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O60344 (ECE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 139. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Endothelin-converting enzyme 2

Short name=ECE-2

Including the following 2 domains:

  1. Methyltransferase-like region
    EC=2.1.1.-
  2. Endothelin-converting enzyme 2 region
    EC=3.4.24.71
Gene names
Name:ECE2
Synonyms:KIAA0604
ORF Names:UNQ403/PRO740
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length883 AA.
Sequence statusComplete.
Protein existenceEvidence 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. Ref.8

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.

Subcellular location

Golgi apparatus membrane; Single-pass type II membrane protein By similarity. Cytoplasmic granule membrane; Single-pass type II membrane protein By similarity.

Tissue specificity

Expressed in brain. Strongly down-regulated in inferior parietal lobe from Alzheimer disease patients (at protein level). Ref.10

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

Kinetic parameters:

KM=0.4 µM for big ET-1 Ref.8

KM=1.4 µM for peptide E

KM=27.4 µM for bradykinin

KM=48.4 µM for dynorphin B

pH dependence:

Optimum pH is 5.0-5.5. Inactive at neutral pH.

Sequence caution

The sequence AAL30386.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence BAA25530.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform A (identifier: O60344-1)

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 B (identifier: O60344-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-159: MASPGAGRAP...GVHTVDQVLS → MNVALQELGA...VEGGASPDAM
Isoform C (identifier: O60344-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: MASPGAGRAP...VHTVDQVLSE → MNVALQELGAGSN
Isoform D (identifier: O60344-4)

The sequence of this isoform differs from the canonical sequence as follows:
     162-261: GFQKGTRQLL...LPDGRSRWNT → SRVLVPGGRF...HEDFLSAIQL
     262-883: Missing.
Isoform 2C (identifier: O60344-5)

The sequence of this isoform differs from the canonical sequence as follows:
     1-160: MASPGAGRAP...VHTVDQVLSE → MNVALQELGA...SISGLCSRTM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 883883Endothelin-converting enzyme 2
PRO_0000078223

Regions

Topological domain1 – 178178Cytoplasmic Potential
Transmembrane179 – 19921Helical; Signal-anchor for type II membrane protein; Potential
Topological domain200 – 883684Lumenal Potential
Region1 – 160160Methyltransferase-like region
Region88 – 892S-adenosyl-L-homocysteine binding
Region113 – 1142S-adenosyl-L-homocysteine binding
Region200 – 883684Endothelin-converting enzyme 2 region

Sites

Active site7211 By similarity
Active site7841Proton donor By similarity
Metal binding7201Zinc; catalytic By similarity
Metal binding7241Zinc; catalytic By similarity
Metal binding7801Zinc; catalytic By similarity
Binding site301S-adenosyl-L-homocysteine
Binding site411S-adenosyl-L-homocysteine; via amide nitrogen
Binding site661S-adenosyl-L-homocysteine; via carbonyl oxygen
Binding site1301S-adenosyl-L-homocysteine

Amino acid modifications

Modified residue391Phosphotyrosine Ref.9
Glycosylation3241N-linked (GlcNAc...) Potential
Glycosylation3841N-linked (GlcNAc...) Potential
Glycosylation4291N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 160160MASPG…QVLSE → MNVALQELGAGSNMVEYKRA TLRDEDAPETPVEGGASPDA MEVGKGASPFSPGPSPGMTP GTPRSSGLFWRVTCPHLRSI SGLCSRTM in isoform 2C.
VSP_039176
Alternative sequence1 – 160160MASPG…QVLSE → MNVALQELGAGSN in isoform C.
VSP_005509
Alternative sequence1 – 159159MASPG…DQVLS → MNVALQELGAGSNMVEYKRA TLRDEDAPETPVEGGASPDA M in isoform B.
VSP_005508
Alternative sequence162 – 261100GFQKG…SRWNT → SRVLVPGGRFISMTSAAPHF RTRHYAQAYYGWSLRHATYG SGFHFHLYLMHKGGKLSVAQ LALGAQILSPPRPPTSPCFL QDSDHEDFLSAIQL in isoform D.
VSP_029333
Alternative sequence262 – 883622Missing in isoform D.
VSP_029334
Natural variant1011H → Y. Ref.6 Ref.7
Corresponds to variant rs7633387 [ dbSNP | Ensembl ].
VAR_047752
Natural variant5711R → Q.
Corresponds to variant rs35875049 [ dbSNP | Ensembl ].
VAR_037085

Experimental info

Sequence conflict4671F → S in AAI42951. Ref.7
Sequence conflict7831A → T in AAQ89362. Ref.4

Secondary structure

.......................................... 883
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform A [UniParc].

