Reviewed, UniProtKB/Swiss-Prot Q10711 (ECE2_BOVIN)

Names and origin

Protein names

Recommended name:
    Endothelin-converting enzyme 2
      Short name=ECE-2
Including the following 2 domains:
    1- Recommended name:
            Methyltransferase-like region
              EC=2.1.1.-
    2- Recommended name:
            Endothelin-converting enzyme 2 region
              EC=3.4.24.71

Gene names

Name:

ECE2

Organism

Bos taurus (Bovine)

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	883 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Converts big endothelin-1 to endothelin-1. Also involved in the processing of various neuroendocrine peptides, including neurotensin, angiotensin I, substance P, proenkephalin-derived peptides, and prodynorphin-derived peptides. May limit beta-amyloid peptide accumulation in brain. May also have methyltransferase activity.
Catalytic activity	Hydrolysis of the 21-Trp-|-Val-22 bond in big endothelin to form endothelin 1.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Inhibited by phosphoramidon.
Subunit structure	Homodimer.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein. Cytoplasmic granule membrane; Single-pass type II membrane protein. Ref.1
Tissue specificity	Isoform 1 and isoform 2 are expressed in liver, kidney, adrenal gland, testis and endothelial cells. Isoform 3 and isoform 4 are expressed in brain and adrenal gland. Ref.1
Sequence similarities	In the N-terminal section; belongs to the methyltransferase superfamily. In the C-terminal section; belongs to the peptidase M13 family.
Biophysicochemical properties	pH dependence: Optimum pH is 5.5. Inactive at neutral pH.
Sequence caution	The sequence AAA82927.1 differs from that shown. Reason: Frameshift at position 78. The sequence AAO72360.1 differs from that shown. Reason: Frameshift at position 78. The sequence AAO72361.1 differs from that shown. Reason: Frameshift at position 78.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal-anchor Transmembrane
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Methyltransferase Protease Transferase
PTM	Glycoprotein Phosphoprotein
Technical term	Multifunctional enzyme
Gene Ontology (GO)
Biological process	brain development Inferred from sequence or structural similarity. Source: UniProtKB cardioblast differentiation Inferred from sequence or structural similarity. Source: UniProtKB embryonic development Ref.3 Traceable author statement. Source: UniProtKB peptide hormone processing Inferred from sequence or structural similarity. Source: UniProtKB proteolysis Inferred from electronic annotation. Source: InterPro regulation of G-protein coupled receptor protein signaling pathway Ref.3 Traceable author statement. Source: UniProtKB vasoconstriction Ref.3 Traceable author statement. Source: UniProtKB
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasmic vesicle membrane Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	metalloendopeptidase activity Ref.3 Inferred from direct assay. Source: UniProtKB methyltransferase activity Inferred from electronic annotation. Source: UniProtKB-KW protein homodimerization activity Ref.3 Traceable author statement. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q10711-1)

Also known as: ECE-2a-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: Q10711-2)

Also known as: ECE-2a-2;

The sequence of this isoform differs from the canonical sequence as follows:
     161-161: A → MVEYKRATLRDEDAPETPVEGGASPDAVEA

Isoform 3 (identifier: Q10711-3)

Also known as: ECE-2b-1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: MACLGPSAQV...VHTVDQVLNE → MRVALQELGGGGN

Isoform 4 (identifier: Q10711-4)

Also known as: ECE-2b-2;

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: MACLGPSAQV...VHTVDQVLNE → MRVALQELGGGGN
     161-161: A → MVEYKRATLRDEDAPETPVEGGASPDAVEA

Isoform 5 (identifier: Q10711-5)

The sequence of this isoform differs from the canonical sequence as follows:
     161-255: AGFRKRTSRL...WIRRNPLPDG → VSRVLVPAGR...HEDFLSAIQL
     256-883: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 883	883	Endothelin-converting enzyme 2		PRO_0000078222
Regions
	Topological domain	1 – 178	178	Cytoplasmic Potential
	Transmembrane	179 – 199	21	Signal-anchor for type II membrane protein Potential
	Topological domain	200 – 883	684	Lumenal Potential
	Region	1 – 160	160	Methyltransferase-like region
	Region	200 – 883	684	Endothelin-converting enzyme 2 region
Sites
	Active site	721	1	By similarity
	Active site	784	1	Proton donor By similarity
	Metal binding	720	1	Zinc; catalytic By similarity
	Metal binding	724	1	Zinc; catalytic By similarity
	Metal binding	780	1	Zinc; catalytic By similarity
Amino acid modifications
	Modified residue	39	1	Phosphotyrosine By similarity
	Glycosylation	283	1	N-linked (GlcNAc...) Potential
	Glycosylation	324	1	N-linked (GlcNAc...) Potential
	Glycosylation	384	1	N-linked (GlcNAc...) Potential
	Glycosylation	429	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	1 – 160	160	MACLG…QVLNE → MRVALQELGGGGN in isoform 3 and isoform 4.		VSP_029329
	Alternative sequence	161 – 255	95	AGFRK…PLPDG → VSRVLVPAGRFISLTSAAPH FRTRHYAQAHYGWSLRHATY GNGFQFHFYLMQKGKELSVA QLAVGAQILSPPRPPTPSCF LQDSDHEDFLSAIQL in isoform 5.		VSP_029330
	Alternative sequence	161	1	A → MVEYKRATLRDEDAPETPVE GGASPDAVEA in isoform 2 and isoform 4.		VSP_029331
	Alternative sequence	256 – 883	628	Missing in isoform 5.		VSP_029332

