Angiotensin-converting enzyme precursor

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Names and origin

Protein names

Recommended 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:

Angiotensin-converting enzyme, soluble form

Gene names

Name:	ACE
Synonyms:	DCP, DCP1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1306 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.
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: K_M=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 component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	angiotensin 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 component	endosome 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 function	actin 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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Natural variant

32

1

S → P. [dbSNP:rs4317]

Natural variant

49

1

S → G. [dbSNP:rs4318]

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Ref.7

Chain

30 – 1306

1277

Angiotensin-converting enzyme

PRO_0000028530

Chain

30 – 1232

1203

Angiotensin-converting enzyme, soluble form

PRO_0000028531

Propeptide

1233 – 1306

74

Removed in soluble form

PRO_0000028532

Regions

Topological domain

30 – 1256

1227

Extracellular Potential

Transmembrane

1257 – 1277

21

Helical; Potential

Topological domain

1278 – 1306

29

Cytoplasmic Potential

Region

30 – 630

601

Peptidase M2 1

Region

631 – 1232

602

Peptidase M2 2

Sites

Active site

391

1

Active site

989

1

2

Metal binding

390

1

Zinc 1; catalytic

Metal binding

394

1

Zinc 1; catalytic

Metal binding

418

1

Zinc 1; catalytic

Metal binding

988

1

Zinc 2; catalytic

Metal binding

992

1

Zinc 2; catalytic

Metal binding

1016

1

Zinc 2; catalytic

Binding site

231

1

Chloride 1

Binding site

529

1

Chloride 1

Binding site

791

1

Chloride 2

Binding site

829

1

Chloride 3

Binding site

1090

1

Chloride 2

Binding site

1094

1

Chloride 2

Binding site

1127

1

Chloride 3

Site

1225

1

Not glycosylated

Amino acid modifications

Modified residue

716

1

Phosphothreonine Ref.22

Modified residue

1299

1

Phosphoserine Ref.16

Glycosylation

38

1

N-linked (GlcNAc...) Probable

Glycosylation

54

1

N-linked (GlcNAc...) Ref.11 Ref.27

Glycosylation

74

1

N-linked (GlcNAc...) Ref.27

Glycosylation

111

1

N-linked (GlcNAc...) Ref.11 Ref.24

Glycosylation

146

1

N-linked (GlcNAc...) Ref.11 Ref.27

Glycosylation

160

1

N-linked (GlcNAc...) Potential

Glycosylation

318

1

N-linked (GlcNAc...) Ref.27

Glycosylation

445

1

N-linked (GlcNAc...) Ref.24

Glycosylation

509

1

N-linked (GlcNAc...) Ref.11 Ref.27 Ref.21

Glycosylation

677

1

N-linked (GlcNAc...) Potential

Glycosylation

695

1

N-linked (GlcNAc...) (complex) Ref.11 Ref.21

Glycosylation

714

1

N-linked (GlcNAc...) (complex) Ref.11 Ref.24 Ref.21

Glycosylation

760

1

N-linked (GlcNAc...); partial Ref.11

Glycosylation

942

1

N-linked (GlcNAc...); partial Ref.11

Glycosylation

1191

1

N-linked (GlcNAc...); partial Ref.11

Disulfide bond

Disulfide bond

Disulfide bond

Disulfide bond

Natural variations

Alternative sequence

1 – 574

574

Missing in isoform Testis-specific.

VSP_035120

Alternative sequence

575 – 641

67

AGSSR…PEGID → MGQGWATAGLPSLLFLLLCY GHPLLVPSQEASQQVTVTHG TSSQATTSSQTTTHQATAHQ TSAQSPN in isoform Testis-specific.

VSP_035121

Alternative sequence

1137 – 1145

9

QFHEALCQA → HPFSQHTAA in isoform Somatic-2.

VSP_029932

Alternative sequence

1146 – 1306

161

Missing in isoform Somatic-2.

VSP_029933

Natural variant

154

1

A → T. [dbSNP:rs13306087]

VAR_029139

Natural variant

183

1

A → T. [dbSNP:rs12720754]

VAR_029140

Natural variant

244

1

Y → C. [dbSNP:rs3730025]

VAR_023430

Natural variant

260

1

R → C. [dbSNP:rs4302]

VAR_054000

Natural variant

260

1

R → L. [dbSNP:rs4303]

VAR_054001

Natural variant

261

1

A → S. [dbSNP:rs4303] Ref.4

VAR_011707

Natural variant

351

1

P → L. [dbSNP:rs2229839]

VAR_023431

Natural variant

354

1

G → R. [dbSNP:rs56394458] Ref.34

VAR_035434

Natural variant

379

1

R → Q. [dbSNP:rs13306085]

VAR_029141

Natural variant

524

1

V → A. [dbSNP:rs12720746]

VAR_029142

Natural variant

561

1

R → W. [dbSNP:rs4314] Ref.4

VAR_011708

Natural variant

592

1

D → G. [dbSNP:rs12709426]

VAR_020053

Natural variant

828

1

M → T. [dbSNP:rs13306091]

VAR_034602

Natural variant

916

1

T → M. [dbSNP:rs3730043]

VAR_023432

Natural variant

1018

1

I → T. [dbSNP:rs4976] Ref.29

VAR_014189

Natural variant

1051

1

F → V. [dbSNP:rs4977] Ref.29

VAR_014190

Natural variant

1187

1

T → M. [dbSNP:rs12709442]

VAR_023433

Natural variant

1228

1

P → 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 variant

1279

1

R → Q. [dbSNP:rs4980] Ref.29

VAR_014191

Natural variant

1286

1

R → S. [dbSNP:rs4364] Ref.4 Ref.29

VAR_011709

Natural variant

1296

1

Q → P. [dbSNP:rs4981] Ref.29

VAR_014192

Experimental info

Mutagenesis

1299

1

S → A: Abolishes phosphorylation and decreases membrane retention. Ref.16

Sequence conflict

35

1

Q → E AA sequence Ref.7

Sequence conflict

42

1

D → R AA sequence Ref.7

Secondary structure

1

.

1306

Helix Strand Turn

Details...

Sequences

Sequence		Length	Mass (Da)
Isoform Somatic-1 [UniParc]. Last modified October 1, 1989. Version 1. Checksum: 1B33BCA7301A26AA Show »	FASTA	1,306	149,715
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 »	FASTA	1,145	131,659
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 SFIIQFHPFS QHTAA « Hide
Isoform Testis-specific (ACE-T) [UniParc] [UniParc]. Checksum: 80E0D19CFA642313 Show »	FASTA	732	83,330
10 20 30 40 50 60 MGQGWATAGL PSLLFLLLCY GHPLLVPSQE ASQQVTVTHG TSSQATTSSQ TTTHQATAHQ 70 80 90 100 110 120 TSAQSPNLVT DEAEASKFVE EYDRTSQVVW NEYAEANWNY NTNITTETSK ILLQKNMQIA 130 140 150 160 170 180 NHTLKYGTQA RKFDVNQLQN TTIKRIIKKV QDLERAALPA QELEEYNKIL LDMETTYSVA 190 200 210 220 230 240 TVCHPNGSCL QLEPDLTNVM ATSRKYEDLL WAWEGWRDKA GRAILQFYPK YVELINQAAR 250 260 270 280 290 300 LNGYVDAGDS WRSMYETPSL EQDLERLFQE LQPLYLNLHA YVRRALHRHY GAQHINLEGP 310 320 330 340 350 360 IPAHLLGNMW AQTWSNIYDL VVPFPSAPSM DTTEAMLKQG WTPRRMFKEA DDFFTSLGLL 370 380 390 400 410 420 PVPPEFWNKS MLEKPTDGRE VVCHASAWDF YNGKDFRIKQ CTTVNLEDLV VAHHEMGHIQ 430 440 450 460 470 480 YFMQYKDLPV ALREGANPGF HEAIGDVLAL SVSTPKHLHS LNLLSSEGGS DEHDINFLMK 490 500 510 520 530 540 MALDKIAFIP FSYLVDQWRW RVFDGSITKE NYNQEWWSLR LKYQGLCPPV PRTQGDFDPG 550 560 570 580 590 600 AKFHIPSSVP YIRYFVSFII QFQFHEALCQ AAGHTGPLHK CDIYQSKEAG QRLATAMKLG 610 620 630 640 650 660 FSRPWPEAMQ LITGQPNMSA SAMLSYFKPL LDWLRTENEL HGEKLGWPQY NWTPNSARSE 670 680 690 700 710 720 GPLPDSGRVS FLGLDLDAQQ ARVGQWLLLF LGIALLVATL GLSQRLFSIR HRSLHRHSHG 730 PQFGSEVELR HS « Hide

References

	« Hide 'large scale' referencesShow '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.

IPI

IPI00028147.
IPI00437751.
IPI00877100.

PIR

A31759.
PW0053.
S05238.

RefSeq

NP_000780.1.
NP_001171528.1.
NP_690043.1.

UniGene

Hs.654434.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1O86	X-ray	2.00	A	642-1230	[»]
1O8A	X-ray	2.00	A	642-1230	[»]
1UZE	X-ray	1.82	A	642-1230	[»]
1UZF	X-ray	2.00	A	642-1230	[»]
2C6F	X-ray	3.01	A/B	30-641	[»]
2C6N	X-ray	3.00	A/B	30-641	[»]
2IUL	X-ray	2.01	A	642-1232	[»]
2IUX	X-ray	2.80	A	642-1232	[»]
2OC2	X-ray	2.25	A	642-1232	[»]
3BKK	X-ray	2.17	A	642-1232	[»]
3BKL	X-ray	2.18	A	642-1232	[»]
3L3N	X-ray	2.30	A	642-1232	[»]

ProteinModelPortal

P12821.

ModBase

Search...

Protein-protein interaction databases

STRING

P12821.

Protein family/group databases

MEROPS

M02.001.
M02.004.

PTM databases

PhosphoSite

P12821.

Proteomic databases

PeptideAtlas

P12821.

PRIDE

P12821.

Genome annotation databases

Ensembl

ENST00000290866; ENSP00000290866; ENSG00000159640; Homo sapiens. [Genome view]

GeneID

1636.

KEGG

hsa:1636.

UCSC

uc002jau.1. human.

Organism-specific databases

CTD

1636.

GeneCards

GC17P061554.

H-InvDB

HIX0027185.

HGNC

HGNC:2707. ACE.

HPA

CAB002426.
CAB002921.

MIM

106180. gene+phenotype.
267430. phenotype.
601367. phenotype.
612624. phenotype.

Orphanet

3033. Renal tubular dysgenesis.

PharmGKB

PA139.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG16721.

HOGENOM

HBG356536.

HOVERGEN

HBG000264.

InParanoid

P12821.

OMA

EFWDKSM.

OrthoDB

EOG9QVFXH.

PhylomeDB

P12821.

Enzyme and pathway databases

BRENDA

3.4.15.1. 247.

Gene expression databases

ArrayExpress

P12821.

Bgee

P12821.

CleanEx

HS_ACE.

Genevestigator

P12821.

GermOnline

ENSG00000159640. Homo sapiens.

Family and domain databases

InterPro

IPR001548. Peptidase_M2.
[Graphical view]

PANTHER

PTHR10514. Peptidase_M2. 1 hit.

Pfam

PF01401. Peptidase_M2. 2 hits.
[Graphical view]

PRINTS

PR00791. PEPDIPTASEA.

PROSITE

PS00142. ZINC_PROTEASE. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00542. 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.

NextBio

6722.

PMAP-CutDB

P12821.

SOURCE

Search...

Entry information

Entry name

ACE_HUMAN

Accession

Primary (citable) accession number: P12821
Secondary accession number(s): B0LPF0

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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.