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P12822 (ACE_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Angiotensin-converting enzyme

Short name=ACE
EC=3.2.1.-
EC=3.4.15.1
Alternative name(s):
Dipeptidyl carboxypeptidase I
Kininase II
CD_antigen=CD143

Cleaved into the following chain:

  1. Angiotensin-converting enzyme, soluble form
Gene names
Name:ACE
Synonyms:DCP1
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

Protein attributes

Sequence length1310 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Catalytic activity

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.

Cofactor

Binds 2 zinc ions per subunit. Isoform Testis-specific only binds 1 zinc ion per subunit By similarity.

Binds 3 chloride ions per subunit By similarity.

Enzyme regulation

Strongly activated by chloride. Specifically inhibited by lisinopril. Ref.11

Subcellular location

Angiotensin-converting enzyme, soluble form: Secreted By similarity.

Cell membrane; Single-pass type I membrane protein By similarity.

Tissue specificity

Testis-specific isoform isexpressed in spermatocytes, adult testis.

Post-translational modification

N-glycosylated. Ref.7

Phosphorylated by CK2 on Ser-1303; which allows membrane retention By similarity.

Sequence similarities

Belongs to the peptidase M2 family.

Biophysicochemical properties

Kinetic parameters:

KM=0.6 mM for Hip-His-Leu Ref.11

KM=0.09 mM for angiotensin I

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Somatic (identifier: P12822-1)

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.
Isoform Testis-specific (identifier: P12822-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3333 Ref.5 Ref.6 Ref.7
Chain34 – 13101277Angiotensin-converting enzyme
PRO_0000028551
Chain34 – 12361203Angiotensin-converting enzyme, soluble form
PRO_0000028552
Propeptide1237 – 131074Removed in secreted form By similarity
PRO_0000028553

Regions

Topological domain34 – 12601227Extracellular Potential
Transmembrane1261 – 128121Helical; Potential
Topological domain1282 – 131029Cytoplasmic Potential
Region35 – 634600Peptidase M2 1
Region635 – 1236602Peptidase M2 2

Sites

Active site39611 By similarity
Active site99312 By similarity
Metal binding3951Zinc 1; catalytic By similarity
Metal binding3991Zinc 1; catalytic By similarity
Metal binding4221Zinc 1; catalytic By similarity
Metal binding9921Zinc 2; catalytic By similarity
Metal binding9961Zinc 2; catalytic By similarity
Metal binding10201Zinc 2; catalytic By similarity
Binding site2361Chloride 1 By similarity
Binding site5331Chloride 1 By similarity
Binding site7951Chloride 2 By similarity
Binding site8331Chloride 3 By similarity
Binding site10941Chloride 2 By similarity
Binding site10981Chloride 2 By similarity
Binding site11311Chloride 3 By similarity
Site1237 – 12382Cleavage

Amino acid modifications

Modified residue13031Phosphoserine By similarity
Glycosylation591N-linked (GlcNAc...) Potential
Glycosylation791N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Potential
Glycosylation3231N-linked (GlcNAc...) Potential
Glycosylation4491N-linked (GlcNAc...) Potential
Glycosylation5131N-linked (GlcNAc...) Potential
Glycosylation6811N-linked (GlcNAc...) Potential
Glycosylation6991N-linked (GlcNAc...) Potential
Glycosylation7181N-linked (GlcNAc...) Potential
Glycosylation9461N-linked (GlcNAc...) Potential
Glycosylation11951N-linked (GlcNAc...) Potential
Disulfide bond162 ↔ 170 By similarity
Disulfide bond761 ↔ 767 By similarity
Disulfide bond961 ↔ 979 By similarity
Disulfide bond1147 ↔ 1159 By similarity

Natural variations

Alternative sequence1 – 573573Missing in isoform Testis-specific.
VSP_037644
Alternative sequence574 – 64572RAVLQ…PEGID → MGQGWAAPGLPSLLLLLLCC GHSLLVPSRVAARRVTVNQG TTSQATTTSKATTSIRATTH QTTAHQTTQSPN in isoform Testis-specific.
VSP_037645

Experimental info

Mutagenesis7271K → E: No effect on activity. 20-fold reduction in catalytic efficiency; when associated with F-809. Ref.11
Mutagenesis8091Y → F: No effect on activity. 20-fold reduction in catalytic efficiency; when associated with E-727. Ref.11
Sequence conflict481E → N AA sequence Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform Somatic [UniParc].

Last modified November 1, 1997. Version 3.
Checksum: 04777FAB17981DEA

FASTA1,310150,406
        10         20         30         40         50         60 
MGAAPGRRGP RLLRPPPPLL LLLLLLRPPP AALTLDPGLL PGDFAADEAG ARLFASSYNS 

        70         80         90        100        110        120 
SAEQVLFRST AASWAHDTNI TAENARRQEE EALLSQEFAE AWGKKAKELY DPVWQNFTDP 

       130        140        150        160        170        180 
ELRRIIGAVR TLGPANLPLA KRQQYNSLLS NMSQIYSTGK VCFPNKTASC WSLDPDLNNI 

       190        200        210        220        230        240 
LASSRSYAML LFAWEGWHNA VGIPLKPLYQ EFTALSNEAY RQDGFSDTGA YWRSWYDSPT 

       250        260        270        280        290        300 
FEEDLERIYH QLEPLYLNLH AYVRRVLHRR YGDRYINLRG PIPAHLLGNM WAQSWESIYD 

       310        320        330        340        350        360 
MVVPFPDKPN LDVTSTMVQK GWNATHMFRV AEEFFTSLGL LPMPPEFWAE SMLEKPEDGR 

       370        380        390        400        410        420 
EVVCHASAWD FYNRKDFRIK QCTQVTMDQL STVHHEMGHV QYYLQYKDQP VSLRRANPGF 

       430        440        450        460        470        480 
HEAIGDVLAL SVSTPAHLHK IGLLDHVTND TESDINYLLK MALEKIAFLP FGYLVDQWRW 

       490        500        510        520        530        540 
GVFSGRTPSS RYNFDWWYLR TKYQGICPPV VRNETHFDAG AKFHIPSVTP YIRYFVSFVL 

       550        560        570        580        590        600 
QFQFHQALCM EAGHQGPLHQ CDIYQSTRAG AKLRAVLQAG CSRPWQEVLK DMVASDALDA 

       610        620        630        640        650        660 
QPLLDYFQPV TQWLQEQNER NGEVLGWPEY QWRPPLPNNY PEGIDLVTDE AEASRFVEEY 

       670        680        690        700        710        720 
DRSFQAVWNE YAEANWNYNT NITTEASKIL LQKNMQIANH TLTYGNWARR FDVSNFQNAT 

       730        740        750        760        770        780 
SKRIIKKVQD LQRAVLPVKE LEEYNQILLD METIYSVANV CRVDGSCLQL EPDLTNLMAT 

       790        800        810        820        830        840 
SRKYDELLWV WTSWRDKVGR AILPYFPKYV EFTNKAARLN GYVDAGDSWR SMYETPTLEQ 

       850        860        870        880        890        900 
DLERLFQELQ PLYLNLHAYV GRALHRHYGA QHINLEGPIP AHLLGNMWAQ TWSNIYDLVA 

       910        920        930        940        950        960 
PFPSASTMDA TEAMIKQGWT PRRMFEEADK FFISLGLLPV PPEFWNKSML EKPTDGREVV 

       970        980        990       1000       1010       1020 
CHASAWDFYN GKDFRIKQCT TVNMEDLVVV HHEMGHIQYF MQYKDLPVAL REGANPGFHE 

      1030       1040       1050       1060       1070       1080 
AIGDVLALSV STPKHLHSIN LLSSEGGGYE HDINFLMKMA LDKIAFIPFS YLVDEWRWRV 

      1090       1100       1110       1120       1130       1140 
FDGSITKENY NQEWWSLRLK YQGLCPPAPR SQGDFDPGAK FHIPSSVPYI RYFVSFIIQF 

      1150       1160       1170       1180       1190       1200 
QFHEALCKAA GHTGPLHTCD IYQSKEAGKR LADAMKLGYS KPWPEAMKVI TGQPNMSASA 

      1210       1220       1230       1240       1250       1260 
MMNYFKPLMD WLLTENGRHG EKLGWPQYTW TPNSARSEGS LPDSGRVNFL GMNLDAQQAR 

      1270       1280       1290       1300       1310 
VGQWVLLFLG VALLLASLGL TQRLFSIRYQ SLRQPHHGPQ FGSEVELRHS 

« Hide

Isoform Testis-specific (ACE-T) [UniParc] [UniParc].

Checksum: FC43CC76655C3DCA
Show »

FASTA73783,924

References

[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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X62551 mRNA. Translation: CAA44428.1.
J05041 mRNA. Translation: AAA31153.1.
M58579 Genomic DNA. Translation: AAA31151.1. Sequence problems.
M58580 Genomic DNA. Translation: AAA31152.1.
PIRA34402.
S35484.
RefSeqNP_001075864.1. NM_001082395.1.
NP_001164540.1. NM_001171069.1.
UniGeneOcu.1824.

3D structure databases

ProteinModelPortalP12822.
SMRP12822. Positions 35-645, 649-1232.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBP12822.
ChEMBLCHEMBL4074.

Protein family/group databases

MEROPSM02.001.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100009274.

Organism-specific databases

CTD1636.

Phylogenomic databases

eggNOGNOG71044.
HOGENOMHOG000007838.
HOVERGENHBG000264.

Enzyme and pathway databases

SABIO-RKP12822.

Family and domain databases

InterProIPR001548. Peptidase_M2.
[Graphical view]
PANTHERPTHR10514. PTHR10514. 1 hit.
PfamPF01401. Peptidase_M2. 2 hits.
[Graphical view]
PRINTSPR00791. PEPDIPTASEA.
PROSITEPS00142. ZINC_PROTEASE. 2 hits.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameACE_RABIT
AccessionPrimary (citable) accession number: P12822
Secondary accession number(s): O02852, P22968
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: November 1, 1997
Last modified: February 19, 2014
This is version 117 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries