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P12821 (ACE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified August 10, 2010. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (9) | Third-party data text xml rdf/xml gff fasta
Customize displayNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Names and origin

Protein namesRecommended name:
Angiotensin-converting enzyme

Short name=ACE
EC=3.4.15.1
EC=3.2.1.-
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:DCP, DCP1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1306 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.

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.

Binds 3 chloride ions per subunit.

Enzyme regulation

Strongly activated by chloride. Specifically inhibited by lisinopril, captopril and enalaprilat.

Subcellular location

Angiotensin-converting enzyme, soluble form: Secreted.

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

Ubiquitously expressed, with highest levels in lung, kidney, heart, gastrointestinal system and prostate. Isoform Testis-specific is expressed in spermatocytes and adult testis. Ref.13 Ref.14 Ref.17 Ref.20

Induction

Up-regulated in failing heart. Ref.20 Ref.19

Post-translational modification

Phosphorylated by CK2 on Ser-1299; which allows membrane retention. Ref.16 Ref.22

Involvement in disease

Genetic variations in ACE may be a cause of susceptibility to ischemic stroke [MIM:601367]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. Ref.32 Ref.33

Defects in ACE are a cause of renal tubular dysgenesis (RTD) [MIM:267430]. RTD is an autosomal recessive severe disorder of renal tubular development characterized by persistent fetal anuria and perinatal death, probably due to pulmonary hypoplasia from early-onset oligohydramnios (the Potter phenotype). Ref.34

Genetic variations in ACE could influence susceptibility to diabetic nephropathy [MIM:612624]; also called susceptibility to microvascular complications of diabetes type 3 (MVCD3) or susceptibility to diabetic end-stage renal disease (ESRD). Diabetic nephropathy is a kidney disease and resultant kidney function impairment due to the long standing effects of diabetes on the microvasculature (glomerulus) of the kidney. Features include increased urine protein and declining kidney function.

Miscellaneous

Inhibitors of ACE are commonly used to treat hypertension and some types of renal and cardiac dysfunction.

The glycosidase activity probably uses different active site residues than the metalloprotease activity.

Sequence similarities

Belongs to the peptidase M2 family.

Biophysicochemical properties

Kinetic parameters:

KM=2.51 mM for Hip-His-Leu Ref.15 Ref.18

Sequence caution

The sequence BAD92208.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentCell membrane
Membrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandMetal-binding
Zinc
   Molecular functionCarboxypeptidase
Hydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processangiotensin catabolic process in blood

Inferred by curator. Source: UniProtKB

arachidonic acid secretion

Inferred from direct assay. Source: BHF-UCL

blood vessel remodeling

Inferred by curator. Source: BHF-UCL

hemopoietic stem cell differentiation

Inferred by curator. Source: BHF-UCL

hormone catabolic process

Inferred from direct assay. Source: BHF-UCL

kidney development Ref.34

Inferred from mutant phenotype. Source: BHF-UCL

mononuclear cell proliferation

Inferred by curator. Source: BHF-UCL

peptide catabolic process

Inferred from direct assay. Source: BHF-UCL

regulation of renal output by angiotensin

Inferred by curator. Source: BHF-UCL

regulation of smooth muscle cell migration

Inferred from sequence or structural similarity. Source: BHF-UCL

regulation of vasoconstriction

Inferred by curator. Source: UniProtKB

regulation of vasodilation

Inferred by curator. Source: BHF-UCL

   Cellular componentendosome

Inferred from direct assay. Source: BHF-UCL

external side of plasma membrane

Inferred from direct assay. Source: BHF-UCL

extracellular space

Inferred from direct assay. Source: BHF-UCL

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane fraction Ref.1

Inferred from direct assay. Source: BHF-UCL

plasma membrane

Inferred from direct assay. Source: UniProtKB

   Molecular functionactin binding

Inferred from direct assay. Source: UniProtKB

bradykinin receptor binding

Inferred from physical interaction. Source: BHF-UCL

carboxypeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

chloride ion binding Ref.25

Inferred from direct assay. Source: BHF-UCL

drug binding

Inferred from direct assay. Source: BHF-UCL

metallopeptidase activity Ref.1

Inferred from direct assay. Source: UniProtKB

peptidyl-dipeptidase activity Ref.1

Inferred from direct assay. Source: UniProtKB

zinc ion binding Ref.25

Inferred from direct assay. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform Somatic-1 (identifier: P12821-1)

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 Somatic-2 (identifier: P12821-2)

Also known as: Soluble;

The sequence of this isoform differs from the canonical sequence as follows:
     1137-1145: QFHEALCQA → HPFSQHTAA
     1146-1306: Missing.
Note: Incomplete sequence.
Isoform Testis-specific (identifier: P12821-3)

Also known as: ACE-T;

The sequence of this isoform differs from the canonical sequence as follows:
     1-574: Missing.
     575-641: AGSSRPWQEV...LPDNYPEGID → MGQGWATAGL...AHQTSAQSPN

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier
Natural variant321S → P. [dbSNP:rs4317]
Natural variant491S → G. [dbSNP:rs4318]

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Ref.7
Chain30 – 13061277Angiotensin-converting enzyme
PRO_0000028530
Chain30 – 12321203Angiotensin-converting enzyme, soluble form
PRO_0000028531
Propeptide1233 – 130674Removed in soluble form
PRO_0000028532

Regions

Topological domain30 – 12561227Extracellular Potential
Transmembrane1257 – 127721Helical; Potential
Topological domain1278 – 130629Cytoplasmic Potential
Region30 – 630601Peptidase M2 1
Region631 – 1232602Peptidase M2 2

Sites

Active site39111
Active site98912
Metal binding3901Zinc 1; catalytic
Metal binding3941Zinc 1; catalytic
Metal binding4181Zinc 1; catalytic
Metal binding9881Zinc 2; catalytic
Metal binding9921Zinc 2; catalytic
Metal binding10161Zinc 2; catalytic
Binding site2311Chloride 1
Binding site5291Chloride 1
Binding site7911Chloride 2
Binding site8291Chloride 3
Binding site10901Chloride 2
Binding site10941Chloride 2
Binding site11271Chloride 3
Site12251Not glycosylated

Amino acid modifications

Modified residue7161Phosphothreonine Ref.22
Modified residue12991Phosphoserine Ref.16
Glycosylation381N-linked (GlcNAc...) Probable
Glycosylation541N-linked (GlcNAc...) Ref.11 Ref.27
Glycosylation741N-linked (GlcNAc...) Ref.27
Glycosylation1111N-linked (GlcNAc...) Ref.11 Ref.24
Glycosylation1461N-linked (GlcNAc...) Ref.11 Ref.27
Glycosylation1601N-linked (GlcNAc...) Potential
Glycosylation3181N-linked (GlcNAc...) Ref.27
Glycosylation4451N-linked (GlcNAc...) Ref.24
Glycosylation5091N-linked (GlcNAc...) Ref.11 Ref.27 Ref.21
Glycosylation6771N-linked (GlcNAc...) Potential
Glycosylation6951N-linked (GlcNAc...) (complex) Ref.11 Ref.21
Glycosylation7141N-linked (GlcNAc...) (complex) Ref.11 Ref.24 Ref.21
Glycosylation7601N-linked (GlcNAc...); partial Ref.11
Glycosylation9421N-linked (GlcNAc...); partial Ref.11
Glycosylation11911N-linked (GlcNAc...); partial Ref.11
Disulfide bond157 ↔ 165 Ref.10
Disulfide bond757 ↔ 763 Ref.10
Disulfide bond957 ↔ 975 Ref.10
Disulfide bond1143 ↔ 1155 Ref.10

