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Protein

Angiotensin-converting enzyme

Gene

ACE

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent vasodilator. Has also a glycosidase activity which releases GPI-anchored proteins from the membrane by cleaving the mannose linkage in the GPI moiety.

Catalytic activityi

Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa, when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion of angiotensin I to angiotensin II, with increase in vasoconstrictor activity, but no action on angiotensin II.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+Note: Binds 2 Zn2+ ions per subunit.
  • chlorideNote: Binds 3 chloride ions per subunit.

Cofactori (for Isoform Testis-specific)

Zn2+Note: Isoform Testis-specific only binds 1 Zn2+ ion per subunit.

Enzyme regulationi

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

Kineticsi

  1. KM=2.51 mM for Hip-His-Leu2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei231Chloride 11
    Metal bindingi390Zinc 1; catalytic1 Publication1
    Active sitei39111
    Metal bindingi394Zinc 1; catalytic1 Publication1
    Metal bindingi418Zinc 1; catalytic1 Publication1
    Binding sitei529Chloride 11
    Binding sitei791Chloride 21
    Binding sitei829Chloride 31
    Metal bindingi988Zinc 2; catalytic1 Publication1
    Active sitei98921
    Metal bindingi992Zinc 2; catalytic1 Publication1
    Metal bindingi1016Zinc 2; catalytic1 Publication1
    Binding sitei1090Chloride 21
    Binding sitei1094Chloride 21
    Binding sitei1127Chloride 31

    GO - Molecular functioni

    • actin binding Source: UniProtKB
    • bradykinin receptor binding Source: BHF-UCL
    • carboxypeptidase activity Source: UniProtKB-KW
    • chloride ion binding Source: BHF-UCL
    • drug binding Source: BHF-UCL
    • endopeptidase activity Source: UniProtKB
    • exopeptidase activity Source: BHF-UCL
    • metallodipeptidase activity Source: Reactome
    • metallopeptidase activity Source: UniProtKB
    • mitogen-activated protein kinase binding Source: BHF-UCL
    • mitogen-activated protein kinase kinase binding Source: BHF-UCL
    • peptidyl-dipeptidase activity Source: UniProtKB
    • tripeptidyl-peptidase activity Source: BHF-UCL
    • zinc ion binding Source: BHF-UCL

    GO - Biological processi

    • angiotensin catabolic process in blood Source: UniProtKB
    • angiotensin maturation Source: Reactome
    • antigen processing and presentation of peptide antigen via MHC class I Source: BHF-UCL
    • arachidonic acid secretion Source: BHF-UCL
    • beta-amyloid metabolic process Source: BHF-UCL
    • blood vessel remodeling Source: BHF-UCL
    • cell proliferation in bone marrow Source: BHF-UCL
    • heart contraction Source: BHF-UCL
    • hematopoietic stem cell differentiation Source: BHF-UCL
    • hormone catabolic process Source: BHF-UCL
    • kidney development Source: BHF-UCL
    • mononuclear cell proliferation Source: BHF-UCL
    • negative regulation of gap junction assembly Source: BHF-UCL
    • negative regulation of gene expression Source: Ensembl
    • negative regulation of protein binding Source: Ensembl
    • neutrophil mediated immunity Source: BHF-UCL
    • peptide catabolic process Source: BHF-UCL
    • positive regulation of peptidyl-cysteine S-nitrosylation Source: BHF-UCL
    • positive regulation of peptidyl-tyrosine autophosphorylation Source: BHF-UCL
    • positive regulation of protein binding Source: Ensembl
    • positive regulation of protein tyrosine kinase activity Source: BHF-UCL
    • positive regulation of systemic arterial blood pressure Source: Ensembl
    • posttranscriptional regulation of gene expression Source: Ensembl
    • regulation of angiotensin metabolic process Source: BHF-UCL
    • regulation of blood pressure Source: BHF-UCL
    • regulation of hematopoietic stem cell proliferation Source: BHF-UCL
    • regulation of renal output by angiotensin Source: BHF-UCL
    • regulation of smooth muscle cell migration Source: BHF-UCL
    • regulation of systemic arterial blood pressure by renin-angiotensin Source: UniProtKB
    • regulation of vasoconstriction Source: UniProtKB
    • regulation of vasodilation Source: BHF-UCL
    • spermatogenesis Source: BHF-UCL
    Complete GO annotation...

