell factor receptor activity	IEA Inferred from Electronic Annotation more info
enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane receptor protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane receptor protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed
enables transmembrane-ephrin receptor activity	IEA Inferred from Electronic Annotation more info
enables vascular endothelial growth factor receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in Kit signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in adult behavior	IEA Inferred from Electronic Annotation more info
involved_in brain-derived neurotrophic factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in collagen-activated tyrosine kinase receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in energy homeostasis	ISS Inferred from Sequence or Structural Similarity more info
involved_in ephrin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in epidermal growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in hepatocyte growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in hippocampus development	IEA Inferred from Electronic Annotation more info
involved_in insulin receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in macrophage colony-stimulating factor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of lipid catabolic process	ISS Inferred from Sequence or Structural Similarity more info
involved_in neuron development	TAS Traceable Author Statement more info	PubMed
involved_in peptidyl-tyrosine autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in platelet-derived growth factor receptor-alpha signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in platelet-derived growth factor receptor-beta signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of NF-kappaB transcription factor activity	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of dendrite development	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein autophosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cell population proliferation	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of dopamine receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in regulation of neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to environmental enrichment	IEA Inferred from Electronic Annotation more info
involved_in response to stress	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in swimming behavior	IEA Inferred from Electronic Annotation more info
involved_in vascular endothelial growth factor receptor-1 signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in vascular endothelial growth factor signaling pathway	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: ALK tyrosine kinase receptor

Names: CD246 antigen; anaplastic lymphoma receptor tyrosine kinase; mutant anaplastic lymphoma kinase

NP_001340694.1

EC 2.7.10.1

NP_004295.2

EC 2.7.10.1

XP_054197220.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009445.1 RefSeqGene

Range

4956..733793

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_488

mRNA and Protein(s)

NM_001353765.2 → NP_001340694.1 ALK tyrosine kinase receptor isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. The promoter and 5' terminal exon sequence is from an endogenous retroviral LTR (PMID: 26444240). The resulting isoform (2, also known as ALKATI) is shorter and has a distinct N-terminus, compared to isoform 1. The encoded protein is expressed in melanoma cells.

Source sequence(s)

LN864494

Consensus CDS

CCDS86828.1

UniProtKB/TrEMBL

A0A0K2YUJ3

Related

ENSP00000493203.1, ENST00000642122.1

Conserved Domains (1) summary

cd05036
Location:41 → 317

PTKc_ALK_LTK; Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase
NM_004304.5 → NP_004295.2 ALK tyrosine kinase receptor isoform 1 precursor

See identical proteins and their annotated locations for NP_004295.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

DA455128, EU788004, U62540

Consensus CDS

CCDS33172.1

UniProtKB/Swiss-Prot

A6P4T4, A6P4V4, Q4ZFX9, Q53QQ6, Q53RZ4, Q59FI3, Q9UM73, Q9Y4K6

UniProtKB/TrEMBL

B6D4Y1, B6D4Y2, B6D4Y3, B6D4Y5, B6D4Y6, B6D4Y7, B6D4Y8, D1MAM0, D1MAM1, D1MAM2, D1MAM3, D1MAM4, D1MAM5, F0UY65, F0UY66

Related

ENSP00000373700.3, ENST00000389048.8

Conserved Domains (6) summary

cd06263
Location:480 → 631

MAM; Meprin, A5 protein, and protein tyrosine phosphatase Mu (MAM) domain. MAM is an extracellular domain which mediates protein-protein interactions and is found in a diverse set of proteins, many of which are known to function in cell adhesion. Members ...

smart00192
Location:441 → 467

LDLa; Low-density lipoprotein receptor domain class A

cd05036
Location:1109 → 1385

PTKc_ALK_LTK; Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase

pfam00629
Location:480 → 636

MAM; MAM domain, meprin/A5/mu

pfam07714
Location:1116 → 1383

Pkinase_Tyr; Protein tyrosine kinase

pfam14670
Location:987 → 1021

FXa_inhibition; Coagulation Factor Xa inhibitory site