LYK5

Protein kinase LYK5, also known as LYK5 or STRADα, is a human protein and also denotes the gene encoding it.

STRADA
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1UPK, 2WTK, 3GNI
Identifiers
Aliases	STRADA, LYK5, NY-BR-96, PMSE, STRAD, Stlk, STE20-related kinase adaptor alpha, STRAD alpha, STE20 related adaptor alpha
External IDs	OMIM: 608626 MGI: 1919399 HomoloGene: 12448 GeneCards: STRADA
Gene location (Human) Chr. Chromosome 17 (human) Band 17q23.3 Start 63,682,336 bp End 63,741,986 bp
Gene location (Mouse) Chr. Chromosome 11 (mouse) Band 11|11 E1 Start 106,054,156 bp End 106,092,994 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube gastric mucosa tibial nerve ganglionic eminence Brodmann area 9 canal of the cervix anterior pituitary right lobe of thyroid gland sural nerve skin of abdomen Top expressed in spermatocyte seminiferous tubule spermatid morula superior frontal gyrus secondary oocyte neural tube yolk sac blastocyst cerebellar cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding protein serine/threonine kinase activator activity protein kinase activator activity protein kinase activity ATP binding nucleotide binding kinase binding protein serine/threonine kinase activity Cellular component nucleoplasm nucleus cytoplasm cytosol Biological process protein export from nucleus cell cycle protein phosphorylation positive regulation of protein serine/threonine kinase activity activation of protein kinase activity regulation of mitotic cell cycle stress-activated protein kinase signaling cascade regulation of apoptotic process MAPK cascade signal transduction neuron projection morphogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 92335 72149 Ensembl ENSG00000266173 ENSMUSG00000069631 UniProt Q7RTN6 Q3UUJ4 RefSeq (mRNA) NM_001003786 NM_001003787 NM_001003788 NM_001165969 NM_001165970 NM_153335 NM_001363786 NM_001363787 NM_001363788 NM_001363789 NM_001363790 NM_001363791 NM_001252448 NM_001252449 NM_028126 RefSeq (protein) NP_001003786 NP_001003787 NP_001003788 NP_001159441 NP_001159442 NP_699166 NP_001350715 NP_001350716 NP_001350717 NP_001350718 NP_001350719 NP_001350720 NP_001239377 NP_001239378 NP_082402 Location (UCSC) Chr 17: 63.68 – 63.74 Mb Chr 11: 106.05 – 106.09 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

Endogenous LKB1 and STRADα form a complex in which STRADα activates LKB1, resulting in phosphorylation of both partners. Removal of endogenous LYK5 by small interfering RNA abrogates LKB1-induced G1 phase arrest. STRADα stabilizes LKB1 protein both in vivo and in vitro, and is capable of eliciting multiple axons in mouse embryonic cortical cultured neurons when overexpressed with LKB1. STRADα is highly spliced in vivo, and this is both developmentally regulated and tissue-specific, but the unique functions of the splice variants are not yet understood.

Disease linkage

Mutations in the LYK5/STRADα gene are associated with polyhydramnios, megalencephaly and symptomatic epilepsy (collectively known as the PMSE syndrome).

Interactions

STRADα has been shown to interact with LKB1 and MO25.

Further reading

• Baas AF, Smit L, Clevers H (2004). "LKB1 tumor suppressor protein: PARtaker in cell polarity". Trends Cell Biol. 14 (6): 312–9. doi:10.1016/j.tcb.2004.04.001. PMID 15183188.
• Scanlan MJ, Gout I, Gordon CM, Williamson B, Stockert E, Gure AO, Jäger D, Chen YT, Mackay A, O'Hare MJ, Old LJ (2003). "Humoral immunity to human breast cancer: antigen definition and quantitative analysis of mRNA expression". Cancer Immun. 1: 4. PMID 12747765.
• Baas AF, Boudeau J, Sapkota GP, Smit L, Medema R, Morrice NA, Alessi DR, Clevers HC (2003). "Activation of the tumour suppressor kinase LKB1 by the STE20-like pseudokinase STRAD". EMBO J. 22 (12): 3062–72. doi:10.1093/emboj/cdg292. PMC 162144. PMID 12805220.
• Boudeau J, Baas AF, Deak M, Morrice NA, Kieloch A, Schutkowski M, Prescott AR, Clevers HC, Alessi DR (2003). "MO25alpha/beta interact with STRADalpha/beta enhancing their ability to bind, activate and localize LKB1 in the cytoplasm". EMBO J. 22 (19): 5102–14. doi:10.1093/emboj/cdg490. PMC 204473. PMID 14517248.
• Milburn CC, Boudeau J, Deak M, Alessi DR, van Aalten DM (2004). "Crystal structure of MO25 alpha in complex with the C terminus of the pseudo kinase STE20-related adaptor". Nat. Struct. Mol. Biol. 11 (2): 193–200. doi:10.1038/nsmb716. PMID 14730349. S2CID 18401688.
• Lizcano JM, Göransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Mäkelä TP, Hardie DG, Alessi DR (2005). "LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1". EMBO J. 23 (4): 833–43. doi:10.1038/sj.emboj.7600110. PMC 381014. PMID 14976552.
• Boudeau J, Scott JW, Resta N, Deak M, Kieloch A, Komander D, Hardie DG, Prescott AR, van Aalten DM, Alessi DR (2005). "Analysis of the LKB1-STRAD-MO25 complex". J. Cell Sci. 117 (Pt 26): 6365–75. doi:10.1242/jcs.01571. PMID 15561763.
• Veleva-Rotse BO, Smart JL, Baas AF, Edmonds B, Zhao ZM, Brown A, Klug LR, Hansen K, Reilly G, Gardner AP, Subbiah K, Gaucher EA, Clevers H, Barnes AP (2014). "STRAD pseudokinases regulate axogenesis and LKB1 stability". Neural Dev. 9 (5): 5. doi:10.1186/1749-8104-9-5. PMC 4016016. PMID 24594058.