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P12822

- ACE_RABIT

UniProt

P12822 - ACE_RABIT

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Protein

Angiotensin-converting enzyme

Gene

ACE

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed - 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 Zn(2+) ions per subunit. Isoform Testis-specific only binds 1 Zn(2+) 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)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
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
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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini34 – 12601227ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1261 – 128121HelicalSequence AnalysisAdd
BLAST
Topological domaini1282 – 131029CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB-KW
  2. extracellular region Source: UniProtKB-KW
  3. integral component of membrane Source: UniProtKB-KW
  4. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

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...

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.
InParanoidiP12822.

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

        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)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:
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.

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 .
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.
InParanoidi P12822.

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: November 26, 2014
This is version 121 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