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
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 in blood pressure regulation and electrolyte balance. It catalyzes 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. ACE also inactivates the vasodilator protein, bradykinin. Accordingly, the encoded enzyme increases blood pressure and is a drug target of ACE inhibitors, which are often prescribed to reduce blood pressure. This enzyme additionally plays a role in fertility through its ability to cleave and release GPI-anchored proteins in testes. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme. This polymorphism, as well as mutations in this gene, have been implicated in a wide variety of diseases including cardiovascular pathophysiologies, psoriasis, renal disease, stroke, and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2020]
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
109.20200522	current	GRCh38.p13 (GCF_000001405.39)	17	NC_000017.11 (63477061..63498373)
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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The current study results suggest that the D allele of the ACE insertion/deletion gene polymorphism might confer risk to AV among the studied patients. Moreover, ACE insertion/deletion gene polymorphism and positive family history were considered as independent predictors of severe acne vulgaris
Title: Angiotensin-converting enzyme gene insertion/deletion polymorphism and family history in severe acne vulgaris.
angiotensin converting enzyme and chitotriosidase analysis improves the laboratory diagnosis of sarcoidosis
Title: Combined application of angiotensin converting enzyme and chitotriosidase analysis improves the laboratory diagnosis of sarcoidosis.
ACE I/D polymorphism of the ACE gene may not be an independent risk factor in the development of atherosclerosis and evaluation of ACE activity level is more important in evaluating the risk of disease.
Title: Study of angiotensin-converting enzyme insertion/deletion polymorphism, enzyme activity and oxidized low density lipoprotein in Western Iranians with atherosclerosis: a case-control study.
The A240T polymorphism in the ACE gene might be related to the risk of cancer.
Title: Association between <i>ACE</i> A240T polymorphism and cancer risk: a meta-analysis.
Angiotensin-converting enzyme gene polymorphism is associated with Behcet's disease.
Title: Angiotensin-converting enzyme gene polymorphism in Behçet's disease in Iranian population.
ACE I/D polymorphism may be associated with psoriasis susceptibility, while ID genotype seemed to have a protective role in Caucasian patients affected by psoriatic arthritis (Meta-Analysis)
Title: Angiotensin-converting enzyme gene insertion/deletion polymorphism and susceptibility to psoriasis: a systematic review and meta-analysis.
Despite the presumed significance of the ins/del ACE on mechanisms inherent to hypertension and vascular diseases, the study did not show an association between these polymorphisms and preeclampsia (PE) occurrence.
Title: Association among ACE, ESR1 polymorphisms and preeclampsia in Brazilian pregnant women.
Findings show that ACE1 catalytic domain activity is significantly altered in Alzheimer disease.
Title: Divergence in the activity of the N- and C- catalytic domains of ACE1 - implications for the role of the renin-angiotensin system in Alzheimer's disease.
ACE1 D/I polymorphism may be regarded as a confounder in the spread of COVID-19 and the outcome of the infection in various European populations.
Title: The host's angiotensin-converting enzyme polymorphism may explain epidemiological findings in COVID-19 infections.
A systematic review and meta-analysis indicates that the insertion in ACE I/D polymorphism was a protection factor for the development of Diabetic Neuropathy in individuals with type 2 diabetes mellitus from both East and South Asian origin, and for End-stage Renal Disease in an East Asian population.
Title: Genetic associations between genes in the renin-angiotensin-aldosterone system and renal disease: a systematic review and meta-analysis.

Submit: New GeneRIF Correction See all GeneRIFs (1504)

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
Disorder of cardiovascular system MedGen: C0007222 GeneReviews: Not available	Compare labs
Hemorrhage, intracerebral, susceptibility to MedGen: C3281105 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

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: 240 organisms have orthologs with human gene ACE
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
drug binding	IDA Inferred from Direct Assay more info	PubMed
endopeptidase activity	IDA Inferred from Direct Assay 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
negative regulation of gene expression	IEA Inferred from Electronic Annotation more info
negative regulation of protein binding	IEA Inferred from Electronic Annotation 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 binding	IEA Inferred from Electronic Annotation 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
posttranscriptional regulation of gene expression	IEA Inferred from Electronic Annotation more info
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	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_001369629.1

EC 3.4.15.1

NP_001369630.1

EC 3.4.15.1

NP_001369631.1

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..26301

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000789.4 → 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, ENST00000290866.10

Conserved Domains (1) summary

pfam01401
Location:643 → 1221

Peptidase_M2; Angiotensin-converting enzyme
NM_001178057.2 → 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, ENST00000413513.7

Conserved Domains (1) summary

pfam01401
Location:69 → 606

Peptidase_M2; Angiotensin-converting enzyme
NM_001382700.1 → NP_001369629.1 angiotensin-converting enzyme isoform 4

Status: REVIEWED

Source sequence(s)

AC113554
NM_001382701.1 → NP_001369630.1 angiotensin-converting enzyme isoform 5

Status: REVIEWED

Source sequence(s)

AC113554
NM_001382702.1 → NP_001369631.1 angiotensin-converting enzyme isoform 6

Status: REVIEWED

Source sequence(s)

AC113554
NM_152830.3 → 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, ENST00000290863.10

Conserved Domains (1) summary

pfam01401
Location:69 → 647

Peptidase_M2; Angiotensin-converting enzyme

RNA

NR_168483.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC113554

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

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000017.11 Reference GRCh38.p13 Primary Assembly

Range

63477061..63498373

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.