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P12821 (ACE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 183. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (9) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·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:DCP, DCP1
OrganismHomo sapiens (Human) [Reference 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.15 Ref.16 Ref.19 Ref.22

Induction

Up-regulated in failing heart. Ref.21 Ref.22

Post-translational modification

Phosphorylated by CK2 on Ser-1299; which allows membrane retention. Ref.18

Involvement in disease

Ischemic stroke (ISCHSTR) [MIM:601367]: 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.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.33

Renal tubular dysgenesis (RTD) [MIM:267430]: 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).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.35

Microvascular complications of diabetes 3 (MVCD3) [MIM:612624]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Intracerebral hemorrhage (ICH) [MIM:614519]: A pathological condition characterized by bleeding into one or both cerebral hemispheres including the basal ganglia and the cerebral cortex. It is often associated with hypertension and craniocerebral trauma. Intracerebral bleeding is a common cause of stroke.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. Ref.34

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.17 Ref.20

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
Reference proteome
Gene Ontology (GO)
   Biological_processangiotensin catabolic process in blood

Inferred by curator PubMed 1668266. Source: UniProtKB

angiotensin maturation

Traceable author statement. Source: Reactome

arachidonic acid secretion

Inferred from direct assay PubMed 17077303. Source: BHF-UCL

blood vessel remodeling

Inferred by curator PubMed 1668266. Source: BHF-UCL

cellular protein metabolic process

Traceable author statement. Source: Reactome

hematopoietic stem cell differentiation

Inferred by curator PubMed 7876104. Source: BHF-UCL

hormone catabolic process

Inferred from direct assay PubMed 7876104. Source: BHF-UCL

kidney development

Inferred from mutant phenotype Ref.35. Source: BHF-UCL

mononuclear cell proliferation

Inferred by curator PubMed 7876104. Source: BHF-UCL

peptide catabolic process

Inferred from direct assay PubMed 4322742. Source: BHF-UCL

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

regulation of blood pressure

Inferred from sequence or structural similarity PubMed 11303049. Source: BHF-UCL

regulation of renal output by angiotensin

Inferred by curator PubMed 1668266. Source: BHF-UCL

regulation of smooth muscle cell migration

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

regulation of systemic arterial blood pressure by renin-angiotensin

Inferred by curator PubMed 1668266. Source: UniProtKB

regulation of vasoconstriction

Inferred by curator PubMed 1668266. Source: UniProtKB

regulation of vasodilation

Inferred by curator PubMed 4322742. Source: BHF-UCL

   Cellular_componentendosome

Inferred from direct assay PubMed 17077303. Source: BHF-UCL

external side of plasma membrane

Inferred from direct assay PubMed 9449382. Source: BHF-UCL

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 15283675. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 15326289PubMed 19056867. Source: UniProt

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 17077303. Source: BHF-UCL

   Molecular_functionactin binding

Inferred from direct assay PubMed 16186248. Source: UniProtKB

bradykinin receptor binding

Inferred from physical interaction PubMed 17077303. Source: BHF-UCL

carboxypeptidase activity

Inferred from electronic annotation. Source: UniProtKB-KW

chloride ion binding

Inferred from direct assay Ref.26. Source: BHF-UCL

drug binding

Inferred from direct assay PubMed 1320019. Source: BHF-UCL

endopeptidase activity

Inferred from direct assay PubMed 15283675. Source: UniProtKB

metallopeptidase activity

Inferred from direct assay PubMed 1320019PubMed 1668266PubMed 17077303Ref.1. Source: UniProtKB

peptidyl-dipeptidase activity

Inferred from direct assay PubMed 1320019PubMed 1668266PubMed 17077303Ref.1. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.26. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 4 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
Isoform 4 (identifier: P12821-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-67: MGAASGRRGP...EQVLFQSVAA → MGQGWATAGL...AHQTSAQSPN
     68-642: Missing.
     1128-1168: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Ref.9
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 residue12991Phosphoserine Ref.18
Glycosylation381N-linked (GlcNAc...) Probable
Glycosylation541N-linked (GlcNAc...) Ref.13 Ref.28
Glycosylation741N-linked (GlcNAc...) Ref.28
Glycosylation1111N-linked (GlcNAc...) Ref.13 Ref.24
Glycosylation1461N-linked (GlcNAc...) Ref.13 Ref.28
Glycosylation1601N-linked (GlcNAc...) Potential
Glycosylation3181N-linked (GlcNAc...) Ref.28
Glycosylation4451N-linked (GlcNAc...) Ref.24
Glycosylation5091N-linked (GlcNAc...) Ref.13 Ref.23 Ref.28
Glycosylation6771N-linked (GlcNAc...) Potential
Glycosylation6951N-linked (GlcNAc...) (complex) Ref.13 Ref.23
Glycosylation7141N-linked (GlcNAc...) (complex) Ref.13 Ref.23 Ref.24
Glycosylation7601N-linked (GlcNAc...); partial Ref.13
Glycosylation9421N-linked (GlcNAc...); partial Ref.13
Glycosylation11911N-linked (GlcNAc...); partial Ref.13
Disulfide bond157 ↔ 165 Ref.12
Disulfide bond757 ↔ 763 Ref.12
Disulfide bond957 ↔ 975 Ref.12
Disulfide bond1143 ↔ 1155 Ref.12

Natural variations

Alternative sequence1 – 574574Missing in isoform Testis-specific.
VSP_035120
Alternative sequence1 – 6767MGAAS…QSVAA → MGQGWATAGLPSLLFLLLCY GHPLLVPSQEASQQVTVTHG TSSQATTSSQTTTHQATAHQ TSAQSPN in isoform 4.
VSP_043522
Alternative sequence68 – 642575Missing in isoform 4.
VSP_043523
Alternative sequence575 – 64167AGSSR…PEGID → MGQGWATAGLPSLLFLLLCY GHPLLVPSQEASQQVTVTHG TSSQATTSSQTTTHQATAHQ TSAQSPN in isoform Testis-specific.
VSP_035121
Alternative sequence1128 – 116841Missing in isoform 4.
VSP_043524
Alternative sequence1137 – 11459QFHEALCQA → HPFSQHTAA in isoform Somatic-2.
VSP_029932
Alternative sequence1146 – 1306161Missing in isoform Somatic-2.
VSP_029933
Natural variant1541A → T.
Corresponds to variant rs13306087 [ dbSNP | Ensembl ].
VAR_029139
Natural variant1831A → T.
Corresponds to variant rs12720754 [ dbSNP | Ensembl ].
VAR_029140
Natural variant2441Y → C.
Corresponds to variant rs3730025 [ dbSNP | Ensembl ].
VAR_023430
Natural variant2601R → C.
Corresponds to variant rs4302 [ dbSNP | Ensembl ].
VAR_054000
Natural variant2601R → L.
Corresponds to variant rs4303 [ dbSNP | Ensembl ].
VAR_054001
Natural variant2611A → S. Ref.4
Corresponds to variant rs4303 [ dbSNP | Ensembl ].
VAR_011707
Natural variant3511P → L.
Corresponds to variant rs2229839 [ dbSNP | Ensembl ].
VAR_023431
Natural variant3541G → R. Ref.35
Corresponds to variant rs56394458 [ dbSNP | Ensembl ].
VAR_035434
Natural variant3791R → Q.
Corresponds to variant rs13306085 [ dbSNP | Ensembl ].
VAR_029141
Natural variant5241V → A.
Corresponds to variant rs12720746 [ dbSNP | Ensembl ].
VAR_029142
Natural variant5611R → W. Ref.4
Corresponds to variant rs4314 [ dbSNP | Ensembl ].
VAR_011708
Natural variant5921D → G.
Corresponds to variant rs12709426 [ dbSNP | Ensembl ].
VAR_020053
Natural variant8281M → T.
Corresponds to variant rs13306091 [ dbSNP | Ensembl ].
VAR_034602
Natural variant9161T → M.
Corresponds to variant rs3730043 [ dbSNP | Ensembl ].
VAR_023432
Natural variant10181I → T. Ref.30
Corresponds to variant rs4976 [ dbSNP | Ensembl ].
VAR_014189
Natural variant10511F → V. Ref.30
Corresponds to variant rs4977 [ dbSNP | Ensembl ].
VAR_014190
Natural variant11871T → M.
Corresponds to variant rs12709442 [ dbSNP | Ensembl ].
VAR_023433
Natural variant12281P → L No effect on activity; increases secretion; rate of solubilization is 2.5-fold higher than wild-type. Ref.17 Ref.31 Ref.32
VAR_023434
Natural variant12791R → Q. Ref.30
Corresponds to variant rs4980 [ dbSNP | Ensembl ].
VAR_014191
Natural variant12861R → S. Ref.4 Ref.30
Corresponds to variant rs4364 [ dbSNP | Ensembl ].
VAR_011709
Natural variant12961Q → P. Ref.30
Corresponds to variant rs4981 [ dbSNP | Ensembl ].
VAR_014192
Isoform Testis-specific:
Natural variant321S → P.
Corresponds to variant rs4317 [ dbSNP | Ensembl ].
Natural variant491S → G.
Corresponds to variant rs4318 [ dbSNP | Ensembl ].

Experimental info

Mutagenesis12991S → A: Abolishes phosphorylation and decreases membrane retention. Ref.18
Sequence conflict351Q → E AA sequence Ref.9
Sequence conflict421D → R AA sequence Ref.9

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) [UniParc].

Checksum: B7EED12CAB675583
Show »

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

Checksum: 80E0D19CFA642313
Show »

FASTA73283,330
Isoform 4 [UniParc].

Checksum: C7FED633D33129B0
Show »

FASTA69078,581

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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-261; TRP-561 AND SER-1286.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Testis.
[6]NHLBI resequencing and genotyping service (RS&G)
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]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.
[8]"DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage."
Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R., Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A., Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J., Chang J.L. expand/collapse author list , Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J., DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S., Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E., Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K., LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J., Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A., Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K., Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D., Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A., Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.
Nature 440:1045-1049(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-46.
Tissue: Lung.
[10]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1114-1306 (ISOFORM SOMATIC-2), ALTERNATIVE SPLICING.
Tissue: Umbilical vein endothelial cell.
[11]"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] [Europe PMC] [Abstract]
Cited for: ZINC-BINDING.
[12]"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] [Europe PMC] [Abstract]
Cited for: DISULFIDE BONDS.
[13]"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] [Europe PMC] [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, IDENTIFICATION BY MASS SPECTROMETRY.
[14]"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] [Europe PMC] [Abstract]
Cited for: CLEAVAGE SITE, IDENTIFICATION BY MASS SPECTROMETRY.
[15]"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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[16]"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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[17]"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] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANT LEU-1228.
[18]"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] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1299, MUTAGENESIS OF SER-1299.
[19]"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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[20]"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] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, CLEAVAGE SITE.
[21]"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] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[22]"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] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION.
[23]"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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-509; ASN-695 AND ASN-714.
Tissue: Plasma.
[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] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-111; ASN-445 AND ASN-714.
Tissue: Liver.
[25]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[26]"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] [Europe PMC] [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.
[27]"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] [Europe PMC] [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.
[28]"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] [Europe PMC] [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.
[29]"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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN DIABETIC NEPHROPATHY SUSCEPTIBILITY.
[30]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS THR-1018; VAL-1051; GLN-1279; SER-1286 AND PRO-1296.
[31]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-1228, ASSOCIATION WITH BENIGN SERUM INCREASE OF ANGIOTENSIN-CONVERTING ENZYME.
[32]"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] [Europe PMC] [Abstract]
Cited for: VARIANT LEU-1228, ASSOCIATION WITH BENIGN SERUM INCREASE OF ANGIOTENSIN-CONVERTING ENZYME.
[33]"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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ISCHSTR.
[34]"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] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO ICH.
[35]"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] [Europe PMC] [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.
AK301988 mRNA. Translation: BAG63395.1.
EU332840 Genomic DNA. Translation: ABY87529.1.
AB208971 mRNA. Translation: BAD92208.1. Different initiation.
AC113554 Genomic DNA. No translation available.
PIRA31759.
PW0053.
S05238.
RefSeqNP_000780.1. NM_000789.3.
NP_001171528.1. NM_001178057.1.
NP_690043.1. NM_152830.2.
UniGeneHs.298469.

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[»]
2XY9X-ray1.97A645-1228[»]
2XYDX-ray2.15A/B30-639[»]
2YDMX-ray2.44A642-1230[»]
3BKKX-ray2.17A642-1232[»]
3BKLX-ray2.18A642-1232[»]
3L3NX-ray2.30A642-1232[»]
3NXQX-ray1.99A/B30-658[»]
4APHX-ray1.99A642-1230[»]
4APJX-ray2.60A642-1230[»]
4BXKX-ray2.20A/B30-657[»]
4BZRX-ray1.84A642-1230[»]
4BZSX-ray2.10A/B30-657[»]
4C2NX-ray2.59A642-1230[»]
4C2OX-ray1.80A642-1230[»]
4C2PX-ray1.99A642-1230[»]
4C2QX-ray2.40A642-1230[»]
4C2RX-ray2.30A642-1230[»]
4CA5X-ray1.85A642-1230[»]
4CA6X-ray1.91A/B30-639[»]
ProteinModelPortalP12821.
SMRP12821. Positions 30-641, 645-1228.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108004. 7 interactions.
MINTMINT-127316.
STRING9606.ENSP00000290866.

Chemistry

BindingDBP12821.
ChEMBLCHEMBL1808.
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.
GuidetoPHARMACOLOGY1613.

Protein family/group databases

MEROPSM02.001.

PTM databases

PhosphoSiteP12821.

Polymorphism databases

DMDM113045.

Proteomic databases

PaxDbP12821.
PeptideAtlasP12821.
PRIDEP12821.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290863; ENSP00000290863; ENSG00000159640. [P12821-3]
ENST00000290866; ENSP00000290866; ENSG00000159640. [P12821-1]
ENST00000413513; ENSP00000392247; ENSG00000159640.
ENST00000428043; ENSP00000397593; ENSG00000159640. [P12821-2]
GeneID1636.
KEGGhsa:1636.
UCSCuc002jau.2. human. [P12821-1]
uc002jav.2. human. [P12821-3]

Organism-specific databases

CTD1636.
GeneCardsGC17P061554.
HGNCHGNC:2707. ACE.
HPACAB002426.
CAB002921.
HPA029298.
MIM106180. gene+phenotype.
267430. phenotype.
601367. phenotype.
612624. phenotype.
614519. phenotype.
neXtProtNX_P12821.
Orphanet97369. Renal tubular dysgenesis of genetic origin.
PharmGKBPA139.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG71044.
HOGENOMHOG000292210.
HOVERGENHBG000264.
InParanoidP12821.
KOK01283.
OrthoDBEOG76HQ13.
PhylomeDBP12821.
TreeFamTF312861.

Enzyme and pathway databases

BioCycMetaCyc:HS08412-MONOMER.
BRENDA3.4.15.1. 2681.
ReactomeREACT_17015. Metabolism of proteins.
SABIO-RKP12821.
SignaLinkP12821.

Gene expression databases

ArrayExpressP12821.
BgeeP12821.
CleanExHS_ACE.
GenevestigatorP12821.

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

EvolutionaryTraceP12821.
GeneWikiAngiotensin-converting_enzyme.
GenomeRNAi1636.
NextBio6722.
PMAP-CutDBP12821.
PROP12821.
SOURCESearch...

Entry information

Entry nameACE_HUMAN
AccessionPrimary (citable) accession number: P12821
Secondary accession number(s): B0LPF0 expand/collapse secondary AC list , B4DXI3, E7EU16, P22966, Q53YX9, Q59GY8, Q7M4L4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: October 1, 1989
Last modified: April 16, 2014
This is version 183 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 17

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

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries

Human cell differentiation molecules

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