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P09470 (ACE_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1312 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. This GPIase activity seems to be crucial for the egg-binding ability of the sperm. Ref.6 Ref.7 Ref.8

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

Peptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat. In contrast, GPIase activity is nearly insensitive to captopril. Ref.8

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.

Induction

Expression is thought to be subject to hormonal regulation by androgens. Ref.8

Post-translational modification

Phosphorylated by CK2 on Ser-1305; which allows membrane retention By similarity.

Disruption phenotype

Low blood pressure, elevated serum potassium, anemia, and renal defects. Male mice have reduced fertility. Ref.7

Sequence similarities

Belongs to the peptidase M2 family.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionCarboxypeptidase
Hydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processheart contraction

Inferred from mutant phenotype PubMed 16585392. Source: MGI

hormone catabolic process

Inferred from direct assay PubMed 11303049. Source: BHF-UCL

kidney development

Inferred from mutant phenotype PubMed 17135368. Source: MGI

neutrophil mediated immunity

Inferred from mutant phenotype PubMed 17082641. Source: MGI

positive regulation of systemic arterial blood pressure

Inferred from mutant phenotype PubMed 17135368PubMed 9231832. Source: MGI

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

spermatogenesis

Inferred from mutant phenotype PubMed 17135368. Source: MGI

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncarboxypeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

metallopeptidase activity

Inferred from direct assay PubMed 11303049. Source: UniProtKB

peptidyl-dipeptidase activity

Inferred from direct assay PubMed 11303049. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Somatic (identifier: P09470-1)

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: P09470-2)

Also known as: ACE-T;

The sequence of this isoform differs from the canonical sequence as follows:
     1-580: Missing.
     581-646: GCSRPWQEVL...LPDNYPEGID → MGQGWATPGL...TIDQTTQIPN

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3434 Ref.5
Chain35 – 13121278Angiotensin-converting enzyme
PRO_0000028539
Chain35 – 12371203Angiotensin-converting enzyme, soluble form
PRO_0000028540
Propeptide1238 – 131275Removed in secreted form By similarity
PRO_0000028541

Regions

Topological domain35 – 12641230Extracellular Potential
Transmembrane1265 – 128117Helical; Potential
Topological domain1282 – 131231Cytoplasmic Potential
Region35 – 635601Peptidase M2 1
Region636 – 1237602Peptidase M2 2

Sites

Active site39611 By similarity
Active site99412
Metal binding3951Zinc 1; catalytic By similarity
Metal binding3991Zinc 1; catalytic By similarity
Metal binding4231Zinc 1; catalytic By similarity
Metal binding9931Zinc 2; catalytic
Metal binding9971Zinc 2; catalytic
Metal binding10211Zinc 2; catalytic By similarity
Binding site2361Chloride 1 By similarity
Binding site5341Chloride 1 By similarity
Binding site7961Chloride 2 By similarity
Binding site8341Chloride 3 By similarity
Binding site10951Chloride 2 By similarity
Binding site10991Chloride 2 By similarity
Binding site11321Chloride 3 By similarity

Amino acid modifications

Modified residue13051Phosphoserine By similarity
Glycosylation591N-linked (GlcNAc...) Potential
Glycosylation791N-linked (GlcNAc...) Potential
Glycosylation1161N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Ref.9
Glycosylation1651N-linked (GlcNAc...) Potential
Glycosylation3231N-linked (GlcNAc...) Potential
Glycosylation5141N-linked (GlcNAc...) Potential
Glycosylation6821N-linked (GlcNAc...) Potential
Glycosylation7001N-linked (GlcNAc...) (complex) By similarity
Glycosylation7191N-linked (GlcNAc...) (complex) By similarity
Glycosylation7651N-linked (GlcNAc...) Potential
Glycosylation9471N-linked (GlcNAc...) Potential
Glycosylation11961N-linked (GlcNAc...) Potential
Disulfide bond162 ↔ 170 By similarity
Disulfide bond762 ↔ 768 By similarity
Disulfide bond962 ↔ 980 By similarity
Disulfide bond1148 ↔ 1160 By similarity

Natural variations

Alternative sequence1 – 580580Missing in isoform Testis-specific.
VSP_037638
Alternative sequence581 – 64666GCSRP…PEGID → MGQGWATPGLPSFLFLLLCC GHHLLVLSQVATDHVTANQG ITNQATTRSQTTTHQATIDQ TTQIPN in isoform Testis-specific.
VSP_037639