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ECE-2a-1) [UniParc]. Last modified November 13, 2007. Version 2. Checksum: 3079A02496E82BE8	FASTA	883	99,601
	10 20 30 40 50 60 MACLGPSAQV PELPEKNCGY REVQYWDQRY QGAADSAPYE WFGDFSCFRD LLEPELRPLD 70 80 90 100 110 120 RILVLGCGNS ALSYELFLGG FPDVTSVDYS SVVVAAMRAR YAHVPTLRWE TMDVRALGFP 130 140 150 160 170 180 SGSFDVVLEK GTLDALLTGE QDPWTVSSEG VHTVDQVLNE AGFRKRTSRL LGLHTQLELV 190 200 210 220 230 240 LAGVSLLLAA LLLGCLVALG VQYHRDPSHS TCLTEACIRV AGKILESLDR GVSPCEDFYQ 250 260 270 280 290 300 FSCGGWIRRN PLPDGRSRWN NSNSLWDQNQ AILKHLLENT TFNSSSEAER KTQRFYLSCL 310 320 330 340 350 360 QVERIEELGA HALRDLIDKI GGWNVTGPWD QDNFMEVLKA VAGTYRATPF FTVYVSADSK 370 380 390 400 410 420 SSNSNIIQVD QSGLFLPSRD YYLNRTANEK VLTAYLDYME ELGMLLGGQP TSTREQMRQV 430 440 450 460 470 480 LELEIQLANI TVPQDQRRDE EKIYHKMSIA ELQALAPSMD WLEFLSFLLS PLELGDSEPV 490 500 510 520 530 540 VVYGTDYLQQ VSELINRTEP SVLNNYLIWN LVQKTTSSLD HRFESAQEKL LETLYGTKKS 550 560 570 580 590 600 CTPRWQTCIS NTDDALGFAL GSLFVKATFD RQSKEIAEGM ISEIRVAFEE ALGHLVWMDE 610 620 630 640 650 660 KTRQAAKEKA DAIYDMIGFP DFILEPKELD DVYDGYEVSE DSFFQNMLNL YNFSAKVMAD 670 680 690 700 710 720 QLRKPPSRDQ WSMTPQTVNA YYLPTKNEIV FPAGILQAPF YTCNHPQALN FGGIGVVMGH 730 740 750 760 770 780 ELTHAFDDQG REYDKEGNLR PWWQNESLAA FRNHTACIEE QYSQYQVNGE KLNGRQTLGE 790 800 810 820 830 840 NIADNGGLKA AYNAYKAWLR KHGEEQQLPA VGLTNHQLFF VGFAQVWCSV RTPESSHEGL 850 860 870 880 VTDPHSPARF RVLGTLSNSR DFLRHFGCPV GSPMNSGQLC EVW
	Isoform 2 (ECE-2a-2). Checksum: 6BA7F597283C189B	FASTA	912	102,717
	10 20 30 40 50 60 MACLGPSAQV PELPEKNCGY REVQYWDQRY QGAADSAPYE WFGDFSCFRD LLEPELRPLD 70 80 90 100 110 120 RILVLGCGNS ALSYELFLGG FPDVTSVDYS SVVVAAMRAR YAHVPTLRWE TMDVRALGFP 130 140 150 160 170 180 SGSFDVVLEK GTLDALLTGE QDPWTVSSEG VHTVDQVLNE MVEYKRATLR DEDAPETPVE 190 200 210 220 230 240 GGASPDAVEA GFRKRTSRLL GLHTQLELVL AGVSLLLAAL LLGCLVALGV QYHRDPSHST 250 260 270 280 290 300 CLTEACIRVA GKILESLDRG VSPCEDFYQF SCGGWIRRNP LPDGRSRWNN SNSLWDQNQA 310 320 330 340 350 360 ILKHLLENTT FNSSSEAERK TQRFYLSCLQ VERIEELGAH ALRDLIDKIG GWNVTGPWDQ 370 380 390 400 410 420 DNFMEVLKAV AGTYRATPFF TVYVSADSKS SNSNIIQVDQ SGLFLPSRDY YLNRTANEKV 430 440 450 460 470 480 LTAYLDYMEE LGMLLGGQPT STREQMRQVL ELEIQLANIT VPQDQRRDEE KIYHKMSIAE 490 500 510 520 530 540 LQALAPSMDW LEFLSFLLSP LELGDSEPVV VYGTDYLQQV SELINRTEPS VLNNYLIWNL 550 560 570 580 590 600 VQKTTSSLDH RFESAQEKLL ETLYGTKKSC TPRWQTCISN TDDALGFALG SLFVKATFDR 610 620 630 640 650 660 QSKEIAEGMI SEIRVAFEEA LGHLVWMDEK TRQAAKEKAD AIYDMIGFPD FILEPKELDD 670 680 690 700 710 720 VYDGYEVSED SFFQNMLNLY NFSAKVMADQ LRKPPSRDQW SMTPQTVNAY YLPTKNEIVF 730 740 750 760 770 780 PAGILQAPFY TCNHPQALNF GGIGVVMGHE LTHAFDDQGR EYDKEGNLRP WWQNESLAAF 790 800 810 820 830 840 RNHTACIEEQ YSQYQVNGEK LNGRQTLGEN IADNGGLKAA YNAYKAWLRK HGEEQQLPAV 850 860 870 880 890 900 GLTNHQLFFV GFAQVWCSVR TPESSHEGLV TDPHSPARFR VLGTLSNSRD FLRHFGCPVG 910 SPMNSGQLCE VW
	Isoform 3 (ECE-2b-1). Checksum: 7ECD124469751D91	FASTA	736	83,129
	10 20 30 40 50 60 MRVALQELGG GGNAGFRKRT SRLLGLHTQL ELVLAGVSLL LAALLLGCLV ALGVQYHRDP 70 80 90 100 110 120 SHSTCLTEAC IRVAGKILES LDRGVSPCED FYQFSCGGWI RRNPLPDGRS RWNNSNSLWD 130 140 150 160 170 180 QNQAILKHLL ENTTFNSSSE AERKTQRFYL SCLQVERIEE LGAHALRDLI DKIGGWNVTG 190 200 210 220 230 240 PWDQDNFMEV LKAVAGTYRA TPFFTVYVSA DSKSSNSNII QVDQSGLFLP SRDYYLNRTA 250 260 270 280 290 300 NEKVLTAYLD YMEELGMLLG GQPTSTREQM RQVLELEIQL ANITVPQDQR RDEEKIYHKM 310 320 330 340 350 360 SIAELQALAP SMDWLEFLSF LLSPLELGDS EPVVVYGTDY LQQVSELINR TEPSVLNNYL 370 380 390 400 410 420 IWNLVQKTTS SLDHRFESAQ EKLLETLYGT KKSCTPRWQT CISNTDDALG FALGSLFVKA 430 440 450 460 470 480 TFDRQSKEIA EGMISEIRVA FEEALGHLVW MDEKTRQAAK EKADAIYDMI GFPDFILEPK 490 500 510 520 530 540 ELDDVYDGYE VSEDSFFQNM LNLYNFSAKV MADQLRKPPS RDQWSMTPQT VNAYYLPTKN 550 560 570 580 590 600 EIVFPAGILQ APFYTCNHPQ ALNFGGIGVV MGHELTHAFD DQGREYDKEG NLRPWWQNES 610 620 630 640 650 660 LAAFRNHTAC IEEQYSQYQV NGEKLNGRQT LGENIADNGG LKAAYNAYKA WLRKHGEEQQ 670 680 690 700 710 720 LPAVGLTNHQ LFFVGFAQVW CSVRTPESSH EGLVTDPHSP ARFRVLGTLS NSRDFLRHFG 730 CPVGSPMNSG QLCEVW
	Isoform 4 (ECE-2b-2). Checksum: 12C3FE747881E1FF	FASTA	765	86,244
	10 20 30 40 50 60 MRVALQELGG GGNMVEYKRA TLRDEDAPET PVEGGASPDA VEAGFRKRTS RLLGLHTQLE 70 80 90 100 110 120 LVLAGVSLLL AALLLGCLVA LGVQYHRDPS HSTCLTEACI RVAGKILESL DRGVSPCEDF 130 140 150 160 170 180 YQFSCGGWIR RNPLPDGRSR WNNSNSLWDQ NQAILKHLLE NTTFNSSSEA ERKTQRFYLS 190 200 210 220 230 240 CLQVERIEEL GAHALRDLID KIGGWNVTGP WDQDNFMEVL KAVAGTYRAT PFFTVYVSAD 250 260 270 280 290 300 SKSSNSNIIQ VDQSGLFLPS RDYYLNRTAN EKVLTAYLDY MEELGMLLGG QPTSTREQMR 310 320 330 340 350 360 QVLELEIQLA NITVPQDQRR DEEKIYHKMS IAELQALAPS MDWLEFLSFL LSPLELGDSE 370 380 390 400 410 420 PVVVYGTDYL QQVSELINRT EPSVLNNYLI WNLVQKTTSS LDHRFESAQE KLLETLYGTK 430 440 450 460 470 480 KSCTPRWQTC ISNTDDALGF ALGSLFVKAT FDRQSKEIAE GMISEIRVAF EEALGHLVWM 490 500 510 520 530 540 DEKTRQAAKE KADAIYDMIG FPDFILEPKE LDDVYDGYEV SEDSFFQNML NLYNFSAKVM 550 560 570 580 590 600 ADQLRKPPSR DQWSMTPQTV NAYYLPTKNE IVFPAGILQA PFYTCNHPQA LNFGGIGVVM 610 620 630 640 650 660 GHELTHAFDD QGREYDKEGN LRPWWQNESL AAFRNHTACI EEQYSQYQVN GEKLNGRQTL 670 680 690 700 710 720 GENIADNGGL KAAYNAYKAW LRKHGEEQQL PAVGLTNHQL FFVGFAQVWC SVRTPESSHE 730 740 750 760 GLVTDPHSPA RFRVLGTLSN SRDFLRHFGC PVGSPMNSGQ LCEVW
	Isoform 5. Checksum: 2B7566ABDFED9C0F	FASTA	255	28,396
	10 20 30 40 50 60 MACLGPSAQV PELPEKNCGY REVQYWDQRY QGAADSAPYE WFGDFSCFRD LLEPELRPLD 70 80 90 100 110 120 RILVLGCGNS ALSYELFLGG FPDVTSVDYS SVVVAAMRAR YAHVPTLRWE TMDVRALGFP 130 140 150 160 170 180 SGSFDVVLEK GTLDALLTGE QDPWTVSSEG VHTVDQVLNE VSRVLVPAGR FISLTSAAPH 190 200 210 220 230 240 FRTRHYAQAH YGWSLRHATY GNGFQFHFYL MQKGKELSVA QLAVGAQILS PPRPPTPSCF 250 LQDSDHEDFL SAIQL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular isolation and characterization of novel four subisoforms of ECE-2." Ikeda S., Emoto N., Alimsardjono H., Yokoyama M., Matsuo M. Biochem. Biophys. Res. Commun. 293:421-426(2002) [PubMed: 12054617] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), NUCLEOTIDE SEQUENCE [MRNA] OF 59-883 (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
[2]	NIH - Mammalian Gene Collection (MGC) project Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5). Strain: Hereford. Tissue: Thymus.
[3]	"Endothelin-converting enzyme-2 is a membrane-bound, phosphoramidon-sensitive metalloprotease with acidic pH optimum." Emoto N., Yanagisawa M. J. Biol. Chem. 270:15262-15268(1995) [PubMed: 7797512] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 59-883 (ISOFORM 1).

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF489573 mRNA. Translation: AAO72360.1. Frameshift. AF489574 mRNA. Translation: AAO72361.1. Frameshift. BC142117 mRNA. Translation: AAI42118.1. U27341 mRNA. Translation: AAA82927.1. Frameshift.
IPI	IPI00691881. IPI00696952. IPI00711229. IPI00712359. IPI00854347.
RefSeq	NP_776471.2. NP_808871.2.
UniGene	Bt.4840
3D structure databases
HSSP	HSSP built from PDB template 1DMT based on UniProtKB P08473.
ModBase	Search...
Protein family/group databases
MEROPS	M13.003.
Genome annotation databases
Ensembl	ENSBTAG00000005658. Bos taurus. [Contig view]
GeneID	281134.
KEGG	bta:281134.
Phylogenomic databases
HOVERGEN	Q10711.
Enzyme and pathway databases
BRENDA	3.4.24.71. 251.
Family and domain databases
InterPro	IPR013216. Methyltransf_11. IPR006025. Pept_M_Zn_BS. IPR000718. Peptidase_M13. IPR018497. Peptidase_M13_C. IPR008753. Peptidase_M13_N. [Graphical view]
PANTHER	PTHR11733. Peptidase_M13. 1 hit.
Pfam	PF08241. Methyltransf_11. 1 hit. PF01431. Peptidase_M13. 1 hit. PF05649. Peptidase_M13_N. 1 hit. [Graphical view]
PRINTS	PR00786. NEPRILYSIN.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ECE2_BOVIN

Accession

Primary (citable) accession number: Q10711
Secondary accession number(s): A5PJH8, Q547G8, Q865C4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 13, 2007
Last modified:	June 16, 2009
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)