Home News About DMDM Database Statistics Research Publications Contact  

 
  Domain Name: PH_PKB
Protein Kinase B-like pleckstrin homology (PH) domain. PKB (also called Akt), a member of the AGC kinase family, is a phosphatidylinositol 3'-kinase (PI3K)-dependent Ser/Thr kinase which alters the activity of the targeted protein. The name AGC is based on the three proteins that it is most similar to cAMP-dependent protein kinase 1 (PKA; also known as PKAC), cGMP-dependent protein kinase (PKG; also known as CGK1) and protein kinase C (PKC). Human Akt has three isoforms derived for distinct genes: Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma. All Akts have an N-terminal PH domain with an activating Thr phosphorylation site, a kinase domain, and a short C-terminal regulatory tail with an activating Ser phosphorylation site. The PH domain recruits Akt to the plasma membrane by binding to phosphoinositides (PtdIns-3,4-P2) and is required for activation. The phosphorylation of Akt at its Thr and Ser phosphorylation sites leads to increased Akt activity toward forkhead transcription factors, the mammalian target of rapamycin (mTOR), and the Bcl-xL/Bcl-2-associated death promoter (BAD), all of which possess a consensus motif R-X-R-XX-ST-B (X = amino acid, B = bulky hydrophobic residue) for Akt phosphorylation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.
No pairwise interactions are available for this conserved domain.

Total Mutations Found: 10
Total Disease Mutations Found: 6
This domain occurred 15 times on human genes (29 proteins).



  BREAST CANCER, SOMATIC
  CAPILLARY MALFORMATION-ARTERIOVENOUS MALFORMATION
  COLORECTAL CANCER, SOMATIC, INCLUDED;;
  COWDEN DISEASE 6
  HYPOINSULINEMIC HYPOGLYCEMIA AND HEMIHYPERTROPHY
  MEGALENCEPHALY-POLYMICROGYRIA-POLYDACTYLY-HYDROCEPHALUS SYNDROME,
  OVARIAN CANCER, SOMATIC, INCLUDED;;
  PROTEUS SYNDROME, S
  SOMATIC


Tips:
 If you've navigated here from a protein, hovering over a position on the weblogo will display the corresponding protein position for that domain position.

 The histograms below the weblogo indicate mutations found on the domain. Red is for disease (OMIM) and blue is for SNPs.

 Functional Features are displayed as orange boxes under the histograms. You can choose which features are displayed in the box below.



Range on the Protein:  

   Protein ID            Protein Position

Domain Position:  


Feature Name:Total Found:
phosphoinositide binding










Weblogos are Copyright (c) 2002 Regents of the University of California




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.

   |   1000 Hilltop Circle, Baltimore, MD 21250   |   Department of Biological Sciences   |   Phone: 410-455-2258