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  Domain Name: PK_STRAD_alpha
Pseudokinase domain of STE20-related kinase adapter protein alpha. Protein Kinase family, STE20-related kinase adapter protein (STRAD) alpha subfamily, pseudokinase domain. The STRAD alpha subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases (STKs), protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the STK, LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha, stabilized through ATP and MO25, may be needed to activate LKB1. A mutation which results in a truncation of a C-terminal part of the human STRAD-alpha pseudokinase domain and disrupts its association with LKB1, leads to PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. Several splice variants of STRAD-alpha exist which exhibit different effects on the localization and activation of LKB1.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 105
Total Disease Mutations Found: 29
This domain occurred 101 times on human genes (215 proteins).



  CARDIOFACIOCUTANEOUS SYNDROME 3
  CARDIOFACIOCUTANEOUS SYNDROME 4
  COFFIN-LOWRY SYNDROME
  COFFIN-LOWRY SYNDROME, MILD
  FG SYNDROME 4
  GLYCOGEN STORAGE DISEASE IXC
  MALFORMATIONS
  MENTAL RETARDATION AND MICROCEPHALY WITH PONTINE AND CEREBELLAR HYPOPLASIA
  MENTAL RETARDATION, X-LINKED 19
  MENTAL RETARDATION, X-LINKED 30
  MENTAL RETARDATION, X-LINKED, WITH NYSTAGMUS
  NEPHRONOPHTHISIS 9 (NPHP9)
  SHORT RIB-POLYDACTYLY SYNDROME, TYPE IIA
  T-CELL IMMUNODEFICIENCY, RECURRENT INFECTIONS, AUTOIMMUNITY, AND CARDIAC


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Range on the Protein:  

   Protein ID            Protein Position

Domain Position:  


Feature Name:Total Found:
ATP binding site
MO25 interaction site
LKB1 interaction site

















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Please Cite: Peterson, T.A., Adadey, A., Santana-Cruz ,I., Sun, Y., Winder A, Kann, M.G., (2010) DMDM: Domain Mapping of Disease Mutations. Bioinformatics 26 (19), 2458-2459.

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