    Keywords - Molecular functioni

    Carboxypeptidase, Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08412-MONOMER.
    ZFISH:HS08412-MONOMER.
    BRENDAi3.4.15.1. 2681.
    ReactomeiR-HSA-2022377. Metabolism of Angiotensinogen to Angiotensins.
    SABIO-RKP12821.
    SignaLinkiP12821.

    Protein family/group databases

    MEROPSiM02.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Angiotensin-converting enzyme (EC:3.2.1.-, EC:3.4.15.1)
    Short name:
    ACE
    Alternative name(s):
    Dipeptidyl carboxypeptidase I
    Kininase II
    CD_antigen: CD143
    Cleaved into the following chain:
    Gene namesi
    Name:ACE
    Synonyms:DCP, DCP1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 17

    Organism-specific databases

    HGNCiHGNC:2707. ACE.

    Subcellular locationi

    Topology

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Topological domaini30 – 1256ExtracellularSequence analysisAdd BLAST1227
    Transmembranei1257 – 1277HelicalSequence analysisAdd BLAST21
    Topological domaini1278 – 1306CytoplasmicSequence analysisAdd BLAST29

    GO - Cellular componenti

    • endosome Source: BHF-UCL
    • external side of plasma membrane Source: BHF-UCL
    • extracellular exosome Source: UniProtKB
    • extracellular region Source: Reactome
    • extracellular space Source: UniProtKB
    • integral component of membrane Source: UniProtKB-KW
    • lysosome Source: BHF-UCL
    • plasma membrane Source: BHF-UCL
    Complete GO annotation...

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Secreted

    Pathology & Biotechi

    Involvement in diseasei

    Ischemic stroke (ISCHSTR)1 Publication
    Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Disease descriptionA 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.
    See also OMIM:601367
    Renal tubular dysgenesis (RTD)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionAutosomal 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).
    See also OMIM:267430
    Microvascular complications of diabetes 3 (MVCD3)1 Publication
    Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Disease descriptionPathological 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.
    See also OMIM:612624
    Intracerebral hemorrhage (ICH)1 Publication
    Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Disease descriptionA 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.
    See also OMIM:614519

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi1299S → A: Abolishes phosphorylation and decreases membrane retention. 1 Publication1

    Organism-specific databases

    DisGeNETi1636.
    MalaCardsiACE.
    MIMi106180. gene+phenotype.
    267430. phenotype.
    601367. phenotype.
    612624. phenotype.
    614519. phenotype.
    OpenTargetsiENSG00000159640.
    Orphaneti97369. Renal tubular dysgenesis of genetic origin.
    PharmGKBiPA139.

    Chemistry databases

    ChEMBLiCHEMBL1808.
    DrugBankiDB00542. Benazepril.
    DB00616. Candoxatril.
    DB01197. Captopril.
    DB01340. Cilazapril.
    DB00584. Enalapril.
    DB00492. Fosinopril.
    DB00722. Lisinopril.
    DB00691. Moexipril.
    DB00790. Perindopril.
    DB00881. Quinapril.
    DB00178. Ramipril.
    DB01180. Rescinnamine.
    DB01348. Spirapril.
    DB00519. Trandolapril.
    GuidetoPHARMACOLOGYi1613.

