08-24-2021-1312 - Anaplastic_lymphoma_kinase II

Molecular function • transferase activity
• nucleotide binding
• protein kinase activity
• kinase activity
• NF-kappaB-inducing kinase activity
• GO:0001948 protein binding
• identical protein binding
• ATP binding
• transmembrane receptor protein tyrosine kinase activity
• protein tyrosine kinase activity

Since the original discovery of the receptor in mammals, several orthologs of ALK have been identified: dAlk in the fruit fly (Drosophila melanogaster) in 2001,[10] scd-2 in the nematode (Caenorhabditis elegans) in 2004,[11] and DrAlk in the zebrafish (Danio rerio) in 2013.[12]


Anaplastic large-cell lymphoma[edit]

The 2;5 chromosomal translocation is associated with approximately 60% of anaplastic large-cell lymphomas(ALCLs), type ALK-positive anaplastic large cell lymphoma and very rare cases of ALCL type primary cutaneous anaplastic large cell lymphoma. The translocation creates a fusion gene consisting of the ALK (anaplastic lymphoma kinase) gene and the nucleophosmin (NPM) gene: the 3' half of ALK, derived from chromosome 2 and coding for the catalytic domain, is fused to the 5' portion of NPM from chromosome 5. The product of the NPM-ALK fusion gene is oncogenic. In a smaller fraction of ALCL patients, the 3' half of ALK is fused to the 5' sequence of TPM3 gene, encoding for tropomyosin 3. In rare cases, ALK is fused to other 5' fusion partners, such as TFG, ATIC, CLTC1, TPM4, MSN, ALO17, MYH9.[58]
Adenocarcinoma of the lung[edit]

The EML4-ALK fusion gene is responsible for approximately 3-5% of non-small-cell lung cancer (NSCLC). The vast majority of cases are adenocarcinomas. The standard test used to detect this gene in tumor samples is fluorescence in situ hybridization (FISH) by a US FDA approved kit. Recently Roche Ventana obtained approval in China and European Union countries to test this mutation by immunohistochemistry.[59] Other techniques like reverse-transcriptase PCR (RT-PCR) can also be used to detect lung cancers with an ALK gene fusion but not recommended.[citation needed] ALK lung cancers are found in patients of all ages, although on average these patients tend to be younger. ALK lung cancers are more common in light cigarette smokers or nonsmokers, but a significant number of patients with this disease are current or former cigarette smokers. EML4-ALK-rearrangement in NSCLC is exclusive and not found in EGFR- or KRAS-mutated tumors.[60]
Gene rearrangements and overexpression in other tumours[edit]
Familial cases of neuroblastoma[61]
Inflammatory myofibroblastic tumor[62][63]
Adult[64][65] and pediatric[66][67] renal cell carcinomas
Esophageal squamous cell carcinoma[68][69]
Breast cancer,[70] notably the inflammatory subtype[71]
Colonic adenocarcinoma[70]
Glioblastoma multiforme[72][73]
Anaplastic thyroid cancer[74]


https://en.wikipedia.org/wiki/Anaplastic_lymphoma_kinase

protein-containing complex
http://amigo.geneontology.org/amigo/term/GO:0032991

extracellular exosome
http://amigo.geneontology.org/amigo/term/GO:0070062

NIK/NF-kappaB signaling
http://amigo.geneontology.org/amigo/term/GO:0038061

swimming behavior
http://amigo.geneontology.org/amigo/term/GO:0036269

A dimer (/ˈdaɪmər/) (di-, "two" + -mer, "parts") is an oligomer consisting of two monomers joined by bonds that can be either strong or weak, covalent or intermolecular. The term homodimer is used when the two molecules are identical (e.g. A–A) and heterodimer when they are not (e.g. A–B). The reverse of dimerisation is often called dissociation. When two oppositely charged ions associate into dimers, they are referred to as Bjerrum pairs,^[1] after Niels Bjerrum.

https://en.wikipedia.org/wiki/Dimer_(chemistry)

Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or  numatrin, is a protein that in humans is encoded by the NPM1 gene.^[4][5]

NPM1 is associated with nucleolar ribonucleoprotein structures and binds single-stranded and double-stranded nucleic acids, but it binds preferentially G-quadruplex forming nucleic acids. It is involved in the biogenesis of ribosomes and may assist small basic proteins in their transport to the nucleolus. Its regulation through SUMOylation (by SENP3 and SENP5) is another facet of the protein's regulation and cellular functions.

It is located in the nucleolus, but it can be translocated to the nucleoplasm in case of serum starvation or treatment with anticancer drugs. The protein is phosphorylated.

Nucleophosmin has multiple functions:^[6]

1. Histone chaperones
2. Ribosome biogenesis and transport
3. Genomic stability and DNA repair
4. Endoribonuclease activity
5. Centrosome duplication during cell cycle
6. Regulation of ARF-p53 tumor suppressor pathway
7. RNA helix destabilizing activity
8. Inhibition of caspase-activated DNase
9. Prevents apoptosis when located in nucleolus

https://en.wikipedia.org/wiki/NPM1

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