Reviewed, UniProtKB/Swiss-Prot P12822 (ACE_RABIT)

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:
    1- Recommended name:
            Angiotensin-converting enzyme, soluble form

Gene names

Name:	ACE
Synonyms:	DCP1

Organism

Oryctolagus cuniculus (Rabbit)

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	1310 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 By similarity.
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. The Testis-specific isoform only binds 1 zinc ion per subunit By similarity. Binds 3 chloride ions per subunit By similarity.
Enzyme regulation	Strongly activated by chloride. Specifically inhibited by lisinopril. Ref.11
Subcellular location	Angiotensin-converting enzyme, soluble form: Secreted By similarity. Cell membrane; Single-pass type I membrane protein By similarity.
Tissue specificity	Testis-specific isoform is expressed in spermatocytes, adult testis.
Post-translational modification	N-glycosylated. Ref.7 Phosphorylated by CK2 on Ser-1303; which allows membrane retention By similarity.
Sequence similarities	Belongs to the peptidase M2 family.
Biophysicochemical properties	Kinetic parameters: KM=0.6 mM for Hip-His_Leu KM=0.09 mM for angiotensin I

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing
Domain	Repeat Signal Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-KW integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	carboxypeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW peptidyl-dipeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

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

Isoform Somatic (identifier: P12822-1)

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 Testis-specific (identifier: P12822-2)

Also known as: ACE-T;

The sequence of this isoform differs from the canonical sequence as follows:
     1-573: Missing.
     574-645: RAVLQAGCSR...LPNNYPEGID → MGQGWAAPGL...TAHQTTQSPN

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 33	33	Ref.7 Ref.5 Ref.6
	Chain	34 – 1310	1277	Angiotensin-converting enzyme		PRO_0000028551
	Chain	34 – 1236	1203	Angiotensin-converting enzyme, soluble form		PRO_0000028552
	Propeptide	1237 – 1310	74	Removed in secreted form By similarity		PRO_0000028553
Regions
	Topological domain	34 – 1260	1227	Extracellular Potential
	Transmembrane	1261 – 1281	21	Potential
	Topological domain	1282 – 1310	29	Cytoplasmic Potential
	Region	35 – 634	600	Peptidase M2 1
	Region	635 – 1236	602	Peptidase M2 2
Sites
	Active site	396	1	1 By similarity
	Active site	993	1	2 By similarity
	Metal binding	395	1	Zinc 1; catalytic By similarity
	Metal binding	399	1	Zinc 1; catalytic By similarity
	Metal binding	422	1	Zinc 1; catalytic By similarity
	Metal binding	992	1	Zinc 2; catalytic By similarity
	Metal binding	996	1	Zinc 2; catalytic By similarity
	Metal binding	1020	1	Zinc 2; catalytic By similarity
	Binding site	236	1	Chloride 1 By similarity
	Binding site	533	1	Chloride 1 By similarity
	Binding site	795	1	Chloride 2 By similarity
	Binding site	833	1	Chloride 3 By similarity
	Binding site	1094	1	Chloride 2 By similarity
	Binding site	1098	1	Chloride 2 By similarity
	Binding site	1131	1	Chloride 3 By similarity
	Site	1237 – 1238	2	Cleavage
Amino acid modifications
	Modified residue	1303	1	Phosphoserine By similarity
	Glycosylation	59	1	N-linked (GlcNAc...) Potential
	Glycosylation	79	1	N-linked (GlcNAc...) Potential
	Glycosylation	151	1	N-linked (GlcNAc...) Potential
	Glycosylation	323	1	N-linked (GlcNAc...) Potential
	Glycosylation	449	1	N-linked (GlcNAc...) Potential
	Glycosylation	513	1	N-linked (GlcNAc...) Potential
	Glycosylation	681	1	N-linked (GlcNAc...) Potential
	Glycosylation	699	1	N-linked (GlcNAc...) Potential
	Glycosylation	718	1	N-linked (GlcNAc...) Potential
	Glycosylation	946	1	N-linked (GlcNAc...) Potential
	Glycosylation	1195	1	N-linked (GlcNAc...) Potential
	Disulfide bond	162 ↔ 170		By similarity
	Disulfide bond	761 ↔ 767		By similarity
	Disulfide bond	961 ↔ 979		By similarity
	Disulfide bond	1147 ↔ 1159		By similarity
Natural variations
	Alternative sequence	1 – 573	573	Missing in isoform Testis-specific.		VSP_037644
	Alternative sequence	574 – 645	72	RAVLQ…PEGID → MGQGWAAPGLPSLLLLLLCC GHSLLVPSRVAARRVTVNQG TTSQATTTSKATTSIRATTH QTTAHQTTQSPN in isoform Testis-specific.		VSP_037645
Experimental info
	Mutagenesis	727	1	K → E: No effect on activity. 20-fold reduction in catalytic efficiency; when associated with F-809. Ref.11
	Mutagenesis	809	1	Y → F: No effect on activity. 20-fold reduction in catalytic efficiency; when associated with E-727. Ref.11
	Sequence conflict	48	1	E → N AA sequence Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform Somatic [UniParc]. Last modified November 1, 1997. Version 3. Checksum: 04777FAB17981DEA	FASTA	1,310	150,406
	10 20 30 40 50 60 MGAAPGRRGP RLLRPPPPLL LLLLLLRPPP AALTLDPGLL PGDFAADEAG ARLFASSYNS 70 80 90 100 110 120 SAEQVLFRST AASWAHDTNI TAENARRQEE EALLSQEFAE AWGKKAKELY DPVWQNFTDP 130 140 150 160 170 180 ELRRIIGAVR TLGPANLPLA KRQQYNSLLS NMSQIYSTGK VCFPNKTASC WSLDPDLNNI 190 200 210 220 230 240 LASSRSYAML LFAWEGWHNA VGIPLKPLYQ EFTALSNEAY RQDGFSDTGA YWRSWYDSPT 250 260 270 280 290 300 FEEDLERIYH QLEPLYLNLH AYVRRVLHRR YGDRYINLRG PIPAHLLGNM WAQSWESIYD 310 320 330 340 350 360 MVVPFPDKPN LDVTSTMVQK GWNATHMFRV AEEFFTSLGL LPMPPEFWAE SMLEKPEDGR 370 380 390 400 410 420 EVVCHASAWD FYNRKDFRIK QCTQVTMDQL STVHHEMGHV QYYLQYKDQP VSLRRANPGF 430 440 450 460 470 480 HEAIGDVLAL SVSTPAHLHK IGLLDHVTND TESDINYLLK MALEKIAFLP FGYLVDQWRW 490 500 510 520 530 540 GVFSGRTPSS RYNFDWWYLR TKYQGICPPV VRNETHFDAG AKFHIPSVTP YIRYFVSFVL 550 560 570 580 590 600 QFQFHQALCM EAGHQGPLHQ CDIYQSTRAG AKLRAVLQAG CSRPWQEVLK DMVASDALDA 610 620 630 640 650 660 QPLLDYFQPV TQWLQEQNER NGEVLGWPEY QWRPPLPNNY PEGIDLVTDE AEASRFVEEY 670 680 690 700 710 720 DRSFQAVWNE YAEANWNYNT NITTEASKIL LQKNMQIANH TLTYGNWARR FDVSNFQNAT 730 740 750 760 770 780 SKRIIKKVQD LQRAVLPVKE LEEYNQILLD METIYSVANV CRVDGSCLQL EPDLTNLMAT 790 800 810 820 830 840 SRKYDELLWV WTSWRDKVGR AILPYFPKYV EFTNKAARLN GYVDAGDSWR SMYETPTLEQ 850 860 870 880 890 900 DLERLFQELQ PLYLNLHAYV GRALHRHYGA QHINLEGPIP AHLLGNMWAQ TWSNIYDLVA 910 920 930 940 950 960 PFPSASTMDA TEAMIKQGWT PRRMFEEADK FFISLGLLPV PPEFWNKSML EKPTDGREVV 970 980 990 1000 1010 1020 CHASAWDFYN GKDFRIKQCT TVNMEDLVVV HHEMGHIQYF MQYKDLPVAL REGANPGFHE 1030 1040 1050 1060 1070 1080 AIGDVLALSV STPKHLHSIN LLSSEGGGYE HDINFLMKMA LDKIAFIPFS YLVDEWRWRV 1090 1100 1110 1120 1130 1140 FDGSITKENY NQEWWSLRLK YQGLCPPAPR SQGDFDPGAK FHIPSSVPYI RYFVSFIIQF 1150 1160 1170 1180 1190 1200 QFHEALCKAA GHTGPLHTCD IYQSKEAGKR LADAMKLGYS KPWPEAMKVI TGQPNMSASA 1210 1220 1230 1240 1250 1260 MMNYFKPLMD WLLTENGRHG EKLGWPQYTW TPNSARSEGS LPDSGRVNFL GMNLDAQQAR 1270 1280 1290 1300 1310 VGQWVLLFLG VALLLASLGL TQRLFSIRYQ SLRQPHHGPQ FGSEVELRHS
	Isoform Testis-specific (ACE-T) [UniParc] [UniParc]. Checksum: FC43CC76655C3DCA	FASTA	737	83,924
	10 20 30 40 50 60 MGQGWAAPGL PSLLLLLLCC GHSLLVPSRV AARRVTVNQG TTSQATTTSK ATTSIRATTH 70 80 90 100 110 120 QTTAHQTTQS PNLVTDEAEA SRFVEEYDRS FQAVWNEYAE ANWNYNTNIT TEASKILLQK 130 140 150 160 170 180 NMQIANHTLT YGNWARRFDV SNFQNATSKR IIKKVQDLQR AVLPVKELEE YNQILLDMET 190 200 210 220 230 240 IYSVANVCRV DGSCLQLEPD LTNLMATSRK YDELLWVWTS WRDKVGRAIL PYFPKYVEFT 250 260 270 280 290 300 NKAARLNGYV DAGDSWRSMY ETPTLEQDLE RLFQELQPLY LNLHAYVGRA LHRHYGAQHI 310 320 330 340 350 360 NLEGPIPAHL LGNMWAQTWS NIYDLVAPFP SASTMDATEA MIKQGWTPRR MFEEADKFFI 370 380 390 400 410 420 SLGLLPVPPE FWNKSMLEKP TDGREVVCHA SAWDFYNGKD FRIKQCTTVN MEDLVVVHHE 430 440 450 460 470 480 MGHIQYFMQY KDLPVALREG ANPGFHEAIG DVLALSVSTP KHLHSINLLS SEGGGYEHDI 490 500 510 520 530 540 NFLMKMALDK IAFIPFSYLV DEWRWRVFDG SITKENYNQE WWSLRLKYQG LCPPAPRSQG 550 560 570 580 590 600 DFDPGAKFHI PSSVPYIRYF VSFIIQFQFH EALCKAAGHT GPLHTCDIYQ SKEAGKRLAD 610 620 630 640 650 660 AMKLGYSKPW PEAMKVITGQ PNMSASAMMN YFKPLMDWLL TENGRHGEKL GWPQYTWTPN 670 680 690 700 710 720 SARSEGSLPD SGRVNFLGMN LDAQQARVGQ WVLLFLGVAL LLASLGLTQR LFSIRYQSLR 730 QPHHGPQFGS EVELRHS

