Most domains can be computationally profiled by Hidden Markov Model (HMM), which can be found in Pfam, SMART, NCBI CDD, Gene3D, Superfamily and similar databases.
|Domain||Function||Human protein number (domain number)||Human protein phosphatase (PP) number||PP subfamily||Length (aa)|
|C1||Bind to secondary messenger DAG||~50|
|FERM||Target proteins to plasma membrane||>30 (~50) |
|PDZ||Bind to specific C-terminal short region||~180 (~260)||80-90|
|PEST||Rapid degradation signal|
|PTB||Bind to pTyr||27||~130|
|SH2||Bind to pTyr||115 (120)||PTPN6||~100|
|SH3||Bind to proline-rich peptide||(~300)||STS||~60|
|THAP||Bind to DNA||12 (12) ||0||80-90|
Note: 1) PP is short for protein phosphatase. 2) Numbers in parenthesis are domain numbers.
ADF: actin cytoskeleton organization
ADF stands for Actin Depolymerizing Factor, involved in the rapid recycling of their actin cytoskeleton to enable a dynamic change in their shape.
C1: DAG binding
C1 domain (also known as phorbol esters/diacylglycerol binding domain) binds an important secondary messenger diacylglycerol (DAG), as well as the analogous phorbol esters. It is characterised by a rich cysteine and histidine content. The C1 domain is originally found in the N-terminal region of conservation in protein kinase C domains. It is usually around 50 aa long.
C2: membrane targeting
"A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. The C2 domain in PTEN, brings the phosphatase domain into contact with the plasma membrane, where it can dephosphorylate its substrate, phosphatidylinositol (3,4,5)-trisphosphate (PIP3), without removing it from the membrane - which would be energetically very costly. The C2 domain is currently only known from eukaryotes. Over 17 distinct clades of C2 domains have been identified. Most C2 families can be traced back to basal eukaryotic species indicating an early diversification before the last eukaryotic common ancestor (LECA). Only the PKC-C2 domain family contains conserved calcium-binding residues, suggesting the typical calcium-dependent membrane interaction is a derived feature limited in PKC-C2 domains. "
EF hand: Ca2+ binding
The EF hand is a helix-loop-helix structural domain or motif found in a large family of calcium-binding proteins. The EF-hand motif contains a helix-loop-helix topology, much like the spread thumb and forefinger of the human hand, in which the Ca2+ ions are coordinated by ligands within the loop. It usually has about 30 aa residues.
FERM: cytoskeletal-associated at the interface between plasma membrane and cytoskeleton
FERM domain (F for 4.1 protein, E for ezrin, R for radixin and M for moesin) is a widespread protein module involved in localising proteins to the plasma membrane. FERM domains are found in a number of cytoskeletal-associated proteins that associate with various proteins at the interface between the plasma membrane and the cytoskeleton. The FERM domain is located at the N terminus in the majority of proteins in which it is found.
IQ: calmodulin (Ca2+ sensor) binding
The IQ calmodulin-binding motif is an amino acid sequence motif containing the following sequence: [FILV]Qxxx[RK]Gxxx[RK]xx[FILVWY]. The term "IQ" refers to the first two amino acids of the motif: isoleucine (commonly) and glutamine (invariably). Calmodulin (CaM) is recognized as a major calcium (Ca2+) sensor and orchestrator of regulatory events through its interaction with a diverse group of cellular proteins.
PDZ: binding to the C-terminal of specific proteins
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of all three kingdoms of life. PDZ is an acronym combining the first letters of three proteins — post synaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), and zonula occludens-1 protein (zo-1) — which were first discovered to share the domain. It has previously been referred to as DHR (Dlg homologous region) or GLGF (glycine-leucine-glycine-phenylalanine) domains.
Proteins with these domains help hold together and organize signaling complexes at cellular membranes. In general PDZ domains bind to a short region of the C-terminus of other specific proteins. These short regions bind to the PDZ domain by beta sheet augmentation. This means that the beta sheet in the PDZ domain is extended by the addition of a further beta strand from the tail of the binding partner protein. About 260 PDZ domains within 180 proteins in human have been found.
PEST: rapid degradation signal
A PEST sequence is a peptide sequence that is rich in proline (P), glutamic acid (E), serine (S), and threonine (T). This sequence is associated with proteins that are rapidly degraded, possibly via the proteasome or cal pain. The computational tool ePESTfind is used to predict PEST sequence.
PH: phosphatidylinositol lipids binding
The PTB domain is a structural domain of ~130 aa (Pfam model). It usually binds to phosphorylated tyrosine. However, PTB domain of SHC can bind to NPLH sequence found in the carboxyl terminus of murine PTPN12/PTP-PEST . PTB domain is found at least in 27 genes in human genome.
SH2: pTyr binding
The SH2 (Src Homology 2) domain is a structurally conserved protein domain of ~100 aa long. SH2 typically binds to pTyr (phosphorylated tyrosine) which usually locates in peptide linear motif of 3-6 aa long. About 120 SH2 domains within 115 proteins in human have been found.
SH3: proline-rich region binding
The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 aa long. SH3 typically via binding to proline-rich peptides in their respective binding partner. Approximately 300 SH3 domains are found in proteins in human genome.
DNA-binding domain similar to P element transposase .
TPR: protein-protein interacting structural motif
TPR is short for tetratricopeptide repeat (TPR). It is a structural motif mediates protein-protein interactions. It consists in a degenerate 34 amino acid sequence motif identified in a wide variety of proteins. It is often but not always found in tandem arrays.
FYVE_PHD: PI3P binding
FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind Phosphatidylinositol 3-phosphate, in a way dependent on its metal ion coordination and basic amino acids. The FYVE domain inserts into cell membranes in a pH dependent manner. The FYVE domain has been connected to vacuolar protein sorting and endosome function.
- Frame MC, Patel H, Serrels B, Lietha D, and Eck MJ. The FERM domain: organizing the structure and function of FAK. Nat Rev Mol Cell Biol. 2010 Nov;11(11):802-14. DOI:10.1038/nrm2996 |
- Roussigne M, Kossida S, Lavigne AC, Clouaire T, Ecochard V, Glories A, Amalric F, and Girard JP. The THAP domain: a novel protein motif with similarity to the DNA-binding domain of P element transposase. Trends Biochem Sci. 2003 Feb;28(2):66-9. DOI:10.1016/S0968-0004(02)00013-0 |
- Charest A, Wagner J, Jacob S, McGlade CJ, and Tremblay ML. Phosphotyrosine-independent binding of SHC to the NPLH sequence of murine protein-tyrosine phosphatase-PEST. Evidence for extended phosphotyrosine binding/phosphotyrosine interaction domain recognition specificity. J Biol Chem. 1996 Apr 5;271(14):8424-9.