    Polymorphism and mutation databases

    BioMutaiACE.
    DMDMi113045.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Signal peptidei1 – 291 PublicationAdd BLAST29
    ChainiPRO_000002853030 – 1306Angiotensin-converting enzymeAdd BLAST1277
    ChainiPRO_000002853130 – 1232Angiotensin-converting enzyme, soluble formAdd BLAST1203
    PropeptideiPRO_00000285321233 – 1306Removed in soluble formAdd BLAST74

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Glycosylationi38N-linked (GlcNAc...)1 Publication1
    Glycosylationi54N-linked (GlcNAc...)2 Publications1
    Glycosylationi74N-linked (GlcNAc...)1 Publication1
    Glycosylationi111N-linked (GlcNAc...)2 Publications1
    Glycosylationi146N-linked (GlcNAc...)2 Publications1
    Disulfide bondi157 ↔ 1651 Publication
    Glycosylationi160N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi318N-linked (GlcNAc...)1 Publication1
    Glycosylationi445N-linked (GlcNAc...)1 Publication1
    Glycosylationi509N-linked (GlcNAc...)3 Publications1
    Glycosylationi677N-linked (GlcNAc...)Sequence analysis1
    Glycosylationi695N-linked (GlcNAc...) (complex)2 Publications1
    Glycosylationi714N-linked (GlcNAc...) (complex)3 Publications1
    Disulfide bondi757 ↔ 7631 Publication
    Glycosylationi760N-linked (GlcNAc...); partial1 Publication1
    Glycosylationi942N-linked (GlcNAc...); partial1 Publication1
    Disulfide bondi957 ↔ 9751 Publication
    Disulfide bondi1143 ↔ 11551 Publication
    Glycosylationi1191N-linked (GlcNAc...); partial1 Publication1
    Modified residuei1299Phosphoserine1 Publication1

    Post-translational modificationi

    Phosphorylated by CK2 on Ser-1299; which allows membrane retention.1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei1225Not glycosylated1

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    EPDiP12821.
    MaxQBiP12821.
    PaxDbiP12821.
    PeptideAtlasiP12821.
    PRIDEiP12821.

    PTM databases

    iPTMnetiP12821.
    PhosphoSitePlusiP12821.

    Miscellaneous databases

    PMAP-CutDBP12821.

    Expressioni

    Tissue specificityi

    Ubiquitously expressed, with highest levels in lung, kidney, heart, gastrointestinal system and prostate. Isoform Testis-specific is expressed in spermatocytes and adult testis.4 Publications

    Inductioni

    Up-regulated in failing heart.2 Publications

    Gene expression databases

    BgeeiENSG00000159640.
    CleanExiHS_ACE.
    ExpressionAtlasiP12821. baseline and differential.
    GenevisibleiP12821. HS.

    Organism-specific databases

    HPAiCAB002426.
    CAB002921.
    HPA029298.

    Interactioni

    GO - Molecular functioni

    • actin binding Source: UniProtKB
    • bradykinin receptor binding Source: BHF-UCL
    • mitogen-activated protein kinase binding Source: BHF-UCL
    • mitogen-activated protein kinase kinase binding Source: BHF-UCL

    Protein-protein interaction databases

    BioGridi108004. 7 interactors.
    IntActiP12821. 1 interactor.
    MINTiMINT-127316.
    STRINGi9606.ENSP00000290866.

    Chemistry databases

    BindingDBiP12821.

