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Protein

Angiotensin-converting enzyme 2

Gene

Ace2

Organism
Rattus norvegicus (Rat)
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.1 Publication

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

Enzyme regulationi

Activated by chloride and fluoride, but not bromide. Inhibited by MLN-4760, cFP_Leu, and EDTA, but not by the ACE inhibitors linosipril, captopril, enalaprilat.1 Publication

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

  • maternal process involved in female pregnancy Source: RGD
  • negative regulation of ERK1 and ERK2 cascade Source: RGD
  • negative regulation of smooth muscle cell proliferation Source: RGD
  • viral entry into host cell Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Chloride, Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.17.23. 5301.

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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi728890. 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-SubCell
  • extracellular space Source: RGD
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: RGD
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Secreted

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL2311.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1717Sequence analysisAdd
BLAST
Chaini18 – 805788Angiotensin-converting enzyme 2PRO_0000028574Add
BLAST
Chaini18 – 708691Processed angiotensin-converting enzyme 2PRO_0000292272Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi53 – 531N-linked (GlcNAc...)Sequence analysis
Glycosylationi82 – 821N-linked (GlcNAc...)Sequence analysis
Glycosylationi90 – 901N-linked (GlcNAc...)Sequence analysis
Disulfide bondi133 ↔ 141By similarity
Glycosylationi299 – 2991N-linked (GlcNAc...)Sequence analysis
Disulfide bondi344 ↔ 361By similarity
Glycosylationi432 – 4321N-linked (GlcNAc...)Sequence analysis
Disulfide bondi530 ↔ 542By similarity
Glycosylationi546 – 5461N-linked (GlcNAc...)Sequence analysis
Glycosylationi601 – 6011N-linked (GlcNAc...)Sequence analysis
Glycosylationi660 – 6601N-linked (GlcNAc...)Sequence analysis
Glycosylationi690 – 6901N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Glycosylated.1 Publication
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

PaxDbiQ5EGZ1.
PRIDEiQ5EGZ1.

PTM databases

SwissPalmiQ5EGZ1.

Expressioni

Tissue specificityi

Expressed in heart, kidney and forebrain. In testis, expression is restricted to Leydig cells. In heart, expressed in endothelial cells from small and large arteries, arterial smooth muscle cells, and myocytes (at protein level). Ubiquitously expressed, with highest levels in ileum, bladder and lung.3 Publications

Inductioni

Down-regulated in hypertensive animals. Up-regulated after myocardial infarction.2 Publications

Interactioni

Subunit structurei

Interacts with ITGB1 and the catalytically active form of TMPRSS2.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000047913.

Chemistry

BindingDBiQ5EGZ1.

Structurei

3D structure databases

ProteinModelPortaliQ5EGZ1.
SMRiQ5EGZ1. 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

Sequence similaritiesi

Belongs to the peptidase M2 family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3690. Eukaryota.
ENOG410XPJ3. LUCA.
HOVERGENiHBG000265.
InParanoidiQ5EGZ1.
KOiK09708.
PhylomeDBiQ5EGZ1.

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]

Sequencei

Sequence statusi: Complete.