Natural variations

Alternative sequence1 – 574574Missing in isoform Testis-specific.
VSP_035120
Alternative sequence575 – 64167AGSSR…PEGID → MGQGWATAGLPSLLFLLLCY GHPLLVPSQEASQQVTVTHG TSSQATTSSQTTTHQATAHQ TSAQSPN in isoform Testis-specific.
VSP_035121
Alternative sequence1137 – 11459QFHEALCQA → HPFSQHTAA in isoform Somatic-2.
VSP_029932
Alternative sequence1146 – 1306161Missing in isoform Somatic-2.
VSP_029933
Natural variant1541A → T. [dbSNP:rs13306087]
VAR_029139
Natural variant1831A → T. [dbSNP:rs12720754]
VAR_029140
Natural variant2441Y → C. [dbSNP:rs3730025]
VAR_023430
Natural variant2601R → C. [dbSNP:rs4302]
VAR_054000
Natural variant2601R → L. [dbSNP:rs4303]
VAR_054001
Natural variant2611A → S. [dbSNP:rs4303] Ref.4
VAR_011707
Natural variant3511P → L. [dbSNP:rs2229839]
VAR_023431
Natural variant3541G → R. [dbSNP:rs56394458] Ref.34
VAR_035434
Natural variant3791R → Q. [dbSNP:rs13306085]
VAR_029141
Natural variant5241V → A. [dbSNP:rs12720746]
VAR_029142
Natural variant5611R → W. [dbSNP:rs4314] Ref.4
VAR_011708
Natural variant5921D → G. [dbSNP:rs12709426]
VAR_020053
Natural variant8281M → T. [dbSNP:rs13306091]
VAR_034602
Natural variant9161T → M. [dbSNP:rs3730043]
VAR_023432
Natural variant10181I → T. [dbSNP:rs4976] Ref.29
VAR_014189
Natural variant10511F → V. [dbSNP:rs4977] Ref.29
VAR_014190
Natural variant11871T → M. [dbSNP:rs12709442]
VAR_023433
Natural variant12281P → L No effect on activity; increases secretion; rate of solubilization is 2.5-fold higher than wild-type. Ref.15 Ref.30 Ref.31
VAR_023434
Natural variant12791R → Q. [dbSNP:rs4980] Ref.29
VAR_014191
Natural variant12861R → S. [dbSNP:rs4364] Ref.4 Ref.29
VAR_011709
Natural variant12961Q → P. [dbSNP:rs4981] Ref.29
VAR_014192

Experimental info

Mutagenesis12991S → A: Abolishes phosphorylation and decreases membrane retention. Ref.16
Sequence conflict351Q → E AA sequence Ref.7
Sequence conflict421D → R AA sequence Ref.7

Secondary structure

................................................................................................................................................................. 1306
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Somatic-1 [UniParc].

Last modified October 1, 1989. Version 1.
Checksum: 1B33BCA7301A26AA

FASTA1,306149,715
        10         20         30         40         50         60 
MGAASGRRGP GLLLPLPLLL LLPPQPALAL DPGLQPGNFS ADEAGAQLFA QSYNSSAEQV 

        70         80         90        100        110        120 
LFQSVAASWA HDTNITAENA RRQEEAALLS QEFAEAWGQK AKELYEPIWQ NFTDPQLRRI 

       130        140        150        160        170        180 
IGAVRTLGSA NLPLAKRQQY NALLSNMSRI YSTAKVCLPN KTATCWSLDP DLTNILASSR 

       190        200        210        220        230        240 
SYAMLLFAWE GWHNAAGIPL KPLYEDFTAL SNEAYKQDGF TDTGAYWRSW YNSPTFEDDL 

       250        260        270        280        290        300 
EHLYQQLEPL YLNLHAFVRR ALHRRYGDRY INLRGPIPAH LLGDMWAQSW ENIYDMVVPF 

       310        320        330        340        350        360 
PDKPNLDVTS TMLQQGWNAT HMFRVAEEFF TSLELSPMPP EFWEGSMLEK PADGREVVCH 

       370        380        390        400        410        420 
ASAWDFYNRK DFRIKQCTRV TMDQLSTVHH EMGHIQYYLQ YKDLPVSLRR GANPGFHEAI 

       430        440        450        460        470        480 
GDVLALSVST PEHLHKIGLL DRVTNDTESD INYLLKMALE KIAFLPFGYL VDQWRWGVFS 

       490        500        510        520        530        540 
GRTPPSRYNF DWWYLRTKYQ GICPPVTRNE THFDAGAKFH VPNVTPYIRY FVSFVLQFQF 

       550        560        570        580        590        600 
HEALCKEAGY EGPLHQCDIY RSTKAGAKLR KVLQAGSSRP WQEVLKDMVG LDALDAQPLL 

       610        620        630        640        650        660 
KYFQPVTQWL QEQNQQNGEV LGWPEYQWHP PLPDNYPEGI DLVTDEAEAS KFVEEYDRTS 

       670        680        690        700        710        720 
QVVWNEYAEA NWNYNTNITT ETSKILLQKN MQIANHTLKY GTQARKFDVN QLQNTTIKRI 

       730        740        750        760        770        780 
IKKVQDLERA ALPAQELEEY NKILLDMETT YSVATVCHPN GSCLQLEPDL TNVMATSRKY 

       790        800        810        820        830        840 
EDLLWAWEGW RDKAGRAILQ FYPKYVELIN QAARLNGYVD AGDSWRSMYE TPSLEQDLER 

       850        860        870        880        890        900 
LFQELQPLYL NLHAYVRRAL HRHYGAQHIN LEGPIPAHLL GNMWAQTWSN IYDLVVPFPS 

       910        920        930        940        950        960 
APSMDTTEAM LKQGWTPRRM FKEADDFFTS LGLLPVPPEF WNKSMLEKPT DGREVVCHAS 

       970        980        990       1000       1010       1020 
AWDFYNGKDF RIKQCTTVNL EDLVVAHHEM GHIQYFMQYK DLPVALREGA NPGFHEAIGD 

      1030       1040       1050       1060       1070       1080 
VLALSVSTPK HLHSLNLLSS EGGSDEHDIN FLMKMALDKI AFIPFSYLVD QWRWRVFDGS 

      1090       1100       1110       1120       1130       1140 
ITKENYNQEW WSLRLKYQGL CPPVPRTQGD FDPGAKFHIP SSVPYIRYFV SFIIQFQFHE 

      1150       1160       1170       1180       1190       1200 
ALCQAAGHTG PLHKCDIYQS KEAGQRLATA MKLGFSRPWP EAMQLITGQP NMSASAMLSY 

      1210       1220       1230       1240       1250       1260 
FKPLLDWLRT ENELHGEKLG WPQYNWTPNS ARSEGPLPDS GRVSFLGLDL DAQQARVGQW 

      1270       1280       1290       1300 
LLLFLGIALL VATLGLSQRL FSIRHRSLHR HSHGPQFGSE VELRHS 

« Hide

Isoform Somatic-2 (Soluble).

Checksum: B7EED12CAB675583
Show »

FASTA1,145131,659
Isoform Testis-specific (ACE-T) [UniParc] [UniParc].

Checksum: 80E0D19CFA642313
Show »

FASTA73283,330

References

« Hide 'large scale' references
[1]"Two putative active centers in human angiotensin I-converting enzyme revealed by molecular cloning."
Soubrier F., Alhenc-Gelas F., Hubert C., Allegrini J., John M., Tregear G., Corbol P.
Proc. Natl. Acad. Sci. U.S.A. 85:9386-9390(1988) [PubMed: 2849100] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC-1).
[2]"The testicular transcript of the angiotensin I-converting enzyme encodes for the ancestral, non-duplicated form of the enzyme."
Lattion A.L., Soubrier F., Allegrini J., Hubert C., Corvol P., Alhenc-Gelas F.
FEBS Lett. 252:99-104(1989) [PubMed: 2547653] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC).
[3]"Molecular cloning of human testicular angiotensin-converting enzyme: the testis isozyme is identical to the C-terminal half of endothelial angiotensin-converting enzyme."
Ehlers M.R.W., Fox E.A., Strydom D.J., Riordan J.F.
Proc. Natl. Acad. Sci. U.S.A. 86:7741-7745(1989) [PubMed: 2554286] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC).
[4]"Sequence variation in the human angiotensin converting enzyme."
Rieder M.J., Taylor S.L., Clark A.G., Nickerson D.A.
Nat. Genet. 22:59-62(1999) [PubMed: 10319862] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-261; TRP-561 AND SER-1286.
[5]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F.
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-1239 (ISOFORM SOMATIC-1).
Tissue: Brain.
[7]"Purification of human lung angiotensin-converting enzyme by high-performance liquid chromatography: properties and N-terminal amino acid sequence."
Takeuchi K., Shimizu T., Ohishi N., Seyama Y., Takaku F., Yotsumoto H.
J. Biochem. 106:442-445(1989) [PubMed: 2558109] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-46.
Tissue: Lung.
[8]"Alternative splicing of the mRNA coding for the human endothelial angiotensin-converting enzyme: a new mechanism for solubilization."
Sugimura K., Tian X.-L., Hoffmann S., Ganten D., Bader M.
Biochem. Biophys. Res. Commun. 247:466-472(1998) [PubMed: 9642152] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1114-1306 (ISOFORM SOMATIC-2), ALTERNATIVE SPLICING.
Tissue: Umbilical vein endothelial cell.
[9]"Angiotensin-converting enzyme: zinc- and inhibitor-binding stoichiometries of the somatic and testis isozymes."
Ehlers M.R.W., Riordan J.F.
Biochemistry 30:7118-7126(1991) [PubMed: 1649623] [Abstract]
Cited for: ZINC-BINDING.
[10]"Assignment of free and disulfide-bonded cysteine residues in testis angiotensin-converting enzyme: functional implications."
Sturrock E.D., Yu X.C., Wu Z., Biemann K., Riordan J.F.
Biochemistry 35:9560-9566(1996) [PubMed: 8755737] [Abstract]
Cited for: DISULFIDE BONDS.
[11]"Identification of N-linked glycosylation sites in human testis angiotensin-converting enzyme and expression of an active deglycosylated form."
Yu X.C., Sturrock E.D., Wu Z., Biemann K., Ehlers M.R.W., Riordan J.F.
J. Biol. Chem. 272:3511-3519(1997) [PubMed: 9013598] [Abstract]
Cited for: GLYCOSYLATION AT ASN-38; ASN-54; ASN-111; ASN-146; ASN-509; ASN-695; ASN-714; ASN-760; ASN-942 AND ASN-1191, MASS SPECTROMETRY.
[12]"Shedding of somatic angiotensin-converting enzyme (ACE) is inefficient compared with testis ACE despite cleavage at identical stalk sites."
Woodman Z.L., Oppong S.Y., Cook S., Hooper N.M., Schwager S.L.U., Brandt W.F., Ehlers M.R.W., Sturrock E.D.
Biochem. J. 347:711-718(2000) [PubMed: 10769174] [Abstract]
Cited for: CLEAVAGE SITE, MASS SPECTROMETRY.
[13]"A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9."
Donoghue M., Hsieh F., Baronas E., Godbout K., Gosselin M., Stagliano N., Donovan M., Woolf B., Robison K., Jeyaseelan R., Breitbart R.E., Acton S.
Circ. Res. 87:E1-E9(2000) [PubMed: 10969042] [Abstract]
Cited for: TISSUE SPECIFICITY.
[14]"A human homolog of angiotensin-converting enzyme. Cloning and functional expression as a captopril-insensitive carboxypeptidase."
Tipnis S.R., Hooper N.M., Hyde R., Karran E., Christie G., Turner A.J.
J. Biol. Chem. 275:33238-33243(2000) [PubMed: 10924499] [Abstract]
Cited for: TISSUE SPECIFICITY.
[15]"Increased shedding of angiotensin-converting enzyme by a mutation identified in the stalk region."
Eyries M., Michaud A., Deinum J., Agrapart M., Chomilier J., Kramers C., Soubrier F.
J. Biol. Chem. 276:5525-5532(2001) [PubMed: 11076943] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANT LEU-1228.
[16]"CK2 phosphorylates the angiotensin-converting enzyme and regulates its retention in the endothelial cell plasma membrane."
Kohlstedt K., Shoghi F., Mueller-Esterl W., Busse R., Fleming I.
Circ. Res. 91:749-756(2002) [PubMed: 12386153] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1299, MUTAGENESIS OF SER-1299.
[17]"Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme."
Harmer D., Gilbert M., Borman R., Clark K.L.
FEBS Lett. 532:107-110(2002) [PubMed: 12459472] [Abstract]
Cited for: TISSUE SPECIFICITY.
[18]"Deglycosylation, processing and crystallization of human testis angiotensin-converting enzyme."
Gordon K., Redelinghuys P., Schwager S.L.U., Ehlers M.R.W., Papageorgiou A.C., Natesh R., Acharya K.R., Sturrock E.D.
Biochem. J. 371:437-442(2003) [PubMed: 12542396] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, CLEAVAGE SITE.
[19]"ACE2 gene expression is up-regulated in the human failing heart."
Goulter A.B., Goddard M.J., Allen J.C., Clark K.L.
BMC Med. 2:19-19(2004) [PubMed: 15151696] [Abstract]
Cited for: INDUCTION.
[20]"Myocardial infarction increases ACE2 expression in rat and humans."
Burrell L.M., Risvanis J., Kubota E., Dean R.G., MacDonald P.S., Lu S., Tikellis C., Grant S.L., Lew R.A., Smith A.I., Cooper M.E., Johnston C.I.
Eur. Heart J. 26:369-375(2005) [PubMed: 15671045] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[21]"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
J. Proteome Res. 4:2070-2080(2005) [PubMed: 16335952] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-509; ASN-695 AND ASN-714, MASS SPECTROMETRY.
Tissue: Plasma.
[22]"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra."
Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.
J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-716, MASS SPECTROMETRY.
Tissue: Cervix carcinoma.
[23]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-111; ASN-445 AND ASN-714, MASS SPECTROMETRY.
Tissue: Liver.
[25]"Crystal structure of the human angiotensin-converting enzyme-lisinopril complex."
Natesh R., Schwager S.L.U., Sturrock E.D., Acharya K.R.
Nature 421:551-554(2003) [PubMed: 12540854] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230, X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230 IN COMPLEX WITH LISINOPRIL.
[26]"Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme."
Natesh R., Schwager S.L.U., Evans H.R., Sturrock E.D., Acharya K.R.
Biochemistry 43:8718-8724(2004) [PubMed: 15236580] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 642-1230 IN COMPLEX WITH ENALAPRILAT, X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 642-1230 IN COMPLEX WITH CAPTOPRIL.
[27]"Crystal structure of the N domain of human somatic angiotensin I-converting enzyme provides a structural basis for domain-specific inhibitor design."
Corradi H.R., Schwager S.L.U., Nchinda A.T., Sturrock E.D., Acharya K.R.
J. Mol. Biol. 357:964-974(2006) [PubMed: 16476442] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 30-641 IN COMPLEX WITH LISINOPRIL; ZINC AND CHLORIDE IONS, GLYCOSYLATION AT ASN-54; ASN-74; ASN-146; ASN-318 AND ASN-509.
[28]"The DD genotype of the ACE gene polymorphism is associated with progression of diabetic nephropathy to end stage renal failure in IDDM."
Vleming L.J., van der Pijl J.W., Lemkes H.H.P.J., Westendorp R.G.J., Maassen J.A., Daha M.R., van Es L.A., van Kooten C.
Clin. Nephrol. 51:133-140(1999) [PubMed: 10099885] [Abstract]
Cited for: INVOLVEMENT IN DIABETIC NEPHROPATHY SUSCEPTIBILITY.
[29]"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis."
Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A.
Nat. Genet. 22:239-247(1999) [PubMed: 10391210] [Abstract]
Cited for: VARIANTS THR-1018; VAL-1051; GLN-1279; SER-1286 AND PRO-1296.
[30]"Point mutation in the stalk of angiotensin-converting enzyme causes a dramatic increase in serum angiotensin-converting enzyme but no cardiovascular disease."
Kramers C., Danilov S.M., Deinum J., Balyasnikova I.V., Scharenborg N., Looman M., Boomsma F., de Keijzer M.H., van Duijn C., Martin S., Soubrier F., Adema G.J.
Circulation 104:1236-1240(2001) [PubMed: 11551873] [Abstract]
Cited for: VARIANT LEU-1228, ASSOCIATION WITH BENIGN SERUM INCREASE OF ANGIOTENSIN-CONVERTING ENZYME.
[31]"Hereditary elevation of angiotensin converting enzyme suggesting neurosarcoidosis."
Linnebank M., Kesper K., Jeub M., Urbach H., Wuellner U., Klockgether T., Schmidt S.
Neurology 61:1819-1820(2003) [PubMed: 14694062] [Abstract]
Cited for: VARIANT LEU-1228, ASSOCIATION WITH BENIGN SERUM INCREASE OF ANGIOTENSIN-CONVERTING ENZYME.
[32]"Meta-analysis of genetic studies in ischemic stroke: thirty-two genes involving approximately 18,000 cases and 58,000 controls."
Casas J.P., Hingorani A.D., Bautista L.E., Sharma P.
Arch. Neurol. 61:1652-1661(2004) [PubMed: 15534175] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ISCHEMIC STROKE.
[33]"DD genotype of ACE gene is a risk factor for intracerebral hemorrhage."
Slowik A., Turaj W., Dziedzic T., Haefele A., Pera J., Malecki M.T., Glodzik-Sobanska L., Szermer P., Figlewicz D.A., Szczudlik A.
Neurology 63:359-361(2004) [PubMed: 15277638] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ISCHEMIC STROKE.
[34]"Mutations in genes in the renin-angiotensin system are associated with autosomal recessive renal tubular dysgenesis."
Gribouval O., Gonzales M., Neuhaus T., Aziza J., Bieth E., Laurent N., Bouton J.M., Feuillet F., Makni S., Ben Amar H., Laube G., Delezoide A.-L., Bouvier R., Dijoud F., Ollagnon-Roman E., Roume J., Joubert M., Antignac C., Gubler M.-C.
Nat. Genet. 37:964-968(2005) [PubMed: 16116425] [Abstract]
Cited for: INVOLVEMENT IN RTD, VARIANT ARG-354.
+Additional computationally mapped references.

Web resources

GeneReviews
SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J04144 mRNA. Translation: AAA51684.1.
M26657 mRNA. Translation: AAA60611.1.
X16295 mRNA. Translation: CAA34362.1.
AF118569 Genomic DNA. Translation: AAD28560.1.
AY436326 Genomic DNA. Translation: AAR03504.1.
EU332840 Genomic DNA. Translation: ABY87529.1.
AB208971 mRNA. Translation: BAD92208.1. Different initiation.
IPIIPI00028147.
IPI00437751.
IPI00877100.
PIRA31759.
PW0053.
S05238.
RefSeqNP_000780.1.
NP_001171528.1.
NP_690043.1.
UniGeneHs.654434.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1O86X-ray2.00A642-1230[»]
1O8AX-ray2.00A642-1230[»]
1UZEX-ray1.82A642-1230[»]
1UZFX-ray2.00A642-1230[»]
2C6FX-ray3.01A/B30-641[»]
2C6NX-ray3.00A/B30-641[»]
2IULX-ray2.01A642-1232[»]
2IUXX-ray2.80A642-1232[»]
2OC2X-ray2.25A642-1232[»]
3BKKX-ray2.17A642-1232[»]
3BKLX-ray2.18A642-1232[»]
3L3NX-ray2.30A642-1232[»]
ProteinModelPortalP12821.
ModBaseSearch...

Protein-protein interaction databases

STRINGP12821.

Protein family/group databases

MEROPSM02.001.
M02.004.

PTM databases

PhosphoSiteP12821.

Proteomic databases

PeptideAtlasP12821.
PRIDEP12821.

Genome annotation databases

EnsemblENST00000290866; ENSP00000290866; ENSG00000159640; Homo sapiens. [Genome view]
GeneID1636.
KEGGhsa:1636.
UCSCuc002jau.1. human.

Organism-specific databases

CTD1636.
GeneCardsGC17P061554.
H-InvDBHIX0027185.
HGNCHGNC:2707. ACE.
HPACAB002426.
CAB002921.
MIM106180. gene+phenotype.
267430. phenotype.
601367. phenotype.
612624. phenotype.
Orphanet3033. Renal tubular dysgenesis.
PharmGKBPA139.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG16721.
HOGENOMHBG356536.
HOVERGENHBG000264.
InParanoidP12821.
OMAEFWDKSM.
OrthoDBEOG9QVFXH.
PhylomeDBP12821.

Enzyme and pathway databases

BRENDA3.4.15.1. 247.

Gene expression databases

ArrayExpressP12821.
BgeeP12821.
CleanExHS_ACE.
GenevestigatorP12821.
GermOnlineENSG00000159640. Homo sapiens.

Family and domain databases

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

Other Resources

DrugBankDB00542. Benazepril.
DB01197. Captopril.
DB01089. Deserpidine.
DB00584. Enalapril.
DB00492. Fosinopril.
DB00722. Lisinopril.
DB00691. Moexipril.
DB00790. Perindopril.
DB00881. Quinapril.
DB00178. Ramipril.
DB01180. Rescinnamine.
DB01348. Spirapril.
DB00519. Trandolapril.
NextBio6722.
PMAP-CutDBP12821.
SOURCESearch...

Entry information

Entry nameACE_HUMAN
AccessionPrimary (citable) accession number: P12821
Secondary accession number(s): B0LPF0 expand/collapse secondary AC list , P22966, Q53YX9, Q59GY8, Q7M4L4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: August 10, 2010
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries

Human chromosome 17

Human chromosome 17: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families