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Protein

Angiotensin-converting enzyme

Gene

ACE

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety (By similarity).By similarity

Catalytic activityi

Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit. Isoform Testis-specific only binds 1 Zn2+ ion per subunit.By similarity
  • chlorideBy similarityNote: Binds 3 chloride ions per subunit.By similarity

Enzyme regulationi

Strongly activated by chloride. Specifically inhibited by lisinopril.1 Publication

Kineticsi

  1. KM=0.6 mM for Hip-His-Leu1 Publication
  2. KM=0.09 mM for angiotensin I1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei236Chloride 1By similarity1
    Metal bindingi395Zinc 1; catalyticBy similarity1
    Active sitei3961PROSITE-ProRule annotation1
    Metal bindingi399Zinc 1; catalyticBy similarity1
    Metal bindingi422Zinc 1; catalyticBy similarity1
    Binding sitei533Chloride 1By similarity1
    Binding sitei795Chloride 2By similarity1
    Binding sitei833Chloride 3By similarity1
    Metal bindingi992Zinc 2; catalyticBy similarity1
    Active sitei9932PROSITE-ProRule annotation1
    Metal bindingi996Zinc 2; catalyticBy similarity1
    Metal bindingi1020Zinc 2; catalyticBy similarity1
    Binding sitei1094Chloride 2By similarity1
    Binding sitei1098Chloride 2By similarity1
    Binding sitei1131Chloride 3By similarity1

    GO - Molecular functioni

    Complete GO annotation...

    Keywords - Molecular functioni

    Carboxypeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    SABIO-RKP12822.

    Protein family/group databases

    MEROPSiM02.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Angiotensin-converting enzyme (EC:3.2.1.-, EC:3.4.15.1)
    Short name:
    ACE
    Alternative name(s):
    Dipeptidyl carboxypeptidase I
    Kininase II
    CD_antigen: CD143
    Cleaved into the following chain:
    Gene namesi
    Name:ACE
    Synonyms:DCP1
    OrganismiOryctolagus cuniculus (Rabbit)
    Taxonomic identifieri9986 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
    Proteomesi
    • UP000001811 Componenti: Unplaced

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini34 – 1260ExtracellularSequence analysisAdd BLAST1227
    Transmembranei1261 – 1281HelicalSequence analysisAdd BLAST21
    Topological domaini1282 – 1310CytoplasmicSequence analysisAdd BLAST29

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi727K → E: No effect on activity. 20-fold reduction in catalytic efficiency; when associated with F-809. 1 Publication1
    Mutagenesisi809Y → F: No effect on activity. 20-fold reduction in catalytic efficiency; when associated with E-727. 1 Publication1

    Chemistry databases

    ChEMBLiCHEMBL4074.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 333 PublicationsAdd BLAST33
    ChainiPRO_000002855134 – 1310Angiotensin-converting enzymeAdd BLAST1277
    ChainiPRO_000002855234 – 1236Angiotensin-converting enzyme, soluble formAdd BLAST1203
    PropeptideiPRO_00000285531237 – 1310Removed in secreted formBy similarityAdd BLAST74

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi59N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi79N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi151N-linked (GlcNAc...)Sequence analysis1
    Disulfide bondi162 ↔ 170By similarity
    Glycosylationi323N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi449N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi513N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi681N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi699N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi718N-linked (GlcNAc...)Sequence analysis1
    Disulfide bondi761 ↔ 767By similarity
    Glycosylationi946N-linked (GlcNAc...)Sequence analysis1
    Disulfide bondi961 ↔ 979By similarity
    Disulfide bondi1147 ↔ 1159By similarity
    Glycosylationi1195N-linked (GlcNAc...)Sequence analysis1
    Modified residuei1303PhosphoserineBy similarity1

    Post-translational modificationi

    N-glycosylated.1 Publication
    Phosphorylated by CK2 on Ser-1303; which allows membrane retention.By similarity

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei1237 – 1238Cleavage2

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    PRIDEiP12822.

    Expressioni

    Tissue specificityi

    Testis-specific isoform is expressed in spermatocytes, adult testis.

    Interactioni

    Protein-protein interaction databases

    STRINGi9986.ENSOCUP00000016378.

    Chemistry databases

    BindingDBiP12822.

