P47820 (ACE_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Angiotensin-converting enzyme
Short name=ACE
EC=3.2.1.-
EC=3.4.15.1

Alternative name(s):
Dipeptidyl carboxypeptidase I
Kininase II
CD_antigen=CD143

Cleaved into the following chain:

1. Angiotensin-converting enzyme, soluble form

Gene names

Name:	Ace
Synonyms:	Dcp1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	1313 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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. This GPIase activity seems to be crucial for the egg-binding ability of the sperm 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. Isoform Testis-specific only binds 1 zinc ion per subunit By similarity. Binds 3 chloride ions per subunit By similarity.
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. Also expressed in brain, kidney, lung, skeletal muscle and heart. Ref.3
Induction	Up-regulated after myocardial infarction. Ref.6
Post-translational modification	Phosphorylated by CK2 on Ser-1306; which allows membrane retention By similarity.
Sequence similarities	Belongs to the peptidase M2 family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Carboxypeptidase Hydrolase Metalloprotease Protease
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	aging Inferred from expression pattern PubMed 22100841. Source: RGD angiogenesis involved in coronary vascular morphogenesis Inferred from mutant phenotype PubMed 22123369. Source: RGD eating behavior Inferred from mutant phenotype PubMed 19361967. Source: RGD heart contraction Inferred from electronic annotation. Source: Compara hormone catabolic process Inferred from electronic annotation. Source: Compara kidney development Inferred from electronic annotation. Source: Compara lung alveolus development Inferred from mutant phenotype PubMed 22587910. Source: RGD neutrophil mediated immunity Inferred from electronic annotation. Source: Compara organ regeneration Inferred from mutant phenotype PubMed 22441330. Source: RGD peptide metabolic process Inferred from mutant phenotype PubMed 10642323. Source: RGD positive regulation of apoptotic process Inferred from mutant phenotype PubMed 19301230. Source: RGD positive regulation of inflammatory response Inferred from mutant phenotype PubMed 20304959. Source: RGD positive regulation of neurogenesis Inferred from mutant phenotype PubMed 20122169. Source: RGD positive regulation of systemic arterial blood pressure Inferred from electronic annotation. Source: Compara proteolysis Inferred from direct assay PubMed 16203874PubMed 16908757. Source: RGD regulation of blood pressure Inferred from direct assay PubMed 1750504. Source: BHF-UCL regulation of smooth muscle cell migration Inferred from direct assay PubMed 1750504. Source: BHF-UCL response to hypoxia Inferred from expression pattern PubMed 14527966. Source: RGD response to lipopolysaccharide Inferred from mutant phenotype PubMed 19114890. Source: RGD response to nutrient levels Inferred from expression pattern PubMed 18389998. Source: RGD sensory perception of pain Inferred from mutant phenotype PubMed 18555989. Source: RGD spermatogenesis Inferred from electronic annotation. Source: Compara vasoconstriction Inferred from mutant phenotype PubMed 20204775. Source: RGD
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay PubMed 3031366. Source: RGD
Molecular_function	carboxypeptidase activity Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW metallopeptidase activity Inferred from direct assay PubMed 16203874. Source: RGD peptide binding Inferred from direct assay PubMed 16203874. Source: RGD peptidyl-dipeptidase activity Inferred from direct assay Ref.1. Source: RGD
Complete GO annotation...

Alternative products

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

Isoform Somatic (identifier: P47820-1)

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: P47820-2)

Also known as: ACE-T;

The sequence of this isoform differs from the canonical sequence as follows:
     1-581: Missing.
     582-646: GCSRPWQEVL...PLPDNYPEGI → MGQGWATPGL...ACLFSSSPPT

