Q9BYF1 (ACE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Angiotensin-converting enzyme 2
EC=3.4.17.23

Alternative name(s):
ACE-related carboxypeptidase
Angiotensin-converting enzyme homolog
Short name=ACEH
Metalloprotease MPROT15

Cleaved into the following chain:

1. Processed angiotensin-converting enzyme 2

Gene names

Name:	ACE2
ORF Names:	UNQ868/PRO1885

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	805 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	Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses. Ref.1 Ref.2 Ref.14
Catalytic activity	Angiotensin II + H2O = angiotensin-1-7 + L-phenylalanine.
Cofactor	Binds 1 zinc ion per subunit. Ref.13 Binds 1 chloride ion per subunit. Ref.13
Enzyme regulation	Activated by chloride and fluoride, but not bromide. Inhibited by MLN-4760, cFP_Leu, and EDTA, but not by the ACE inhibitors linosipril, captopril and enalaprilat. Ref.1 Ref.2 Ref.3 Ref.13
Subunit structure	Interacts with ITGB1. Interacts with SARS-CoV and HCoV-NL63 spike glycoprotein. Ref.11 Ref.14 Ref.17 Ref.20 Ref.22
Subcellular location	Processed angiotensin-converting enzyme 2: Secreted Ref.3. Cell membrane; Single-pass type I membrane protein Ref.3.
Tissue specificity	Expressed in endothelial cells from small and large arteries, and in arterial smooth muscle cells. Expressed in lung alveolar epithelial cells, enterocytes of the small intestine, Leydig cells and Sertoli cells (at protein level). Expressed in heart, kidney, testis, and gastrointestinal system. Ref.1 Ref.2 Ref.3 Ref.12 Ref.16 Ref.19
Induction	Up-regulated in failing heart. Ref.1 Ref.2 Ref.3 Ref.13 Ref.15 Ref.19
Post-translational modification	N-glycosylation on Asn-90 may limit SARS infectivity.
Sequence similarities	Belongs to the peptidase M2 family.
Biophysicochemical properties	Kinetic parameters: KM=6.9 µM for angiotensin I Ref.13 KM=2 µM for angiotensin II KM=6.8 µM for apelin-13 KM=5.5 µM for dynorphin-13 pH dependence: Optimum pH is 6.5 in the presence of 1 M NaCl. Active from pH 6 to 9.

Ontologies

Keywords
Biological process	Host-virus interaction
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Ligand	Chloride Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	angiotensin catabolic process in blood Inferred by curator Ref.2. Source: BHF-UCL angiotensin-mediated drinking behavior Inferred from mutant phenotype. Source: BHF-UCL positive regulation of reactive oxygen species metabolic process Inferred by curator. Source: BHF-UCL proteolysis Inferred from electronic annotation. Source: UniProtKB-KW receptor biosynthetic process Inferred from mutant phenotype. Source: BHF-UCL regulation of cell proliferation Traceable author statement. Source: BHF-UCL regulation of cytokine production Inferred by curator. Source: BHF-UCL regulation of inflammatory response Inferred by curator. Source: BHF-UCL regulation of vasoconstriction Inferred by curator. Source: BHF-UCL regulation of vasodilation Inferred by curator. Source: BHF-UCL virion attachment, binding of host cell surface receptor Inferred from direct assay. Source: BHF-UCL
Cellular component	cell surface 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 raft Traceable author statement. Source: BHF-UCL plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	carboxypeptidase activity Inferred from direct assay Ref.1. Source: UniProtKB glycoprotein binding Inferred from physical interaction. Source: BHF-UCL metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-dipeptidase activity Inferred from electronic annotation. Source: InterPro viral receptor activity Inferred from direct assay. Source: BHF-UCL zinc ion binding Traceable author statement Ref.2. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9BYF1-1)

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 2 (identifier: Q9BYF1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     555-555: F → L
     556-805: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Potential

Chain

18 – 805

788

Angiotensin-converting enzyme 2

PRO_0000028570

Chain

18 – ?