    Structurei

    Secondary structure

    11306
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi32 – 34Combined sources3
    Helixi43 – 72Combined sources30
    Helixi77 – 105Combined sources29
    Turni106 – 108Combined sources3
    Helixi109 – 111Combined sources3
    Helixi115 – 124Combined sources10
    Helixi128 – 131Combined sources4
    Helixi134 – 153Combined sources20
    Beta strandi155 – 157Combined sources3
    Beta strandi159 – 161Combined sources3
    Beta strandi165 – 167Combined sources3
    Turni168 – 170Combined sources3
    Helixi171 – 178Combined sources8
    Helixi182 – 216Combined sources35
    Turni217 – 219Combined sources3
    Helixi223 – 229Combined sources7
    Helixi236 – 266Combined sources31
    Turni268 – 270Combined sources3
    Beta strandi281 – 284Combined sources4
    Helixi291 – 293Combined sources3
    Helixi294 – 297Combined sources4
    Helixi309 – 314Combined sources6
    Helixi319 – 332Combined sources14
    Helixi340 – 345Combined sources6
    Beta strandi352 – 354Combined sources3
    Beta strandi362 – 365Combined sources4
    Beta strandi367 – 370Combined sources4
    Beta strandi372 – 375Combined sources4
    Helixi382 – 401Combined sources20
    Helixi406 – 408Combined sources3
    Helixi414 – 428Combined sources15
    Helixi431 – 436Combined sources6
    Helixi447 – 461Combined sources15
    Helixi464 – 479Combined sources16
    Helixi485 – 487Combined sources3
    Helixi488 – 500Combined sources13
    Helixi514 – 517Combined sources4
    Turni519 – 524Combined sources6
    Helixi528 – 547Combined sources20
    Helixi554 – 556Combined sources3
    Helixi563 – 575Combined sources13
    Helixi581 – 589Combined sources9
    Helixi597 – 617Combined sources21
    Turni634 – 638Combined sources5
    Helixi641 – 643Combined sources3
    Helixi646 – 675Combined sources30
    Helixi680 – 704Combined sources25
    Helixi709 – 711Combined sources3
    Helixi715 – 724Combined sources10
    Helixi728 – 731Combined sources4
    Helixi734 – 753Combined sources20
    Beta strandi755 – 757Combined sources3
    Beta strandi759 – 761Combined sources3
    Beta strandi763 – 765Combined sources3
    Turni766 – 768Combined sources3
    Helixi769 – 776Combined sources8
    Helixi780 – 793Combined sources14
    Helixi795 – 799Combined sources5
    Helixi802 – 815Combined sources14
    Helixi821 – 827Combined sources7
    Helixi834 – 844Combined sources11
    Helixi846 – 864Combined sources19
    Helixi866 – 868Combined sources3
    Beta strandi879 – 882Combined sources4
    Helixi889 – 891Combined sources3
    Helixi892 – 895Combined sources4
    Helixi906 – 912Combined sources7
    Helixi917 – 930Combined sources14
    Helixi938 – 943Combined sources6
    Beta strandi945 – 947Combined sources3
    Beta strandi950 – 952Combined sources3
    Beta strandi960 – 963Combined sources4
    Beta strandi965 – 968Combined sources4
    Beta strandi970 – 973Combined sources4
    Helixi980 – 998Combined sources19
    Turni999 – 1001Combined sources3
    Helixi1004 – 1006Combined sources3
    Helixi1012 – 1026Combined sources15
    Helixi1029 – 1034Combined sources6
    Helixi1045 – 1077Combined sources33
    Turni1083 – 1085Combined sources3
    Helixi1086 – 1098Combined sources13
    Helixi1112 – 1115Combined sources4
    Turni1117 – 1122Combined sources6
    Helixi1126 – 1145Combined sources20
    Helixi1152 – 1154Combined sources3
    Helixi1161 – 1171Combined sources11
    Turni1172 – 1175Combined sources4
    Helixi1179 – 1187Combined sources9
    Beta strandi1188 – 1191Combined sources4
    Helixi1195 – 1215Combined sources21

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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[»]
    4UFAX-ray1.80A/B30-657[»]
    4UFBX-ray1.80A/B/C/D30-657[»]
    5AM8X-ray1.90A/B/C/D30-658[»]
    5AM9X-ray1.80A/B/C/D30-658[»]
    5AMAX-ray1.80A/B/C/D30-658[»]
    5AMBX-ray1.55A/B30-658[»]
    5AMCX-ray1.65A/B30-658[»]
    ProteinModelPortaliP12821.
    SMRiP12821.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP12821.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni30 – 630Peptidase M2 1Add BLAST601
    Regioni631 – 1232Peptidase M2 2Add BLAST602

    Sequence similaritiesi

    Belongs to the peptidase M2 family.Curated

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiKOG3690. Eukaryota.
    ENOG410XPJ3. LUCA.
    GeneTreeiENSGT00520000055576.
    HOGENOMiHOG000007838.
    HOVERGENiHBG000264.
    InParanoidiP12821.
    KOiK01283.
    OMAiVTMEQLF.
    OrthoDBiEOG091G033S.
    PhylomeDBiP12821.
    TreeFamiTF312861.

    Family and domain databases

    CDDicd06461. M2_ACE. 2 hits.
    InterProiIPR001548. Peptidase_M2.
    [Graphical view]
    PANTHERiPTHR10514. PTHR10514. 1 hit.
    PfamiPF01401. Peptidase_M2. 2 hits.
    [Graphical view]
    PRINTSiPR00791. PEPDIPTASEA.
    PROSITEiPS00142. ZINC_PROTEASE. 2 hits.
    [Graphical view]

    Sequences (4)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

    Isoform Somatic-1 (identifier: P12821-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

            10         20         30         40         50
    MGAASGRRGP GLLLPLPLLL LLPPQPALAL DPGLQPGNFS ADEAGAQLFA
    60 70 80 90 100
    QSYNSSAEQV LFQSVAASWA HDTNITAENA RRQEEAALLS QEFAEAWGQK
    110 120 130 140 150
    AKELYEPIWQ NFTDPQLRRI IGAVRTLGSA NLPLAKRQQY NALLSNMSRI
    160 170 180 190 200
    YSTAKVCLPN KTATCWSLDP DLTNILASSR SYAMLLFAWE GWHNAAGIPL
    210 220 230 240 250
    KPLYEDFTAL SNEAYKQDGF TDTGAYWRSW YNSPTFEDDL EHLYQQLEPL
    260 270 280 290 300
    YLNLHAFVRR ALHRRYGDRY INLRGPIPAH LLGDMWAQSW ENIYDMVVPF
    310 320 330 340 350
    PDKPNLDVTS TMLQQGWNAT HMFRVAEEFF TSLELSPMPP EFWEGSMLEK
    360 370 380 390 400
    PADGREVVCH ASAWDFYNRK DFRIKQCTRV TMDQLSTVHH EMGHIQYYLQ
    410 420 430 440 450
    YKDLPVSLRR GANPGFHEAI GDVLALSVST PEHLHKIGLL DRVTNDTESD
    460 470 480 490 500
    INYLLKMALE KIAFLPFGYL VDQWRWGVFS GRTPPSRYNF DWWYLRTKYQ
    510 520 530 540 550
    GICPPVTRNE THFDAGAKFH VPNVTPYIRY FVSFVLQFQF HEALCKEAGY
    560 570 580 590 600
    EGPLHQCDIY RSTKAGAKLR KVLQAGSSRP WQEVLKDMVG LDALDAQPLL
    610 620 630 640 650
    KYFQPVTQWL QEQNQQNGEV LGWPEYQWHP PLPDNYPEGI DLVTDEAEAS
    660 670 680 690 700
    KFVEEYDRTS QVVWNEYAEA NWNYNTNITT ETSKILLQKN MQIANHTLKY
    710 720 730 740 750
    GTQARKFDVN QLQNTTIKRI IKKVQDLERA ALPAQELEEY NKILLDMETT
    760 770 780 790 800
    YSVATVCHPN GSCLQLEPDL TNVMATSRKY EDLLWAWEGW RDKAGRAILQ
    810 820 830 840 850
    FYPKYVELIN QAARLNGYVD AGDSWRSMYE TPSLEQDLER LFQELQPLYL
    860 870 880 890 900
    NLHAYVRRAL HRHYGAQHIN LEGPIPAHLL GNMWAQTWSN IYDLVVPFPS
    910 920 930 940 950
    APSMDTTEAM LKQGWTPRRM FKEADDFFTS LGLLPVPPEF WNKSMLEKPT
    960 970 980 990 1000
    DGREVVCHAS AWDFYNGKDF RIKQCTTVNL EDLVVAHHEM GHIQYFMQYK
    1010 1020 1030 1040 1050
    DLPVALREGA NPGFHEAIGD VLALSVSTPK HLHSLNLLSS EGGSDEHDIN
    1060 1070 1080 1090 1100
    FLMKMALDKI AFIPFSYLVD QWRWRVFDGS ITKENYNQEW WSLRLKYQGL
    1110 1120 1130 1140 1150
    CPPVPRTQGD FDPGAKFHIP SSVPYIRYFV SFIIQFQFHE ALCQAAGHTG
    1160 1170 1180 1190 1200
    PLHKCDIYQS KEAGQRLATA MKLGFSRPWP EAMQLITGQP NMSASAMLSY
    1210 1220 1230 1240 1250
    FKPLLDWLRT ENELHGEKLG WPQYNWTPNS ARSEGPLPDS GRVSFLGLDL
    1260 1270 1280 1290 1300
    DAQQARVGQW LLLFLGIALL VATLGLSQRL FSIRHRSLHR HSHGPQFGSE

    VELRHS
    Length:1,306
    Mass (Da):149,715
    Last modified:October 1, 1989 - v1
    Checksum:i1B33BCA7301A26AA
    GO
    Isoform Somatic-2 (identifier: P12821-2) [UniParc]FASTAAdd to basket
    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.
    Show »
    Length:1,145
    Mass (Da):131,659
    Checksum:iB7EED12CAB675583
    GO
    Isoform Testis-specific (identifier: P12821-3) [UniParc] [UniParc]FASTAAdd to basket
    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

    Show »
    Length:732
    Mass (Da):83,330
    Checksum:i80E0D19CFA642313
    GO
    Isoform 4 (identifier: P12821-4) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-641: MGAASGRRGP...LPDNYPEGID → MGQGWATAGL...AHQTSAQSPN
         1128-1168: Missing.

    Note: No experimental confirmation available.
    Show »
    Length:691
    Mass (Da):78,694
    Checksum:iF31FE078F52FF0B2
    GO

    Sequence cautioni

    The sequence BAD92208 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sequence conflicti35Q → E AA sequence (PubMed:2558109).Curated1
    Sequence conflicti42D → R AA sequence (PubMed:2558109).Curated1

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_029139154A → T.Corresponds to variant rs13306087dbSNPEnsembl.1
    Natural variantiVAR_029140183A → T.Corresponds to variant rs12720754dbSNPEnsembl.1
    Natural variantiVAR_023430244Y → C.Corresponds to variant rs3730025dbSNPEnsembl.1
    Natural variantiVAR_054000260R → C.Corresponds to variant rs4302dbSNPEnsembl.1
    Natural variantiVAR_054001260R → L.Corresponds to variant rs4303dbSNPEnsembl.1
    Natural variantiVAR_011707261A → S.1 PublicationCorresponds to variant rs4303dbSNPEnsembl.1
    Natural variantiVAR_074173295D → N.1 Publication1
    Natural variantiVAR_023431351P → L.Corresponds to variant rs2229839dbSNPEnsembl.1
    Natural variantiVAR_035434354G → R.1 PublicationCorresponds to variant rs56394458dbSNPEnsembl.1
    Natural variantiVAR_029141379R → Q.Corresponds to variant rs13306085dbSNPEnsembl.1
    Natural variantiVAR_029142524V → A.Corresponds to variant rs12720746dbSNPEnsembl.1
    Natural variantiVAR_011708561R → W.1 PublicationCorresponds to variant rs4314dbSNPEnsembl.1
    Natural variantiVAR_020053592D → G.Corresponds to variant rs12709426dbSNPEnsembl.1
    Natural variantiVAR_034602828M → T.Corresponds to variant rs13306091dbSNPEnsembl.1
    Natural variantiVAR_023432916T → M.Corresponds to variant rs3730043dbSNPEnsembl.1
    Natural variantiVAR_0141891018I → T.1 PublicationCorresponds to variant rs4976dbSNPEnsembl.1
    Natural variantiVAR_0141901051F → V.1 PublicationCorresponds to variant rs4977dbSNPEnsembl.1
    Natural variantiVAR_0234331187T → M.Corresponds to variant rs12709442dbSNPEnsembl.1
    Natural variantiVAR_0234341228P → L No effect on activity; increases secretion; rate of solubilization is 2.5-fold higher than wild-type. 3 PublicationsCorresponds to variant rs121912703dbSNPEnsembl.1
    Natural variantiVAR_0141911279R → Q.1 PublicationCorresponds to variant rs4980dbSNPEnsembl.1
    Natural variantiVAR_0117091286R → S.2 PublicationsCorresponds to variant rs4364dbSNPEnsembl.1
    Natural variantiVAR_0141921296Q → P.1 PublicationCorresponds to variant rs4981dbSNPEnsembl.1
    Isoform Testis-specific (identifier: P12821-3)
    Natural varianti32S → P.Corresponds to variant rs4317dbSNPEnsembl.1
    Natural varianti49S → G.Corresponds to variant rs4318dbSNPEnsembl.1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0548361 – 641MGAAS…PEGID → MGQGWATAGLPSLLFLLLCY GHPLLVPSQEASQQVTVTHG TSSQATTSSQTTTHQATAHQ TSAQSPN in isoform 4. 1 PublicationAdd BLAST641
    Alternative sequenceiVSP_0351201 – 574Missing in isoform Testis-specific. 2 PublicationsAdd BLAST574
    Alternative sequenceiVSP_035121575 – 641AGSSR…PEGID → MGQGWATAGLPSLLFLLLCY GHPLLVPSQEASQQVTVTHG TSSQATTSSQTTTHQATAHQ TSAQSPN in isoform Testis-specific. 2 PublicationsAdd BLAST67
    Alternative sequenceiVSP_0548371128 – 1168Missing in isoform 4. 1 PublicationAdd BLAST41
    Alternative sequenceiVSP_0299321137 – 1145QFHEALCQA → HPFSQHTAA in isoform Somatic-2. 1 Publication9
    Alternative sequenceiVSP_0299331146 – 1306Missing in isoform Somatic-2. 1 PublicationAdd BLAST161

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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.
    CCDSiCCDS11637.1. [P12821-1]
    CCDS45755.1. [P12821-3]
    CCDS54155.1. [P12821-4]
    PIRiA31759.
    PW0053.
    S05238.
    RefSeqiNP_000780.1. NM_000789.3. [P12821-1]
    NP_001171528.1. NM_001178057.1. [P12821-4]
    NP_690043.1. NM_152830.2. [P12821-3]
    UniGeneiHs.298469.

    Genome annotation databases

    EnsembliENST00000290863; ENSP00000290863; ENSG00000159640. [P12821-3]
    ENST00000290866; ENSP00000290866; ENSG00000159640. [P12821-1]
    ENST00000413513; ENSP00000392247; ENSG00000159640. [P12821-4]
    GeneIDi1636.
    KEGGihsa:1636.
    UCSCiuc002jau.3. human. [P12821-1]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    SHMPD

    The Singapore human mutation and polymorphism database

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    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.
    CCDSiCCDS11637.1. [P12821-1]
    CCDS45755.1. [P12821-3]
    CCDS54155.1. [P12821-4]
    PIRiA31759.
    PW0053.
    S05238.
    RefSeqiNP_000780.1. NM_000789.3. [P12821-1]
    NP_001171528.1. NM_001178057.1. [P12821-4]
    NP_690043.1. NM_152830.2. [P12821-3]
    UniGeneiHs.298469.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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[»]
    4UFAX-ray1.80A/B30-657[»]
    4UFBX-ray1.80A/B/C/D30-657[»]
    5AM8X-ray1.90A/B/C/D30-658[»]
    5AM9X-ray1.80A/B/C/D30-658[»]
    5AMAX-ray1.80A/B/C/D30-658[»]
    5AMBX-ray1.55A/B30-658[»]
    5AMCX-ray1.65A/B30-658[»]
    ProteinModelPortaliP12821.
    SMRiP12821.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108004. 7 interactors.
    IntActiP12821. 1 interactor.
    MINTiMINT-127316.
    STRINGi9606.ENSP00000290866.

