Gene Report

Basic Information

Approved Symbol	ACE
Approved Name	angiotensin I converting enzyme (peptidyl-dipeptidase A) 1
Previous Symbol	DCP1
Symbol Alias	ACE1, CD143
Location	17q23.3
Position	chr17:61554422-61575741 (+)
External Links	Entrez Gene: 1636 Ensembl: ENSG00000159640 UCSC: uc002jau.2 HGNC ID: 2707
No. of Studies (Positive/Negative)	7(6/1)
Type	Literature-origin; SNP mapped; Protein mapped

Positive relationships between ACE and MDD (count: 5)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
ACE	Bondy B, 2002	Patients and nomal controls	chi(2) = 6.43; df=3; P = 0.04	We found a significant increase in the Gbeta3 T allele (OR ...... We found a significant increase in the Gbeta3 T allele (OR = 1.61, 95% CI 1.17-2.2, P = 0.0035) and a marginal altered genotype distribution of the ACE ID polymorphism with decrease in the II genotypes (chi(2) = 6.43, df=3, P = 0.04) in the patients' group. Analysing the data for both genes we found that the combined actions of ACE and Gbeta3 genotypes accumulate in carriers of the ACE D allele (ID and DD) and Gbeta3 TT homozygotes with ID/DD-TT carriers showing a more than five-fold increase in risk for major depression (crude OR = 5.83, 95% CI 1.99-17.08, P = 0.0002). More...
Angiotensin-converting enzyme (ACE)	Baghai, 2006	patients and normal controls		In the screening sample, two SNPs within the ACE gene were s...... In the screening sample, two SNPs within the ACE gene were significantly associated with unipolar major depression. More...
ACE	Angunsri, 2009	patients and normal controls	P-value=0.002 on chi(2) test, emP-valueirical P-value=0.004	Haplotype frequency analysis revealed that the -240T/-93T co...... Haplotype frequency analysis revealed that the -240T/-93T combination was significantly over-represented in patients with MDD in comparison with controls (13.6% and 6.8%, p=0.002 on chi(2) test, empirical p=0.004) More...
ACE	Firouzabadi N, 2012	patients and normal controls	P-value =0.001; odds ratio (OR)=6.2; 95% confidence interval (CI)=2.1-18.3	The results showed, for the first time, that GG genotype of ...... The results showed, for the first time, that GG genotype of ACE A2350G was significantly associated with MDD among Iranian participants (P=0.001; odds ratio (OR)=6.2; 95% confidence interval (CI)=2.1-18.3). More...
ACE	Zill P, 2012	patients and normal controls	P-value = 0.008	We detected intensive DNA methylation within a recently desc...... We detected intensive DNA methylation within a recently described, functional important region of the ACE gene promoter including hypermethylation in depressed patients (p = 0.008) More...

Positive relationships between ACE and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description	All
Name in Literature	Related Components
ACE		Hypothalamic-pituitary-adrenal axis(hypothalamic-pituitary-adrenocortical (HPA) system)	neurobiological system	Baghai, 2002	patients and normal controls		The Dex/CRH test is one of the most reliable neuroendocrine ...... The Dex/CRH test is one of the most reliable neuroendocrine function tests for hypothalamic-pituitary-adrenocortical (HPA) system dysregulation, angiotensin converting enzyme (ACE) gene D/D genotypes showed a higher cortisol stimulation during the first Dex/CRH test after admission than homozygous I-allele carriers (repeated measurement ANOVA: P=0.034). More...

Positive relationship network of ACE in MK4MDD

Network loading ...

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 ACE and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
ACE	Segman RH, 2002	Patients and nomal controls		There was no evidence for allelic or genotypic association o...... There was no evidence for allelic or genotypic association of the polymorphism with any of the disorders or with tardive dyskinesia (TD) in patients with schizophrenia More...

Negative relationships between ACE and other components at different levels (count: 0)

ACE related SNPs in MK4MDD (count: 8)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs867640	chr17:61601945(Forward)	downstream_gene_variant; intron_variant; NMD_transcript_variant	1(1/0)
rs4461142	chr17:61578048(Forward)	downstream_gene_variant; intron_variant; NMD_transcript_variant	1(1/0)
rs4311	chr17:61560763(Forward)	downstream_gene_variant; intron_variant; nc_transcript_variant; NMD_transcript_variant; upstream_gene_variant	1(1/0)
rs4329	chr17:61563458(Forward)	downstream_gene_variant; intron_variant; NMD_transcript_variant; upstream_gene_variant	1(1/0)
rs4333	chr17:61564522(Forward)	downstream_gene_variant; intron_variant; nc_transcript_variant; NMD_transcript_variant; upstream_gene_variant	1(1/0)
rs4305	chr17:61558229(Forward)	downstream_gene_variant; intron_variant; nc_transcript_variant; NMD_transcript_variant; upstream_gene_variant	1(1/0)
rs4295	chr17:61556298(Forward)	downstream_gene_variant; intron_variant; nc_transcript_variant; NMD_transcript_variant	1(1/0)
rs4309	chr17:61559923(Forward)	3_prime_UTR_variant; downstream_gene_variant; nc_transcript_variant; NMD_transcript_variant; non_coding_exon_variant; synonymous_variant; upstream_gene_variant	1(1/0)

