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P12822

- ACE_RABIT

UniProt

P12822 - ACE_RABIT

Protein

Angiotensin-converting enzyme

Gene

ACE

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 3 (01 Nov 1997)
      Previous versions | rss
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    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

    Binds 2 zinc ions per subunit. Isoform Testis-specific only binds 1 zinc ion per subunit By similarity.By similarity
    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)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei236 – 2361Chloride 1By similarity
    Metal bindingi395 – 3951Zinc 1; catalyticBy similarity
    Active sitei396 – 39611PROSITE-ProRule annotation
    Metal bindingi399 – 3991Zinc 1; catalyticBy similarity
    Metal bindingi422 – 4221Zinc 1; catalyticBy similarity
    Binding sitei533 – 5331Chloride 1By similarity
    Binding sitei795 – 7951Chloride 2By similarity
    Binding sitei833 – 8331Chloride 3By similarity
    Metal bindingi992 – 9921Zinc 2; catalyticBy similarity
    Active sitei993 – 99312PROSITE-ProRule annotation
    Metal bindingi996 – 9961Zinc 2; catalyticBy similarity
    Metal bindingi1020 – 10201Zinc 2; catalyticBy similarity
    Binding sitei1094 – 10941Chloride 2By similarity
    Binding sitei1098 – 10981Chloride 2By similarity
    Binding sitei1131 – 11311Chloride 3By similarity
    Sitei1237 – 12382Cleavage

    GO - Molecular functioni

    1. carboxypeptidase activity Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. metallopeptidase activity Source: UniProtKB-KW
    4. peptidyl-dipeptidase activity Source: InterPro

    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
    ProteomesiUP000001811: Unplaced

    Subcellular locationi

    Cell membrane By similarity; Single-pass type I membrane protein By similarity. Cytoplasm By similarity
    Note: Detected in both cell membrane and cytoplasm in neurons.By similarity

    GO - Cellular componenti

    1. extracellular region Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. plasma membrane Source: UniProtKB-SubCell

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Secreted

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi727 – 7271K → E: No effect on activity. 20-fold reduction in catalytic efficiency; when associated with F-809. 1 Publication
    Mutagenesisi809 – 8091Y → F: No effect on activity. 20-fold reduction in catalytic efficiency; when associated with E-727. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 33333 PublicationsAdd
    BLAST
    Chaini34 – 13101277Angiotensin-converting enzymePRO_0000028551Add
    BLAST
    Chaini34 – 12361203Angiotensin-converting enzyme, soluble formPRO_0000028552Add
    BLAST
    Propeptidei1237 – 131074Removed in secreted formBy similarityPRO_0000028553Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi59 – 591N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi79 – 791N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi151 – 1511N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi162 ↔ 170By similarity
    Glycosylationi323 – 3231N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi449 – 4491N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi513 – 5131N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi681 – 6811N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi699 – 6991N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi718 – 7181N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi761 ↔ 767By similarity
    Glycosylationi946 – 9461N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi961 ↔ 979By similarity
    Disulfide bondi1147 ↔ 1159By similarity
    Glycosylationi1195 – 11951N-linked (GlcNAc...)Sequence Analysis
    Modified residuei1303 – 13031PhosphoserineBy similarity

    Post-translational modificationi

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

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Expressioni

    Tissue specificityi

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

    Interactioni

    Structurei

    3D structure databases

    ProteinModelPortaliP12822.
    SMRiP12822. Positions 35-645, 649-1232.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini34 – 12601227ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1282 – 131029CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1261 – 128121HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni35 – 634600Peptidase M2 1Add
    BLAST
    Regioni635 – 1236602Peptidase M2 2Add
    BLAST

    Sequence similaritiesi

    Belongs to the peptidase M2 family.Curated

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG71044.
    HOGENOMiHOG000007838.
    HOVERGENiHBG000264.

    Family and domain databases

    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. Align

    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

    MGAAPGRRGP RLLRPPPPLL LLLLLLRPPP AALTLDPGLL PGDFAADEAG     50
    ARLFASSYNS SAEQVLFRST AASWAHDTNI TAENARRQEE EALLSQEFAE 100
    AWGKKAKELY DPVWQNFTDP ELRRIIGAVR TLGPANLPLA KRQQYNSLLS 150
    NMSQIYSTGK VCFPNKTASC WSLDPDLNNI LASSRSYAML LFAWEGWHNA 200
    VGIPLKPLYQ EFTALSNEAY RQDGFSDTGA YWRSWYDSPT FEEDLERIYH 250
    QLEPLYLNLH AYVRRVLHRR YGDRYINLRG PIPAHLLGNM WAQSWESIYD 300
    MVVPFPDKPN LDVTSTMVQK GWNATHMFRV AEEFFTSLGL LPMPPEFWAE 350
    SMLEKPEDGR EVVCHASAWD FYNRKDFRIK QCTQVTMDQL STVHHEMGHV 400
    QYYLQYKDQP VSLRRANPGF HEAIGDVLAL SVSTPAHLHK IGLLDHVTND 450
    TESDINYLLK MALEKIAFLP FGYLVDQWRW GVFSGRTPSS RYNFDWWYLR 500
    TKYQGICPPV VRNETHFDAG AKFHIPSVTP YIRYFVSFVL QFQFHQALCM 550
    EAGHQGPLHQ CDIYQSTRAG AKLRAVLQAG CSRPWQEVLK DMVASDALDA 600
    QPLLDYFQPV TQWLQEQNER NGEVLGWPEY QWRPPLPNNY PEGIDLVTDE 650
    AEASRFVEEY DRSFQAVWNE YAEANWNYNT NITTEASKIL LQKNMQIANH 700
    TLTYGNWARR FDVSNFQNAT SKRIIKKVQD LQRAVLPVKE LEEYNQILLD 750
    METIYSVANV CRVDGSCLQL EPDLTNLMAT SRKYDELLWV WTSWRDKVGR 800
    AILPYFPKYV EFTNKAARLN GYVDAGDSWR SMYETPTLEQ DLERLFQELQ 850
    PLYLNLHAYV GRALHRHYGA QHINLEGPIP AHLLGNMWAQ TWSNIYDLVA 900
    PFPSASTMDA TEAMIKQGWT PRRMFEEADK FFISLGLLPV PPEFWNKSML 950
    EKPTDGREVV CHASAWDFYN GKDFRIKQCT TVNMEDLVVV HHEMGHIQYF 1000
    MQYKDLPVAL REGANPGFHE AIGDVLALSV STPKHLHSIN LLSSEGGGYE 1050
    HDINFLMKMA LDKIAFIPFS YLVDEWRWRV FDGSITKENY NQEWWSLRLK 1100
    YQGLCPPAPR SQGDFDPGAK FHIPSSVPYI RYFVSFIIQF QFHEALCKAA 1150
    GHTGPLHTCD IYQSKEAGKR LADAMKLGYS KPWPEAMKVI TGQPNMSASA 1200
    MMNYFKPLMD WLLTENGRHG EKLGWPQYTW TPNSARSEGS LPDSGRVNFL 1250
    GMNLDAQQAR VGQWVLLFLG VALLLASLGL TQRLFSIRYQ SLRQPHHGPQ 1300
    FGSEVELRHS 1310
    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)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti48 – 481E → N AA sequence (PubMed:6314908)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 573573Missing in isoform Testis-specific. 1 PublicationVSP_037644Add
    BLAST
    Alternative sequencei574 – 64572RAVLQ…PEGID → MGQGWAAPGLPSLLLLLLCC GHSLLVPSRVAARRVTVNQG TTSQATTTSKATTSIRATTH QTTAHQTTQSPN in isoform Testis-specific. 1 PublicationVSP_037645Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    PIRi A34402.
    S35484.
    RefSeqi NP_001075864.1. NM_001082395.1. [P12822-1 ]
    NP_001164540.1. NM_001171069.1. [P12822-2 ]
    UniGenei Ocu.1824.