    Chemistry databases

    BindingDBiP12821.
    ChEMBLiCHEMBL1808.
    DrugBankiDB00542. Benazepril.
    DB00616. Candoxatril.
    DB01197. Captopril.
    DB01340. Cilazapril.
    DB00584. Enalapril.
    DB00492. Fosinopril.
    DB00722. Lisinopril.
    DB00691. Moexipril.
    DB00790. Perindopril.
    DB00881. Quinapril.
    DB00178. Ramipril.
    DB01180. Rescinnamine.
    DB01348. Spirapril.
    DB00519. Trandolapril.
    GuidetoPHARMACOLOGYi1613.

    Protein family/group databases

    MEROPSiM02.001.

    PTM databases

    iPTMnetiP12821.
    PhosphoSitePlusiP12821.

    Polymorphism and mutation databases

    BioMutaiACE.
    DMDMi113045.

    Proteomic databases

    EPDiP12821.
    MaxQBiP12821.
    PaxDbiP12821.
    PeptideAtlasiP12821.
    PRIDEiP12821.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000290863; ENSP00000290863; ENSG00000159640. [P12821-3]
    ENST00000290866; ENSP00000290866; ENSG00000159640. [P12821-1]
    ENST00000413513; ENSP00000392247; ENSG00000159640. [P12821-4]
    GeneIDi1636.
    KEGGihsa:1636.
    UCSCiuc002jau.3. human. [P12821-1]

    Organism-specific databases

    CTDi1636.
    DisGeNETi1636.
    GeneCardsiACE.
    HGNCiHGNC:2707. ACE.
    HPAiCAB002426.
    CAB002921.
    HPA029298.
    MalaCardsiACE.
    MIMi106180. gene+phenotype.
    267430. phenotype.
    601367. phenotype.
    612624. phenotype.
    614519. phenotype.
    neXtProtiNX_P12821.
    OpenTargetsiENSG00000159640.
    Orphaneti97369. Renal tubular dysgenesis of genetic origin.
    PharmGKBiPA139.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG3690. Eukaryota.
    ENOG410XPJ3. LUCA.
    GeneTreeiENSGT00520000055576.
    HOGENOMiHOG000007838.
    HOVERGENiHBG000264.
    InParanoidiP12821.
    KOiK01283.
    OMAiVTMEQLF.
    OrthoDBiEOG091G033S.
    PhylomeDBiP12821.
    TreeFamiTF312861.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS08412-MONOMER.
    ZFISH:HS08412-MONOMER.
    BRENDAi3.4.15.1. 2681.
    ReactomeiR-HSA-2022377. Metabolism of Angiotensinogen to Angiotensins.
    SABIO-RKP12821.
    SignaLinkiP12821.

    Miscellaneous databases

    EvolutionaryTraceiP12821.
    GeneWikiiAngiotensin-converting_enzyme.
    GenomeRNAii1636.
    PMAP-CutDBP12821.
    PROiP12821.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000159640.
    CleanExiHS_ACE.
    ExpressionAtlasiP12821. baseline and differential.
    GenevisibleiP12821. HS.

    Family and domain databases

    CDDicd06461. M2_ACE. 2 hits.
    InterProiIPR001548. Peptidase_M2.
    [Graphical view]
    PANTHERiPTHR10514. PTHR10514. 1 hit.
    PfamiPF01401. Peptidase_M2. 2 hits.
    [Graphical view]
    PRINTSiPR00791. PEPDIPTASEA.
    PROSITEiPS00142. ZINC_PROTEASE. 2 hits.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiACE_HUMAN
    AccessioniPrimary (citable) accession number: P12821
    Secondary accession number(s): B0LPF0
    , B4DXI3, E7EU16, P22966, Q53YX9, Q59GY8, Q7M4L4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: October 1, 1989
    Last modified: November 30, 2016
    This is version 212 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (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.

    Miscellaneousi

    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.

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Glycosyl hydrolases
      Classification of glycosyl hydrolase families and list of entries
    3. Human chromosome 17
      Human chromosome 17: entries, gene names and cross-references to MIM
    4. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    5. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    6. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    7. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    8. Peptidase families
      Classification of peptidase families and list of entries
    9. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.