Welcome to cider

Field	Query

	Field	Term

General Information:

Id:	14,450
Diseases:	SARS-CoV infection
Organism:	Mammalia
Publication type:	review
Reference:	Perlot T and Penninger JM(2013) ACE2 - from the renin-angiotensin system to gut microbiota and malnutrition Microbes Infect 15: 866-873 [PMID: 23962453]

Interaction Information:

Comment	ACE2 can potentially act on the apelin/APJ system. Apelin is produced as a 77 amino acid pre-pro-hormone which is further processed to apelin-36 and apelin-13. Apelin signals through its receptor APJ and was shown to have vasodilatory effects. ACE2 can cleave the carboxyterminal phenylalanine of apelin-36 and apelin-13, thereby removing the vasodilator apelin, and might therefore counteract its own vasodilatory role within the RAS.
Formal Description Interaction-ID: 136360	gene/protein ACE2 affects_activity of process apelin receptor signaling pathway
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	ACE2 can potentially act on the apelin/APJ system. Apelin is produced as a 77 amino acid pre-pro-hormone which is further processed to apelin-36 and apelin-13. Apelin signals through its receptor APJ and was shown to have vasodilatory effects. ACE2 can cleave the carboxyterminal phenylalanine of apelin-36 and apelin-13, thereby removing the vasodilator apelin, and might therefore counteract its own vasodilatory role within the RAS.
Formal Description Interaction-ID: 136361	gene/protein Apelin increases_activity of gene/protein APLNR

Comment	ACE2 can potentially act on the apelin/APJ system. Apelin is produced as a 77 amino acid pre-pro-hormone which is further processed to apelin-36 and apelin-13. Apelin signals through its receptor APJ and was shown to have vasodilatory effects. ACE2 can cleave the carboxyterminal phenylalanine of apelin-36 and apelin-13, thereby removing the vasodilator apelin, and might therefore counteract its own vasodilatory role within the RAS.
Formal Description Interaction-ID: 136362	gene/protein Apelin increases_activity of process vasodilation

Comment	ACE2 can potentially act on the apelin/APJ system. Apelin is produced as a 77 amino acid pre-pro-hormone which is further processed to apelin-36 and apelin-13. Apelin signals through its receptor APJ and was shown to have vasodilatory effects. ACE2 can cleave the carboxyterminal phenylalanine of apelin-36 and apelin-13, thereby removing the vasodilator apelin, and might therefore counteract its own vasodilatory role within the RAS.
Formal Description Interaction-ID: 136363	gene/protein ACE2 decreases_quantity of gene/protein Apelin-13
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	ACE2 can potentially act on the apelin/APJ system. Apelin is produced as a 77 amino acid pre-pro-hormone which is further processed to apelin-36 and apelin-13. Apelin signals through its receptor APJ and was shown to have vasodilatory effects. ACE2 can cleave the carboxyterminal phenylalanine of apelin-36 and apelin-13, thereby removing the vasodilator apelin, and might therefore counteract its own vasodilatory role within the RAS.
Formal Description Interaction-ID: 136364	gene/protein ACE2 decreases_quantity of gene/protein Apelin-36
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	ACE2 can potentially act on the apelin/APJ system. Apelin is produced as a 77 amino acid pre-pro-hormone which is further processed to apelin-36 and apelin-13. Apelin signals through its receptor APJ and was shown to have vasodilatory effects. ACE2 can cleave the carboxyterminal phenylalanine of apelin-36 and apelin-13, thereby removing the vasodilator apelin, and might therefore counteract its own vasodilatory role within the RAS.
Formal Description Interaction-ID: 136365	gene/protein Apelin-13 increases_activity of process vasodilation

Comment	ACE2 can potentially act on the apelin/APJ system. Apelin is produced as a 77 amino acid pre-pro-hormone which is further processed to apelin-36 and apelin-13. Apelin signals through its receptor APJ and was shown to have vasodilatory effects. ACE2 can cleave the carboxyterminal phenylalanine of apelin-36 and apelin-13, thereby removing the vasodilator apelin, and might therefore counteract its own vasodilatory role within the RAS.
Formal Description Interaction-ID: 136366	gene/protein Apelin-36 increases_activity of process vasodilation