ACE related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Angiotensin-converting enzyme	P12821	1(1/0)	Literature-origin

ACE related GO terms (count: 30)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0003081	regulation of systemic arterial blood pressure by renin-angiotensin	biological process	IC[1668266]
GO:0014910	regulation of smooth muscle cell migration	biological process	ISS
GO:0004175	endopeptidase activity	molecular function	IDA[15283675]
GO:0060218	hematopoietic stem cell differentiation	biological process	IC[7876104]
GO:0016021	integral to membrane	cellular component	IEA
GO:0003779	actin binding	molecular function	IDA[16186248]
GO:0019229	regulation of vasoconstriction	biological process	IC[1668266]
GO:0001974	blood vessel remodeling	biological process	IC[1668266]
GO:0002019	regulation of renal output by angiotensin	biological process	IC[1668266]
GO:0002005	angiotensin catabolic process in blood	biological process	IC[1668266]
GO:0005886	plasma membrane	cellular component	IDA[17077303]
GO:0031711	bradykinin receptor binding	molecular function	IPI[17077303]
GO:0008217	regulation of blood pressure	biological process	ISS[11303049]
GO:0009897	external side of plasma membrane	cellular component	IDA[9449382]
GO:0008270	zinc ion binding	molecular function	IDA[12540854]
GO:0005615	extracellular space	cellular component	IDA[4322742]
GO:0006508	proteolysis	biological process	IEA
GO:0008241	peptidyl-dipeptidase activity	molecular function	IDA[2849100]; ISS[11303049]
GO:0008144	drug binding	molecular function	IDA[1320019]
GO:0005768	endosome	cellular component	IDA[17077303]
GO:0043171	peptide catabolic process	biological process	IDA[4322742]
GO:0031404	chloride ion binding	molecular function	IDA[12540854]
GO:0001822	kidney development	biological process	IMP[16116425]
GO:0032943	mononuclear cell proliferation	biological process	IC[7876104]
GO:0004180	carboxypeptidase activity	molecular function	IEA
GO:0042447	hormone catabolic process	biological process	IDA[7876104]; ISS[11303049]
GO:0050482	arachidonic acid secretion	biological process	IDA[17077303]
GO:0042312	regulation of vasodilation	biological process	IC[4322742]
GO:0008237	metallopeptidase activity	molecular function	IDA[17077303]; ISS
GO:0005515	protein binding	molecular function	IPI[16186248]

ACE related KEGG pathways (count: 2)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa05410	hypertrophic cardiomyopathy_hcm	Hypertrophic cardiomyopathy (HCM)	Hypertrophic cardiomyopathy (HCM) is a primary myocardial di...... Hypertrophic cardiomyopathy (HCM) is a primary myocardial disorder with an autosomal dominant pattern of inheritance that is characterized by hypertrophy of the left ventricles with histological features of myocyte hypertrophy, myofibrillar disarray, and interstitial fibrosis. HCM is one of the most common inherited cardiac disorders, with a prevalence in young adults of 1 in 500. Hundreds of mutations in 11 genes that encode protein constituents of the sarcomere have been identified in HCM. These mutations increase the Ca2+ sensitivity of cardiac myofilaments. Increased myofilament Ca2+ sensitivity is expected to increase the ATP utilization by actomyosin at submaximal Ca2+ concentrations, which might cause an imbalance in energy supply and demand in the heart under severe stress. The inefficient use of ATP suggests that an inability to maintain normal ATP levels could be the central abnormality. This theory might be supported by the discovery of the role of a mutant PRKAG2 gene in HCM, which in active form acts as a central sensing mechanism protecting cells from depletion of ATP supplies. The increase in the myofilament Ca2+ sensitivity well account for the diastolic dysfunction of model animals as well as human patients of HCM. It has been widely proposed that left ventricular hypertrophy is not a primary manifestation but develops as compensatory response to sarcomere dysfunction. More...
hsa04614	renin angiotensin_system	Renin-angiotensin system

ACE related BioCarta pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
ACE2_PATHWAY	ace2 pathway	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...

ACE related Reactome pathways (count: 0)

ACE related interactors from protein-protein interaction data in HPRD (count: 3)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
ACE	COMT	Yes	in vivo	12729939
ACE	BDKRB2	No	in vivo	10748135
ACE	AGTR2	No	in vivo	11459796

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways