ACER_DROME
ID ACER_DROME Reviewed; 630 AA.
AC Q9VLJ6; Q24222;
DT 30-AUG-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Angiotensin-converting enzyme-related protein;
DE EC=3.4.15.1;
DE Flags: Precursor;
GN Name=Acer; ORFNames=CG10593;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND DEVELOPMENTAL STAGE.
RX PubMed=8973330; DOI=10.1016/s0378-1119(96)00503-3;
RA Taylor C.A.M., Coates D., Shirras A.D.;
RT "The Acer gene of Drosophila codes for an angiotensin-converting enzyme
RT homologue.";
RL Gene 181:191-197(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION, SUBCELLULAR LOCATION, AND
RP ACTIVITY REGULATION.
RX PubMed=9839949; DOI=10.1046/j.1432-1327.1998.2570599.x;
RA Houard X., Williams T.A., Michaud A., Dani P., Isaac R.E., Shirras A.D.,
RA Coates D., Corvol P.;
RT "The Drosophila melanogaster-related angiotensin-I-converting enzymes Acer
RT and Ance -- distinct enzymic characteristics and alternative expression
RT during pupal development.";
RL Eur. J. Biochem. 257:599-606(1998).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12075344; DOI=10.1038/nature00786;
RA Crackower M.A., Sarao R., Oudit G.Y., Yagil C., Kozieradzki I.,
RA Scanga S.E., Oliveira-dos-Santos A.J., da Costa J., Zhang L., Pei Y.,
RA Scholey J., Ferrario C.M., Manoukian A.S., Chappell M.C., Backx P.H.,
RA Yagil Y., Penninger J.M.;
RT "Angiotensin-converting enzyme 2 is an essential regulator of heart
RT function.";
RL Nature 417:822-828(2002).
CC -!- FUNCTION: May be involved in the specific maturation or degradation of
CC a number of bioactive peptides. May have a role in the specification of
CC heart progenitors. {ECO:0000269|PubMed:12075344}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Release of a C-terminal dipeptide, oligopeptide-|-Xaa-Yaa,
CC when Xaa is not Pro, and Yaa is neither Asp nor Glu. Thus, conversion
CC of angiotensin I to angiotensin II, with increase in vasoconstrictor
CC activity, but no action on angiotensin II.; EC=3.4.15.1;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by captopril, lisinopril,
CC trandolaprilat, fosinoprilat and enalaprilat.
CC {ECO:0000269|PubMed:9839949}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.2 mM for Hip-His-Leu {ECO:0000269|PubMed:9839949};
CC KM=4.35 mM for Hip-His-Leu-NH(2) {ECO:0000269|PubMed:9839949};
CC KM=40.6 uM for (Leu5)enkephalin {ECO:0000269|PubMed:9839949};
CC KM=949 uM for (Leu5)enkephalinamide {ECO:0000269|PubMed:9839949};
CC pH dependence:
CC Optimum pH is 8.6. {ECO:0000269|PubMed:9839949};
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC {ECO:0000269|PubMed:9839949}.
CC -!- DEVELOPMENTAL STAGE: Expressed in presumptive heart cells during dorsal
CC closure. {ECO:0000269|PubMed:8973330}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:9839949}.
CC -!- DISRUPTION PHENOTYPE: Defective heart morphogenesis leading to
CC lethality. {ECO:0000269|PubMed:12075344}.
CC -!- MISCELLANEOUS: In contrast to ance, does not hydrolyze angiotensin I.
CC -!- SIMILARITY: Belongs to the peptidase M2 family. {ECO:0000305}.
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DR EMBL; X96913; CAA65632.1; -; mRNA.
DR EMBL; AE014134; AAF52693.1; -; Genomic_DNA.
DR EMBL; AY051750; AAK93174.1; -; mRNA.
DR PIR; JC5374; JC5374.
DR RefSeq; NP_001260258.1; NM_001273329.1.
DR RefSeq; NP_477195.1; NM_057847.4.
DR AlphaFoldDB; Q9VLJ6; -.
DR SMR; Q9VLJ6; -.
DR BioGRID; 60309; 2.
DR IntAct; Q9VLJ6; 2.
DR STRING; 7227.FBpp0305608; -.
DR MEROPS; M02.002; -.
DR PaxDb; Q9VLJ6; -.
DR PRIDE; Q9VLJ6; -.
DR DNASU; 34189; -.
DR EnsemblMetazoa; FBtr0079685; FBpp0079297; FBgn0016122.