Processed angiotensin-converting enzyme 2

PRO_0000292268

Regions

Topological domain

18 – 740

723

Extracellular Potential

Transmembrane

741 – 761

21

Helical; Potential

Topological domain

762 – 805

44

Cytoplasmic Potential

Region

30 – 41

12

Interaction with SARS-CoV spike glycoprotein

Region

82 – 84

3

Interaction with SARS-CoV spike glycoprotein

Region

353 – 357

5

Interaction with SARS-CoV spike glycoprotein

Sites

Active site

375

1

Active site

505

1

Metal binding

374

1

Zinc; catalytic

Metal binding

378

1

Zinc; catalytic

Metal binding

402

1

Zinc; catalytic

Binding site

169

1

Chloride

Binding site

273

1

Substrate

Binding site

345

1

Substrate

Binding site

346

1

Substrate; via carbonyl oxygen

Binding site

371

1

Substrate

Binding site

477

1

Chloride

Binding site

481

1

Chloride

Binding site

515

1

Substrate

Amino acid modifications

Glycosylation

53

1

N-linked (GlcNAc...) Probable

Glycosylation

90

1

N-linked (GlcNAc...) Ref.18 Ref.24

Glycosylation

103

1

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

Glycosylation

322

1

N-linked (GlcNAc...) Probable

Glycosylation

432

1

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

Glycosylation

546

1

N-linked (GlcNAc...) Ref.23 Ref.24

Glycosylation

690

1

N-linked (GlcNAc...) Potential

Disulfide bond

133 ↔ 141

Ref.24

Disulfide bond

344 ↔ 361

Ref.24

Disulfide bond

530 ↔ 542

Ref.24

Natural variations

Alternative sequence

555

1

F → L in isoform 2.

VSP_014901

Alternative sequence

556 – 805

250

Missing in isoform 2.

VSP_014902

Natural variant

26

1

K → R. Ref.8
Corresponds to variant rs4646116 [ dbSNP | Ensembl ].

VAR_023082

Natural variant

638

1

N → S. Ref.4

VAR_023083

Experimental info

Mutagenesis

24 – 26

3

QAK → KAE: Slightly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

31

1

K → D: Abolishes interaction with SARS-CoV spike glycoprotein.

Mutagenesis

37

1

E → A: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

38

1

D → A: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

41

1

Y → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

68

1

K → D: Slightly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

82 – 84

3

MYP → NFS: Inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

110

1

E → P: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

135 – 136

2

PD → SM: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

160

1

E → R: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

192

1

R → D: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

219

1

R → D: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

239

1

H → Q: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

309

1

K → D: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

312

1

E → A: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

324

1

T → A: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

338 – 340

3

NVQ → DDR: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

350

1

D → A: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

353

1

K → H, A or D: Abolishes interaction with SARS-CoV spike glycoprotein.

Mutagenesis

355

1

D → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

357

1

R → A: Strongly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

359

1

L → K or A: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

383

1

M → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

389

1

P → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

393

1

R → A: Slightly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

425 – 427

3

SPD → PSN: Slightly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

465 – 467

3

KGE → QDK: No effect on interaction with SARS-CoV spike glycoprotein.

Mutagenesis

559

1

R → S: Slightly inhibits interaction with SARS-CoV spike glycoprotein.

Mutagenesis

603

1

F → T: No effect on interaction with SARS-CoV spike glycoprotein.

Sequence conflict

18

1

Q → H in CAB53682. Ref.10

Sequence conflict

508

1

N → D in AAQ89076. Ref.7

Sequence conflict

631

1

K → R in BAB40370. Ref.5

Secondary structure

1

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805

Helix Strand Turn

Details...

