ACE2 angiotensin converting enzyme 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACE2provided by HGNC
Official Full Name: angiotensin converting enzyme 2provided by HGNC
Primary source: HGNC:HGNC:13557
See related: Ensembl:ENSG00000130234 MIM:300335; AllianceGenome:HGNC:13557
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: ACEH
Summary: The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. ACE2 is known to be expressed in various human organs, and its organ- and cell-specific expression suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronavirus HCoV-NL63 and the human severe acute respiratory syndrome coronaviruses, SARS-CoV and SARS-CoV-2, the latter is the causative agent of coronavirus disease-2019 (COVID-19). Multiple splice variants have been found for this gene and the dACE2 (or MIRb-ACE2) splice variant has been found to be interferon inducible. [provided by RefSeq, Nov 2020]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
Expression: Biased expression in small intestine (RPKM 93.7), duodenum (RPKM 69.0) and 5 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: Xp22.2

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	X	NC_000023.11 (15518197..15607211, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	X	NC_060947.1 (15101170..15190203, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	X	NC_000023.10 (15536320..15625334, complement)

Chromosome X - NC_000023.11 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?

Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral Replication and Nonlethal Disease Progression.
Title: Human ACE2 Gene Replacement Mice Support SARS-CoV-2 Viral Replication and Nonlethal Disease Progression.
Mapping ACE2 and TMPRSS2 co-expression in human brain tissue: implications for SARS-CoV-2 neurological manifestations.
Title: Mapping ACE2 and TMPRSS2 co-expression in human brain tissue: implications for SARS-CoV-2 neurological manifestations.
Interaction of SARS-CoV-2 Spike protein with ACE2 induces cortical actin modulation, including dephosphorylation of ERM proteins and reduction of cortical stiffness.
Title: Interaction of SARS-CoV-2 Spike protein with ACE2 induces cortical actin modulation, including dephosphorylation of ERM proteins and reduction of cortical stiffness.
Ubiquitination of angiotensin-converting enzyme 2 contributes to the development of pulmonary arterial hypertension mediated by neural precursor cell-expressed developmentally down-regulated gene 4-Like.
Title: Ubiquitination of angiotensin-converting enzyme 2 contributes to the development of pulmonary arterial hypertension mediated by neural precursor cell-expressed developmentally down-regulated gene 4-Like.
Role of ACE2 and TMPRSS2 polymorphisms on COVID-19 outcome and disease severity in adult patients: A prospective cohort study in a tertiary hospital, Indonesia.
Title: Role of ACE2 and TMPRSS2 polymorphisms on COVID-19 outcome and disease severity in adult patients: A prospective cohort study in a tertiary hospital, Indonesia.
ACE2 expression and spike S1 protein-mediated immune responses in oral mucosal cells.
Title: ACE2 expression and spike S1 protein-mediated immune responses in oral mucosal cells.
Gene variants rs5182, rs2074192, and rs4343 in the renin-angiotensin-aldosterone system are associated with symptom severity, higher odds of hospitalization, and death in COVID-19.
Title: Gene variants rs5182, rs2074192, and rs4343 in the renin-angiotensin-aldosterone system are associated with symptom severity, higher odds of hospitalization, and death in COVID-19.
A Comparative Analysis of SARS-CoV-2 Variants of Concern (VOC) Spike Proteins Interacting with hACE2 Enzyme.
Title: A Comparative Analysis of SARS-CoV-2 Variants of Concern (VOC) Spike Proteins Interacting with hACE2 Enzyme.
Glycosylation Modulation Dictates Trafficking and Interaction of SARS-CoV-2 S1 Subunit and ACE2 in Intestinal Epithelial Caco-2 Cells.
Title: Glycosylation Modulation Dictates Trafficking and Interaction of SARS-CoV-2 S1 Subunit and ACE2 in Intestinal Epithelial Caco-2 Cells.
No evidence that ACE2 or TMPRSS2 drive population disparity in COVID risks.
Title: No evidence that ACE2 or TMPRSS2 drive population disparity in COVID risks.

Submit: New GeneRIF Correction See all GeneRIFs (952)

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-143063 (e-PCR)
- UniSTS:171779

RH92830 (e-PCR)
- UniSTS:89684

ACE2_1659 (e-PCR)
- UniSTS:280430

DXS7698 (e-PCR)
- UniSTS:35779

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
NOT enables carboxypeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables carboxypeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metallopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metallopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptidyl-dipeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
NOT enables virus receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables virus receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables virus receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables zinc ion binding	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in angiotensin maturation	IC Inferred by Curator more info	PubMed
involved_in angiotensin-mediated drinking behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in blood vessel diameter maintenance	IC Inferred by Curator more info	PubMed
involved_in entry receptor-mediated virion attachment to host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in maternal process involved in female pregnancy	IEA Inferred from Electronic Annotation more info
involved_in membrane fusion	NAS Non-traceable Author Statement more info	PubMed
involved_in negative regulation of ERK1 and ERK2 cascade	IEA Inferred from Electronic Annotation more info
acts_upstream_of negative regulation of signaling receptor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of L-proline import across plasma membrane	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of amino acid transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cardiac muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gap junction assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of reactive oxygen species metabolic process	IC Inferred by Curator more info	PubMed
involved_in receptor-mediated endocytosis of virus by host cell	NAS Non-traceable Author Statement more info	PubMed
involved_in receptor-mediated virion attachment to host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in receptor-mediated virion attachment to host cell	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of cardiac conduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of cell population proliferation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of cytokine production	IC Inferred by Curator more info	PubMed
involved_in regulation of inflammatory response	IC Inferred by Curator more info	PubMed
involved_in regulation of systemic arterial blood pressure by renin-angiotensin	IC Inferred by Curator more info	PubMed
involved_in regulation of systemic arterial blood pressure by renin-angiotensin	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transmembrane transporter activity	IGI Inferred from Genetic Interaction more info	PubMed
involved_in regulation of vasoconstriction	IC Inferred by Curator more info	PubMed
acts_upstream_of_positive_effect symbiont entry into host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in symbiont entry into host cell	IDA Inferred from Direct Assay more info	PubMed
involved_in symbiont entry into host cell	NAS Non-traceable Author Statement more info	PubMed
involved_in symbiont entry into host cell	TAS Traceable Author Statement more info	PubMed
involved_in tryptophan transport	IEA Inferred from Electronic Annotation more info
involved_in viral life cycle	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in apical plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in brush border membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cilium	IEA Inferred from Electronic Annotation more info
located_in endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum lumen	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	IDA Inferred from Direct Assay more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in membrane raft	TAS Traceable Author Statement more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: angiotensin-converting enzyme 2

Names: ACE-related carboxypeptidase; angiotensin I converting enzyme (peptidyl-dipeptidase A) 2; angiotensin I converting enzyme 2; angiotensin-converting enzyme homolog; angiotensin-converting enzyme-related carboxypeptidase; metalloprotease MPROT15; peptidyl-dipeptidase A

NP_001358344.1

EC 3.4.17.23

NP_001373188.1

EC 3.4.17.23

NP_001373189.1

EC 3.4.17.23

NP_001375381.1

EC 3.4.17.23

NP_001376331.1

EC 3.4.17.23

NP_068576.1

EC 3.4.17.23

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_012575.3 RefSeqGene

Range

11251..51178

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001371415.1 → NP_001358344.1 angiotensin-converting enzyme 2 isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1 and 2 encode the same isoform.

Source sequence(s)

AC097625

Consensus CDS

CCDS14169.1

UniProtKB/Swiss-Prot

A0A7D6JAD5, C7ECU1, Q6UWP0, Q86WT0, Q9BYF1, Q9NRA7, Q9UFZ6

UniProtKB/TrEMBL

A0A8S0M502, B2RCJ5

Related

ENSP00000252519.3, ENST00000252519.8

Conserved Domains (2) summary

pfam01401
Location:19 → 606

Peptidase_M2; Angiotensin-converting enzyme

pfam16959
Location:617 → 770

Collectrin; Renal amino acid transporter
NM_001386259.1 → NP_001373188.1 angiotensin-converting enzyme 2 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (3) includes an alternate penultimate exon, compared to variant 1, resulting in a novel 3' coding region and alternate 3' UTR. It encodes isoform 2 which has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC097625

Consensus CDS

CCDS94557.1

UniProtKB/TrEMBL

A0A7I2V2E9, A0A7I2V4H0

Related

ENSP00000504010.1, ENST00000679278.1

Conserved Domains (2) summary

pfam01401
Location:19 → 606

Peptidase_M2; Angiotensin-converting enzyme

pfam16959
Location:617 → 770

Collectrin; Renal amino acid transporter
NM_001386260.1 → NP_001373189.1 angiotensin-converting enzyme 2 isoform 3 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks multiple exons in the 3' coding region, compared to variant 1. The encoded isoform (3) is shorter, compared to isoform 1.

Source sequence(s)

AC097625

UniProtKB/TrEMBL

A0A8S0M502, B2RCJ5

Conserved Domains (2) summary

pfam01401
Location:19 → 556

Peptidase_M2; Angiotensin-converting enzyme

pfam16959
Location:557 → 659

Collectrin; Renal amino acid transporter
NM_001388452.1 → NP_001375381.1 angiotensin-converting enzyme 2 isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (5, also known as dAce2 or MIRb-ACE2) represents use of an alternate promoter and therefore differs in the 5' UTR and 5' coding region, compared to variant 1. These differences cause translation initiation at a downstream start codon and result in an isoform (4) with a shorter N-terminus, compared to isoform 1. This isoform lacks carboxypeptidase activity and cannot bind the SARS-CoV-2 spike protein.

Source sequence(s)

AC097625

Consensus CDS

CCDS94556.1

Related

ENSP00000504747.1, ENST00000677282.1

Conserved Domains (2) summary

pfam16959
Location:271 → 424

Collectrin; Renal amino acid transporter

cl14813
Location:11 → 260

GluZincin; Gluzincin Peptidase family (thermolysin-like proteinases, TLPs) which includes peptidases M1, M2, M3, M4, M13, M32 and M36 (fungalysins)
NM_001389402.1 → NP_001376331.1 angiotensin-converting enzyme 2 isoform 3 precursor

Status: REVIEWED

Source sequence(s)

AC097625

UniProtKB/TrEMBL

A0A8S0M502, B2RCJ5

Conserved Domains (2) summary

pfam01401
Location:19 → 556

Peptidase_M2; Angiotensin-converting enzyme

pfam16959
Location:557 → 659

Collectrin; Renal amino acid transporter
NM_021804.3 → NP_068576.1 angiotensin-converting enzyme 2 isoform 1 precursor

See identical proteins and their annotated locations for NP_068576.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents the longest transcript, with a longer 5' UTR compared to variant 2. Variants 1 and 2 encode the same isoform (1).

Source sequence(s)

AB193259, AC097625

Consensus CDS

CCDS14169.1

UniProtKB/Swiss-Prot

A0A7D6JAD5, C7ECU1, Q6UWP0, Q86WT0, Q9BYF1, Q9NRA7, Q9UFZ6

UniProtKB/TrEMBL

A0A8S0M502, B2RCJ5

Related

ENSP00000389326.1, ENST00000427411.2

Conserved Domains (2) summary

pfam01401
Location:19 → 606

Peptidase_M2; Angiotensin-converting enzyme

pfam16959
Location:617 → 770

Collectrin; Renal amino acid transporter