ACE angiotensin I converting enzyme [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACEprovided by HGNC
Official Full Name: angiotensin I converting enzymeprovided by HGNC
Primary source: HGNC:HGNC:2707
See related: Ensembl:ENSG00000159640 MIM:106180; Vega:OTTHUMG00000154927
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DCP; ACE1; DCP1; CD143
Summary: This gene encodes an enzyme involved in catalyzing the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This enzyme plays a key role in the renin-angiotensin system. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme or cardiovascular pathophysiologies. Multiple alternatively spliced transcript variants encoding different isoforms have been identified, and two most abundant spliced variants encode the somatic form and the testicular form, respectively, that are equally active. [provided by RefSeq, May 2010]
Expression: Biased expression in small intestine (RPKM 118.5), duodenum (RPKM 76.7) and 7 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 17q23.3

Exon count:: 26

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	17	NC_000017.11 (63477061..63498380)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	17	NC_000017.10 (61554422..61575741)

Chromosome 17 - NC_000017.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Data suggest that the insertion/deletion (I/D) ACE (angiotensin converting enzyme) gene polymorphism may be associated with MI occurrence among younger patients.
Title: Impact of I/D polymorphism of angiotensin-converting enzyme (ACE) gene on myocardial infarction susceptibility among young Moroccan patients.
The analysis of genotype coexistence revealed a higher incidence of the combination of the ACE II and the PAI-1 4G/4G genotypes in the control group (10.0 vs.5.9% in control group; p = 0.17). CONCLUSIONS: The obtained results suggest no apparent association between the ACE I/D, PAI-1 4G/5G polymorphisms and increased RM susceptibility in the analyzed Polish population.
Title: Coexistence of ACE (I/D) and PAI-1 (4G/5G) gene variants in recurrent miscarriage in Polish population.
An involvement of the ACE polymorphism in element imbalances in hypertension
Title: Macro- and Microelement Status in Animal and Human Hypertension: the Role of the ACE Gene I/D Polymorphism.
Concomitant presence of non-functional variant in ACTN3 gene decreased this beneficiary effect of ACE mutation on SBPR3.
Title: Polymorphisms in ACE and ACTN3 Genes and Blood Pressure Response to Acute Exercise in Elite Male Athletes from Serbia.
There were significant differences in sarcopenic obesity according to ACE I/D genotype, Women who were ACE DD presented lower risk of sarcopenic obesity than those in the ACE II and ACE ID groups
Title: [Sarcopenic obesity in elderly women: influence of I/D polymorphism of the angiotension converter enzyme].
Patients with Alzheimer's disease who were homozygous for angiotensin-converting enzyme (ACE) Insertion allele presented with a more rapid AD deterioration than did those who had other ACE genotypes, particularly those patients without hypertension.
Title: Angiotensin-converting enzyme insertion/deletion polymorphism and the longitudinal progression of Alzheimer's disease.
The ACE D allele may be predictive in individuals who may be at risk of developing CAD. Further investigations of these polymorphisms and their possible synergisms with traditional risk factors for CAD could help to ascertain better predictability for CAD susceptibility.
Title: The Effect of ACE I/D Polymorphisms Alone and With Concomitant Risk Factors on Coronary Artery Disease.
ACE DD genotype and overall frequency of D allele is significantly higher in patients with PPCM. Also, the presence of DD genotype is associated with worse systolic performance indices measured echocardiographically.
Title: Insertion/deletion polymorphism of ACE gene in females with peripartum cardiomyopathy: A case-control study.
There was an independent association of the angiotensin-converting enzyme polymorphism with central and ambulatory blood pressure in Chinese patients with Hypertension.
Title: Relationship of renin-angiotensin system polymorphisms with ambulatory and central blood pressure in patients with hypertension.
expression not increased in the maternal vascular endothelium in subjects with preeclampsia compared with normal pregnant controls
Title: Upregulation of cathepsin C expression contributes to endothelial chymase activation in preeclampsia.

Submit: New GeneRIF Correction See all GeneRIFs (1411)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Alzheimer's disease MedGen: C0002395 OMIM: 104300 GeneReviews: Alzheimer Disease Overview, Early-Onset Familial Alzheimer Disease	Compare labs
Disorder of cardiovascular system MedGen: C0007222 GeneReviews: Not available	Compare labs
Hemorrhage, intracerebral, susceptibility to MedGen: C0019191 OMIM: 614519 GeneReviews: Not available	Compare labs
Microvascular complications of diabetes 3 MedGen: C2675470 OMIM: 612624 GeneReviews: Not available	Compare labs
Renal dysplasia MedGen: C0266313 OMIM: 267430 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

Description
A genome-wide assessment of variability in human serum metabolism. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A genome-wide association study identifies new loci for ACE activity: potential implications for response to ACE inhibitor. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
An atlas of genetic influences on human blood metabolites. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetic determinants influencing human serum metabolome among African Americans. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-Wide Association Study of CSF Levels of 59 Alzheimer's Disease Candidate Proteins: Significant Associations with Proteins Involved in Amyloid Processing and Inflammation. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Human metabolic individuality in biomedical and pharmaceutical research. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160-derived peptide p18 presented by H-2Dd class I major histocompatibility complex molecules is processed by angiotensin-1 converting enzyme (ACE) prior to T cell stimulation by the peptide p18	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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ACE Inhibitor Pathway, organism-specific biosystem (from WikiPathways)
ACE Inhibitor Pathway, organism-specific biosystemThe core of this pathway was elucidated over a century ago and involves the conversion of angiotensinogen to angiotensin I (Ang I) by renin, its subsequent conversion to angiotensin II (Ang II) by an...
Chagas disease (American trypanosomiasis), organism-specific biosystem (from KEGG)
Chagas disease (American trypanosomiasis), organism-specific biosystemTrypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. The parasite life cycle involves hematophagous reduviid bugs as vectors. Once parasites enter the host body, they ...
Chagas disease (American trypanosomiasis), conserved biosystem (from KEGG)
Chagas disease (American trypanosomiasis), conserved biosystemTrypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. The parasite life cycle involves hematophagous reduviid bugs as vectors. Once parasites enter the host body, they ...
Hypertrophic cardiomyopathy (HCM), organism-specific biosystem (from KEGG)
Hypertrophic cardiomyopathy (HCM), organism-specific biosystemHypertrophic 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 feat...
Hypertrophic cardiomyopathy (HCM), conserved biosystem (from KEGG)
Hypertrophic cardiomyopathy (HCM), conserved biosystemHypertrophic 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 feat...
Metabolism of Angiotensinogen to Angiotensins, organism-specific biosystem (from REACTOME)
Metabolism of Angiotensinogen to Angiotensins, organism-specific biosystemAngiotensinogen, a prohormone, is synthesized and secreted mainly by the liver but also from other tissues (reviewed in Fyhrquist and Saijonmaa 2008, Cat and Touyz 2011). Renin, an aspartyl protease ...
Metabolism of proteins, organism-specific biosystem (from REACTOME)
Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
Peptide hormone metabolism, organism-specific biosystem (from REACTOME)
Peptide hormone metabolism, organism-specific biosystemPeptide hormones are cleaved from larger precursors in the secretory system (endoplasmic reticulum, Golgi apparatus, secretory granules) of the cell. After secretion peptide hormones are modified and...
Renin secretion, organism-specific biosystem (from KEGG)
Renin secretion, organism-specific biosystemThe aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in extracellular fluid volume and blood pressure homeostasis of the body. R...
Renin secretion, conserved biosystem (from KEGG)
Renin secretion, conserved biosystemThe aspartyl-protease renin is the key regulator of the renin-angiotensin-aldosterone system, which is critically involved in extracellular fluid volume and blood pressure homeostasis of the body. R...
Renin-angiotensin system, organism-specific biosystem (from KEGG)
Renin-angiotensin system, organism-specific biosystemThe renin-angiotensin system (RAS) is a peptidergic system with endocrine characteristics regarding to the regulation of the blood pressure and hydro-electrolytic balance. In the classical RAS, the ...
Renin-angiotensin system, conserved biosystem (from KEGG)
Renin-angiotensin system, conserved biosystemThe renin-angiotensin system (RAS) is a peptidergic system with endocrine characteristics regarding to the regulation of the blood pressure and hydro-electrolytic balance. In the classical RAS, the ...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-57821 (e-PCR)
- UniSTS:19461

SHGC-175 (e-PCR)
- UniSTS:25620

ACE (e-PCR)
- UniSTS:504596

GDB:186915 (e-PCR)
- UniSTS:155520

PMC310924P2 (e-PCR)
- UniSTS:272813

PMC310924P3 (e-PCR)
- UniSTS:272814

G59596 (e-PCR)
- UniSTS:136900

RH17589 (e-PCR)
- UniSTS:50661

GDB:631883 (e-PCR)
- UniSTS:158438

GDB:631894 (e-PCR)
- UniSTS:158439

Homology

Homologs of the ACE gene: The ACE gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, mosquito, and frog.
Orthologs from Annotation Pipeline: 171 organisms have orthologs with human gene ACE
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
bradykinin receptor binding	IPI Inferred from Physical Interaction more info	PubMed
carboxypeptidase activity	IEA Inferred from Electronic Annotation more info
chloride ion binding	IDA Inferred from Direct Assay more info	PubMed
dipeptidyl-peptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
drug binding	IDA Inferred from Direct Assay more info	PubMed
endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
exopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
exopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
metallodipeptidase activity	EXP Inferred from Experiment more info	PubMed
metallopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
metallopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
metallopeptidase activity	ISS Inferred from Sequence or Structural Similarity more info
metallopeptidase activity	TAS Traceable Author Statement more info	PubMed
mitogen-activated protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
mitogen-activated protein kinase kinase binding	IPI Inferred from Physical Interaction more info	PubMed
peptidyl-dipeptidase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
peptidyl-dipeptidase activity	IDA Inferred from Direct Assay more info	PubMed
peptidyl-dipeptidase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
peptidyl-dipeptidase activity	TAS Traceable Author Statement more info	PubMed
tripeptidyl-peptidase activity	IDA Inferred from Direct Assay more info	PubMed
zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
amyloid-beta metabolic process	IDA Inferred from Direct Assay more info	PubMed
angiotensin maturation	IC Inferred by Curator more info	PubMed
angiotensin maturation	TAS Traceable Author Statement more info
antigen processing and presentation of peptide antigen via MHC class I	TAS Traceable Author Statement more info	PubMed
arachidonic acid secretion	IDA Inferred from Direct Assay more info	PubMed
blood vessel remodeling	IC Inferred by Curator more info	PubMed
cell proliferation in bone marrow	ISS Inferred from Sequence or Structural Similarity more info
heart contraction	ISS Inferred from Sequence or Structural Similarity more info
hematopoietic stem cell differentiation	IC Inferred by Curator more info	PubMed
hormone catabolic process	IDA Inferred from Direct Assay more info	PubMed
hormone catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
kidney development	IMP Inferred from Mutant Phenotype more info	PubMed
mononuclear cell proliferation	IC Inferred by Curator more info	PubMed
negative regulation of gap junction assembly	ISS Inferred from Sequence or Structural Similarity more info
neutrophil mediated immunity	ISS Inferred from Sequence or Structural Similarity more info
peptide catabolic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of blood pressure	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of peptidyl-cysteine S-nitrosylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of peptidyl-tyrosine autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of systemic arterial blood pressure	IBA Inferred from Biological aspect of Ancestor more info	PubMed
proteolysis	TAS Traceable Author Statement more info	PubMed
regulation of angiotensin metabolic process	IDA Inferred from Direct Assay more info	PubMed
regulation of blood pressure	ISS Inferred from Sequence or Structural Similarity more info	PubMed
regulation of blood vessel diameter	IC Inferred by Curator more info	PubMed
regulation of hematopoietic stem cell proliferation	IC Inferred by Curator more info	PubMed
regulation of hematopoietic stem cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
regulation of renal output by angiotensin	IC Inferred by Curator more info	PubMed
regulation of smooth muscle cell migration	ISS Inferred from Sequence or Structural Similarity more info
regulation of systemic arterial blood pressure by renin-angiotensin	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of systemic arterial blood pressure by renin-angiotensin	IC Inferred by Curator more info	PubMed
regulation of systemic arterial blood pressure by renin-angiotensin	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of vasoconstriction	IC Inferred by Curator more info	PubMed
spermatogenesis	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
endosome	IDA Inferred from Direct Assay more info	PubMed
external side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
extracellular exosome	HDA more info	PubMed
extracellular exosome	IDA Inferred from Direct Assay more info	PubMed
extracellular region	TAS Traceable Author Statement more info
extracellular space	HDA more info	PubMed
extracellular space	IBA Inferred from Biological aspect of Ancestor more info	PubMed
extracellular space	IDA Inferred from Direct Assay more info	PubMed
integral component of membrane	IEA Inferred from Electronic Annotation more info
lysosome	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: angiotensin-converting enzyme

Names: CD143 antigen; angiotensin I converting enzyme (peptidyl-dipeptidase A) 1; angiotensin converting enzyme, somatic isoform; carboxycathepsin; dipeptidyl carboxypeptidase 1; dipeptidyl carboxypeptidase I; kininase II; peptidase P

NP_000780.1

EC 3.4.15.1

NP_001171528.1

EC 3.4.15.1

NP_690043.1

EC 3.4.15.1

XP_006721800.2

EC 3.4.15.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011648.1 RefSeqGene

Range

4989..26308

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000789.3 → NP_000780.1 angiotensin-converting enzyme isoform 1 precursor

See identical proteins and their annotated locations for NP_000780.1

Status: REVIEWED

Description

Transcript Variant: This variant (1), also known as the endothelial or somatic form, represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AB208971, AC113554, AK296566

Consensus CDS

CCDS11637.1

UniProtKB/Swiss-Prot

P12821

UniProtKB/TrEMBL

B4DKH4

Related

ENSP00000290866.4, OTTHUMP00000206956, ENST00000290866.9, OTTHUMT00000337675

Conserved Domains (1) summary

pfam01401
Location:643 → 1221

Peptidase_M2; Angiotensin-converting enzyme
NM_001178057.1 → NP_001171528.1 angiotensin-converting enzyme isoform 3 precursor

See identical proteins and their annotated locations for NP_001171528.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks multiple 5' exons and an in-frame exon in the 3' region, but has an alternate 5' exon, compared to variant 1. The resulting isoform (3) is shorter, and has a distinct N-terminus and lacks an internal segment, compared to isoform 1.

Source sequence(s)

AB208971, AC113554, AK301988, BM908222, M26657

Consensus CDS

CCDS54155.1

UniProtKB/Swiss-Prot

P12821

Related

ENSP00000392247.3, OTTHUMP00000260277, ENST00000413513.7, OTTHUMT00000443838

Conserved Domains (1) summary

pfam01401
Location:69 → 606

Peptidase_M2; Angiotensin-converting enzyme
NM_152830.2 → NP_690043.1 angiotensin-converting enzyme isoform 2 precursor

See identical proteins and their annotated locations for NP_690043.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as the testicular form, lacks multiple 5' exons, but has an alternate 5' exon, compared to variant 1. The resulting isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AB208971, AC113554, BM908222, M26657

Consensus CDS

CCDS45755.1

UniProtKB/Swiss-Prot

P12821

Related

ENSP00000290863.6, OTTHUMP00000260274, ENST00000290863.10, OTTHUMT00000443835

Conserved Domains (1) summary

pfam01401
Location:69 → 647

Peptidase_M2; Angiotensin-converting enzyme

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p12 Primary Assembly

Range

63477061..63498380

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006721737.3 → XP_006721800.2 angiotensin-converting enzyme isoform X1

Conserved Domains (1) summary

pfam01401
Location:89 → 667

Peptidase_M2; Angiotensin-converting enzyme

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_152831.1: Suppressed sequence

Description

NM_152831.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.