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 35	35	By similarity
	Chain	36 – 1313	1278	Angiotensin-converting enzyme		PRO_0000028557
	Chain	36 – 1238	1203	Angiotensin-converting enzyme, soluble form		PRO_0000028558
	Propeptide	1239 – 1313	75	Removed in secreted form By similarity		PRO_0000028559
Regions
	Topological domain	36 – 1265	1230	Extracellular Potential
	Transmembrane	1266 – 1282	17	Helical; Potential
	Topological domain	1283 – 1313	31	Cytoplasmic Potential
	Region	36 – 636	601	Peptidase M2 1
	Region	637 – 1238	602	Peptidase M2 2
Sites
	Active site	397	1	1 By similarity
	Active site	995	1	2 By similarity
	Metal binding	396	1	Zinc 1; catalytic By similarity
	Metal binding	400	1	Zinc 1; catalytic By similarity
	Metal binding	424	1	Zinc 1; catalytic By similarity
	Metal binding	994	1	Zinc 2; catalytic By similarity
	Metal binding	998	1	Zinc 2; catalytic By similarity
	Metal binding	1022	1	Zinc 2; catalytic By similarity
	Binding site	237	1	Chloride 1 By similarity
	Binding site	535	1	Chloride 1 By similarity
	Binding site	797	1	Chloride 2 By similarity
	Binding site	835	1	Chloride 3 By similarity
	Binding site	1096	1	Chloride 2 By similarity
	Binding site	1100	1	Chloride 2 By similarity
	Binding site	1133	1	Chloride 3 By similarity
Amino acid modifications
	Modified residue	1306	1	Phosphoserine By similarity
	Glycosylation	44	1	N-linked (GlcNAc...) Potential
	Glycosylation	60	1	N-linked (GlcNAc...) Potential
	Glycosylation	80	1	N-linked (GlcNAc...) Potential
	Glycosylation	117	1	N-linked (GlcNAc...) Potential
	Glycosylation	152	1	N-linked (GlcNAc...) Potential
	Glycosylation	166	1	N-linked (GlcNAc...) Potential
	Glycosylation	324	1	N-linked (GlcNAc...) Potential
	Glycosylation	515	1	N-linked (GlcNAc...) Potential
	Glycosylation	683	1	N-linked (GlcNAc...) Potential
	Glycosylation	701	1	N-linked (GlcNAc...) Potential
	Glycosylation	720	1	N-linked (GlcNAc...) Potential
	Glycosylation	766	1	N-linked (GlcNAc...) Potential
	Glycosylation	948	1	N-linked (GlcNAc...) Potential
	Glycosylation	1197	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 581	581	Missing in isoform Testis-specific.		VSP_037642
	Alternative sequence	582 – 646	65	GCSRP…YPEGI → MGQGWATPGLPRFLFLLLCC GHLLPVLSQVAADHVTANQG ITNQATTRSQTTHQSTISQT IQTSNGTPGRGQGHEGARSQ GPAGGNSNKTTPCGKEGEAC LFSSSPPT in isoform Testis-specific.		VSP_037643
	Natural variant	207	1	R → K. Ref.1 Ref.5
Experimental info
	Sequence conflict	341	1	L → F in AAG35596. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform Somatic [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 8CB5D0015F129591	FASTA	1,313	150,908
	10 20 30 40 50 60 MGAASGQRGR WPLSPPLLML SLLLLLLLPP SPAPALDPGL QPGNFSADEA GAQLFADSYN 70 80 90 100 110 120 SSAEVVMFQS TAASWAHDTN ITEENARLQE EAALINQEFA EVWGKKAKEL YESIWQNFTD 130 140 150 160 170 180 QKLRRIIGSV QTLGPANLPL TQRLQYNSLL SNMSRIYSTG KVCFPNKTAT CWSLDPELTN 190 200 210 220 230 240 ILASSRNYAK VLFAWEGWHD AVGIPLRPLY QDFTALSNEA YRQDGFSDTG AYWRSWYESP 250 260 270 280 290 300 SFEESLEHLY HQVEPLYLNL HAFVRRALHR RYGDKYINLR GPIPAHLLGD MWAQSWENIY 310 320 330 340 350 360 DMVVPFPDKP NLDVTSTMVQ KGWNATHMFR VAEEFFTSLG LSPMPPEFWA ESMLEKPADG 370 380 390 400 410 420 REVVCHASAW DFYNRKDFRI KQCTRVTMDQ LSTVHHEMGH VQYYLQYKDL HVSLRRGANP 430 440 450 460 470 480 GFHEAIGDVL ALSVSTPAHL HKIGLLDRVA NDIESDINYL LKMALEKIAF LPFGYLVDQW 490 500 510 520 530 540 RWGVFSGRTP PSRYNYDWWY LRTKYQGICP PVARNETHFD AGAKFHIPSV TPYIRYFVSF 550 560 570 580 590 600 VLQFQFHQAL CKEAGHQGPL HQCDIYQSTK AGAKLQQVLQ AGCSRPWQEV LKDLVGSDAL 610 620 630 640 650 660 DASALMEYFQ PVSQWLQEQN QRNGEVLGWP EYQWRPPLPD NYPEGIDLET DEAKANRFVE 670 680 690 700 710 720 EYDRTAKVLW NEYAEANWHY NTNITIEGSK ILLQKNKEVS NHTLKYGTWA KTFDVSNFQN 730 740 750 760 770 780 STIKRIIKKV QNVDRAVLPP NELEEYNQIL LDMETTYSVA NVCYTNGTCL SLEPDLTNIM 790 800 810 820 830 840 ATSRKYEELL WVWKSWRDKV GRAILPFFPK YVDFSNKIAK LNGYSDAGDS WRSSYESDDL 850 860 870 880 890 900 EQDLEKLYQE LQPLYLNLHA YVRRSLHRHY GSEYINLDGP IPAHLLGNMW AQTWSNIYDL 910 920 930 940 950 960 VAPFPSAPSI DATEAMIKQG WTPRRIFKEA DNFFTSLGLL PVPPEFWNKS MLEKPTDGRE 970 980 990 1000 1010 1020 VVCHASAWDF YNGKDFRIKQ CTSVNMEELV IAHHEMGHIQ YFMQYKDLPV TFREGANPGF 1030 1040 1050 1060 1070 1080 HEAIGDVLAL SVSTPKHLHS LNLLSSEGSG YEHDINFLMK MALDKIAFIP FSYLIDQWRW 1090 1100 1110 1120 1130 1140 RVFDGSITKE NYNQEWWSLR LKYQGLCPPV PRSQGDFDPG SKFHVPANVP YIRYFISFII 1150 1160 1170 1180 1190 1200 QFQFHEALCR AAGHTGPLYK CDIYQSKEAG KLLADAMKLG YSKQWPEAMK IITGQPNMSA 1210 1220 1230 1240 1250 1260 SAIMNYFKPL TEWLVTENRR HGETLGWPEY TWTPNTARAE GSLPESSRVN FLGMYLEPQQ 1270 1280 1290 1300 1310 ARVGQWVLLF LGVALLVATV GLAHRLYNIH NHHSLRRPHR GPQFGSEVEL RHS
	Isoform Testis-specific (ACE-T) [UniParc] [UniParc]. Checksum: 5967406D21CAD52A	FASTA	775	88,170
	10 20 30 40 50 60 MGQGWATPGL PRFLFLLLCC GHLLPVLSQV AADHVTANQG ITNQATTRSQ TTHQSTISQT 70 80 90 100 110 120 IQTSNGTPGR GQGHEGARSQ GPAGGNSNKT TPCGKEGEAC LFSSSPPTDL ETDEAKANRF 130 140 150 160 170 180 VEEYDRTAKV LWNEYAEANW HYNTNITIEG SKILLQKNKE VSNHTLKYGT WAKTFDVSNF 190 200 210 220 230 240 QNSTIKRIIK KVQNVDRAVL PPNELEEYNQ ILLDMETTYS VANVCYTNGT CLSLEPDLTN 250 260 270 280 290 300 IMATSRKYEE LLWVWKSWRD KVGRAILPFF PKYVDFSNKI AKLNGYSDAG DSWRSSYESD 310 320 330 340 350 360 DLEQDLEKLY QELQPLYLNL HAYVRRSLHR HYGSEYINLD GPIPAHLLGN MWAQTWSNIY 370 380 390 400 410 420 DLVAPFPSAP SIDATEAMIK QGWTPRRIFK EADNFFTSLG LLPVPPEFWN KSMLEKPTDG 430 440 450 460 470 480 REVVCHASAW DFYNGKDFRI KQCTSVNMEE LVIAHHEMGH IQYFMQYKDL PVTFREGANP 490 500 510 520 530 540 GFHEAIGDVL ALSVSTPKHL HSLNLLSSEG SGYEHDINFL MKMALDKIAF IPFSYLIDQW 550 560 570 580 590 600 RWRVFDGSIT KENYNQEWWS LRLKYQGLCP PVPRSQGDFD PGSKFHVPAN VPYIRYFISF 610 620 630 640 650 660 IIQFQFHEAL CRAAGHTGPL YKCDIYQSKE AGKLLADAMK LGYSKQWPEA MKIITGQPNM 670 680 690 700 710 720 SASAIMNYFK PLTEWLVTEN RRHGETLGWP EYTWTPNTAR AEGSLPESSR VNFLGMYLEP 730 740 750 760 770 QQARVGQWVL LFLGVALLVA TVGLAHRLYN IHNHHSLRRP HRGPQFGSEV ELRHS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Angiotensin converting enzyme and genetic hypertension: cloning of rat cDNAs and characterization of the enzyme." Koike G., Krieger J.E., Jacob H.J., Mukoyama M., Pratt R.E., Dzau V.J. Biochem. Biophys. Res. Commun. 198:380-386(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC), VARIANT LYS-207. Tissue: Lung.
[2]	"Characterization of a missense mutation in the angiotensin I-converting enzyme cDNA in exudative inflammation resistant F344/N rats." Jafarian-Tehrani M., Listwak S., Barrientos R.M., Michaud A., Corvol P., Sternberg E.M. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SOMATIC). Strain: Fischer 344/N and Lewis/N. Tissue: Lung.
[3]	"Species-specific splicing and expression of angiotensin converting enzyme." Tian X.-L., Paul M. Biochem. Pharmacol. 66:1037-1044(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM TESTIS-SPECIFIC), TISSUE SPECIFICITY. Strain: Sprague-Dawley. Tissue: Testis.
[4]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SOMATIC). Tissue: Lung.
[5]	"Analysis of the angiotensin converting enzyme (Ace) cDNA sequence and mRNA level of expression in WAG and ISIAH rats." Tsetsarkin K.A., Dymshits G.M., Markel A.L., Redina O.E. Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-1313 (ISOFORM SOMATIC), VARIANT LYS-207. Tissue: Kidney.
[6]	"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] [Europe PMC] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U03708 mRNA. Translation: AAA82110.1. U03734 mRNA. Translation: AAA82111.1. AF201331 mRNA. Translation: AAG35596.1. AF201332 mRNA. Translation: AAG35597.1. AF539425 mRNA. Translation: AAN17280.1. BC085760 mRNA. Translation: AAH85760.1. AF532783 mRNA. Translation: AAP80808.1. AF532784 mRNA. Translation: AAP80809.1.
IPI	IPI00191364. IPI00324300.
PIR	JC2038.
RefSeq	NP_036676.1. NM_012544.1.
UniGene	Rn.10149.
3D structure databases
ProteinModelPortal	P47820.
SMR	P47820. Positions 36-647, 651-1234.
ModBase	Search...
Protein family/group databases
MEROPS	M02.001.
PTM databases
PhosphoSite	P47820.
Proteomic databases
PRIDE	P47820.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	24310.
KEGG	rno:24310.
UCSC	RGD:2493. rat.
Organism-specific databases
CTD	1636.
RGD	2493. Ace.
Phylogenomic databases
eggNOG	NOG71044.
HOGENOM	HOG000007838.
HOVERGEN	HBG000264.
InParanoid	P47820.
KO	K01283.
OMA	MEQLFTV.
OrthoDB	EOG495ZQZ.
Gene expression databases
ArrayExpress	P47820.
Genevestigator	P47820.
GermOnline	ENSRNOG00000007467. Rattus norvegicus.
Family and domain databases
InterPro	IPR001548. Peptidase_M2. [Graphical view]
PANTHER	PTHR10514. PTHR10514. 1 hit.
Pfam	PF01401. Peptidase_M2. 2 hits. [Graphical view]
PRINTS	PR00791. PEPDIPTASEA.
PROSITE	PS00142. ZINC_PROTEASE. 2 hits. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P47820.
ChEMBL	CHEMBL2625.
NextBio	602945.

Entry information

Entry name

ACE_RAT

Accession

Primary (citable) accession number: P47820
Secondary accession number(s): Q7TMC6, Q8CFN1, Q9EQM9

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	April 3, 2013
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program