Helix

23 – 52

30

Helix

56 – 77

22

Turn

78 – 82

5

Helix

91 – 100

10

Helix

104 – 107

4

Helix

110 – 129

20

Beta strand

131 – 134

4

Beta strand

137 – 143

7

Turn

144 – 146

3

Helix

148 – 154

7

Helix

158 – 171

14

Helix

173 – 193

21

Helix

199 – 204

6

Turn

205 – 207

3

Turn

213 – 215

3

Helix

220 – 251

32

Turn

253 – 255

3

Helix

264 – 266

3

Beta strand

267 – 271

5

Helix

276 – 278

3

Helix

279 – 282

4

Turn

284 – 287

4

Turn

294 – 297

4

Helix

298 – 300

3

Helix

304 – 316

13

Turn

317 – 319

3

Helix

327 – 330

4

Beta strand

347 – 352

6

Beta strand

355 – 359

5

Helix

366 – 384

19

Turn

385 – 387

3

Helix

390 – 392

3

Helix

400 – 413

14

Helix

415 – 420

6

Helix

432 – 446

15

Helix

449 – 465

17

Helix

470 – 472

3

Helix

473 – 483

11

Helix

499 – 502

4

Helix

504 – 507

4

Helix

514 – 531

18

Turn

532 – 534

3

Helix

539 – 541

3

Helix

548 – 558

11

Turn

559 – 562

4

Helix

566 – 574

9

Beta strand

575 – 578

4

Helix

582 – 598

17

Beta strand

600 – 602

3

Beta strand

607 – 609

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 2, 2005. Version 2. Checksum: 8EE6EB0A931550E8	FASTA	805	92,463
	10 20 30 40 50 60 MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ 70 80 90 100 110 120 NMNNAGDKWS AFLKEQSTLA QMYPLQEIQN LTVKLQLQAL QQNGSSVLSE DKSKRLNTIL 130 140 150 160 170 180 NTMSTIYSTG KVCNPDNPQE CLLLEPGLNE IMANSLDYNE RLWAWESWRS EVGKQLRPLY 190 200 210 220 230 240 EEYVVLKNEM ARANHYEDYG DYWRGDYEVN GVDGYDYSRG QLIEDVEHTF EEIKPLYEHL 250 260 270 280 290 300 HAYVRAKLMN AYPSYISPIG CLPAHLLGDM WGRFWTNLYS LTVPFGQKPN IDVTDAMVDQ 310 320 330 340 350 360 AWDAQRIFKE AEKFFVSVGL PNMTQGFWEN SMLTDPGNVQ KAVCHPTAWD LGKGDFRILM 370 380 390 400 410 420 CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF HEAVGEIMSL SAATPKHLKS 430 440 450 460 470 480 IGLLSPDFQE DNETEINFLL KQALTIVGTL PFTYMLEKWR WMVFKGEIPK DQWMKKWWEM 490 500 510 520 530 540 KREIVGVVEP VPHDETYCDP ASLFHVSNDY SFIRYYTRTL YQFQFQEALC QAAKHEGPLH 550 560 570 580 590 600 KCDISNSTEA GQKLFNMLRL GKSEPWTLAL ENVVGAKNMN VRPLLNYFEP LFTWLKDQNK 610 620 630 640 650 660 NSFVGWSTDW SPYADQSIKV RISLKSALGD KAYEWNDNEM YLFRSSVAYA MRQYFLKVKN 670 680 690 700 710 720 QMILFGEEDV RVANLKPRIS FNFFVTAPKN VSDIIPRTEV EKAIRMSRSR INDAFRLNDN 730 740 750 760 770 780 SLEFLGIQPT LGPPNQPPVS IWLIVFGVVM GVIVVGIVIL IFTGIRDRKK KNKARSGENP 790 800 YASIDISKGE NNPGFQNTDD VQTSF
	Isoform 2 [UniParc]. Checksum: 3A3842AB792E2DBC	FASTA	555	63,912
	10 20 30 40 50 60 MSSSSWLLLS LVAVTAAQST IEEQAKTFLD KFNHEAEDLF YQSSLASWNY NTNITEENVQ 70 80 90 100 110 120 NMNNAGDKWS AFLKEQSTLA QMYPLQEIQN LTVKLQLQAL QQNGSSVLSE DKSKRLNTIL 130 140 150 160 170 180 NTMSTIYSTG KVCNPDNPQE CLLLEPGLNE IMANSLDYNE RLWAWESWRS EVGKQLRPLY 190 200 210 220 230 240 EEYVVLKNEM ARANHYEDYG DYWRGDYEVN GVDGYDYSRG QLIEDVEHTF EEIKPLYEHL 250 260 270 280 290 300 HAYVRAKLMN AYPSYISPIG CLPAHLLGDM WGRFWTNLYS LTVPFGQKPN IDVTDAMVDQ 310 320 330 340 350 360 AWDAQRIFKE AEKFFVSVGL PNMTQGFWEN SMLTDPGNVQ KAVCHPTAWD LGKGDFRILM 370 380 390 400 410 420 CTKVTMDDFL TAHHEMGHIQ YDMAYAAQPF LLRNGANEGF HEAVGEIMSL SAATPKHLKS 430 440 450 460 470 480 IGLLSPDFQE DNETEINFLL KQALTIVGTL PFTYMLEKWR WMVFKGEIPK DQWMKKWWEM 490 500 510 520 530 540 KREIVGVVEP VPHDETYCDP ASLFHVSNDY SFIRYYTRTL YQFQFQEALC QAAKHEGPLH 550 KCDISNSTEA GQKLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, FUNCTION, ENZYME REGULATION. Tissue: Heart.
[2]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, GLYCOSYLATION, FUNCTION, ENZYME REGULATION. Tissue: Lymphoma.
[3]	"The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis." Douglas G.C., O'Bryan M.K., Hedger M.P., Lee D.K.L., Yarski M.A., Smith A.I., Lew R.A. Endocrinology 145:4703-4711(2004) [PubMed: 15231706] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, ENZYME REGULATION. Tissue: Testis.
[4]	"Identification of an alternative 5'-untranslated exon and new polymorphisms of angiotensin-converting enzyme 2 gene: lack of association with SARS in the Vietnamese population." Itoyama S., Keicho N., Hijikata M., Quy T., Phi N.C., Long H.T., Ha L.D., Ban V.V., Matsushita I., Yanai H., Kirikae F., Kirikae T., Kuratsuji T., Sasazuki T. Am. J. Med. Genet. A 136:52-57(2005) [PubMed: 15937940] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-638. Tissue: Lung and Testis.
[5]	"Cloning, expression analysis and chromosomal localization of a novel ACE like enzyme." Suzuki Y., Watanabe M., Sugano S. Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[6]	"MPROT15 polypeptide and MPROT15 polynucleotide." Southan C., Burgess N. Patent number JP11318472, 24-NOV-1999 Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[7]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[8]	SeattleSNPs variation discovery resource Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ARG-26.
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain and Testis.
[10]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-805 (ISOFORM 1). Tissue: Testis.
[11]	"Interaction of ACE2 and integrin beta1 in failing human heart." Lin Q., Keller R.S., Weaver B., Zisman L.S. Biochim. Biophys. Acta 1689:175-178(2004) [PubMed: 15276642] [Abstract] Cited for: PROTEIN SEQUENCE OF 679-689, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH ITGB1.
[12]	"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.
[13]	"Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase." Vickers C., Hales P., Kaushik V., Dick L., Gavin J., Tang J., Godbout K., Parsons T., Baronas E., Hsieh F., Acton S., Patane M.A., Nichols A., Tummino P. J. Biol. Chem. 277:14838-14843(2002) [PubMed: 11815627] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, COFACTOR.
[14]	"Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus." Li W., Moore M.J., Vasilieva N., Sui J., Wong S.-K., Berne M.A., Somasundaran M., Sullivan J.L., Luzuriaga K., Greenough T.C., Choe H., Farzan M. Nature 426:450-454(2003) [PubMed: 14647384] [Abstract] Cited for: FUNCTION, INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN, GLYCOSYLATION, IDENTIFICATION BY MASS SPECTROMETRY.
[15]	"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.
[16]	"Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis." Hamming I., Timens W., Bulthuis M.L.C., Lely A.T., Navis G.J., van Goor H. J. Pathol. 203:631-637(2004) [PubMed: 15141377] [Abstract] Cited for: TISSUE SPECIFICITY.
[17]	"Efficient replication of severe acute respiratory syndrome coronavirus in mouse cells is limited by murine angiotensin-converting enzyme 2." Li W., Greenough T.C., Moore M.J., Vasilieva N., Somasundaran M., Sullivan J.L., Farzan M., Choe H. J. Virol. 78:11429-11433(2004) [PubMed: 15452268] [Abstract] Cited for: INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN.
[18]	"A proteomic analysis of human bile." Kristiansen T.Z., Bunkenborg J., Gronborg M., Molina H., Thuluvath P.J., Argani P., Goggins M.G., Maitra A., Pandey A. Mol. Cell. Proteomics 3:715-728(2004) [PubMed: 15084671] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-90, MASS SPECTROMETRY. Tissue: Bile.
[19]	"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.
[20]	"Receptor and viral determinants of SARS-coronavirus adaptation to human ACE2." Li W., Zhang C., Sui J., Kuhn J.H., Moore M.J., Luo S., Wong S.-K., Huang I.-C., Xu K., Vasilieva N., Murakami A., He Y., Marasco W.A., Guan Y., Choe H., Farzan M. EMBO J. 24:1634-1643(2005) [PubMed: 15791205] [Abstract] Cited for: INTERACTION WITH SARS-COV SPIKE GLYCOPROTEIN, MUTAGENESIS.
[21]	"Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)." Lambert D.W., Yarski M., Warner F.J., Thornhill P., Parkin E.T., Smith A.I., Hooper N.M., Turner A.J. J. Biol. Chem. 280:30113-30119(2005) [PubMed: 15983030] [Abstract] Cited for: PROTEOLYTIC CLEAVAGE.
[22]	"Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry." Hofmann H., Pyrc K., van der Hoek L., Geier M., Berkhout B., Poehlmann S. Proc. Natl. Acad. Sci. U.S.A. 102:7988-7993(2005) [PubMed: 15897467] [Abstract] Cited for: INTERACTION WITH HCOV-NL63 SPIKE GLYCOPROTEIN.
[23]	"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-546, MASS SPECTROMETRY. Tissue: Liver.
[24]	"ACE2 X-ray structures reveal a large hinge-bending motion important for inhibitor binding and catalysis." Towler P., Staker B., Prasad S.G., Menon S., Tang J., Parsons T., Ryan D., Fisher M., Williams D., Dales N.A., Patane M.A., Pantoliano M.W. J. Biol. Chem. 279:17996-18007(2004) [PubMed: 14754895] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 19-615, X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 19-615 IN COMPLEX WITH MLN-4760, DISULFIDE BONDS, GLYCOSYLATION AT ASN-53; ASN-90; ASN-103; ASN-322; ASN-432 AND ASN-546.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF291820 mRNA. Translation: AAF99721.1.
AF241254 mRNA. Translation: AAF78220.1.
AY623811 mRNA. Translation: AAT45083.1.
AB193259 mRNA. Translation: BAD99266.1.
AB193260 mRNA. Translation: BAD99267.1.
AB046569 mRNA. Translation: BAB40370.1.
E39033 mRNA. No translation available.
AY358714 mRNA. Translation: AAQ89076.1.
AY217547 Genomic DNA. Translation: AAO25651.1.
BC039902 mRNA. Translation: AAH39902.1.
BC048094 mRNA. Translation: AAH48094.2.
AL110224 mRNA. Translation: CAB53682.1.

IPI

IPI00465187.
IPI00619939.

PIR

T14762.

RefSeq

NP_068576.1. NM_021804.2.

UniGene

Hs.178098.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1R42	X-ray	2.20	A	1-615	[»]
1R4L	X-ray	3.00	A	1-615	[»]
1XJP	model	-	B	19-615	[»]
2AJF	X-ray	2.90	A/B	19-615	[»]
3D0G	X-ray	2.80	A/B	56-615	[»]
3D0H	X-ray	3.10	A/B	56-615	[»]
3D0I	X-ray	2.90	A/B	56-615	[»]
3KBH	X-ray	3.31	A/B/C/D	19-615	[»]

ProteinModelPortal

Q9BYF1.

SMR

Q9BYF1. Positions 19-615.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-44689N.

MINT

MINT-4538816.

STRING

Q9BYF1.

Protein family/group databases

MEROPS

M02.006.

PTM databases

PhosphoSite

Q9BYF1.

Polymorphism databases

DMDM

71658783.

Proteomic databases

PRIDE

Q9BYF1.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000252519; ENSP00000252519; ENSG00000130234.
ENST00000427411; ENSP00000389326; ENSG00000130234.

GeneID

59272.

KEGG

hsa:59272.

UCSC

uc004cwz.1. human.

Organism-specific databases

CTD

59272.

GeneCards

GC0XM015489.

H-InvDB

HIX0016670.

HGNC

HGNC:13557. ACE2.

HPA

CAB026174.
HPA000288.

MIM

300335. gene.

neXtProt

NX_Q9BYF1.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG09542.

GeneTree

ENSGT00520000055576.

HOGENOM

HBG314770.

HOVERGEN

HBG000265.

InParanoid

Q9BYF1.

OMA

HPTAWDM.

OrthoDB

EOG4VHK5W.

PhylomeDB

Q9BYF1.

Enzyme and pathway databases

BRENDA

3.4.15.1. 2681.

Gene expression databases

ArrayExpress

Q9BYF1.

Bgee

Q9BYF1.

CleanEx

HS_ACE2.

Genevestigator

Q9BYF1.

GermOnline

ENSG00000130234. Homo sapiens.

Family and domain databases

InterPro

IPR001548. Peptidase_M2.
[Graphical view]

KO

K09708.

PANTHER

PTHR10514. Peptidase_M2. 1 hit.

Pfam

PF01401. Peptidase_M2. 1 hit.
[Graphical view]

PRINTS

PR00791. PEPDIPTASEA.

PROSITE

PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00691. Moexipril.

NextBio

65154.

PMAP-CutDB

Q9BYF1.

SOURCE

Search...

Entry information

Entry name

ACE2_HUMAN

Accession

Primary (citable) accession number: Q9BYF1
Secondary accession number(s): Q6UWP0 , Q86WT0, Q9NRA7, Q9UFZ6

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 2, 2005
Last sequence update:	August 2, 2005
Last modified:	January 25, 2012
This is version 100 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.