    Structurei

    3D structure databases

    ProteinModelPortaliP12822.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni35 – 634Peptidase M2 1Add BLAST600
    Regioni635 – 1236Peptidase M2 2Add BLAST602

    Sequence similaritiesi

    Belongs to the peptidase M2 family.Curated

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3690. Eukaryota.
    ENOG410XPJ3. LUCA.
    HOGENOMiHOG000007838.
    HOVERGENiHBG000264.
    InParanoidiP12822.
    KOiK01283.

    Family and domain databases

    CDDicd06461. M2_ACE. 2 hits.
    InterProiIPR001548. Peptidase_M2.
    [Graphical view]
    PANTHERiPTHR10514. PTHR10514. 1 hit.
    PfamiPF01401. Peptidase_M2. 2 hits.
    [Graphical view]
    PRINTSiPR00791. PEPDIPTASEA.
    PROSITEiPS00142. ZINC_PROTEASE. 2 hits.
    [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 Somatic (identifier: P12822-1) [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
    MGAAPGRRGP RLLRPPPPLL LLLLLLRPPP AALTLDPGLL PGDFAADEAG
    60 70 80 90 100
    ARLFASSYNS SAEQVLFRST AASWAHDTNI TAENARRQEE EALLSQEFAE
    110 120 130 140 150
    AWGKKAKELY DPVWQNFTDP ELRRIIGAVR TLGPANLPLA KRQQYNSLLS
    160 170 180 190 200
    NMSQIYSTGK VCFPNKTASC WSLDPDLNNI LASSRSYAML LFAWEGWHNA
    210 220 230 240 250
    VGIPLKPLYQ EFTALSNEAY RQDGFSDTGA YWRSWYDSPT FEEDLERIYH
    260 270 280 290 300
    QLEPLYLNLH AYVRRVLHRR YGDRYINLRG PIPAHLLGNM WAQSWESIYD
    310 320 330 340 350
    MVVPFPDKPN LDVTSTMVQK GWNATHMFRV AEEFFTSLGL LPMPPEFWAE
    360 370 380 390 400
    SMLEKPEDGR EVVCHASAWD FYNRKDFRIK QCTQVTMDQL STVHHEMGHV
    410 420 430 440 450
    QYYLQYKDQP VSLRRANPGF HEAIGDVLAL SVSTPAHLHK IGLLDHVTND
    460 470 480 490 500
    TESDINYLLK MALEKIAFLP FGYLVDQWRW GVFSGRTPSS RYNFDWWYLR
    510 520 530 540 550
    TKYQGICPPV VRNETHFDAG AKFHIPSVTP YIRYFVSFVL QFQFHQALCM
    560 570 580 590 600
    EAGHQGPLHQ CDIYQSTRAG AKLRAVLQAG CSRPWQEVLK DMVASDALDA
    610 620 630 640 650
    QPLLDYFQPV TQWLQEQNER NGEVLGWPEY QWRPPLPNNY PEGIDLVTDE
    660 670 680 690 700
    AEASRFVEEY DRSFQAVWNE YAEANWNYNT NITTEASKIL LQKNMQIANH
    710 720 730 740 750
    TLTYGNWARR FDVSNFQNAT SKRIIKKVQD LQRAVLPVKE LEEYNQILLD
    760 770 780 790 800
    METIYSVANV CRVDGSCLQL EPDLTNLMAT SRKYDELLWV WTSWRDKVGR
    810 820 830 840 850
    AILPYFPKYV EFTNKAARLN GYVDAGDSWR SMYETPTLEQ DLERLFQELQ
    860 870 880 890 900
    PLYLNLHAYV GRALHRHYGA QHINLEGPIP AHLLGNMWAQ TWSNIYDLVA
    910 920 930 940 950
    PFPSASTMDA TEAMIKQGWT PRRMFEEADK FFISLGLLPV PPEFWNKSML
    960 970 980 990 1000
    EKPTDGREVV CHASAWDFYN GKDFRIKQCT TVNMEDLVVV HHEMGHIQYF
    1010 1020 1030 1040 1050
    MQYKDLPVAL REGANPGFHE AIGDVLALSV STPKHLHSIN LLSSEGGGYE
    1060 1070 1080 1090 1100
    HDINFLMKMA LDKIAFIPFS YLVDEWRWRV FDGSITKENY NQEWWSLRLK
    1110 1120 1130 1140 1150
    YQGLCPPAPR SQGDFDPGAK FHIPSSVPYI RYFVSFIIQF QFHEALCKAA
    1160 1170 1180 1190 1200
    GHTGPLHTCD IYQSKEAGKR LADAMKLGYS KPWPEAMKVI TGQPNMSASA
    1210 1220 1230 1240 1250
    MMNYFKPLMD WLLTENGRHG EKLGWPQYTW TPNSARSEGS LPDSGRVNFL
    1260 1270 1280 1290 1300
    GMNLDAQQAR VGQWVLLFLG VALLLASLGL TQRLFSIRYQ SLRQPHHGPQ
    1310
    FGSEVELRHS
    Length:1,310
    Mass (Da):150,406
    Last modified:November 1, 1997 - v3
    Checksum:i04777FAB17981DEA
    GO
    Isoform Testis-specific (identifier: P12822-2) [UniParc] [UniParc]FASTAAdd to basket
    Also known as: ACE-T