    3D structure databases

    ProteinModelPortali P12822.
    SMRi P12822. Positions 35-645, 649-1232.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi P12822.
    ChEMBLi CHEMBL4074.

    Protein family/group databases

    MEROPSi M02.001.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    GeneIDi 100009274.

    Organism-specific databases

    CTDi 1636.

    Phylogenomic databases

    eggNOGi NOG71044.
    HOGENOMi HOG000007838.
    HOVERGENi HBG000264.

    Enzyme and pathway databases

    SABIO-RK P12822.

    Family and domain databases

    InterProi IPR001548. Peptidase_M2.
    [Graphical view ]
    PANTHERi PTHR10514. PTHR10514. 1 hit.
    Pfami PF01401. Peptidase_M2. 2 hits.
    [Graphical view ]
    PRINTSi PR00791. PEPDIPTASEA.
    PROSITEi PS00142. ZINC_PROTEASE. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Use of alternative polyadenylation sites for tissue-specific transcription of two angiotensin-converting enzyme mRNAs."
      Thekkumkara T.J., Livingston W. III, Kumar R.S., Sen G.C.
      Nucleic Acids Res. 20:683-687(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC).
      Tissue: Lung.
    2. Sen G.C.
      Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: SEQUENCE REVISION.
    3. "Structure of testicular angiotensin-converting enzyme. A segmental mosaic isozyme."
      Kumar R.S., Kusari J., Roy S.N., Soffer R.L., Sen G.C.
      J. Biol. Chem. 264:16754-16758(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC).
      Strain: New Zealand white.
      Tissue: Testis.
    4. "The mRNAs encoding the two angiotensin-converting isozymes are transcribed from the same gene by a tissue-specific choice of alternative transcription initiation sites."
      Kumar R.S., Thekkumkara T.J., Sen G.C.
      J. Biol. Chem. 266:3854-3862(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-88, ALTERNATIVE SPLICING.
      Tissue: Liver.
    5. "The NH2- and COOH-terminal sequences of the angiotensin-converting enzyme isozymes from rabbit lung and testis."
      Iwata K., Lai C.Y., El-Dorry H.A., Soffer R.L.
      Biochem. Biophys. Res. Commun. 107:1097-1103(1982) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 34-44 AND 755-758.
    6. "Rabbit pulmonary angiotensin-converting enzyme: the NH2-terminal fragment with enzymatic activity and its formation from the native enzyme by NH4OH treatment."
      Iwata K., Blacher R., Soffer R.L., Lai C.Y.
      Arch. Biochem. Biophys. 227:188-201(1983) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 34-55.
      Tissue: Lung.
    7. "The Mg(2+)-ATPase of rabbit skeletal-muscle transverse tubule is a highly glycosylated multiple-subunit enzyme."
      Kirley T.L.
      Biochem. J. 278:375-380(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 34-55, GLYCOSYLATION.
    8. "Angiotensin-converting enzyme: structural relationship of the testicular and the pulmonary forms."
      Sen G.C., Thekkumkara T.J., Kumar R.S.
      J. Cardiovasc. Pharmacol. 16:S14-S18(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE OF 646-746.
    9. "Identification of essential tyrosine and lysine residues in angiotensin converting enzyme: evidence for a single active site."
      Chen Y.N., Riordan J.F.
      Biochemistry 29:10493-10498(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 727-733 AND 809-815.
    10. "Regulated cleavage-secretion of the membrane-bound angiotensin-converting enzyme."
      Ramchandran R., Sen G.C., Misono K., Sen I.
      J. Biol. Chem. 269:2125-2130(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 1237-1259, CLEAVAGE SITE.
    11. "Mutations in two specific residues of testicular angiotensin-converting enzyme change its catalytic properties."
      Sen I., Kasturi S., Abdul-Jabbar M., Sen G.C.
      J. Biol. Chem. 268:25748-25754(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: MUTAGENESIS OF LYS-727 AND TYR-809, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.

    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: October 1, 2014
    This is version 119 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

    External Data

    Dasty 3