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

Q5EGZ1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSSSCWLLLS LVAVATAQSL IEEKAESFLN KFNQEAEDLS YQSSLASWNY
60 70 80 90 100
NTNITEENAQ KMNEAAAKWS AFYEEQSKIA QNFSLQEIQN ATIKRQLKAL
110 120 130 140 150
QQSGSSALSP DKNKQLNTIL NTMSTIYSTG KVCNSMNPQE CFLLEPGLDE
160 170 180 190 200
IMATSTDYNR RLWAWEGWRA EVGKQLRPLY EEYVVLKNEM ARANNYEDYG
210 220 230 240 250
DYWRGDYEAE GVEGYNYNRN QLIEDVENTF KEIKPLYEQL HAYVRTKLME
260 270 280 290 300
VYPSYISPTG CLPAHLLGDM WGRFWTNLYP LTTPFLQKPN IDVTDAMVNQ
310 320 330 340 350
SWDAERIFKE AEKFFVSVGL PQMTPGFWTN SMLTEPGDDR KVVCHPTAWD
360 370 380 390 400
LGHGDFRIKM CTKVTMDNFL TAHHEMGHIQ YDMAYAKQPF LLRNGANEGF
410 420 430 440 450
HEAVGEIMSL SAATPKHLKS IGLLPSNFQE DNETEINFLL KQALTIVGTL
460 470 480 490 500
PFTYMLEKWR WMVFQDKIPR EQWTKKWWEM KREIVGVVEP LPHDETYCDP
510 520 530 540 550
ASLFHVSNDY SFIRYYTRTI YQFQFQEALC QAAKHDGPLH KCDISNSTEA
560 570 580 590 600
GQKLLNMLSL GNSGPWTLAL ENVVGSRNMD VKPLLNYFQP LFVWLKEQNR
610 620 630 640 650
NSTVGWSTDW SPYADQSIKV RISLKSALGK NAYEWTDNEM YLFRSSVAYA
660 670 680 690 700
MREYFSREKN QTVPFGEADV WVSDLKPRVS FNFFVTSPKN VSDIIPRSEV
710 720 730 740 750
EEAIRMSRGR INDIFGLNDN SLEFLGIYPT LKPPYEPPVT IWLIIFGVVM
760 770 780 790 800
GTVVVGIVIL IVTGIKGRKK KNETKREENP YDSMDIGKGE SNAGFQNSDD

AQTSF
Length:805
Mass (Da):92,491
Last modified:March 15, 2005 - v1
Checksum:iA4079F2407960D28
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY881244 mRNA. Translation: AAW78017.1.
RefSeqiNP_001012006.1. NM_001012006.1.
UniGeneiRn.230337.

Genome annotation databases

GeneIDi302668.
KEGGirno:302668.
UCSCiRGD:728890. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY881244 mRNA. Translation: AAW78017.1.
RefSeqiNP_001012006.1. NM_001012006.1.
UniGeneiRn.230337.

3D structure databases

ProteinModelPortaliQ5EGZ1.
SMRiQ5EGZ1. Positions 19-615.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000047913.

Chemistry

BindingDBiQ5EGZ1.
ChEMBLiCHEMBL2311.

Protein family/group databases

MEROPSiM02.006.

PTM databases

SwissPalmiQ5EGZ1.

Proteomic databases

PaxDbiQ5EGZ1.
PRIDEiQ5EGZ1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi302668.
KEGGirno:302668.
UCSCiRGD:728890. rat.

Organism-specific databases

CTDi59272.
RGDi728890. Ace2.

Phylogenomic databases

eggNOGiKOG3690. Eukaryota.
ENOG410XPJ3. LUCA.
HOVERGENiHBG000265.
InParanoidiQ5EGZ1.
KOiK09708.
PhylomeDBiQ5EGZ1.

Enzyme and pathway databases

BRENDAi3.4.17.23. 5301.

Miscellaneous databases

PROiQ5EGZ1.

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

  1. "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: NUCLEOTIDE SEQUENCE [MRNA], LACK OF INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN.
    Strain: Sprague-Dawley.
  2. Cited for: FUNCTION, INDUCTION.
  3. "The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis."
    Douglas G.C., O'Bryan M.K., Hedger M.P., Lee D.K.L., Yarski M.A., Smith A.I., Lew R.A.
    Endocrinology 145:4703-4711(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, GLYCOSYLATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  4. Cited for: TISSUE SPECIFICITY, INDUCTION.
  5. "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.

Entry informationi

Entry nameiACE2_RAT
AccessioniPrimary (citable) accession number: Q5EGZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: March 15, 2005
Last modified: June 8, 2016
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

In contrast to its human and palm-civet orthologs, does not interact with SARS-CoV spike glycoprotein.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

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.