Last modified November 25, 2008. Version 4.
Checksum: EE1C0F4AA4C6B225

FASTA88399,773
        10         20         30         40         50         60 
MASPGAGRAP PELPERNCGY REVEYWDQRY QGAADSAPYD WFGDFSSFRA LLEPELRPED 

        70         80         90        100        110        120 
RILVLGCGNS ALSYELFLGG FPNVTSVDYS SVVVAAMQAR HAHVPQLRWE TMDVRKLDFP 

       130        140        150        160        170        180 
SASFDVVLEK GTLDALLAGE RDPWTVSSEG VHTVDQVLSE VGFQKGTRQL LGSRTQLELV 

       190        200        210        220        230        240 
LAGASLLLAA LLLGCLVALG VQYHRDPSHS TCLTEACIRV AGKILESLDR GVSPCEDFYQ 

       250        260        270        280        290        300 
FSCGGWIRRN PLPDGRSRWN TFNSLWDQNQ AILKHLLENT TFNSSSEAEQ KTQRFYLSCL 

       310        320        330        340        350        360 
QVERIEELGA QPLRDLIEKI GGWNITGPWD QDNFMEVLKA VAGTYRATPF FTVYISADSK 

       370        380        390        400        410        420 
SSNSNVIQVD QSGLFLPSRD YYLNRTANEK VLTAYLDYME ELGMLLGGRP TSTREQMQQV 

       430        440        450        460        470        480 
LELEIQLANI TVPQDQRRDE EKIYHKMSIS ELQALAPSMD WLEFLSFLLS PLELSDSEPV 

       490        500        510        520        530        540 
VVYGMDYLQQ VSELINRTEP SILNNYLIWN LVQKTTSSLD RRFESAQEKL LETLYGTKKS 

       550        560        570        580        590        600 
CVPRWQTCIS NTDDALGFAL GSLFVKATFD RQSKEIAEGM ISEIRTAFEE ALGQLVWMDE 

       610        620        630        640        650        660 
KTRQAAKEKA DAIYDMIGFP DFILEPKELD DVYDGYEISE DSFFQNMLNL YNFSAKVMAD 

       670        680        690        700        710        720 
QLRKPPSRDQ WSMTPQTVNA YYLPTKNEIV FPAGILQAPF YARNHPKALN FGGIGVVMGH 

       730        740        750        760        770        780 
ELTHAFDDQG REYDKEGNLR PWWQNESLAA FRNHTACMEE QYNQYQVNGE RLNGRQTLGE 

       790        800        810        820        830        840 
NIADNGGLKA AYNAYKAWLR KHGEEQQLPA VGLTNHQLFF VGFAQVWCSV RTPESSHEGL 

       850        860        870        880 
VTDPHSPARF RVLGTLSNSR DFLRHFGCPV GSPMNPGQLC EVW 

« Hide

Isoform B [UniParc].

Checksum: 89D1B831B5628694
Show »

FASTA76586,470
Isoform C [UniParc].

Checksum: 77F14FE5AC80E187
Show »

FASTA73683,322
Isoform D [UniParc].

Checksum: 39389C81C0798805
Show »

FASTA25528,306
Isoform 2C [UniParc].

Checksum: 7379F7AFEA937FCE
Show »