Experimental info

Mutagenesis9931H → K: Abolishes peptidase activity but no effect on GPIase activity; when associated to K-997. Ref.8
Mutagenesis9941E → D: Abolishes peptidase activity but no effect on GPIase activity. Ref.8
Mutagenesis9971H → K: Abolishes peptidase activity but no effect on GPIase activity; when associated to K-993. Ref.8
Sequence conflict5681A → T in AAA37147. Ref.1

Sequences

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

Last modified August 30, 2005. Version 3.
Checksum: 7DF9F5BE91762DFF

FASTA1,312150,918
        10         20         30         40         50         60 
MGAASGQRGR WPLSPPLLML SLLVLLLQPS PAPALDPGLQ PGNFSPDEAG AQLFAESYNS 

        70         80         90        100        110        120 
SAEVVMFQST VASWAHDTNI TEENARRQEE AALVSQEFAE VWGKKAKELY ESIWQNFTDS 

       130        140        150        160        170        180 
KLRRIIGSIR TLGPANLPLA QRQQYNSLLS NMSRIYSTGK VCFPNKTATC WSLDPELTNI 

       190        200        210        220        230        240 
LASSRSYAKL LFAWEGWHDA VGIPLKPLYQ DFTAISNEAY RQDDFSDTGA FWRSWYESPS 

       250        260        270        280        290        300 
FEESLEHIYH QLEPLYLNLH AYVRRALHRR YGDKYVNLRG PIPAHLLGDM WAQSWENIYD 

       310        320        330        340        350        360 
MVVPFPDKPN LDVTSTMVQK GWNATHMFRV SEEFFTSLGL SPMPPEFWAE SMLEKPTDGR 

       370        380        390        400        410        420 
EVVCHASAWD FYNRKDFRIK QCTRVTMEQL ATVHHEMGHV QYYLQYKDLH VSLRRGANPG 

       430        440        450        460        470        480 
FHEAIGDVLA LSVSTPAHLH KIGLLDHVTN DIESDINYLL KMALEKIAFL PFGYLVDQWR 

       490        500        510        520        530        540 
WGVFSGRTPP SRYNFDWWYL RTKYQGICPP VARNETHFDA GAKFHIPNVT PYIRYFVSFV 

       550        560        570        580        590        600 
LQFQFHQALC KEAGHQGPLH QCDIYQSAQA GAKLKQVLQA GCSRPWQEVL KDLVGSDALD 

       610        620        630        640        650        660 
AKALLEYFQP VSQWLEEQNQ RNGEVLGWPE NQWRPPLPDN YPEGIDLETD EAKADRFVEE 

       670        680        690        700        710        720 
YDRTAQVLLN EYAEANWQYN TNITIEGSKI LLEKSTEVSN HTLKYGTRAK TFDVSNFQNS 

       730        740        750        760        770        780 
SIKRIIKKLQ NLDRAVLPPK ELEEYNQILL DMETTYSLSN ICYTNGTCMP LEPDLTNMMA 

       790        800        810        820        830        840 
TSRKYEELLW AWKSWRDKVG RAILPFFPKY VEFSNKIAKL NGYTDAGDSW RSLYESDNLE 

       850        860        870        880        890        900 
QDLEKLYQEL QPLYLNLHAY VRRSLHRHYG SEYINLDGPI PAHLLGNMWA QTWSNIYDLV 

       910        920        930        940        950        960 
APFPSAPNID ATEAMIKQGW TPRRIFKEAD NFFTSLGLLP VPPEFWNKSM LEKPTDGREV 

       970        980        990       1000       1010       1020 
VCHPSAWDFY NGKDFRIKQC TSVNMEDLVI AHHEMGHIQY FMQYKDLPVT FREGANPGFH 

      1030       1040       1050       1060       1070       1080 
EAIGDIMALS VSTPKHLYSL NLLSTEGSGY EYDINFLMKM ALDKIAFIPF SYLIDQWRWR 

      1090       1100       1110       1120       1130       1140 
VFDGSITKEN YNQEWWSLRL KYQGLCPPVP RSQGDFDPGS KFHVPANVPY VRYFVSFIIQ 

      1150       1160       1170       1180       1190       1200 
FQFHEALCRA AGHTGPLHKC DIYQSKEAGK LLADAMKLGY SKPWPEAMKL ITGQPNMSAS 

      1210       1220       1230       1240       1250       1260 
AMMNYFKPLT EWLVTENRRH GETLGWPEYN WAPNTARAEG STAESNRVNF LGLYLEPQQA 

      1270       1280       1290       1300       1310 
RVGQWVLLFL GVALLVATVG LAHRLYNIRN HHSLRRPHRG PQFGSEVELR HS 

« Hide

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

Checksum: 16C817E7FBD09BD9
Show »

FASTA73284,047

References

« Hide 'large scale' references
[1]"Mouse angiotensin-converting enzyme is a protein composed of two homologous domains."
Bernstein K.E., Martin B.M., Edwards A.S., Bernstein E.A.
J. Biol. Chem. 264:11945-11951(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC).
[2]"Transcription of testicular angiotensin-converting enzyme (ACE) is initiated within the 12th intron of the somatic ACE gene."
Howard T.E., Shai S.-Y., Langford K.G., Martin B.M., Bernstein K.E.
Mol. Cell. Biol. 10:4294-4302(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SOMATIC).
Strain: FVB/N.
Tissue: Mammary gland.
[4]"The isolation of angiotensin-converting enzyme cDNA."
Bernstein K.E., Martin B.M., Bernstein E.A., Linton J., Striker L., Striker G.
J. Biol. Chem. 263:11021-11024(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-332 (ISOFORM SOMATIC), PARTIAL PROTEIN SEQUENCE.
[5]"Partial protein sequence of mouse and bovine kidney angiotensin converting enzyme."
Bernstein K.E., Martin B.M., Striker L., Striker G.
Kidney Int. 33:652-655(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 35-54.
Tissue: Kidney.
[6]"Male-female differences in fertility and blood pressure in ACE-deficient mice."
Krege J.H., John S.W., Langenbach L.L., Hodgin J.B., Hagaman J.R., Bachman E.S., Jennette J.C., O'Brien D.A., Smithies O.
Nature 375:146-148(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Mice lacking angiotensin-converting enzyme have low blood pressure, renal pathology, and reduced male fertility."
Esther C.R. Jr., Howard T.E., Marino E.M., Goddard J.M., Capecchi M.R., Bernstein K.E.
Lab. Invest. 74:953-965(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[8]"Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization."
Kondoh G., Tojo H., Nakatani Y., Komazawa N., Murata C., Yamagata K., Maeda Y., Kinoshita T., Okabe M., Taguchi R., Takeda J.
Nat. Med. 11:160-166(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, MUTAGENESIS OF HIS-993; GLU-994 AND HIS-997.
[9]"Proteome-wide characterization of N-glycosylation events by diagonal chromatography."
Ghesquiere B., Van Damme J., Martens L., Vandekerckhove J., Gevaert K.
J. Proteome Res. 5:2438-2447(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-151.
Strain: C57BL/6.
Tissue: Plasma.
[10]"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations."
Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M.
Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain cortex.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04946 mRNA. Translation: AAA37147.1.
J04947 mRNA. Translation: AAA37148.1.
M55333 mRNA. Translation: AAA37149.1.
M61094 Genomic DNA. Translation: AAA37150.1.
BC040404 mRNA. Translation: AAH40404.1.
J03940 mRNA. Translation: AAA37146.1.
PIRA34171.
A35655.
RefSeqNP_033728.1. NM_009598.2.
NP_997507.1. NM_207624.5.
UniGeneMm.754.

3D structure databases

ProteinModelPortalP09470.
SMRP09470. Positions 35-646, 650-1227.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid197920. 1 interaction.
IntActP09470. 3 interactions.
MINTMINT-4086662.

Chemistry

BindingDBP09470.
ChEMBLCHEMBL2994.

Protein family/group databases

MEROPSM02.001.

PTM databases

PhosphoSiteP09470.

Proteomic databases

PaxDbP09470.
PRIDEP09470.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000001963; ENSMUSP00000001963; ENSMUSG00000020681. [P09470-1]
ENSMUST00000001964; ENSMUSP00000001964; ENSMUSG00000020681. [P09470-2]
GeneID11421.
KEGGmmu:11421.
UCSCuc007lxu.2. mouse. [P09470-1]

Organism-specific databases

CTD1636.
MGIMGI:87874. Ace.

Phylogenomic databases

eggNOGNOG71044.
GeneTreeENSGT00520000055576.
HOGENOMHOG000007838.
HOVERGENHBG000264.
InParanoidP09470.
KOK01283.
OMAMEQLFTV.
OrthoDBEOG76HQ13.
TreeFamTF312861.

Gene expression databases

ArrayExpressP09470.
BgeeP09470.
GenevestigatorP09470.

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...

Other

ChiTaRSACE. mouse.
NextBio278668.
PROP09470.
SOURCESearch...

Entry information

Entry nameACE_MOUSE
AccessionPrimary (citable) accession number: P09470
Secondary accession number(s): P22967, Q6GTS2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: August 30, 2005
Last modified: March 19, 2014
This is version 139 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries