Genes altered in major depressive disorder
Genes altered in major depressive disorder
Positive relationships between COL4A5 and other components at different levels (count: 0)
Positive relationship network of COL4A5 in MK4MDD
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Note:
1. The different color of the nodes denotes the level of the nodes.
Genetic/Epigenetic Locus
Protein and Other Molecule
Cell and Molecular Pathway
Neural System
Cognition and Behavior
Symptoms and Signs
Environment
MDD
2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network.
If the mapped gene or protein is not from literature, square node would be used instead of Circle node.
Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node.
Right-click will show also the menus to link to the report page of the node and remove the node and related edges.
Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web
Negative relationships between COL4A5 and MDD (count: 0)
Negative relationships between COL4A5 and other components at different levels (count: 0)
Myocardial infraction (MI)is the condition of irreversible n......
Myocardial infraction (MI)is the condition of irreversible necrosis of the heart muscle that results from prolonged ischemia. Nearly 1.5 million people in US sustain an MI each year, and this event proves fatal in approximately one third of patients. Approximately 90% of MI result from formation of an acute thrombus that obstructs an atherosclerotic coronary artery. The thrombus transforms a region of plaque narrowing to one of complete vessel occlusion (top right in pink). The responsible thrombus appears to be generated by interactions between the atherosclerotic plaque, the coronary endothelium, circulating platelets, and dynamic vasomotor tone of the vessel wall, all of which overwhelm natural protective mechanisms. The endogenous protective mechanisms against thrombosis include: 1. Inactivation of thrombin by antithrombin III (ATIII), the effectiveness of which is enhanced by binding of ATIII to heparin sulafate. The antithrombin binding region of commercial heparin consists of sulfated disaccharide units (bottom panel). 2. Inactivation of clotting factors Va and VIIIa by activated protein C (protein C*), an action that is enhanced by protein S. Protein C is activated by the thrombomodulin (TM)-thrombin complex. 3. Inactivation of factor VII/tissue factor complex by tissue factor pathway inhibitor (TFPI). Coumarin drugs (Warfarin) blocks the g-carboxylation of Glu residues in prothrombin and factors VII, IX and X which results in incomplete molecules that are biologically inactive in coagulation (left panel). 4. Lysis of fibrin clots by tissue plasminogen activator (tPA). 5. Inhibition of platelet activation by prostacyclin and EDRF-NO. Platelets adhere to exposed collagen and are activated at the site of endothelial damage in the blood vessel. Activated platelets release adenosine diphosphate (ADP), serotonin (5-HT), and thromboxane A2 (TXA2), which activate additional platelets. Binding of thrombin further activates the platelets. Three adjoining platelets are shown in the process of viscous metamorphosis (top right). Increased cellular Ca2+ facilitates binding of fibrinogen. If the intraluminal thrombus at the site of plaque disruption totally occludes the vessel, blood flow beyond the obstruction will cease, prolonged ischemia will occur and MI (usually Q-wave MI) will likely result.More...
Blood coagulation or clotting takes place in 3 essential pha......
Blood coagulation or clotting takes place in 3 essential phases. The first phase is the activation of a prothrombin activator complex. The second phase is the activation of prothrombin. The third stage is clot formation as a result of fibrinogen cleavage by activated thrombin. The prothrombin activation complex is formed by two pathways each of which results in a different form of the prothrombin activator. The intrinsic mechanism of prothrombin activator formation begins with trauma to the blood or exposure of blood to collagen in a traumatized vessel wall. This usually also results in damage to fragile platelets. The formation of a clot by this mechanism usually takes 1 to 6 minutes. This cascade begins with the activation of factor XII and the release of platelet factor 3 (PF3) from damaged platelets. Activated factor XII cleaves and actives factor XI and prekallikrein (PK). Factor XII is also activated by activated prekallikrein (aPK) in an internal amplification loop. Calcium (Ca++) is required for the initial three steps. The prothrombin activator in the intrinsic pathway is very similar to the activator in the extrinsic pathway. Antithrombin III inhibits the activity of thrombin and also two of the steps in the formation of the activator. Protein C is activated by thrombin and with the Protein S cofactor provides a strong negative feedback in this phase of clot formation. When blood is collected, the intrinsic pathway is activated by contact with the collection devices causing damage to the platelets and activation of factor XII. Antithrombin III is a hundred to a thousand times more effective when bound by heparin. Use of nonwettable surface materials can increase the clot formation time to over an hour. Disease Significance: Most of the clotting factors are formed in the liver. Diseases of the liver or damage to the liver can depress the levels of these factors in the blood resulting in excessive bleeding. Vitamin K deficiency can also result in a similar condition since Vitamin K is essential for the formation of factor VII, IX, X and prothrombin. Vitamin K is synthesized in the intestinal tract by bacteria.More...