References

[1]	"Use of alternative polyadenylation sites for tissue-specific transcription of two angiotensin-converting enzyme mRNAs." Thekkumkara T.J., Livingston W. III, Kumar R.S., Sen G.C. Nucleic Acids Res. 20:683-687(1992) [PubMed: 1311831] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC). Tissue: Lung.
[2]	Sen G.C. Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Structure of testicular angiotensin-converting enzyme. A segmental mosaic isozyme." Kumar R.S., Kusari J., Roy S.N., Soffer R.L., Sen G.C. J. Biol. Chem. 264:16754-16758(1989) [PubMed: 2550457] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC). Strain: New Zealand white. Tissue: Testis.
[4]	"The mRNAs encoding the two angiotensin-converting isozymes are transcribed from the same gene by a tissue-specific choice of alternative transcription initiation sites." Kumar R.S., Thekkumkara T.J., Sen G.C. J. Biol. Chem. 266:3854-3862(1991) [PubMed: 1847388] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-88, ALTERNATIVE SPLICING. Tissue: Liver.
[5]	"The NH2- and COOH-terminal sequences of the angiotensin-converting enzyme isozymes from rabbit lung and testis." Iwata K., Lai C.Y., El-Dorry H.A., Soffer R.L. Biochem. Biophys. Res. Commun. 107:1097-1103(1982) [PubMed: 6291514] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-44 AND 755-758.
[6]	"Rabbit pulmonary angiotensin-converting enzyme: the NH2-terminal fragment with enzymatic activity and its formation from the native enzyme by NH4OH treatment." Iwata K., Blacher R., Soffer R.L., Lai C.Y. Arch. Biochem. Biophys. 227:188-201(1983) [PubMed: 6314908] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-55. Tissue: Lung.
[7]	"The Mg(2+)-ATPase of rabbit skeletal-muscle transverse tubule is a highly glycosylated multiple-subunit enzyme." Kirley T.L. Biochem. J. 278:375-380(1991) [PubMed: 1654880] [Abstract] Cited for: PROTEIN SEQUENCE OF 34-55, GLYCOSYLATION.
[8]	"Angiotensin-converting enzyme: structural relationship of the testicular and the pulmonary forms." Sen G.C., Thekkumkara T.J., Kumar R.S. J. Cardiovasc. Pharmacol. 16:S14-S18(1990) [PubMed: 1705622] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 646-746.
[9]	"Identification of essential tyrosine and lysine residues in angiotensin converting enzyme: evidence for a single active site." Chen Y.N., Riordan J.F. Biochemistry 29:10493-10498(1990) [PubMed: 2176870] [Abstract] Cited for: PROTEIN SEQUENCE OF 727-733 AND 809-815.
[10]	"Regulated cleavage-secretion of the membrane-bound angiotensin-converting enzyme." Ramchandran R., Sen G.C., Misono K., Sen I. J. Biol. Chem. 269:2125-2130(1994) [PubMed: 8294466] [Abstract] Cited for: PROTEIN SEQUENCE OF 1237-1259, CLEAVAGE SITE.
[11]	"Mutations in two specific residues of testicular angiotensin-converting enzyme change its catalytic properties." Sen I., Kasturi S., Abdul-Jabbar M., Sen G.C. J. Biol. Chem. 268:25748-25754(1993) [PubMed: 7902354] [Abstract] Cited for: MUTAGENESIS OF LYS-727 AND TYR-809, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.

Cross-references

Sequence databases
EMBLGenBankDDBJ	X62551 mRNA. Translation: CAA44428.1. J05041 mRNA. Translation: AAA31153.1. M58579 Genomic DNA. Translation: AAA31151.1. Sequence problems. M58580 Genomic DNA. Translation: AAA31152.1.
PIR	A34402. S35484.
RefSeq	NP_001075864.1.
UniGene	Ocu.1824
3D structure databases
HSSP	HSSP built from PDB template 1J36 based on UniProtKB Q10714.
SMR	P12822. Positions 649-1226.
ModBase	Search...
Protein-protein interaction databases
STRING	P12822.
Protein family/group databases
MEROPS	M02.001. M02.004.
Genome annotation databases
GeneID	100009274.
Phylogenomic databases
HOVERGEN	P12822.
Enzyme and pathway databases
BRENDA	3.4.15.1. 255.
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. 2 hits. [Graphical view]
PRINTS	PR00791. PEPDIPTASEA.
ProDom	PD004184. Peptidase_M2. 2 hits. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00142. ZINC_PROTEASE. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ACE_RABIT

Accession

Primary (citable) accession number: P12822
Secondary accession number(s): O02852, P22968

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	November 1, 1997
Last modified:	October 13, 2009
This is version 92 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)