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Protein

Angiotensin-converting enzyme 2

Gene

Ace2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. May have a protective role in acute lung injury.3 Publications

Catalytic activityi

Angiotensin II + H2O = angiotensin-1-7 + L-phenylalanine.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
  • chlorideBy similarityNote: Binds 1 Cl- ion per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei169 – 1691ChlorideBy similarity
Binding sitei273 – 2731SubstrateBy similarity
Binding sitei345 – 3451SubstrateBy similarity
Binding sitei346 – 3461Substrate; via carbonyl oxygenBy similarity
Binding sitei371 – 3711SubstrateBy similarity
Metal bindingi374 – 3741Zinc; catalyticPROSITE-ProRule annotation
Active sitei375 – 3751PROSITE-ProRule annotation
Metal bindingi378 – 3781Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi402 – 4021Zinc; catalyticPROSITE-ProRule annotation
Binding sitei477 – 4771ChlorideBy similarity
Binding sitei481 – 4811ChlorideBy similarity
Active sitei505 – 5051PROSITE-ProRule annotation
Binding sitei515 – 5151SubstrateBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Chloride, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.17.23. 3474.
ReactomeiR-MMU-2022377. Metabolism of Angiotensinogen to Angiotensins.

Protein family/group databases

MEROPSiM02.006.

Names & Taxonomyi

Protein namesi
Recommended name:
Angiotensin-converting enzyme 2 (EC:3.4.17.23)
Alternative name(s):
ACE-related carboxypeptidase
Cleaved into the following chain:
Gene namesi
Name:Ace2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome X

Organism-specific databases

MGIiMGI:1917258. Ace2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini18 – 740723ExtracellularSequence analysisAdd
BLAST
Transmembranei741 – 76121HelicalSequence analysisAdd
BLAST
Topological domaini762 – 80544CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: MGI
  • extracellular region Source: MGI
  • extracellular space Source: MGI
  • integral component of membrane Source: UniProtKB-KW
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Mice are viable and fertile, exhibit normal kidney and lung function, but show a severe reduction in cardiac contractility, and are highly sensitive to severe acute lung failure. Transgenic mice overexpressing ACE2 in the heart appear healthy but show conduction disturbances and ventricular arrhythmias which can lead to sudden death.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Chaini18 – 805788Angiotensin-converting enzyme 2PRO_0000028571Add
BLAST
Chaini18 – 708691Processed angiotensin-converting enzyme 2PRO_0000292269Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi53 – 531N-linked (GlcNAc...)Sequence analysis
Disulfide bondi133 ↔ 141By similarity
Disulfide bondi344 ↔ 361By similarity
Disulfide bondi530 ↔ 542By similarity
Glycosylationi536 – 5361N-linked (GlcNAc...)Sequence analysis
Glycosylationi546 – 5461N-linked (GlcNAc...)Sequence analysis
Glycosylationi660 – 6601N-linked (GlcNAc...)Sequence analysis
Glycosylationi690 – 6901N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Proteolytic cleavage by ADAM17 generates a secreted form. Also cleaved by serine proteases: TMPRSS2, TMPRSS11D and HPN/TMPRSS1 (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiQ8R0I0.
PaxDbiQ8R0I0.
PRIDEiQ8R0I0.

PTM databases

iPTMnetiQ8R0I0.
PhosphoSiteiQ8R0I0.

Expressioni

Tissue specificityi

Expressed in heart, kidney and forebrain (at protein level). Ubiquitously expressed, with highest levels in ileum, kidney and lung. In lung, expressed on vascular endothelial and airway epithelial cells.3 Publications

Inductioni

Down-regulated in lung after acute injury.1 Publication

Gene expression databases

BgeeiQ8R0I0.
ExpressionAtlasiQ8R0I0. baseline and differential.
GenevisibleiQ8R0I0. MM.

Interactioni

Subunit structurei

Interacts with ITGB1 and the catalytically active form of TMPRSS2 (By similarity). Weakly interacts with SARS-CoV S protein.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ8R0I0. 1 interaction.
MINTiMINT-4118343.
STRINGi10090.ENSMUSP00000073626.

Structurei

3D structure databases

ProteinModelPortaliQ8R0I0.
SMRiQ8R0I0. Positions 19-615.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni652 – 6598Essential for cleavage by ADAM17By similarity
Regioni697 – 71620Essential for cleavage by TMPRSS11D and TMPRSS2By similarityAdd
BLAST

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3690. Eukaryota.
ENOG410XPJ3. LUCA.
GeneTreeiENSGT00520000055576.
HOGENOMiHOG000292210.
HOVERGENiHBG000265.
InParanoidiQ8R0I0.
KOiK09708.
OMAiCNPNNPQ.
OrthoDBiEOG76HQ13.
PhylomeDBiQ8R0I0.
TreeFamiTF312861.