Comment	In all mouse models generated, ACE2 protects from heart failure. In line with a beneficial effect of ACE2, treatment with Ang 1-7 has been shown to improve myocardial performance, cardiac remodeling, and survival in rodent heart failure models, including ischemia/reperfusion injury, myocardial infarction, or hypertension-induced cardiomyopathy. Of note, beside the beneficial effects of ACE2 in cardiovascular diseases, overexpression of ACE2 can have deleterious effects resulting in cardiac fibrosis and arrhythmia.
Formal Description Interaction-ID: 136367	gene/protein ACE2 decreases_activity of phenotype heart failure
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	In all mouse models generated, ACE2 protects from heart failure. In line with a beneficial effect of ACE2, treatment with Ang 1-7 has been shown to improve myocardial performance, cardiac remodeling, and survival in rodent heart failure models, including ischemia/reperfusion injury, myocardial infarction, or hypertension-induced cardiomyopathy. Of note, beside the beneficial effects of ACE2 in cardiovascular diseases, overexpression of ACE2 can have deleterious effects resulting in cardiac fibrosis and arrhythmia.
Formal Description Interaction-ID: 136368	gene/protein ACE2 affects_activity of phenotype cardiac fibrosis
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	In all mouse models generated, ACE2 protects from heart failure. In line with a beneficial effect of ACE2, treatment with Ang 1-7 has been shown to improve myocardial performance, cardiac remodeling, and survival in rodent heart failure models, including ischemia/reperfusion injury, myocardial infarction, or hypertension-induced cardiomyopathy. Of note, beside the beneficial effects of ACE2 in cardiovascular diseases, overexpression of ACE2 can have deleterious effects resulting in cardiac fibrosis and arrhythmia.
Formal Description Interaction-ID: 136369	gene/protein ACE2 affects_activity of phenotype irregular heartbeat
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	In the lung, increased Ang II levels were shown to promote development of pulmonary hypertension and pulmonary fibrosis and ACE2 was reported to protect both from pulmonary hypertension and pulmonary fibrosis.
Formal Description Interaction-ID: 136370	gene/protein Angiotensin II increases_activity of phenotype pulmonary hypertension

Comment	In the lung, increased Ang II levels were shown to promote development of pulmonary hypertension and pulmonary fibrosis and ACE2 was reported to protect both from pulmonary hypertension and pulmonary fibrosis.
Formal Description Interaction-ID: 136371	gene/protein Angiotensin II increases_activity of phenotype pulmonary fibrosis

Comment	In the lung, increased Ang II levels were shown to promote development of pulmonary hypertension and pulmonary fibrosis and ACE2 was reported to protect both from pulmonary hypertension and pulmonary fibrosis.
Formal Description Interaction-ID: 136372	gene/protein ACE2 decreases_activity of phenotype pulmonary hypertension
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	In the lung, increased Ang II levels were shown to promote development of pulmonary hypertension and pulmonary fibrosis and ACE2 was reported to protect both from pulmonary hypertension and pulmonary fibrosis.
Formal Description Interaction-ID: 136373	gene/protein ACE2 decreases_activity of phenotype pulmonary fibrosis
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	The renin-angiotensin system (RAS) is involved in acute lung injury and its severest form acute respiratory distress syndrome (ARDS).
Formal Description Interaction-ID: 136374	process renin-angiotensin system affects_activity of phenotype acute respiratory distress syndrome

Comment	ACE2 plays a major role in infections with severe acute respiratory syndrome corona-virus (SARS-CoV). This virus first emerged in 2003 and caused respiratory disease which could trigger ARDS and often ended fatal. In the same year ACE2 was identified to be a potential receptor for the SARS-CoVin vitro, which was thereafter genetically confirmed in in vivo mouse studies, providing definitive evidence that ACE2 is the essential SARS receptor in vivo.
Formal Description Interaction-ID: 136375	gene/protein ACE2 affects_activity of disease SARS-CoV infection
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	SARS infections are initiated by binding of spike protein trimers of the SARS-CoV to a hydrophobic pocket of the extracellular catalytic domain of ACE2. This interaction enables endocytosis, membrane fusion, and entry of the SARS-CoV into the host cell. Following virus entry, the ACE2 protein is downregulated which leads to local increase of AngII levels, providing a molecular explanation for the frequent development of ARDS during SARS-CoV infections, which was untypical for other coronaviruses.
Formal Description Interaction-ID: 136376	environment SARS-CoV decreases_activity of gene/protein ACE2
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	SARS infections are initiated by binding of spike protein trimers of the SARS-CoV to a hydrophobic pocket of the extracellular catalytic domain of ACE2. This interaction enables endocytosis, membrane fusion, and entry of the SARS-CoV into the host cell. Following virus entry, the ACE2 protein is downregulated which leads to local increase of AngII levels, providing a molecular explanation for the frequent development of ARDS during SARS-CoV infections, which was untypical for other coronaviruses.
Formal Description Interaction-ID: 136377	environment SARS-CoV increases_quantity of gene/protein Angiotensin II

