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P09470

- ACE_MOUSE

UniProt

P09470 - ACE_MOUSE

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Protein
Angiotensin-converting enzyme
Gene
Ace, Dcp1
Organism
Mus musculus (Mouse)
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. This GPIase activity seems to be crucial for the egg-binding ability of the sperm.3 Publications

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.
Binds 3 chloride ions per subunit By similarity.

Enzyme regulationi

Peptidase activity is specifically inhibited by lisinopril, captopril and enalaprilat. In contrast, GPIase activity is nearly insensitive to captopril.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei236 – 2361Chloride 1 By similarity
Metal bindingi395 – 3951Zinc 1; catalytic By similarity
Active sitei396 – 39611 By similarity
Metal bindingi399 – 3991Zinc 1; catalytic By similarity
Metal bindingi423 – 4231Zinc 1; catalytic By similarity
Binding sitei534 – 5341Chloride 1 By similarity
Binding sitei796 – 7961Chloride 2 By similarity
Binding sitei834 – 8341Chloride 3 By similarity
Metal bindingi993 – 9931Zinc 2; catalytic
Active sitei994 – 99412
Metal bindingi997 – 9971Zinc 2; catalytic
Metal bindingi1021 – 10211Zinc 2; catalytic By similarity
Binding sitei1095 – 10951Chloride 2 By similarity
Binding sitei1099 – 10991Chloride 2 By similarity
Binding sitei1132 – 11321Chloride 3 By similarity

GO - Molecular functioni

  1. carboxypeptidase activity Source: UniProtKB-KW
  2. metal ion binding Source: UniProtKB-KW
  3. metallopeptidase activity Source: UniProtKB
  4. peptidase activity Source: MGI
  5. peptidyl-dipeptidase activity Source: UniProtKB
  6. protein binding Source: MGI

GO - Biological processi

  1. heart contraction Source: MGI
  2. hormone catabolic process Source: BHF-UCL
  3. kidney development Source: MGI
  4. neutrophil mediated immunity Source: MGI
  5. positive regulation of systemic arterial blood pressure Source: MGI
  6. regulation of blood pressure Source: BHF-UCL
  7. spermatogenesis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Carboxypeptidase, Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_196539. Metabolism of Angiotensinogen to Angiotensins.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:87874. Ace.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini35 – 12641230Extracellular Reviewed prediction
Add
BLAST
Transmembranei1265 – 128117Helical; Reviewed prediction
Add
BLAST
Topological domaini1282 – 131231Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Low blood pressure, elevated serum potassium, anemia, and renal defects. Male mice have reduced fertility.1 Publication

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi993 – 9931H → K: Abolishes peptidase activity but no effect on GPIase activity; when associated to K-997. 1 Publication
Mutagenesisi994 – 9941E → D: Abolishes peptidase activity but no effect on GPIase activity. 1 Publication
Mutagenesisi997 – 9971H → K: Abolishes peptidase activity but no effect on GPIase activity; when associated to K-993. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 34341 Publication
Add
BLAST
Chaini35 – 13121278Angiotensin-converting enzyme
PRO_0000028539Add
BLAST
Chaini35 – 12371203Angiotensin-converting enzyme, soluble form
PRO_0000028540Add
BLAST
Propeptidei1238 – 131275Removed in secreted form By similarity
PRO_0000028541Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi59 – 591N-linked (GlcNAc...) Reviewed prediction
Glycosylationi79 – 791N-linked (GlcNAc...) Reviewed prediction
Glycosylationi116 – 1161N-linked (GlcNAc...) Reviewed prediction
Glycosylationi151 – 1511N-linked (GlcNAc...)1 Publication
Disulfide bondi162 ↔ 170 By similarity
Glycosylationi165 – 1651N-linked (GlcNAc...) Reviewed prediction
Glycosylationi323 – 3231N-linked (GlcNAc...) Reviewed prediction
Glycosylationi514 – 5141N-linked (GlcNAc...) Reviewed prediction
Glycosylationi682 – 6821N-linked (GlcNAc...) Reviewed prediction
Glycosylationi700 – 7001N-linked (GlcNAc...) (complex) By similarity
Glycosylationi719 – 7191N-linked (GlcNAc...) (complex) By similarity
Disulfide bondi762 ↔ 768 By similarity
Glycosylationi765 – 7651N-linked (GlcNAc...) Reviewed prediction
Glycosylationi947 – 9471N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi962 ↔ 980 By similarity
Disulfide bondi1148 ↔ 1160 By similarity
Glycosylationi1196 – 11961N-linked (GlcNAc...) Reviewed prediction
Modified residuei1305 – 13051Phosphoserine By similarity

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiP09470.
PaxDbiP09470.
PRIDEiP09470.

PTM databases

PhosphoSiteiP09470.

Expressioni

Tissue specificityi

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

Inductioni

Expression is thought to be subject to hormonal regulation by androgens.1 Publication

Gene expression databases

ArrayExpressiP09470.
BgeeiP09470.
GenevestigatoriP09470.

Interactioni

Protein-protein interaction databases

BioGridi197920. 1 interaction.
IntActiP09470. 3 interactions.
MINTiMINT-4086662.

Structurei

3D structure databases

ProteinModelPortaliP09470.
SMRiP09470. Positions 35-646, 650-1235.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni35 – 635601Peptidase M2 1
Add
BLAST
Regioni636 – 1237602Peptidase M2 2
Add
BLAST

Sequence similaritiesi

Belongs to the peptidase M2 family.

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG71044.
GeneTreeiENSGT00520000055576.
HOGENOMiHOG000007838.
HOVERGENiHBG000264.
InParanoidiP09470.
KOiK01283.
OMAiMEQLFTV.
OrthoDBiEOG76HQ13.
PhylomeDBiP09470.
TreeFamiTF312861.

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: P09470-1) [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

MGAASGQRGR WPLSPPLLML SLLVLLLQPS PAPALDPGLQ PGNFSPDEAG     50
AQLFAESYNS SAEVVMFQST VASWAHDTNI TEENARRQEE AALVSQEFAE 100
VWGKKAKELY ESIWQNFTDS KLRRIIGSIR TLGPANLPLA QRQQYNSLLS 150
NMSRIYSTGK VCFPNKTATC WSLDPELTNI LASSRSYAKL LFAWEGWHDA 200
VGIPLKPLYQ DFTAISNEAY RQDDFSDTGA FWRSWYESPS FEESLEHIYH 250
QLEPLYLNLH AYVRRALHRR YGDKYVNLRG PIPAHLLGDM WAQSWENIYD 300
MVVPFPDKPN LDVTSTMVQK GWNATHMFRV SEEFFTSLGL SPMPPEFWAE 350
SMLEKPTDGR EVVCHASAWD FYNRKDFRIK QCTRVTMEQL ATVHHEMGHV 400
QYYLQYKDLH VSLRRGANPG FHEAIGDVLA LSVSTPAHLH KIGLLDHVTN 450
DIESDINYLL KMALEKIAFL PFGYLVDQWR WGVFSGRTPP SRYNFDWWYL 500
RTKYQGICPP VARNETHFDA GAKFHIPNVT PYIRYFVSFV LQFQFHQALC 550
KEAGHQGPLH QCDIYQSAQA GAKLKQVLQA GCSRPWQEVL KDLVGSDALD 600
AKALLEYFQP VSQWLEEQNQ RNGEVLGWPE NQWRPPLPDN YPEGIDLETD 650
EAKADRFVEE YDRTAQVLLN EYAEANWQYN TNITIEGSKI LLEKSTEVSN 700
HTLKYGTRAK TFDVSNFQNS SIKRIIKKLQ NLDRAVLPPK ELEEYNQILL 750
DMETTYSLSN ICYTNGTCMP LEPDLTNMMA TSRKYEELLW AWKSWRDKVG 800
RAILPFFPKY VEFSNKIAKL NGYTDAGDSW RSLYESDNLE QDLEKLYQEL 850
QPLYLNLHAY VRRSLHRHYG SEYINLDGPI PAHLLGNMWA QTWSNIYDLV 900
APFPSAPNID ATEAMIKQGW TPRRIFKEAD NFFTSLGLLP VPPEFWNKSM 950
LEKPTDGREV VCHPSAWDFY NGKDFRIKQC TSVNMEDLVI AHHEMGHIQY 1000
FMQYKDLPVT FREGANPGFH EAIGDIMALS VSTPKHLYSL NLLSTEGSGY 1050
EYDINFLMKM ALDKIAFIPF SYLIDQWRWR VFDGSITKEN YNQEWWSLRL 1100
KYQGLCPPVP RSQGDFDPGS KFHVPANVPY VRYFVSFIIQ FQFHEALCRA 1150
AGHTGPLHKC DIYQSKEAGK LLADAMKLGY SKPWPEAMKL ITGQPNMSAS 1200
AMMNYFKPLT EWLVTENRRH GETLGWPEYN WAPNTARAEG STAESNRVNF 1250
LGLYLEPQQA RVGQWVLLFL GVALLVATVG LAHRLYNIRN HHSLRRPHRG 1300
PQFGSEVELR HS 1312
Length:1,312
Mass (Da):150,918
Last modified:August 30, 2005 - v3
Checksum:i7DF9F5BE91762DFF
GO
Isoform Testis-specific (identifier: P09470-2) [UniParc] [UniParc]FASTAAdd to Basket

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

Show »
Length:732
Mass (Da):84,047
Checksum:i16C817E7FBD09BD9
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 580580Missing in isoform Testis-specific.
VSP_037638Add
BLAST
Alternative sequencei581 – 64666GCSRP…PEGID → MGQGWATPGLPSFLFLLLCC GHHLLVLSQVATDHVTANQG ITNQATTRSQTTTHQATIDQ TTQIPN in isoform Testis-specific.
VSP_037639Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti568 – 5681A → T in AAA37147. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS25543.1. [P09470-1]
CCDS25544.1. [P09470-2]
PIRiA34171.
A35655.
RefSeqiNP_033728.1. NM_009598.2. [P09470-2]
NP_997507.1. NM_207624.5. [P09470-1]
UniGeneiMm.754.

Genome annotation databases

EnsembliENSMUST00000001963; ENSMUSP00000001963; ENSMUSG00000020681. [P09470-1]
ENSMUST00000001964; ENSMUSP00000001964; ENSMUSG00000020681. [P09470-2]
GeneIDi11421.
KEGGimmu:11421.
UCSCiuc007lxu.2. mouse. [P09470-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS25543.1. [P09470-1 ]
CCDS25544.1. [P09470-2 ]
PIRi A34171.
A35655.
RefSeqi NP_033728.1. NM_009598.2. [P09470-2 ]
NP_997507.1. NM_207624.5. [P09470-1 ]
UniGenei Mm.754.

3D structure databases

ProteinModelPortali P09470.
SMRi P09470. Positions 35-646, 650-1235.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 197920. 1 interaction.
IntActi P09470. 3 interactions.
MINTi MINT-4086662.

Chemistry

BindingDBi P09470.
ChEMBLi CHEMBL2994.

Protein family/group databases

MEROPSi M02.001.

PTM databases

PhosphoSitei P09470.

Proteomic databases

MaxQBi P09470.
PaxDbi P09470.
PRIDEi P09470.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000001963 ; ENSMUSP00000001963 ; ENSMUSG00000020681 . [P09470-1 ]
ENSMUST00000001964 ; ENSMUSP00000001964 ; ENSMUSG00000020681 . [P09470-2 ]
GeneIDi 11421.
KEGGi mmu:11421.
UCSCi uc007lxu.2. mouse. [P09470-1 ]

Organism-specific databases

CTDi 1636.
MGIi MGI:87874. Ace.

Phylogenomic databases

eggNOGi NOG71044.
GeneTreei ENSGT00520000055576.
HOGENOMi HOG000007838.
HOVERGENi HBG000264.
InParanoidi P09470.
KOi K01283.
OMAi MEQLFTV.
OrthoDBi EOG76HQ13.
PhylomeDBi P09470.
TreeFami TF312861.

Enzyme and pathway databases

Reactomei REACT_196539. Metabolism of Angiotensinogen to Angiotensins.

Miscellaneous databases

ChiTaRSi ACE. mouse.
NextBioi 278668.
PROi P09470.
SOURCEi Search...

Gene expression databases

ArrayExpressi P09470.
Bgeei P09470.
Genevestigatori P09470.

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

« Hide 'large scale' publications
  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.

Entry informationi

Entry nameiACE_MOUSE
AccessioniPrimary (citable) accession number: P09470
Secondary accession number(s): P22967, Q6GTS2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: August 30, 2005
Last modified: September 3, 2014
This is version 144 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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