Family and domain databases

InterProiIPR031588. Collectrin_dom.
IPR001548. Peptidase_M2.
[Graphical view]
PANTHERiPTHR10514. PTHR10514. 2 hits.
PfamiPF16959. Collectrin. 1 hit.
PF01401. Peptidase_M2. 1 hit.
[Graphical view]
PRINTSiPR00791. PEPDIPTASEA.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8R0I0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSSSSWLLLS LVAVTTAQSL TEENAKTFLN NFNQEAEDLS YQSSLASWNY
60 70 80 90 100
NTNITEENAQ KMSEAAAKWS AFYEEQSKTA QSFSLQEIQT PIIKRQLQAL
110 120 130 140 150
QQSGSSALSA DKNKQLNTIL NTMSTIYSTG KVCNPKNPQE CLLLEPGLDE
160 170 180 190 200
IMATSTDYNS RLWAWEGWRA EVGKQLRPLY EEYVVLKNEM ARANNYNDYG
210 220 230 240 250
DYWRGDYEAE GADGYNYNRN QLIEDVERTF AEIKPLYEHL HAYVRRKLMD
260 270 280 290 300
TYPSYISPTG CLPAHLLGDM WGRFWTNLYP LTVPFAQKPN IDVTDAMMNQ
310 320 330 340 350
GWDAERIFQE AEKFFVSVGL PHMTQGFWAN SMLTEPADGR KVVCHPTAWD
360 370 380 390 400
LGHGDFRIKM CTKVTMDNFL TAHHEMGHIQ YDMAYARQPF LLRNGANEGF
410 420 430 440 450
HEAVGEIMSL SAATPKHLKS IGLLPSDFQE DSETEINFLL KQALTIVGTL
460 470 480 490 500
PFTYMLEKWR WMVFRGEIPK EQWMKKWWEM KREIVGVVEP LPHDETYCDP
510 520 530 540 550
ASLFHVSNDY SFIRYYTRTI YQFQFQEALC QAAKYNGSLH KCDISNSTEA
560 570 580 590 600
GQKLLKMLSL GNSEPWTKAL ENVVGARNMD VKPLLNYFQP LFDWLKEQNR
610 620 630 640 650
NSFVGWNTEW SPYADQSIKV RISLKSALGA NAYEWTNNEM FLFRSSVAYA
660 670 680 690 700
MRKYFSIIKN QTVPFLEEDV RVSDLKPRVS FYFFVTSPQN VSDVIPRSEV
710 720 730 740 750
EDAIRMSRGR INDVFGLNDN SLEFLGIHPT LEPPYQPPVT IWLIIFGVVM
760 770 780 790 800
ALVVVGIIIL IVTGIKGRKK KNETKREENP YDSMDIGKGE SNAGFQNSDD

AQTSF
Length:805
Mass (Da):92,368
Last modified:June 1, 2002 - v1
Checksum:iD8B883AAC966A8D9
GO
Isoform 2 (identifier: Q8R0I0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     354-805: Missing.

Show »
Length:353
Mass (Da):40,340
Checksum:iD165D8C01739668F
GO

Sequence cautioni

The sequence BAB40431.1 differs from that shown. Reason: Frameshift at position 784. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti167 – 1671G → S in BAB40432 (PubMed:12487024).Curated
Sequence conflicti352 – 3521G → E in BAB40432 (PubMed:12487024).Curated
Sequence conflicti779 – 7791N → S in BAB40431 (PubMed:12487024).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei354 – 805452Missing in isoform 2. 1 PublicationVSP_014903Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB053181 mRNA. Translation: BAB40431.1. Frameshift.
AB053182 mRNA. Translation: BAB40432.1.
BC026801 mRNA. Translation: AAH26801.1.
CCDSiCCDS30518.1. [Q8R0I0-1]
RefSeqiNP_001123985.1. NM_001130513.1. [Q8R0I0-1]
NP_081562.2. NM_027286.4. [Q8R0I0-1]
UniGeneiMm.13451.

Genome annotation databases

EnsembliENSMUST00000073973; ENSMUSP00000073626; ENSMUSG00000015405. [Q8R0I0-1]
ENSMUST00000112271; ENSMUSP00000107890; ENSMUSG00000015405. [Q8R0I0-1]
GeneIDi70008.
KEGGimmu:70008.
UCSCiuc009uvf.2. mouse. [Q8R0I0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB053181 mRNA. Translation: BAB40431.1. Frameshift.
AB053182 mRNA. Translation: BAB40432.1.
BC026801 mRNA. Translation: AAH26801.1.
CCDSiCCDS30518.1. [Q8R0I0-1]
RefSeqiNP_001123985.1. NM_001130513.1. [Q8R0I0-1]
NP_081562.2. NM_027286.4. [Q8R0I0-1]
UniGeneiMm.13451.

