| YopH_N terminal protein domain | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Crystal structure of the Yersinia pestis type III secretion chaperone sych in complex with a stable fragment of YSCM2 | |||||||||
| Identifiers | |||||||||
| Symbol | YopH_N | ||||||||
| Pfam | PF09013 | ||||||||
| InterPro | IPR015103 | ||||||||
| |||||||||
In molecular biology, YopH, N-terminal refers to an evolutionary conserved protein domain. This entry represents the N-terminal domain of YopH protein tyrosine phosphatase (PTP).
Protein tyrosine (pTyr) phosphorylation is a common post-translational modification which can create novel recognition motifs for protein interactions and cellular localisation, affect protein stability, and regulate enzyme activity. Consequently, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases (PTPase; EC) catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways (such as the MAP kinase pathway) and cell cycle control, and are important in the control of cell growth, proliferation, differentiation and transformation. [1] [2]
The PTP superfamily can be divided into four subfamilies: [3]
Based on their cellular localisation, PTPases are also classified as:
This domain has a compact structure composed of four alpha-helices and two beta-hairpins. Helices alpha-1 and alpha-3 are parallel to each other and antiparallel to helices alpha-2 and alpha-4. This domain targets YopH for secretion from the bacterium and translocation into eukaryotic cells, and has phosphotyrosyl peptide-binding activity, allowing for recognition of p130Cas and paxillin. [6] YopH from Yersinia sp. is essential for pathogenesis, as it allows the bacteria to resist phagocytosis by host macrophages through its ability to dephosphorylate host proteins, thereby interfering with the host signalling process. Yersinia has one of the most active PTP enzymes known. YopH contains a loop of ten amino acids (the WPD loop) that covers the entrance of the active site of the enzyme during substrate binding. [7]
All PTPases carry the highly conserved active site motif C(X)5R (PTP signature motif), employ a common catalytic mechanism, and share a similar core structure made of a central parallel beta-sheet with flanking alpha-helices containing a beta-loop-alpha-loop that encompasses the PTP signature motif. [8] Functional diversity between PTPases is endowed by regulatory domains and subunits.
A homologous domain is found in YscM (Yop secretion protein M), which acts as a Yop protein translocation protein. Several Yop proteins are involved in pathogenesis. YscM is produced by the virulence operon virC, which encodes thirteen genes, yscA-M. [9] Transcription of the virC operon was subjected to the same regulation as the yop genes.
A protein phosphatase is a phosphatase enzyme that removes a phosphate group from the phosphorylated amino acid residue of its substrate protein. Protein phosphorylation is one of the most common forms of reversible protein posttranslational modification (PTM), with up to 30% of all proteins being phosphorylated at any given time. Protein kinases (PKs) are the effectors of phosphorylation and catalyse the transfer of a γ-phosphate from ATP to specific amino acids on proteins. Several hundred PKs exist in mammals and are classified into distinct super-families. Proteins are phosphorylated predominantly on Ser, Thr and Tyr residues, which account for 79.3, 16.9 and 3.8% respectively of the phosphoproteome, at least in mammals. In contrast, protein phosphatases (PPs) are the primary effectors of dephosphorylation and can be grouped into three main classes based on sequence, structure and catalytic function. The largest class of PPs is the phosphoprotein phosphatase (PPP) family comprising PP1, PP2A, PP2B, PP4, PP5, PP6 and PP7, and the protein phosphatase Mg2+- or Mn2+-dependent (PPM) family, composed primarily of PP2C. The protein Tyr phosphatase (PTP) super-family forms the second group, and the aspartate-based protein phosphatases the third. The protein pseudophosphatases form part of the larger phosphatase family, and in most cases are thought to be catalytically inert, instead functioning as phosphate-binding proteins, integrators of signalling or subcellular traps. Examples of membrane-spanning protein phosphatases containing both active (phosphatase) and inactive (pseudophosphatase) domains linked in tandem are known, conceptually similar to the kinase and pseudokinase domain polypeptide structure of the JAK pseudokinases. A complete comparative analysis of human phosphatases and pseudophosphatases has been completed by Manning and colleagues, forming a companion piece to the ground-breaking analysis of the human kinome, which encodes the complete set of ~536 human protein kinases.