Comment	Collectrin was discovered in 2001 as a protein expressed in the kidney with high sequence homology to the carboxy-terminal end of ACE2. Collectrin and ACE2 both are type 1 transmembrane proteins, but, in contrast to ACE2, Collectrin lacks catalytic activity. The collectrin gene is located on the X chromosome immediately upstream of the ace2 gene in all species examined and both genes share similar transcription factor binding sites. Collectrin was shown to be under transcriptional control of hepatocyte nuclear factor alpha (HNF-1alpha), which is involved in pancreatic insulin secretion. In vitro studies and in vivo overexpression experiments supported a role for Collectrin in insulin exocytosis through interaction with the SNARE complex. However, Collectrin deficient mice did not exhibit impaired insulin secretion.
Formal Description Interaction-ID: 136378	gene/protein CLTRN affects_activity of process insulin granule exocytosis

Comment	Collectrin was discovered in 2001 as a protein expressed in the kidney with high sequence homology to the carboxy-terminal end of ACE2. Collectrin and ACE2 both are type 1 transmembrane proteins, but, in contrast to ACE2, Collectrin lacks catalytic activity. The collectrin gene is located on the X chromosome immediately upstream of the ace2 gene in all species examined and both genes share similar transcription factor binding sites. Collectrin was shown to be under transcriptional control of hepatocyte nuclear factor alpha (HNF-1alpha), which is involved in pancreatic insulin secretion. In vitro studies and in vivo overexpression experiments supported a role for Collectrin in insulin exocytosis through interaction with the SNARE complex. However, Collectrin deficient mice did not exhibit impaired insulin secretion.
Formal Description Interaction-ID: 136379	gene/protein HNF1A affects_expression of gene/protein CLTRN
Drugbank entries	Show/Hide entries for HNF1A
Drugbank DB04419	Norleucine not specified HNF1A
Drugbank DB04419	Norleucine not specified HNF1A

Comment	Collectrin was discovered in 2001 as a protein expressed in the kidney with high sequence homology to the carboxy-terminal end of ACE2. Collectrin and ACE2 both are type 1 transmembrane proteins, but, in contrast to ACE2, Collectrin lacks catalytic activity. The collectrin gene is located on the X chromosome immediately upstream of the ace2 gene in all species examined and both genes share similar transcription factor binding sites. Collectrin was shown to be under transcriptional control of hepatocyte nuclear factor alpha (HNF-1alpha), which is involved in pancreatic insulin secretion. In vitro studies and in vivo overexpression experiments supported a role for Collectrin in insulin exocytosis through interaction with the SNARE complex. However, Collectrin deficient mice did not exhibit impaired insulin secretion.
Formal Description Interaction-ID: 136380	gene/protein CLTRN interacts (colocalizes) with complex/PPI SNARE complex

Comment	Analysis of Collectrin knock-out mice revealed that Collectrin is a regulator of neutral amino acid transporters expression on brush border membranes of renal proximal tubules.
Formal Description Interaction-ID: 136381	gene/protein CLTRN affects_activity of process neutral amino acid transport in renal proximal tubule

Comment	Collectrin non-covalently associates with the Slc6 family of neutral amino acid transporters (B0AT1 (Slc6a19) and B0AT3 (Slc6a18)), the imino transporter SIT1 (Slc6a20) and the Slc1 glutamate and aspartate transporter EAAT3 (Slc1a1). Collectrin stabilizes amino acid transporter expression on the cell surface but does not affect mRNA expression of these transporters.
Formal Description Interaction-ID: 136382	gene/protein CLTRN interacts (colocalizes) with gene/protein SLC6A19 in kidney

Comment	Collectrin non-covalently associates with the Slc6 family of neutral amino acid transporters (B0AT1 (Slc6a19) and B0AT3 (Slc6a18)), the imino transporter SIT1 (Slc6a20) and the Slc1 glutamate and aspartate transporter EAAT3 (Slc1a1). Collectrin stabilizes amino acid transporter expression on the cell surface but does not affect mRNA expression of these transporters.
Formal Description Interaction-ID: 136383	gene/protein CLTRN interacts (colocalizes) with gene/protein SLC6A18 in kidney

Comment	Collectrin non-covalently associates with the Slc6 family of neutral amino acid transporters (B0AT1 (Slc6a19) and B0AT3 (Slc6a18)), the imino transporter SIT1 (Slc6a20) and the Slc1 glutamate and aspartate transporter EAAT3 (Slc1a1). Collectrin stabilizes amino acid transporter expression on the cell surface but does not affect mRNA expression of these transporters.
Formal Description Interaction-ID: 136384	gene/protein CLTRN interacts (colocalizes) with gene/protein SLC6A20 in kidney

Comment	Collectrin non-covalently associates with the Slc6 family of neutral amino acid transporters (B0AT1 (Slc6a19) and B0AT3 (Slc6a18)), the imino transporter SIT1 (Slc6a20) and the Slc1 glutamate and aspartate transporter EAAT3 (Slc1a1). Collectrin stabilizes amino acid transporter expression on the cell surface but does not affect mRNA expression of these transporters.
Formal Description Interaction-ID: 136385	gene/protein CLTRN interacts (colocalizes) with gene/protein SLC1A1 in kidney
Drugbank entries	Show/Hide entries for SLC1A1
Drugbank DB00128	L-Aspartic Acid not specified SLC1A1
Drugbank DB00142	L-Glutamic Acid not specified SLC1A1
Drugbank DB00128	L-Aspartic Acid not specified SLC1A1
Drugbank DB00142	L-Glutamic Acid not specified SLC1A1

Comment	B0AT1 is not only expressed in the kidney but also in the small intestine where Collectrin is absent. The closest ‚Äúrelative‚ÄĚ of Collectrin, i.e. ACE2, can bind and stabilize the neutral amino acid transporter B0AT1 in the small intestine. B0AT1 andACE2 colocalize on enterocytes of the small intestine, an interaction confirmed by co-immunoprecipitation experiments and overexpression in Xenopus laevis oocytes.
Formal Description Interaction-ID: 136386	gene/protein ACE2 interacts (colocalizes) with gene/protein SLC6A19 in small intestine
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	In the gut, ACE2 also interacts with SIT1, a transporter for proline, sarcosine, or betaine.
Formal Description Interaction-ID: 136387	gene/protein ACE2 interacts (colocalizes) with gene/protein SLC6A20 in intestine
Drugbank entries	Show/Hide entries for ACE2
Drugbank DB00691	Moexipril inhibitor ACE2
Drugbank DB00722	Lisinopril inhibitor ACE2

Comment	In the gut, ACE2 also interacts with SIT1, a transporter for proline, sarcosine, or betaine.
Formal Description Interaction-ID: 136388	gene/protein SLC6A20 increases_transport of drug/chemical compound Proline in intestine

Comment	In the gut, ACE2 also interacts with SIT1, a transporter for proline, sarcosine, or betaine.
Formal Description Interaction-ID: 136389	gene/protein SLC6A20 increases_transport of drug/chemical compound Sarcosine in intestine

Comment	In the gut, ACE2 also interacts with SIT1, a transporter for proline, sarcosine, or betaine.
Formal Description Interaction-ID: 136390	gene/protein SLC6A20 increases_transport of drug/chemical compound Betaine in intestine

Comment	Reduced tryptophan levels lead to reduced mTOR pathway activity in the small intestine.
Formal Description Interaction-ID: 136391	phenotype decreased tryptophan level decreases_activity of process TOR signaling in small intestine

Comment	Aberrant mTOR activation resulted in impaired expression of antimicrobial peptides from small intestinal Paneth cells. The impaired expression of antimicrobial peptides in turn resulted in an altered composition of the intestinal microbiota.
Formal Description Interaction-ID: 136392	process TOR signaling increases_activity of process antimicrobial peptide production in paneth cells

Comment	Aberrant mTOR activation resulted in impaired expression of antimicrobial peptides from small intestinal Paneth cells. The impaired expression of antimicrobial peptides in turn resulted in an altered composition of the intestinal microbiota.
Formal Description Interaction-ID: 136393	process antimicrobial peptide production affects_activity of phenotype abnormal gut flora balance

Home
Contact

The Helmholtz Zentrum München Imprint and Privacy Policy apply.

© 2013 - Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH) Ingolstädter Landstraße 1, D-85764 Neuherberg, Germany

Disclaimer: IBIS Databases and associated information are protected by copyright. This server and its associated data and services are for academic, non-commercial use only. The Helmholtz Zentrum München has no liability for the use of results, data or information which have been provided through this server. Neither the use for commercial purposes, nor the redistribution of IBIS database files to third parties nor the distribution of parts of files or derivative products to any third parties is permitted. Commercial users shall contact the Helmholtz Zentrum München for a separate users license.