CIDeRplusGeneral Information:
| Id: | 11,656 |
| Diseases: |
Cardiovascular disease
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| Mammalia | |
| review | |
| Reference: | Cortada E et al.Trafficking and Function of the Voltage-Gated Sodium Channel beta2 Subunit [PMID: 31614896] |
Interaction Information:
| Comment | A well-known arrhythmia is Brugada syndrome (BrS), a disorder characterized by an abnormal electrocardiogram (ECG) that causes ventricular fibrillation. |
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Formal Description Interaction-ID: 115924 |
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| Comment | The voltage-gated sodium (NaV) channel often shows alterations leading to cardiac channelopathies. For instance, about 20 % of Brugada syndrome (BrS) cases are caused by mutations in SCN5A, a gene mapping to the chromosomal region 3p21 and encoding NaV1.5, the pore-forming, alpha subunit, of the main cardiac NaV channel. |
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Formal Description Interaction-ID: 115925 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | In the heart, the NaV channel is responsible for generating the rising phase of the action potential (AP), thus playing a central role in myocardial excitability. The abnormal ECG observed in Brugada syndrome (BrS) is due to loss-of-function of the NaV channel. |
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Formal Description Interaction-ID: 115927 |
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| Comment | In the heart, the NaV channel is responsible for generating the rising phase of the action potential (AP), thus playing a central role in myocardial excitability. The abnormal ECG observed in Brugada syndrome (BrS) is due to loss-of-function of the NaV channel. |
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Formal Description Interaction-ID: 115953 |
disease Brugada syndrome decreases_activity of complex/PPI Voltage-gated sodium channel |
| Comment | Mutations in SCN5A have been associated with LQTS, atrial fibrillation and even cardiomyopathies. In fact, the NaV channel also plays an important role in electrical impulse propagation in the heart. |
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Formal Description Interaction-ID: 115956 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | Mutations in SCN5A have been associated with LQTS, atrial fibrillation and even cardiomyopathies. In fact, the NaV channel also plays an important role in electrical impulse propagation in the heart. |
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Formal Description Interaction-ID: 115957 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | Mutations in SCN5A have been associated with LQTS, atrial fibrillation and even cardiomyopathies. In fact, the NaV channel also plays an important role in electrical impulse propagation in the heart. |
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Formal Description Interaction-ID: 115958 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | NaV1.5 is located at intercalated discs (ID), that is, the region between cardiomyocytes containing cell adhesion complexes, and also in the lateral membrane, where costameres and transverse tubules (T tubules) are found; costameres are protein complexes connecting the cardiomyocyte sarcomeres with the extracellular matrix, while T tubules are deep invaginations of the sarcolemma in the Z-disk region (or Z-line, which borders the sarcomeres), allowing electrical coupling with Ca2+ release from the sarcoplasmic reticulum. The distribution of NaV1.5 in ID and T tubules depends in part on ankyrin-G (AnkG). |
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Formal Description Interaction-ID: 115959 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | NaV1.5 is located at intercalated discs (ID), that is, the region between cardiomyocytes containing cell adhesion complexes, and also in the lateral membrane, where costameres and transverse tubules (T tubules) are found; costameres are protein complexes connecting the cardiomyocyte sarcomeres with the extracellular matrix, while T tubules are deep invaginations of the sarcolemma in the Z-disk region (or Z-line, which borders the sarcomeres), allowing electrical coupling with Ca2+ release from the sarcoplasmic reticulum. The distribution of NaV1.5 in ID and T tubules depends in part on ankyrin-G (AnkG). |
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Formal Description Interaction-ID: 115960 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | NaV1.5 is located at intercalated discs (ID), that is, the region between cardiomyocytes containing cell adhesion complexes, and also in the lateral membrane, where costameres and transverse tubules (T tubules) are found; costameres are protein complexes connecting the cardiomyocyte sarcomeres with the extracellular matrix, while T tubules are deep invaginations of the sarcolemma in the Z-disk region (or Z-line, which borders the sarcomeres), allowing electrical coupling with Ca2+ release from the sarcoplasmic reticulum. The distribution of NaV1.5 in ID and T tubules depends in part on ankyrin-G (AnkG). AnkG is also associated with NaV1.5 in T tubules. Yet, AnkG is clearly required for NaV1.5 targeting to the ID. |
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Formal Description Interaction-ID: 115961 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | Plakophilin 2 (PKP2) and SAP97 (synapse-associated protein 97; a member of the family of membrane-associated guanylate kinases) would control NaV1.5 localization at the intercalated discs (ID). It has been proposed that PKP2 is part of a complex with connexin 43 (Cx43) and AnkG, possibly independent of the interaction with SAP97. |
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Formal Description Interaction-ID: 115962 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | Plakophilin 2 (PKP2) and SAP97 (synapse-associated protein 97; a member of the family of membrane-associated guanylate kinases) would control NaV1.5 localization at the intercalated discs (ID). It has been proposed that PKP2 is part of a complex with connexin 43 (Cx43) and AnkG, possibly independent of the interaction with SAP97. |
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Formal Description Interaction-ID: 115963 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | NaV1.5 is also located in the lateral membrane, whose targeting is regulated by the syntrophin/dystrophin complex connected to the actin cytoskeleton. |
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Formal Description Interaction-ID: 115964 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | It was shown by super-resolution microscopy that a complex formed by Cx43, PKP2 and N-cadherin is responsible for the delivery of microtubule cargo to the intercalated discs (ID), including NaV1.5; the components and location of this molecular complex define the so-called connexome, which regulates electrical coupling, cell adhesion, and cell excitability. |
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Formal Description Interaction-ID: 115965 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | It was shown by super-resolution microscopy that a complex formed by Cx43, PKP2 and N-cadherin is responsible for the delivery of microtubule cargo to the intercalated discs (ID), including NaV1.5; the components and location of this molecular complex define the so-called connexome, which regulates electrical coupling, cell adhesion, and cell excitability. |
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Formal Description Interaction-ID: 115966 |
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| Comment | It was shown by super-resolution microscopy that a complex formed by Cx43, PKP2 and N-cadherin is responsible for the delivery of microtubule cargo to the intercalated discs (ID), including NaV1.5; the components and location of this molecular complex define the so-called connexome, which regulates electrical coupling, cell adhesion, and cell excitability. |
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Formal Description Interaction-ID: 115967 |
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| Comment | It was shown by super-resolution microscopy that a complex formed by Cx43, PKP2 and N-cadherin is responsible for the delivery of microtubule cargo to the intercalated discs (ID), including NaV1.5; the components and location of this molecular complex define the so-called connexome, which regulates electrical coupling, cell adhesion, and cell excitability. |
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Formal Description Interaction-ID: 115968 |
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| Drugbank entries | Show/Hide entries for GJA1 |
| Comment | NaV1.5 has been found associated with lipid rafts, which are membrane domains rich in cholesterol and glycosphingolipids where ionic channel regulatory proteins concentrate. |
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Formal Description Interaction-ID: 115969 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | A mutation associated with Brugada Syndrome (BrS) was found in SCN2B, the gene encoding the beta2 subunit of the NaV1.5 channel. |
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Formal Description Interaction-ID: 115970 |
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| Drugbank entries | Show/Hide entries for SCN2B |
| Comment | A mutation associated with Brugada Syndrome (BrS) was found in SCN2B, the gene encoding the beta2 subunit of the NaV1.5 channel. |
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Formal Description Interaction-ID: 115971 |
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| Drugbank entries | Show/Hide entries for SCN2B |
| Comment | A mutation associated with Brugada Syndrome (BrS) was found in SCN2B, the gene encoding the beta2 subunit of the NaV1.5 channel. The beta2 D211G mutation (a substitution of Asp by Gly) causes an INa reduction of 40% due to decreased cell surface levels of NaV1.5. |
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Formal Description Interaction-ID: 115972 |
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| Drugbank entries | Show/Hide entries for SCN5A |
| Comment | Concerning cardiac function, Scn2b knockout mice suffer from ventricular and atrial arrhythmias, which is consistent with SCN2B mutations described in humans. |
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Formal Description Interaction-ID: 115973 |
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| Drugbank entries | Show/Hide entries for SCN2B |
| Comment | Concerning cardiac function, Scn2b knockout mice suffer from ventricular and atrial arrhythmias, which is consistent with SCN2B mutations described in humans. |
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Formal Description Interaction-ID: 115977 |
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| Drugbank entries | Show/Hide entries for SCN2B |
| Comment | Human beta2 can be sequentially cleaved by secretases; cleavage of beta2 takes place analogously to the processing of the amyloid precursor protein (APP). Beta2 cleavage by alpha-secretase, and subsequently by gamma-secretase, appears required for cell-cell adhesion and migration of beta2-expressing cells. |
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Formal Description Interaction-ID: 115978 |
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| Drugbank entries | Show/Hide entries for SCN2B |
| Comment | Human beta2 can be sequentially cleaved by secretases; cleavage of beta2 takes place analogously to the processing of the amyloid precursor protein (APP). Beta2 cleavage by alpha-secretase, and subsequently by gamma-secretase, appears required for cell-cell adhesion and migration of beta2-expressing cells. |
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Formal Description Interaction-ID: 115979 |
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| Drugbank entries | Show/Hide entries for SCN2B |
| Comment | Human beta2 can be sequentially cleaved by secretases; cleavage of beta2 takes place analogously to the processing of the amyloid precursor protein (APP). Beta2 cleavage by alpha-secretase, and subsequently by gamma-secretase, appears required for cell-cell adhesion and migration of beta2-expressing cells. |
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Formal Description Interaction-ID: 115980 |
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| Drugbank entries | Show/Hide entries for SCN2B |
| Comment | At least in mouse, the four beta subunits (beta1-4) can actually be processed by beta-secretase, i.e., the beta-site APP cleaving enzyme (BACE1) |
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Formal Description Interaction-ID: 115981 |
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| Drugbank entries | Show/Hide entries for BACE1 or SCN2B |
| Comment | At least in mouse, the four beta subunits (beta1-4) can actually be processed by beta-secretase, i.e., the beta-site APP cleaving enzyme (BACE1) |
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Formal Description Interaction-ID: 115982 |
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| Drugbank entries | Show/Hide entries for BACE1 or SCN1B |
| Comment | At least in mouse, the four beta subunits (beta1-4) can actually be processed by beta-secretase, i.e., the beta-site APP cleaving enzyme (BACE1) |
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Formal Description Interaction-ID: 115983 |
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| Drugbank entries | Show/Hide entries for BACE1 or SCN3B |
| Comment | At least in mouse, the four beta subunits (beta1-4) can actually be processed by beta-secretase, i.e., the beta-site APP cleaving enzyme (BACE1) |
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Formal Description Interaction-ID: 115984 |
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| Drugbank entries | Show/Hide entries for BACE1 or SCN4B |
| Comment | Beta1 was conclusively shown to promote neurite outgrowth in vivo through a signaling process triggered by trans-homophilic cell adhesion and association with lipid rafts, which was suggested to be essential for postnatal development of the central nervous system. |
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Formal Description Interaction-ID: 115985 |
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| Drugbank entries | Show/Hide entries for SCN1B |
| Comment | Within the context of cardiac function, an important result in this regard is the recent finding showing that beta1, by mediating cell-cell adhesion, contributes to spreading of the AP along ventricular cardiomyocytes. Beta1 facilitates coupling of adjacent cells for ion exchange, being located within clefts of the perinexus, i.e., the narrow stretch of membranes closely apposed and adjacent to the gap junctions. |
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Formal Description Interaction-ID: 115986 |
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| Drugbank entries | Show/Hide entries for SCN1B |
| Comment | Beta2 binds laminin, which is the most abundant cell adhesion molecule in the extracellular matrix of the peripheral nervous system. |
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Formal Description Interaction-ID: 115987 |
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| Drugbank entries | Show/Hide entries for SCN2B |