    The sequence of this isoform differs from the canonical sequence as follows:
         1-573: Missing.
         574-645: RAVLQAGCSR...LPNNYPEGID → MGQGWAAPGL...TAHQTTQSPN

    Show »
    Length:737
    Mass (Da):83,924
    Checksum:iFC43CC76655C3DCA
    GO

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti48E → N AA sequence (PubMed:6314908).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0376441 – 573Missing in isoform Testis-specific. 1 PublicationAdd BLAST573
    Alternative sequenceiVSP_037645574 – 645RAVLQ…PEGID → MGQGWAAPGLPSLLLLLLCC GHSLLVPSRVAARRVTVNQG TTSQATTTSKATTSIRATTH QTTAHQTTQSPN in isoform Testis-specific. 1 PublicationAdd BLAST72

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X62551 mRNA. Translation: CAA44428.1.
    J05041 mRNA. Translation: AAA31153.1.
    M58579 Genomic DNA. Translation: AAA31151.1. Sequence problems.
    M58580 Genomic DNA. Translation: AAA31152.1.
    PIRiA34402.
    S35484.
    RefSeqiNP_001075864.1. NM_001082395.1. [P12822-1]
    NP_001164540.1. NM_001171069.1. [P12822-2]
    UniGeneiOcu.1824.

    Genome annotation databases

    GeneIDi100009274.
    KEGGiocu:100009274.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    X62551 mRNA. Translation: CAA44428.1.
    J05041 mRNA. Translation: AAA31153.1.
    M58579 Genomic DNA. Translation: AAA31151.1. Sequence problems.
    M58580 Genomic DNA. Translation: AAA31152.1.
    PIRiA34402.
    S35484.
    RefSeqiNP_001075864.1. NM_001082395.1. [P12822-1]
    NP_001164540.1. NM_001171069.1. [P12822-2]
    UniGeneiOcu.1824.

    3D structure databases

    ProteinModelPortaliP12822.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi9986.ENSOCUP00000016378.

    Chemistry databases

    BindingDBiP12822.
    ChEMBLiCHEMBL4074.

    Protein family/group databases

    MEROPSiM02.001.

    Proteomic databases

    PRIDEiP12822.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    GeneIDi100009274.
    KEGGiocu:100009274.

    Organism-specific databases

    CTDi1636.

    Phylogenomic databases

    eggNOGiKOG3690. Eukaryota.
    ENOG410XPJ3. LUCA.
    HOGENOMiHOG000007838.
    HOVERGENiHBG000264.
    InParanoidiP12822.
    KOiK01283.

    Enzyme and pathway databases

    SABIO-RKP12822.

    Family and domain databases

    CDDicd06461. M2_ACE. 2 hits.
    InterProiIPR001548. Peptidase_M2.
    [Graphical view]
    PANTHERiPTHR10514. PTHR10514. 1 hit.
    PfamiPF01401. Peptidase_M2. 2 hits.
    [Graphical view]
    PRINTSiPR00791. PEPDIPTASEA.
    PROSITEiPS00142. ZINC_PROTEASE. 2 hits.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiACE_RABIT
    AccessioniPrimary (citable) accession number: P12822
    Secondary accession number(s): O02852, P22968
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: November 1, 1997
    Last modified: November 30, 2016
    This is version 131 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Glycosyl hydrolases
      Classification of glycosyl hydrolase families and list of entries
    2. Peptidase families
      Classification of peptidase families and list of entries
    3. 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.