FASTA81191,211

References

« Hide 'large scale' references
[1]"Human endothelin converting enzyme-2 (ECE2): characterization of mRNA species and chromosomal localization."
Lorenzo M.-N., Khan R.Y., Wang Y., Tai S.C., Chan G.C., Cheung A.H., Marsden P.A.
Biochim. Biophys. Acta 1522:46-52(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B AND C), NUCLEOTIDE SEQUENCE [MRNA] OF 13-883 (ISOFORM A).
[2]"Human endothelin-converting enzyme-2C (ECE-2C): a new ECE-2 variant."
Funke-Kaiser H., Scheuch K., Behrouzi T., Synowitz M., Draheim N., Schwaneberg B., Thomas A., Zollmann F.S., Paul M., Orzechowski H.D.
Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2C).
Tissue: Thalamus.
[3]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
Tissue: Brain.
[4]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM C).
[5]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT TYR-101.
[7]"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] (ISOFORMS C AND D), VARIANT TYR-101.
Tissue: Lung and Ovary.
[8]"Characterization of endothelin-converting enzyme-2. Implication for a role in the nonclassical processing of regulatory peptides."
Mzhavia N., Pan H., Che F.-Y., Fricker L.D., Devi L.A.
J. Biol. Chem. 278:14704-14711(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[9]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-39, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Alterations in immunological and neurological gene expression patterns in Alzheimer's disease tissues."
Weeraratna A.T., Kalehua A., Deleon I., Bertak D., Maher G., Wade M.S., Lustig A., Becker K.G., Wood W. III, Walker D.G., Beach T.G., Taub D.D.
Exp. Cell Res. 313:450-461(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[11]"An intact SAM-dependent methyltransferase fold is encoded by the human endothelin-converting enzyme-2 gene."
Tempel W., Wu H., Dombrovsky L., Zeng H., Loppnau P., Zhu H., Plotnikov A.N., Bochkarev A.
Proteins 74:789-793(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 19-161 IN COMPLEX WITH S-ADENOSYL-L-HOMOCYSTEINE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF428263 mRNA. Translation: AAL30386.1. Different initiation.
AF428264 mRNA. Translation: AAL30387.1.
AF192531 mRNA. Translation: AAG28399.1.
AF521189 mRNA. Translation: AAM77664.1.
AB011176 mRNA. Translation: BAA25530.2. Different initiation.
AY359003 mRNA. Translation: AAQ89362.1.
AC061705 Genomic DNA. No translation available.
AC078797 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW78277.1.
BC005835 mRNA. Translation: AAH05835.1.
BC012449 mRNA. Translation: AAH12449.1.
BC069005 mRNA. Translation: AAH69005.1.
BC142950 mRNA. Translation: AAI42951.1.
CCDSCCDS3255.1. [O60344-4]
CCDS3256.2. [O60344-1]
CCDS33899.1. [O60344-3]
CCDS43179.1. [O60344-5]
CCDS46969.1. [O60344-2]
RefSeqNP_001032401.1. NM_001037324.2. [O60344-3]
NP_001093590.1. NM_001100120.1. [O60344-5]
NP_001093591.1. NM_001100121.1. [O60344-2]
NP_055508.3. NM_014693.3. [O60344-1]
NP_115707.2. NM_032331.3. [O60344-4]
UniGeneHs.146161.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2PXXX-ray1.30A19-161[»]
ProteinModelPortalO60344.
SMRO60344. Positions 19-161, 214-883.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115067. 4 interactions.
IntActO60344. 3 interactions.
MINTMINT-8417701.
STRING9606.ENSP00000384223.

Chemistry

BindingDBO60344.
ChEMBLCHEMBL5890.

Protein family/group databases

MEROPSM13.003.

PTM databases

PhosphoSiteO60344.

Proteomic databases

MaxQBO60344.
PaxDbO60344.
PRIDEO60344.

Protocols and materials databases

DNASU9718.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000324557; ENSP00000314295; ENSG00000145194. [O60344-4]
ENST00000357474; ENSP00000350066; ENSG00000145194. [O60344-5]
ENST00000359140; ENSP00000352052; ENSG00000145194. [O60344-3]
ENST00000402825; ENSP00000384223; ENSG00000145194. [O60344-1]
ENST00000404464; ENSP00000385846; ENSG00000145194. [O60344-2]
GeneID9718.
KEGGhsa:9718.
UCSCuc003fnh.4. human. [O60344-4]
uc003fni.4. human. [O60344-1]
uc003fnk.4. human. [O60344-3]
uc003fnl.4. human. [O60344-5]
uc003fnm.4. human. [O60344-2]

Organism-specific databases

CTD9718.
GeneCardsGC03P183967.
H-InvDBHIX0003914.
HGNCHGNC:13275. ECE2.
HPAHPA043346.
MIM610145. gene.
neXtProtNX_O60344.
PharmGKBPA134886910.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3590.
HOVERGENHBG005554.
InParanoidO60344.
KOK01415.
OMAINTTWFL.
OrthoDBEOG7PZRWQ.
PhylomeDBO60344.
TreeFamTF315192.

Enzyme and pathway databases

SABIO-RKO60344.

Gene expression databases

ArrayExpressO60344.
BgeeO60344.
CleanExHS_ECE2.
GenevestigatorO60344.

Family and domain databases

Gene3D3.40.390.10. 2 hits.
3.40.50.150. 1 hit.
InterProIPR024079. MetalloPept_cat_dom.
IPR013216. Methyltransf_11.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
IPR029063. SAM-dependent_MTases-like.
[Graphical view]
PANTHERPTHR11733. PTHR11733. 1 hit.
PfamPF08241. Methyltransf_11. 1 hit.
PF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSPR00786. NEPRILYSIN.
SUPFAMSSF53335. SSF53335. 1 hit.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO60344.
GenomeRNAi9718.
NextBio36537.
PROO60344.
SOURCESearch...

Entry information

Entry nameECE2_HUMAN
AccessionPrimary (citable) accession number: O60344
Secondary accession number(s): A5PLK8 expand/collapse secondary AC list , Q6NTG7, Q6UW36, Q8NFD7, Q96NX3, Q96NX4, Q9BRZ8
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 25, 2008
Last modified: July 9, 2014
This is version 139 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM