Reviewed, UniProtKB/Swiss-Prot Q10714 (ACE_DROME)

Names and origin

Protein names

Recommended name:
    Angiotensin-converting enzyme
    EC=3.4.15.1
Alternative name(s):
    Dipeptidyl carboxypeptidase I
    Kininase II

Gene names

Name:	Ance
Synonyms:	Race
ORF Names:	CG8827

Organism

Drosophila melanogaster (Fruit fly) [Complete proteome]

Taxonomic identifier

7227 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Endopterygota › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora

Protein attributes

Sequence length	615 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	May be involved in the specific maturation or degradation of a number of bioactive peptides. May play a role in the contractions of the heart, gut and testes, and in spermatid differentiation. Ref.11
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. Ref.2
Cofactor	Binds 1 zinc ion per subunit.
Enzyme regulation	Inhibited by captopril and, to a lesser extent, by lisinopril, trandolaprilat, fosinoprilat and enalaprilat. Ref.2 Ref.9
Subcellular location	Secreted › extracellular space.
Tissue specificity	Expressed in vesicular structures in spermatocytes and early spermatids (at protein level). Ref.11
Developmental stage	Expressed in the amnioserosa during germ band elongation, shortening and heart morphogenesis. Expressed in midgut throughout embryogenesis.
Post-translational modification	Glycosylated. Ref.9
Disruption phenotype	Male flies are sterile. Ref.11
Sequence similarities	Belongs to the peptidase M2 family.
Biophysicochemical properties	Kinetic parameters: KM=33.5 µM for angiotensin I KM=53.4 µM for N-acetyl-Ser-Asp-Lys-Pro KM=2.59 mM for Hip-His-Leu KM=10.26 mM for Hip-His-Leu-NH2 KM=372 µM for (Leu5)enkephalin KM=1.88 mM for (Leu5)enkephalinamide

Ontologies

Keywords
Cellular component	Secreted
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	metamorphosis Inferred from expression pattern. Source: FlyBase proteolysis Inferred from electronic annotation. Source: InterPro sperm individualization Ref.11 Inferred from mutant phenotype. Source: FlyBase spermatid nucleus differentiation Ref.11 Inferred from mutant phenotype. Source: FlyBase
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: InterPro
Molecular function	carboxypeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-dipeptidase activity Ref.2 Inferred from direct assay. Source: FlyBase zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 17

17

Chain

18 – 615

598

Angiotensin-converting enzyme

PRO_0000028563

Sites

Active site

368

1

Metal binding

367

1

Zinc; catalytic

Metal binding

371

1

Zinc; catalytic

Metal binding

395

1

Zinc; catalytic

Amino acid modifications

Glycosylation

53

1

N-linked (GlcNAc...) Probable

Glycosylation

196

1

N-linked (GlcNAc...) Probable

Glycosylation

311

1

N-linked (GlcNAc...) Probable

Disulfide bond

133 ↔ 141

Disulfide bond

336 ↔ 354

Disulfide bond

467 ↔ 612

Disulfide bond

522 ↔ 540

Experimental info

Sequence conflict

48 – 51

4

WAYG → GPMR in AAC46902. Ref.4

Sequence conflict

141

1

C → S in AAC46902. Ref.4

Sequence conflict

293

1

G → A in AAB02171. Ref.2

Sequence conflict

346

1

T → I Ref.1

Sequence conflict

346

1

T → I in AAB02171. Ref.2

Sequence conflict

346

1

T → I in AAC46902. Ref.4

Sequence conflict

346

1

T → I Ref.5

Sequence conflict

365

1

V → E Ref.1

Sequence conflict

402

1

S → A Ref.1

Sequence conflict

414

1

I → T Ref.1

Sequence conflict

486

1

S → T in AAC46902. Ref.4

Sequence conflict

533

1

V → M in AAC46902. Ref.4

Sequence conflict

547

1

A → R in AAB02171. Ref.2

Secondary structure

1

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615

Helix Strand Turn

Details...

Helix

26 – 50

25

Helix

56 – 77

22

Helix

79 – 81

3

Helix

85 – 87

3

Helix

93 – 101

9

Helix

105 – 107

3

Helix

110 – 128

19

Turn

145 – 147

3

Helix

148 – 155

8

Helix

159 – 173

15

Helix

175 – 177

3

Helix

178 – 194

17

Helix

200 – 206

7

Helix

213 – 228

16

Turn

229 – 231

3

Helix

232 – 243

12

Turn

245 – 247

3

Beta strand

258 – 261

4

Helix

268 – 270

3

Helix

271 – 274

4

Helix

286 – 291

6

Helix

296 – 308

13

Turn

309 – 311

3

Helix

317 – 322

6

Beta strand

329 – 331

3

Beta strand

339 – 342

4

Beta strand

344 – 347

4

Beta strand

349 – 352

4

Helix

359 – 378

20

Helix

383 – 385

3

Helix

390 – 406

17

Helix

408 – 413

6

Beta strand

416 – 419

4

Helix

428 – 435

8

Turn

436 – 440

5

Helix

441 – 456

16

Helix

462 – 464

3

Helix

465 – 477

13

Helix

492 – 494

3

Helix

496 – 500

5

Helix

505 – 524

20

Helix

537 – 539

3

Helix

546 – 556

11

Turn

557 – 560

4

Helix

564 – 572

9

Helix

582 – 585

4

Helix

587 – 599

13

Beta strand

612 – 614

3

Sequences

	Sequence		Length	Mass (Da)
	Q10714-1 [UniParc]. Last modified September 11, 2007. Version 3. Checksum: 9E3691BCC51D6C48	FASTA	615	70,914
	10 20 30 40 50 60 MRLFLLALLA TLAVTQALVK EEIQAKEYLE NLNKELAKRT NVETEAAWAY GSNITDENEK 70 80 90 100 110 120 KKNEISAELA KFMKEVASDT TKFQWRSYQS EDLKRQFKAL TKLGYAALPE DDYAELLDTL 130 140 150 160 170 180 SAMESNFAKV KVCDYKDSTK CDLALDPEIE EVISKSRDHE ELAYYWREFY DKAGTAVRSQ 190 200 210 220 230 240 FERYVELNTK AAKLNNFTSG AEAWLDEYED DTFEQQLEDI FADIRPLYQQ IHGYVRFRLR 250 260 270 280 290 300 KHYGDAVVSE TGPIPMHLLG NMWAQQWSEI ADIVSPFPEK PLVDVSAEME KQGYTPLKMF 310 320 330 340 350 360 QMGDDFFTSM NLTKLPQDFW DKSIIEKPTD GRDLVCHASA WDFYLTDDVR IKQCTRVTQD 370 380 390 400 410 420 QLFTVHHELG HIQYFLQYQH QPFVYRTGAN PGFHEAVGDV LSLSVSTPKH LEKIGLLKDY 430 440 450 460 470 480 VRDDEARINQ LFLTALDKIV FLPFAFTMDK YRWSLFRGEV DKANWNCAFW KLRDEYSGIE 490 500 510 520 530 540 PPVVRSEKDF DAPAKYHISA DVEYLRYLVS FIIQFQFYKS ACIKAGQYDP DNVELPLDNC 550 560 570 580 590 600 DIYGSAAAGA AFHNMLSMGA SKPWPDALEA FNGERIMSGK AIAEYFEPLR VWLEAENIKN 610 NVHIGWTTSN KCVSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterisation of putative Drosophila angiotensin converting enzyme cDNA clones." Cornell M.J., Coates D., Isaac R.E. Biochem. Soc. Trans. 21:243-243(1993) [PubMed: 8224398] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Embryo.
[2]	"Cloning and expression of an evolutionary conserved single-domain angiotensin converting enzyme from Drosophila melanogaster." Cornell M.J., Williams T.A., Lamango N.S., Coates D., Corvol P., Soubrier F., Hoheisel J., Lehrach H., Isaac R.E. J. Biol. Chem. 270:13613-13619(1995) [PubMed: 7775412] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION.
[3]	Cornell M.J. Submitted (JUN-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"Race: a Drosophila homologue of the angiotensin converting enzyme." Tatei K., Cai H., Ip Y.T., Levine M. Mech. Dev. 51:157-168(1995) [PubMed: 7547464] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Canton-S.
[5]	"An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region." Ashburner M., Misra S., Roote J., Lewis S.E., Blazej R.G., Davis T., Doyle C., Galle R.F., George R.A., Harris N.L., Hartzell G., Harvey D.A., Hong L., Houston K.A., Hoskins R.A., Johnson G., Martin C., Moshrefi A.R. , Palazzolo M., Reese M.G., Spradling A.C., Tsang G., Wan K.H., Whitelaw K., Celniker S.E., Rubin G.M. Genetics 153:179-219(1999) [PubMed: 10471707] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[6]	"The genome sequence of Drosophila melanogaster." Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., Sutton G.G., Wortman J.R., Yandell M.D. , Zhang Q., Chen L.X., Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C. Science 287:2185-2195(2000) [PubMed: 10731132] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: Berkeley.
[7]	"Annotation of the Drosophila melanogaster euchromatic genome: a systematic review." Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., Bettencourt B.R., Celniker S.E., de Grey A.D.N.J. , Drysdale R.A., Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E. Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002) [PubMed: 12537572] [Abstract] Cited for: GENOME REANNOTATION.
[8]	"A Drosophila full-length cDNA resource." Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., Celniker S.E. Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002) [PubMed: 12537569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Berkeley. Tissue: Embryo.
[9]	"Drosophila melanogaster angiotensin I-converting enzyme expressed in Pichia pastoris resembles the C domain of the mammalian homologue and does not require glycosylation for secretion and enzymic activity." Williams T.A., Michaud A., Houard X., Chauvet M.-T., Soubrier F., Corvol P. Biochem. J. 318:125-131(1996) [PubMed: 8761461] [Abstract] Cited for: CLEAVAGE SITE, GLYCOSYLATION, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
[10]	"The Drosophila melanogaster-related angiotensin-I-converting enzymes Acer and Ance -- distinct enzymic characteristics and alternative expression during pupal development." Houard X., Williams T.A., Michaud A., Dani P., Isaac R.E., Shirras A.D., Coates D., Corvol P. Eur. J. Biochem. 257:599-606(1998) [PubMed: 9839949] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES.
[11]	"The Drosophila angiotensin-converting enzyme homologue Ance is required for spermiogenesis." Hurst D., Rylett C.M., Isaac R.E., Shirras A.D. Dev. Biol. 254:238-247(2003) [PubMed: 12591244] [Abstract] Cited for: TISSUE SPECIFICITY, FUNCTION, DISRUPTION PHENOTYPE.
[12]	"Crystal structure of Drosophila angiotensin I-converting enzyme bound to captopril and lisinopril." Kim H.M., Shin D.R., Yoo O.J., Lee H., Lee J.-O. FEBS Lett. 538:65-70(2003) [PubMed: 12633854] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 14-615, X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 14-615 IN COMPLEX WITH CAPTOPRIL, X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 14-615 IN COMPLEX WITH LISINOPRIL.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U25344 mRNA. Translation: AAB02171.1.
U34599 mRNA. Translation: AAC46902.1.
AE014134 Genomic DNA. Translation: AAF53353.2.
AE014134 Genomic DNA. Translation: AAN10856.1.
AY061129 mRNA. Translation: AAL28677.1.

RefSeq

NP_477046.1.
NP_723852.1.

UniGene

Dm.2157

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1J36	X-ray	2.40	A/B	14-615	[»]
1J37	X-ray	2.40	A/B	14-615	[»]
1J38	X-ray	2.60	A/B	14-615	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q10714. 1 interaction.

Protein family/group databases

MEROPS

M02.003.

Genome annotation databases

Ensembl

FBtr0080552; FBpp0080129; FBgn0012037; Drosophila melanogaster. [Genome view]

GeneID

34805.

KEGG

dme:Dmel_CG8827.

Organism-specific databases

CTD

34805.

FlyBase

FBgn0012037. Ance.

Phylogenomic databases

HOGENOM

Q10714.

OMA

YITDDTE.

Enzyme and pathway databases

BRENDA

3.4.15.1. 48.

Gene expression databases

ArrayExpress

Q10714.

Bgee

Q10714.

GermOnline

CG8827. Drosophila melanogaster.

Family and domain databases

InterPro

IPR006025. Pept_M_Zn_BS.
IPR001548. Peptidase_M2.
[Graphical view]

PANTHER

PTHR10514. Peptidase_M2. 1 hit.

Pfam

PF01401. Peptidase_M2. 1 hit.
[Graphical view]

PRINTS

PR00791. PEPDIPTASEA.

ProDom

PD004184. Peptidase_M2. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

790306.

Entry information

Entry name

ACE_DROME

Accession

Primary (citable) accession number: Q10714
Secondary accession number(s): A4V0P3 , Q27572, Q9NKE4, Q9TX66, Q9VJV3

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	September 11, 2007
Last modified:	November 3, 2009
This is version 97 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

Drosophila annotation project