DR EnsemblMetazoa; FBtr0333416; FBpp0305608; FBgn0016122.
DR GeneID; 34189; -.
DR KEGG; dme:Dmel_CG10593; -.
DR CTD; 34189; -.
DR FlyBase; FBgn0016122; Acer.
DR VEuPathDB; VectorBase:FBgn0016122; -.
DR eggNOG; KOG3690; Eukaryota.
DR GeneTree; ENSGT00940000163600; -.
DR HOGENOM; CLU_014364_3_3_1; -.
DR InParanoid; Q9VLJ6; -.
DR OMA; IPSDCCG; -.
DR OrthoDB; 422699at2759; -.
DR PhylomeDB; Q9VLJ6; -.
DR Reactome; R-DME-2022377; Metabolism of Angiotensinogen to Angiotensins.
DR SABIO-RK; Q9VLJ6; -.
DR BioGRID-ORCS; 34189; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 34189; -.
DR PRO; PR:Q9VLJ6; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0016122; Expressed in head capsule and 33 other tissues.
DR ExpressionAtlas; Q9VLJ6; baseline and differential.
DR Genevisible; Q9VLJ6; DM.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:FlyBase.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0004180; F:carboxypeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:FlyBase.
DR GO; GO:0008237; F:metallopeptidase activity; IBA:GO_Central.
DR GO; GO:0008241; F:peptidyl-dipeptidase activity; IDA:FlyBase.
DR GO; GO:0008270; F:zinc ion binding; ISM:FlyBase.
DR GO; GO:0007507; P:heart development; IMP:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; IMP:FlyBase.
DR GO; GO:0045938; P:positive regulation of circadian sleep/wake cycle, sleep; IMP:FlyBase.
DR GO; GO:0006508; P:proteolysis; IDA:FlyBase.
DR GO; GO:0002027; P:regulation of heart rate; IMP:FlyBase.
DR CDD; cd06461; M2_ACE; 1.
DR InterPro; IPR001548; Peptidase_M2.
DR PANTHER; PTHR10514; PTHR10514; 1.
DR Pfam; PF01401; Peptidase_M2; 1.
DR PRINTS; PR00791; PEPDIPTASEA.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Carboxypeptidase; Disulfide bond; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..630
FT /note="Angiotensin-converting enzyme-related protein"
FT /id="PRO_0000028564"
FT ACT_SITE 376
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 375
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 379
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 403
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT DISULFID 142..150
FT /evidence="ECO:0000250"
FT DISULFID 344..362
FT /evidence="ECO:0000250"
FT DISULFID 530..548
FT /evidence="ECO:0000250"
FT CONFLICT 236
FT /note="F -> L (in Ref. 1; CAA65632)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="H -> Q (in Ref. 1; CAA65632)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="A -> V (in Ref. 1; CAA65632)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 630 AA; 73057 MW; 6D9355EB57773289 CRC64;
MGACNITVLL LVIMLWLPHG LSMGNSCSAS VLEARRFFEL ENEQLRRRFH EEFLSGYNYN
TNVTEANRQA MIEVYARNAE LNKRLAQQIK SSDYVQSEDA DIRRQAEHLS KLGASALNAD
DYLALQNAIS SMQTNYATAT VCSYTNRSDC SLTLEPHIQE RLSHSRDPAE LAWYWREWHD
KSGTPMRQNF AEYVRLTRKA SQLNGHRSYA DYWVQFYEDP DFERQLDATF KQLLPFYRQL
HGYVRFRLRQ HYGPDVMPAE GNIPISLLGN MWGQSWNELL DLFTPYPEKP FVDVKAEMEK
QGYTVQKLFE LGDQFFQSLG MRALPPSFWN LSVLTRPDDR HVVCHASAWD FYQDSDVRIK
MCTEVDSHYF YVVHHELGHI QYYLQYEQQP AVYRGAPNPG FHEAVGDVIA LSVMSAKHLK
AIGLIENGRL DEKSRINQLF KQALSKIVFL PFGYAVDKYR YAVFRNELDE SQWNCGFWQM
RSEFGGVEPP VFRTEKDFDP PAKYHIDADV EYLRYFAAHI FQFQFHKALC RKAGQYAPNN
SRLTLDNCDI FGSKAAGRSL SQFLSKGNSR HWKEVLEEFT GETEMDPAAL LEYFEPLYQW
LKQENSRLGV PLGWGPTDKI PSDCCGTFST