Protein tyrosine phosphatases are a group of enzymes that remove phosphate groups from phosphorylated tyrosine residues on proteins. Protein tyrosine (pTyr) phosphorylation is a common post-translational modification that can create novel recognition motifs for protein interactions and cellular localization, affect protein stability, and regulate enzyme activity. As a consequence, maintaining an appropriate level of protein tyrosine phosphorylation is essential for many cellular functions. Tyrosine-specific protein phosphatases catalyse the removal of a phosphate group attached to a tyrosine residue, using a cysteinyl-phosphate enzyme intermediate. These enzymes are key regulatory components in signal transduction pathways and cell cycle control, and are important in the control of cell growth, proliferation, differentiation, transformation, and synaptic plasticity.
Yersinia pseudotuberculosis is a Gram-negative bacterium that causes Far East scarlet-like fever in humans, who occasionally get infected zoonotically, most often through the food-borne route. Animals are also infected by Y. pseudotuberculosis. The bacterium is urease positive.
Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the PTPN6 gene.
Tyrosine-protein phosphatase non-receptor type 1 also known as protein-tyrosine phosphatase 1B (PTP1B) is an enzyme that is the founding member of the protein tyrosine phosphatase (PTP) family. In humans it is encoded by the PTPN1 gene. PTP1B is a negative regulator of the insulin signaling pathway and is considered a promising potential therapeutic target, in particular for treatment of type 2 diabetes. It has also been implicated in the development of breast cancer and has been explored as a potential therapeutic target in that avenue as well.
Receptor-type tyrosine-protein phosphatase alpha is an enzyme that in humans is encoded by the PTPRA gene.
Tyrosine-protein phosphatase non-receptor type 13 is an enzyme that in humans is encoded by the PTPN13 gene.
Receptor-type tyrosine-protein phosphatase F is an enzyme that in humans is encoded by the PTPRF gene.
Protein tyrosine phosphatase non-receptor type 7 is an enzyme that in humans is encoded by the PTPN7 gene.
Receptor-type tyrosine-protein phosphatase mu is an enzyme that in humans is encoded by the PTPRM gene.
Protein tyrosine phosphatase type IVA 1 is an enzyme that in humans is encoded by the PTP4A1 gene.
Receptor-type tyrosine-protein phosphatase S, also known as R-PTP-S, R-PTP-sigma, or PTPσ, is an enzyme that in humans is encoded by the PTPRS gene.
Receptor-type tyrosine-protein phosphatase PCP-2, is an enzyme that in humans is encoded by the PTPRU gene.
Protein tyrosine phosphatase receptor-type R is an enzyme that in humans is encoded by the PTPRR gene.
Receptor-type tyrosine-protein phosphatase gamma is an enzyme that in humans is encoded by the PTPRG gene.
Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2) also known as islet cell autoantigen-related protein (ICAAR) and phogrin is an enzyme that in humans is encoded by the PTPRN2 gene. PTPRN and PTPRN2 are both found to be major autoantigens associated with insulin-dependent diabetes mellitus.
Tyrosine-protein phosphatase non-receptor type 9 is an enzyme that in humans is encoded by the PTPN9 gene.
A non-receptor tyrosine kinase (nRTK) is cytosolic enzyme that is responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.
In molecular biology, YopR is a protein domain commonly found in gram negative bacteria, in particular Yersinia and is a core domain. Proteins in this entry are type III secretion system effectors. They are named differently in different species and in Yersinia has been designated YopR which is encoded by the YscH gene. This Yop protein is unusual in that it is released to the extracellular environment rather than injected directly into the target cell as are most Yop proteins. A hallmark of Yersinia type III machines is the presence of needles extending from the bacterial surface. Needles perform two functions, firstly, as a channel to export effectors into the immune cells and secondly as a sensor.
Tyrosine phosphorylation is the addition of a phosphate (PO43−) group to the amino acid tyrosine on a protein. It is one of the main types of protein phosphorylation. This transfer is made possible through enzymes called tyrosine kinases. Tyrosine phosphorylation is a key step in signal transduction and the regulation of enzymatic activity.
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