ACE

Protein identityUniProt · HPA

UniProt accession

P12821

Gene

ACE

Ensembl

ENSG00000159640

Chromosome

17

Canonical length

1306 aa

Protein class

Candidate cardiovascular disease genes, CD markers, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Vesicles

Secretome location

Secreted to blood

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes an enzyme involved 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. This angiotensin converting enzyme (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 membrane proteins in spermatozoa. 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. Regulation of the homologous ACE2 gene may be involved in progression of disease caused by several human coronaviruses, including SARS-CoV and SARS-CoV-2. Alternative splicing results in multiple transcript variants encoding both somatic (sACE) and male-specific testicular (tACE) isoforms. [provided by RefSeq, Sep 2020]

Canonical amino-acid sequenceUniProt

1306 residues, UniProt reviewed canonical sequence.

>P12821|ACE
     1  MGAASGRRGP GLLLPLPLLL LLPPQPALAL DPGLQPGNFS ADEAGAQLFA QSYNSSAEQV
    61  LFQSVAASWA HDTNITAENA RRQEEAALLS QEFAEAWGQK AKELYEPIWQ NFTDPQLRRI
   121  IGAVRTLGSA NLPLAKRQQY NALLSNMSRI YSTAKVCLPN KTATCWSLDP DLTNILASSR
   181  SYAMLLFAWE GWHNAAGIPL KPLYEDFTAL SNEAYKQDGF TDTGAYWRSW YNSPTFEDDL
   241  EHLYQQLEPL YLNLHAFVRR ALHRRYGDRY INLRGPIPAH LLGDMWAQSW ENIYDMVVPF
   301  PDKPNLDVTS TMLQQGWNAT HMFRVAEEFF TSLELSPMPP EFWEGSMLEK PADGREVVCH
   361  ASAWDFYNRK DFRIKQCTRV TMDQLSTVHH EMGHIQYYLQ YKDLPVSLRR GANPGFHEAI
   421  GDVLALSVST PEHLHKIGLL DRVTNDTESD INYLLKMALE KIAFLPFGYL VDQWRWGVFS
   481  GRTPPSRYNF DWWYLRTKYQ GICPPVTRNE THFDAGAKFH VPNVTPYIRY FVSFVLQFQF
   541  HEALCKEAGY EGPLHQCDIY RSTKAGAKLR KVLQAGSSRP WQEVLKDMVG LDALDAQPLL
   601  KYFQPVTQWL QEQNQQNGEV LGWPEYQWHP PLPDNYPEGI DLVTDEAEAS KFVEEYDRTS
   661  QVVWNEYAEA NWNYNTNITT ETSKILLQKN MQIANHTLKY GTQARKFDVN QLQNTTIKRI
   721  IKKVQDLERA ALPAQELEEY NKILLDMETT YSVATVCHPN GSCLQLEPDL TNVMATSRKY
   781  EDLLWAWEGW RDKAGRAILQ FYPKYVELIN QAARLNGYVD AGDSWRSMYE TPSLEQDLER
   841  LFQELQPLYL NLHAYVRRAL HRHYGAQHIN LEGPIPAHLL GNMWAQTWSN IYDLVVPFPS
   901  APSMDTTEAM LKQGWTPRRM FKEADDFFTS LGLLPVPPEF WNKSMLEKPT DGREVVCHAS
   961  AWDFYNGKDF RIKQCTTVNL EDLVVAHHEM GHIQYFMQYK DLPVALREGA NPGFHEAIGD
  1021  VLALSVSTPK HLHSLNLLSS EGGSDEHDIN FLMKMALDKI AFIPFSYLVD QWRWRVFDGS
  1081  ITKENYNQEW WSLRLKYQGL CPPVPRTQGD FDPGAKFHIP SSVPYIRYFV SFIIQFQFHE
  1141  ALCQAAGHTG PLHKCDIYQS KEAGQRLATA MKLGFSRPWP EAMQLITGQP NMSASAMLSY
  1201  FKPLLDWLRT ENELHGEKLG WPQYNWTPNS ARSEGPLPDS GRVSFLGLDL DAQQARVGQW
  1261  LLLFLGIALL VATLGLSQRL FSIRHRSLHR HSHGPQFGSE VELRHS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACE can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

250 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACE.

Disease | AllUniProt

Conditions ACE is implicated in, by any mechanism.

• Ischemic stroke (ISCHSTR) MIM:601367
• Renal tubular dysgenesis (RTD) MIM:267430
• Microvascular complications of diabetes 3 (MVCD3) MIM:612624
• Intracerebral hemorrhage (ICH) MIM:614519

Disease | GeneticClinVar

65 pathogenic / likely-pathogenic of 850 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Renal tubular dysgenesis of genetic origin
• Microvascular complications of diabetes, susceptibility to, 3
• Hemorrhage, intracerebral, susceptibility to
• Renal tubular dysgenesis
• ACE-related disorder

ReferencesPubMed · IEDB

Publications for ACE from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.08

gnomAD pLI

0

gnomAD missense Z

-0.69

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• amyloid-beta metabolic process
• angiotensin maturation
• angiotensin-activated signaling pathway
• antigen processing and presentation of peptide antigen via MHC class I
• arachidonate secretion
• blood vessel diameter maintenance
• blood vessel remodeling
• bradykinin catabolic process
• cell proliferation in bone marrow
• heart contraction
• hematopoietic stem cell differentiation
• hormone catabolic process
• hormone metabolic process
• kidney development
• male gonad development
• negative regulation of gap junction assembly
• negative regulation of gene expression
• neutrophil mediated immunity
• peptide catabolic process
• positive regulation of systemic arterial blood pressure
• post-transcriptional regulation of gene expression
• proteolysis
• regulation of angiotensin metabolic process
• regulation of blood pressure
• regulation of heart rate by cardiac conduction
• regulation of hematopoietic stem cell proliferation
• regulation of renal output by angiotensin
• regulation of smooth muscle cell migration
• regulation of synaptic plasticity
• regulation of systemic arterial blood pressure by renin-angiotensin
• regulation of vasoconstriction
• spermatogenesis
• substance P catabolic process
• mononuclear cell proliferation

Molecular functions

• actin binding
• bradykinin receptor binding
• calmodulin binding
• chloride ion binding
• endopeptidase activity
• exopeptidase activity
• metallocarboxypeptidase activity
• metallodipeptidase activity
• metalloendopeptidase activity
• metallopeptidase activity
• mitogen-activated protein kinase binding
• mitogen-activated protein kinase kinase binding
• peptidase activity
• peptidyl-dipeptidase activity
• tripeptidyl-peptidase activity
• zinc ion binding

Cellular components

• endosome
• external side of plasma membrane
• extracellular exosome
• extracellular region
• extracellular space
• lysosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Peptidase M2, peptidyl-dipeptidase A
• Angiotensin-converting enzyme

KeywordsUniProt

• Alternative promoter usage
• Calmodulin-binding
• Carboxypeptidase
• Cell membrane
• Cytoplasm
• Disulfide bond
• Glycoprotein
• Hydrolase
• Membrane
• Metal-binding
• Metalloprotease
• Phosphoprotein
• Protease
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix
• Zinc