Pleckstrin homology domain

Pleckstrin homology domain (PH domain) or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton.^{[1][2][3][4][5][6][7]}

This domain can bind

Lipid binding specificity

Individual PH domains possess specificities for phosphoinositides phosphorylated at different sites within the

• Pleckstrin, the protein where this domain was first detected, is the major substrate of protein kinase C in platelets. Pleckstrin contains two PH domains. ARAP proteins contain five PH domains.
• Serine/threonine-specific protein kinases such as the Akt/Rac family, protein kinase D1, and the trypanosomal NrkA family.
• Non-receptor tyrosine kinases belonging to the Btk/Itk/Tec subfamily.
• Insulin receptor substrate 1 (
  IRS-1
  ).
• Regulators of
  small G-proteins: 64 RhoGEFs of the Dbl-like family.,^[13]
  and several GTPase activating proteins like ABR, BCR or ARAP proteins.
• Cytoskeletal proteins such as dynamin (see InterPro: IPR001401), Caenorhabditis elegans kinesin-like protein unc-104 (see InterPro: IPR001752), spectrin beta-chain, syntrophin (2 PH domains), and S. cerevisiae nuclear migration protein NUM1.
• Oxysterol-binding proteins OSBP, S. cerevisiae OSH1 and YHR073w.
• Ceramide kinase, a lipid kinase that phosphorylates ceramides to ceramide-1-phosphate.^[14]
• G protein receptor kinases (GRK) of GRK2 subfamily (beta-adrenergic receptor kinases): GRK2 and GRK3.^[15]

Subfamilies

• Spectrin/pleckstrin-like InterPro: IPR001605

Examples

Human genes encoding proteins containing this domain include:

• ADRBK2, AFAP, AFAP1, AFAP1L1, AFAP1L2, AKAP13, AKT1, AKT2, AKT3, ANLN, APBB1IP, APPL1, APPL2, ARHGAP10, ARHGAP12, ARHGAP15, ARHGAP21, ARHGAP22, ARHGAP23, ARHGAP24, ARHGAP25, ARHGAP26, ARHGAP27, ARHGAP9, ARHGEF16, ARHGEF18, ARHGEF19, ARHGEF2, ARHGEF3, ARHGEF4, ARHGEF5, ARHGEF6, ARHGEF7, ARHGEF9, ASEF2
  ,
• BMX, BTK,
• CIT, CNKSR1, CNKSR2, COL4A3BP, CTGLF1, CTGLF2, CTGLF3, * CTGLF4, CTGLF5, CTGLF6
  ,
• DOCK9, DOK1, DOK2, DOK3, DOK4, DOK5, DOK6, DTGCU2
  ,
• EXOC8,
• FAM109A, FAM109B, FARP1, FARP2, FGD1, FGD2, FGD3, FGD4, FGD5, FGD6,
• GAB3, GAB4, GRB10, GRB14, GRB7
  ,
• ITSN2
  ,
• KALRN, KIF1A, KIF1B, KIF1Bbeta
  ,
• MRIP, MYO10
  ,
• NET1, NGEF,
• OBSCN, OPHN1, OSBP, OSBP2, OSBPL10, OSBPL11, OSBPL3, OSBPL5, OSBPL6, OSBPL7, OSBPL8, OSBPL9
  ,
• PSD2, PSD3, PSD4, RALGPS1, RALGPS2, RAPH1
  ,
• RASA1, RASA2, RASA3, RASA4, RASAL1, RASGRF1, RGNEF, ROCK1, ROCK2, RTKN
  ,
• SNTA1, SNTB1, SNTB2, SOS1, SOS2, SPATA13, SPNB4, SPTBN1, SPTBN2, SPTBN4, SPTBN5, STAP1, SWAP70, SYNGAP1
  ,
• TIAM1, TRIO, TRIOBP, TYL
  ,
• URP1, URP2,
• VAV1, VAV2, VAV3, VEPH1

See also

• Pleckstrin
• The unrelated FYVE domain binds Phosphatidylinositol 3-phosphate and has been found in over 60 proteins.
• The GRAM domain is a structurally related protein domain.

References