3D structure databases

ProteinModelPortaliQ8R0I0.
SMRiQ8R0I0. Positions 19-615.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ8R0I0. 1 interaction.
MINTiMINT-4118343.
STRINGi10090.ENSMUSP00000073626.

Protein family/group databases

MEROPSiM02.006.

PTM databases

iPTMnetiQ8R0I0.
PhosphoSiteiQ8R0I0.

Proteomic databases

MaxQBiQ8R0I0.
PaxDbiQ8R0I0.
PRIDEiQ8R0I0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000073973; ENSMUSP00000073626; ENSMUSG00000015405. [Q8R0I0-1]
ENSMUST00000112271; ENSMUSP00000107890; ENSMUSG00000015405. [Q8R0I0-1]
GeneIDi70008.
KEGGimmu:70008.
UCSCiuc009uvf.2. mouse. [Q8R0I0-1]

Organism-specific databases

CTDi59272.
MGIiMGI:1917258. Ace2.

Phylogenomic databases

eggNOGiKOG3690. Eukaryota.
ENOG410XPJ3. LUCA.
GeneTreeiENSGT00520000055576.
HOGENOMiHOG000292210.
HOVERGENiHBG000265.
InParanoidiQ8R0I0.
KOiK09708.
OMAiCNPNNPQ.
OrthoDBiEOG76HQ13.
PhylomeDBiQ8R0I0.
TreeFamiTF312861.

Enzyme and pathway databases

BRENDAi3.4.17.23. 3474.
ReactomeiR-MMU-2022377. Metabolism of Angiotensinogen to Angiotensins.

Miscellaneous databases

PROiQ8R0I0.
SOURCEiSearch...

Gene expression databases

BgeeiQ8R0I0.
ExpressionAtlasiQ8R0I0. baseline and differential.
GenevisibleiQ8R0I0. MM.

Family and domain databases

InterProiIPR031588. Collectrin_dom.
IPR001548. Peptidase_M2.
[Graphical view]
PANTHERiPTHR10514. PTHR10514. 2 hits.
PfamiPF16959. Collectrin. 1 hit.
PF01401. Peptidase_M2. 1 hit.
[Graphical view]
PRINTSiPR00791. PEPDIPTASEA.
PROSITEiPS00678. WD_REPEATS_1. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning, mRNA expression, and chromosomal localization of mouse angiotensin-converting enzyme-related carboxypeptidase (mACE2)."
    Komatsu T., Suzuki Y., Imai J., Sugano S., Hida M., Tanigami A., Muroi S., Yamada Y., Hanaoka K.
    DNA Seq. 13:217-220(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: FVB/N.
    Tissue: Kidney.
  3. Cited for: FUNCTION, DISRUPTION PHENOTYPE.
  4. "Heart block, ventricular tachycardia, and sudden death in ACE2 transgenic mice with downregulated connexins."
    Donoghue M., Wakimoto H., Maguire C.T., Acton S., Hales P., Stagliano N., Fairchild-Huntress V., Xu J., Lorenz J.N., Kadambi V., Berul C.I., Breitbart R.E.
    J. Mol. Cell. Cardiol. 35:1043-1053(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2."
    Li W., Greenough T.C., Moore M.J., Vasilieva N., Somasundaran M., Sullivan J.L., Farzan M., Choe H.
    J. Virol. 78:11429-11433(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SARS-COV S PROTEIN.
  6. Cited for: TISSUE SPECIFICITY, INDUCTION, FUNCTION.
  7. "Organ-specific distribution of ACE2 mRNA and correlating peptidase activity in rodents."
    Gembardt F., Sterner-Kock A., Imboden H., Spalteholz M., Reibitz F., Schultheiss H.-P., Siems W.-E., Walther T.
    Peptides 26:1270-1277(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney.
  9. "Angiotensin II regulates ACE and ACE2 in neurons through p38 mitogen-activated protein kinase and extracellular signal-regulated kinase 1/2 signaling."
    Xiao L., Haack K.K., Zucker I.H.
    Am. J. Physiol. 304:C1073-C1079(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.

Entry informationi

Entry nameiACE2_MOUSE
AccessioniPrimary (citable) accession number: Q8R0I0
Secondary accession number(s): Q99N70, Q99N71
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: June 1, 2002
Last modified: June 8, 2016
This is version 115 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.