P09470 (ACE_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1312 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 is expressed 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 component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from electronic annotation. Source: Compara angiogenesis involved in coronary vascular morphogenesis Inferred from electronic annotation. Source: Compara eating behavior Inferred from electronic annotation. Source: Compara heart 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 lung alveolus development Inferred from electronic annotation. Source: Compara neutrophil mediated immunity Inferred from mutant phenotype PubMed 17082641. Source: MGI organ regeneration Inferred from electronic annotation. Source: Compara peptide metabolic process Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of inflammatory response Inferred from electronic annotation. Source: Compara positive regulation of neurogenesis Inferred from electronic annotation. Source: Compara positive regulation of systemic arterial blood pressure Inferred from mutant phenotype PubMed 17135368PubMed 9231832. Source: MGI proteolysis Inferred from electronic annotation. Source: UniProtKB-KW regulation of smooth muscle cell migration Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from electronic annotation. Source: Compara response to nutrient levels Inferred from electronic annotation. Source: Compara sensory perception of pain Inferred from electronic annotation. Source: Compara spermatogenesis Inferred from mutant phenotype PubMed 17135368. Source: MGI vasoconstriction Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	carboxypeptidase 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 peptide binding Inferred from electronic annotation. Source: Compara 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 34	34	Ref.5
	Chain	35 – 1312	1278	Angiotensin-converting enzyme		PRO_0000028539
	Chain	35 – 1237	1203	Angiotensin-converting enzyme, soluble form		PRO_0000028540
	Propeptide	1238 – 1312	75	Removed in secreted form By similarity		PRO_0000028541
Regions
	Topological domain	35 – 1264	1230	Extracellular Potential
	Transmembrane	1265 – 1281	17	Helical; Potential
	Topological domain	1282 – 1312	31	Cytoplasmic Potential
	Region	35 – 635	601	Peptidase M2 1
	Region	636 – 1237	602	Peptidase M2 2
Sites
	Active site	396	1	1 By similarity
	Active site	994	1	2
	Metal binding	395	1	Zinc 1; catalytic By similarity
	Metal binding	399	1	Zinc 1; catalytic By similarity
	Metal binding	423	1	Zinc 1; catalytic By similarity
	Metal binding	993	1	Zinc 2; catalytic
	Metal binding	997	1	Zinc 2; catalytic
	Metal binding	1021	1	Zinc 2; catalytic By similarity
	Binding site	236	1	Chloride 1 By similarity
	Binding site	534	1	Chloride 1 By similarity
	Binding site	796	1	Chloride 2 By similarity
	Binding site	834	1	Chloride 3 By similarity
	Binding site	1095	1	Chloride 2 By similarity
	Binding site	1099	1	Chloride 2 By similarity
	Binding site	1132	1	Chloride 3 By similarity
Amino acid modifications
	Modified residue	1305	1	Phosphoserine Ref.10
	Glycosylation	59	1	N-linked (GlcNAc...) Potential
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Glycosylation	116	1	N-linked (GlcNAc...) Potential
	Glycosylation	151	1	N-linked (GlcNAc...) Ref.9
	Glycosylation	165	1	N-linked (GlcNAc...) Potential
	Glycosylation	323	1	N-linked (GlcNAc...) Potential
	Glycosylation	514	1	N-linked (GlcNAc...) Potential
	Glycosylation	682	1	N-linked (GlcNAc...) Potential
	Glycosylation	700	1	N-linked (GlcNAc...) (complex) By similarity
	Glycosylation	719	1	N-linked (GlcNAc...) (complex) By similarity
	Glycosylation	765	1	N-linked (GlcNAc...) Potential
	Glycosylation	947	1	N-linked (GlcNAc...) Potential
	Glycosylation	1196	1	N-linked (GlcNAc...) Potential
	Disulfide bond	162 ↔ 170		By similarity
	Disulfide bond	762 ↔ 768		By similarity
	Disulfide bond	962 ↔ 980		By similarity
	Disulfide bond	1148 ↔ 1160		By similarity
Natural variations
	Alternative sequence	1 – 580	580	Missing in isoform Testis-specific.		VSP_037638
	Alternative sequence	581 – 646	66	GCSRP…PEGID → MGQGWATPGLPSFLFLLLCC GHHLLVLSQVATDHVTANQG ITNQATTRSQTTTHQATIDQ TTQIPN in isoform Testis-specific.		VSP_037639
Experimental info
	Mutagenesis	993	1	H → K: Abolishes peptidase activity but no effect on GPIase activity; when associated to K-997. Ref.8
	Mutagenesis	994	1	E → D: Abolishes peptidase activity but no effect on GPIase activity. Ref.8
	Mutagenesis	997	1	H → K: Abolishes peptidase activity but no effect on GPIase activity; when associated to K-993. Ref.8
	Sequence conflict	568	1	A → T in AAA37147. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform Somatic [UniParc]. Last modified August 30, 2005. Version 3. Checksum: 7DF9F5BE91762DFF	FASTA	1,312	150,918
	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
	Isoform Testis-specific (ACE-T) [UniParc] [UniParc]. Checksum: 16C817E7FBD09BD9	FASTA	732	84,047
	10 20 30 40 50 60 MGQGWATPGL PSFLFLLLCC GHHLLVLSQV ATDHVTANQG ITNQATTRSQ TTTHQATIDQ 70 80 90 100 110 120 TTQIPNLETD EAKADRFVEE YDRTAQVLLN EYAEANWQYN TNITIEGSKI LLEKSTEVSN 130 140 150 160 170 180 HTLKYGTRAK TFDVSNFQNS SIKRIIKKLQ NLDRAVLPPK ELEEYNQILL DMETTYSLSN 190 200 210 220 230 240 ICYTNGTCMP LEPDLTNMMA TSRKYEELLW AWKSWRDKVG RAILPFFPKY VEFSNKIAKL 250 260 270 280 290 300 NGYTDAGDSW RSLYESDNLE QDLEKLYQEL QPLYLNLHAY VRRSLHRHYG SEYINLDGPI 310 320 330 340 350 360 PAHLLGNMWA QTWSNIYDLV APFPSAPNID ATEAMIKQGW TPRRIFKEAD NFFTSLGLLP 370 380 390 400 410 420 VPPEFWNKSM LEKPTDGREV VCHPSAWDFY NGKDFRIKQC TSVNMEDLVI AHHEMGHIQY 430 440 450 460 470 480 FMQYKDLPVT FREGANPGFH EAIGDIMALS VSTPKHLYSL NLLSTEGSGY EYDINFLMKM 490 500 510 520 530 540 ALDKIAFIPF SYLIDQWRWR VFDGSITKEN YNQEWWSLRL KYQGLCPPVP RSQGDFDPGS 550 560 570 580 590 600 KFHVPANVPY VRYFVSFIIQ FQFHEALCRA AGHTGPLHKC DIYQSKEAGK LLADAMKLGY 610 620 630 640 650 660 SKPWPEAMKL ITGQPNMSAS AMMNYFKPLT EWLVTENRRH GETLGWPEYN WAPNTARAEG 670 680 690 700 710 720 STAESNRVNF LGLYLEPQQA RVGQWVLLFL GVALLVATVG LAHRLYNIRN HHSLRRPHRG 730 PQFGSEVELR HS

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1305, MASS SPECTROMETRY. 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.
IPI	IPI00272690. IPI00284824.
PIR	A34171. A35655.
RefSeq	NP_033728.1. NM_009598.2. NP_997507.1. NM_207624.5.
UniGene	Mm.754.
3D structure databases
ProteinModelPortal	P09470.
SMR	P09470. Positions 35-646, 650-1227.
ModBase	Search...
Protein family/group databases
MEROPS	M02.001.
PTM databases
PhosphoSite	P09470.
Proteomic databases
PaxDb	P09470.
PRIDE	P09470.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000001963; ENSMUSP00000001963; ENSMUSG00000020681. ENSMUST00000001964; ENSMUSP00000001964; ENSMUSG00000020681.
GeneID	11421.
KEGG	mmu:11421.
Organism-specific databases
CTD	1636.
MGI	MGI:87874. Ace.
Phylogenomic databases
eggNOG	NOG71044.
GeneTree	ENSGT00520000055576.
HOGENOM	HOG000007838.
HOVERGEN	HBG000264.
InParanoid	P09470.
KO	K01283.
OMA	MEQLFTV.
OrthoDB	EOG495ZQZ.
Gene expression databases
ArrayExpress	P09470.
Bgee	P09470.
Genevestigator	P09470.
GermOnline	ENSMUSG00000020681. Mus musculus.
Family and domain databases
InterPro	IPR001548. Peptidase_M2. [Graphical view]
PANTHER	PTHR10514. PTHR10514. 1 hit.
Pfam	PF01401. Peptidase_M2. 2 hits. [Graphical view]
PRINTS	PR00791. PEPDIPTASEA.
PROSITE	PS00142. ZINC_PROTEASE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P09470.
ChEMBL	CHEMBL2994.
ChiTaRS	ACE. mouse.
NextBio	278668.
SOURCE	Search...

Entry information

Entry name

ACE_MOUSE

Accession

Primary (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:	April 3, 2013
This is version 131 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program