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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)DescriptionActionsGraphical viewLength
Binding sitei169ChlorideBy similarity1
Binding sitei273SubstrateBy similarity1
Binding sitei345SubstrateBy similarity1
Binding sitei346Substrate; via carbonyl oxygenBy similarity1
Binding sitei371SubstrateBy similarity1
Metal bindingi374Zinc; catalyticPROSITE-ProRule annotation1
Active sitei375PROSITE-ProRule annotation1
Metal bindingi378Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi402Zinc; catalyticPROSITE-ProRule annotation1
Binding sitei477ChlorideBy similarity1
Binding sitei481ChlorideBy similarity1
Active sitei505PROSITE-ProRule annotation1
Binding sitei515SubstrateBy similarity1

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)DescriptionActionsGraphical viewLength
Topological domaini18 – 740ExtracellularSequence analysisAdd BLAST723
Transmembranei741 – 761HelicalSequence analysisAdd BLAST21
Topological domaini762 – 805CytoplasmicSequence analysisAdd BLAST44

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)DescriptionActionsGraphical viewLength
Signal peptidei1 – 17Sequence analysisAdd BLAST17
ChainiPRO_000002857118 – 805Angiotensin-converting enzyme 2Add BLAST788
ChainiPRO_000029226918 – 708Processed angiotensin-converting enzyme 2Add BLAST691

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi53N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi133 ↔ 141By similarity
Disulfide bondi344 ↔ 361By similarity
Disulfide bondi530 ↔ 542By similarity
Glycosylationi536N-linked (GlcNAc...)Sequence analysis1
Glycosylationi546N-linked (GlcNAc...)Sequence analysis1
Glycosylationi660N-linked (GlcNAc...)Sequence analysis1
Glycosylationi690N-linked (GlcNAc...)Sequence analysis1

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

PaxDbiQ8R0I0.
PeptideAtlasiQ8R0I0.
PRIDEiQ8R0I0.

PTM databases

iPTMnetiQ8R0I0.
PhosphoSitePlusiQ8R0I0.

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

BgeeiENSMUSG00000015405.
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

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ8R0I0.
SMRiQ8R0I0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni652 – 659Essential for cleavage by ADAM17By similarity8
Regioni697 – 716Essential for cleavage by TMPRSS11D and TMPRSS2By similarityAdd BLAST20

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3690. Eukaryota.
ENOG410XPJ3. LUCA.
GeneTreeiENSGT00520000055576.
HOGENOMiHOG000292210.
HOVERGENiHBG000265.
InParanoidiQ8R0I0.
KOiK09708.
OMAiCNPNNPQ.
OrthoDBiEOG091G033S.
PhylomeDBiQ8R0I0.
TreeFamiTF312861.

Family and domain databases

CDDicd06461. M2_ACE. 1 hit.
InterProiIPR033591. ACE2.
IPR031588. Collectrin_dom.
IPR001548. Peptidase_M2.
[Graphical view]
PANTHERiPTHR10514. PTHR10514. 2 hits.
PTHR10514:SF24. PTHR10514:SF24. 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 differs from that shown. Reason: Frameshift at position 784.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti167G → S in BAB40432 (PubMed:12487024).Curated1
Sequence conflicti352G → E in BAB40432 (PubMed:12487024).Curated1
Sequence conflicti779N → S in BAB40431 (PubMed:12487024).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014903354 – 805Missing in isoform 2. 1 PublicationAdd BLAST452

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Protein family/group databases

MEROPSiM02.006.

PTM databases

iPTMnetiQ8R0I0.
PhosphoSitePlusiQ8R0I0.

Proteomic databases

PaxDbiQ8R0I0.
PeptideAtlasiQ8R0I0.
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.
OrthoDBiEOG091G033S.
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

BgeeiENSMUSG00000015405.
ExpressionAtlasiQ8R0I0. baseline and differential.
GenevisibleiQ8R0I0. MM.

Family and domain databases

CDDicd06461. M2_ACE. 1 hit.
InterProiIPR033591. ACE2.
IPR031588. Collectrin_dom.
IPR001548. Peptidase_M2.
[Graphical view]
PANTHERiPTHR10514. PTHR10514. 2 hits.
PTHR10514:SF24. PTHR10514:SF24. 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...

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: November 30, 2016
This is version 120 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.