LYK5

Protein-coding gene in the species Homo sapiens
STRADA
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1UPK, 2WTK, 3GNI

Identifiers
AliasesSTRADA, LYK5, NY-BR-96, PMSE, STRAD, Stlk, STE20-related kinase adaptor alpha, STRAD alpha, STE20 related adaptor alpha
External IDsOMIM: 608626; MGI: 1919399; HomoloGene: 12448; GeneCards: STRADA; OMA:STRADA - orthologs
Gene location (Human)
Chromosome 17 (human)
Chr.Chromosome 17 (human)[1]
Chromosome 17 (human)
Genomic location for STRADA
Genomic location for STRADA
Band17q23.3Start63,682,336 bp[1]
End63,741,986 bp[1]
Gene location (Mouse)
Chromosome 11 (mouse)
Chr.Chromosome 11 (mouse)[2]
Chromosome 11 (mouse)
Genomic location for STRADA
Genomic location for STRADA
Band11|11 E1Start106,054,156 bp[2]
End106,092,994 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • right uterine tube

  • gastric mucosa

  • left testis

  • right testis

  • tibial nerve

  • right hemisphere of cerebellum

  • right frontal lobe

  • ganglionic eminence

  • right ovary

  • body of uterus
Top expressed in
  • spermatocyte

  • seminiferous tubule

  • spermatid

  • neural layer of retina

  • morula

  • granulocyte

  • tail of embryo

  • zygote

  • ventricular zone

  • superior frontal gyrus
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
SpeciesHumanMouse
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 MbChr 11: 106.05 – 106.09 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Protein kinase LYK5, also known as LYK5 or STRADα, is a human protein and also denotes the gene encoding it.[5][6]

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.[6] 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,[7] and this is both developmentally regulated and tissue-specific, but the unique functions of the splice variants are not yet understood.[8]

Disease linkage

Mutations in the LYK5/STRADα gene are associated with polyhydramnios, megalencephaly and symptomatic epilepsy (collectively known as the PMSE syndrome).[9]

Interactions

STRADα has been shown to interact with LKB1 and MO25.[6][10]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000266173 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000069631 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: LYK5 protein kinase LYK5".
  6. ^ a b c Baas AF, Boudeau J, Sapkota GP, Smit L, Medema R, Morrice NA, Alessi DR, Clevers HC (June 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.
  7. ^ Marignani, Paola A.; Scott, Kristine; Bagnulo, Rosanna; Cannone, Domenico; Ferrari, Eleonora; Stella, Alessandro; Guanti, Ginevra; Simone, Cristiano; Resta, Nicoletta (October 2007). "Novel splice isoforms of STRADα differentially affect LKB1 activity, complex assembly and subcellular localization". Cancer Biology & Therapy. 6 (10): 1627–1631. doi:10.4161/cbt.6.10.4787. ISSN 1538-4047. PMID 17921699.
  8. ^ 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./
  9. ^ Puffenberger EG, Strauss KA, Ramsey KE, Craig DW, Stephan DA, Robinson DL, Hendrickson CL, Gottlieb S, Ramsay DA, Siu VM, Heuer GG, Crino PB, Morton DH (July 2007). "Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5". Brain. 130 (Pt 7): 1929–41. doi:10.1093/brain/awm100. PMID 17522105.
  10. ^ Boudeau J, Scott JW, Resta N, Deak M, Kieloch A, Komander D, Hardie DG, Prescott AR, van Aalten DM, Alessi DR (Dec 2004). "Analysis of the LKB1-STRAD-MO25 complex". J. Cell Sci. 117 (Pt 26): 6365–75. doi:10.1242/jcs.01571. PMID 15561763.

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.


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