Vitamin C (ascorbic acid) was first identified by virtue of ......
Vitamin C (ascorbic acid) was first identified by virtue of the essential role it plays in collagen modification, preventing the nutritional deficiency scurvy. Vitamin C acts as a cofactor for hydroxylase enzymes that post-translationally modify collagen to increase the strength and elasticity of tissues. Vitamin C reduces the metal ion prosthetic groups of many enzymes, maintaining activity of enzymes, also acts as an anti-oxidant. Although the prevention of scurvy through modification of collagen may be the most obvious role for vitamin C, it is not necessarily the only role of vitamin C. Svct1 and Svct2 are ascorbate transporters for vitamin C import into tissues and into cells. Both of these transporters specifically transport reduced L-ascorbic acid against a concentration gradient using the intracellular sodium gradient to drive ascorbate transport. Svct1 is expressed in epithelial cells in the intestine, upregulated in cellular models for intestinal epithelium and appears to be responsible for the import of dietary vitamin C from the intestinal lumen. The vitamin C imported from the intestine is present in plasma at approximately 50 uM, almost exclusively in the reduced form, and is transported to tissues to play a variety of roles. Svct2 imports reduced ascorbate from the plasma into very active tissues like the brain. Deletion in mice of the gene for Svct2 revealed that ascorbate is required for normal development of the lungs and brain during pregnancy. A high concentration of vitamin C in neurons of the developing brain may help protect the developing brain from free radical damage. The oxidized form of ascorbate, dehydroascorbic acid, is transported into a variety of cells by the glucose transporter Glut-1. Glut-1, Glut-3 and Glut-4 can transport dehydroascorbate, but may not transport significant quantities of ascorbic acid in vivo.More...
The amyloid -beta peptide (Ab), a proteolytic fragment of am......
The amyloid -beta peptide (Ab), a proteolytic fragment of amyloid precursor protein (APP), is the major componenet of senile plaques, the hallmark of alzhemiers disease. Platelets contain both APP and Ab and probably contribute greater than 90% of circulating APP. The soluble APP is the major inhibitor of coagulation factors IXa and XIa, and platelet aggregation. Agonists such as ADP, thrombin, epinephrine and collagen activate the release of APP and plasminogen activator inhibitor I (an important regulator of coagulation) from platelet storage granules. These important molecules released from platelets are key regulators of hemostasis, the physiologic arrest of hemorrhage at site of vascular leakage.More...
Angiotensin-converting enzyme 2 regulates heart function
Cardiovascular diseases are predicted to be the most common ......
Cardiovascular diseases are predicted to be the most common cause of death worldwide by 2020. The major regulator of blood pressure homeostasis is the renin-angiotensis system. Angiotensinogen is digested by renin to produce angiotensin I (AGT I). AGT I is an inactive 10 amino-acid peptide that is further degraded to produce angiotensin II by the agiotensin-converting enzyme (ACE). Angiotensis II is the master regulator of blood pressure increase acting on the heart, kidneys and blood vessels. Angiotensin II causes direct constriction of the resistance vessels and stimulation of the adrenal cortex to increase blood volume and sodium absorption. In 2000, Tipnis et al., discovered ACE 2 a second carboxypeptidase that digests angiotensin. ACE is a di-peptidase, cleaving off 2 peptides from the c-terminal end of angiotensin. ACE 2 only cleaves 1 amino acid to produce angiotensin 1-9 (AGT 1-9) which has no identified function at this time. AGT 1-9 is not converted to angiotensin II but further degraded by ACE to AGT 1-7, a vasodilator. It would appear that ACE 2 inhibits the formation of angiotensin and reduces blood pressure increases. Crackower et al determined that ace2 -/- mice suffered significant heart defects at 6 months. Further deletion of ACE resulted in restored cardiac functions.More...
The neural cell adhesion molecule, NCAM1 is generally consid......
The neural cell adhesion molecule, NCAM1 is generally considered as a cell adhesion mediator, but it is also considered to be a signal transducing receptor molecule. NCAM1 is involved in multiple cis- and trans-homophilic interactions. It is also involved in several heterophilic interactions with a broad range of other molecules, thereby modulating diverse biological phenomena including cellular adhesion, migration, proliferation, differentiation, survival and synaptic plasticity.More...
Platelet-derived Growth Factor (PDGF) is a potent stimulator......
Platelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary endothelial cells and neurons.The PDGF family of growth factors is composed of four different polypeptide chains encoded by four different genes. The classical PDGF chains, PDGF-A and PDGF-B, and more recently discovered PDGF-C and PDGF-D. The four PDGF chains assemble into disulphide-bonded dimers via homo- or heterodimerization, and five different dimeric isoforms have been described so far; PDGF-AA, PDGF-AB, PDGF-BB, PDGF-CC and PDGF-DD. It is notable that no heterodimers involving PDGF-C and PDGF-D chains have been described. PDGF exerts its effects by binding to, and activating, two protein tyrosine kinase (PTK) receptors, alpha and beta. These receptors dimerize and undergo autophosphorylation. The phosphorylation sites then attract downstream effectors to transduct the signal into the cell.More...
The extracellular matrix (ECM) is a network of macro-molecul......
The extracellular matrix (ECM) is a network of macro-molecules that underlies all epithelia and endothelia and that surrounds all connective tissue cells. This matrix provides the mechanical strength and also influences the behavior and differentiation state of cells in contact with it. The ECM are diverse in composition, but they generally comprise a mixture of fibrillar proteins, polysaccharides synthesized, secreted and organized by neighboring cells. Collagens, fibronectin, and laminins are the principal components involved in cell matrix interactions; other components, such as vitronectin, thrombospondin, and osteopontin, although less abundant, are also important adhesive molecules. Integrins are the receptors that mediate cell adhesion to ECM. Integrins consists of one alpha and one beta subunit forming a noncovalently bound heterodimer. 18 alpha and 8 beta subunits have been identified in humans that combine to form 24 different receptors. The integrin dimers can be broadly divided into three families consisting of the beta1, beta2/beta7, and beta3/alphaV integrins. beta1 associates with 12 alpha-subunits and can be further divided into RGD-, collagen-, or laminin binding and the related alpha4/alpha9 integrins that recognise both matrix and vascular ligands. beta2/beta7 integrins are restricted to leukocytes and mediate cell-cell rather than cell-matrix interactions, although some recognize fibrinogen. The beta3/alphaV family members are all RGD receptors and comprise aIIbb3, an important receptor on platelets, and the remaining b-subunits, which all associate with alphaV. It is the collagen receptors and leukocyte-specific integrins that contain alpha A-domains.More...
The neural cell adhesion molecule, NCAM, is a member of the ......
The neural cell adhesion molecule, NCAM, is a member of the immunoglobulin (Ig) superfamily and is involved in a variety of cellular processes of importance for the formation and maintenance of the nervous system. The role of NCAM in neural differentiation and synaptic plasticity is presumed to depend on the modulation of intracellular signal transduction cascades. NCAM based signaling complexes can initiate downstream intracellular signals by at least two mechanisms: (1) activation of FGFR and (2) formation of intracellular signaling complexes by direct interaction with cytoplasmic interaction partners such as Fyn and FAK. Tyrosine kinases Fyn and FAK interact with NCAM and undergo phosphorylation and this transiently activates the MAPK, ERK 1 and 2, cAMP response element binding protein (CREB) and transcription factors ELK and NFkB. CREB activates transcription of genes which are important for axonal growth, survival, and synaptic plasticity in neurons. NCAM1 mediated intracellular signal transduction is represented in the figure below. The Ig domains in NCAM1 are represented in orange ovals and Fn domains in green squares. The tyrosine residues susceptible to phosphorylation are represented in red circles and their positions are numbered. Phosphorylation is represented by red arrows and dephosphorylation by yellow. Ig, Immunoglobulin domain; Fn, Fibronectin domain; Fyn, Proto-oncogene tyrosine-protein kinase Fyn; FAK, focal adhesion kinase; RPTPalpha, Receptor-type tyrosine-protein phosphatase; Grb2, Growth factor receptor-bound protein 2; SOS, Son of sevenless homolog; Raf, RAF proto-oncogene serine/threonine-protein kinase; MEK, MAPK and ERK kinase; ERK, Extracellular signal-regulated kinase; MSK1, Mitogen and stress activated protein kinase 1; CREB, Cyclic AMP-responsive element-binding protein; CRE, cAMP response elements.More...
Axon guidance / axon pathfinding is the process by which neu......
Axon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, which senses the guidance cues in the environment through guidance cue receptors and responds by undergoing cytoskeletal changes that determine the direction of axon growth. Guidance cues present in the surrounding environment provide the necessary directional information for the trip. These extrinsic cues have been divided into attractive or repulsive signals that tell the growth cone where and where not to grow. Genetic and biochemical studies have led to the identification of highly conserved families of guidance molecules and their receptors that guide axons. These include netrins, Slits, semaphorins, and ephrins, and their cognate receptors, DCC and or uncoordinated-5 (UNC5), roundabouts (Robo), neuropilin and Eph. In addition, many other classes of adhesion molecules are also used by growth cones to navigate properly which include NCAM and L1CAM.More...
COL4A5 related interactors from protein-protein interaction data in HPRD (count: 11)
Basic Information
Positive relationships between COL4A5 and other components at different levels (count: 0)
