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P0C1T0 (MMEL1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 58. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | 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:
Membrane metallo-endopeptidase-like 1

EC=3.4.24.11
Alternative name(s):
NEP2(m)
Neprilysin II
Short name=NEPII
Neprilysin-2
Short name=NEP2
Short name=NL2

Cleaved into the following chain:

  1. Membrane metallo-endopeptidase-like 1, soluble form
    Alternative name(s):
    Neprilysin-2 secreted
    Short name=NEP2(s)
Gene names
Name:Mmel1
Synonyms:Mell1, Nep2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length774 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Metalloprotease involved in sperm function, possibly by modulating the processes of fertilization and early embryonic development. Degrades a broad variety of small peptides with a preference for peptides shorter than 3 kDa containing neutral bulky aliphatic or aromatic amino acid residues. Shares the same substrate specificity with MME and cleaves peptides at the same amide bond By similarity.

Catalytic activity

Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Enzyme regulation

Inhibited by thiorphan and phosphoramidon.

Subcellular location

Membrane; Single-pass type II membrane protein. Secreted. Note: A secreted form produced by proteollytic cleavage also exists Probable.

Tissue specificity

Specifically expressed in testis and central nervous system (CNS) (at protein level). Restricted to developing and differentiating fields of the CNS. The soluble form is expressed in round spermatides. Ref.1 Ref.4

Post-translational modification

N-glycosylated. Ref.6

Sequence similarities

Belongs to the peptidase M13 family.

Biophysicochemical properties

Kinetic parameters:

KM=62 µM for Tyrosyl-D-Ala(2)-Leu(5)-enkephalin Ref.5 Ref.6

KM=27 µM for Suc-AA-F-AMC (Membrane metallo-endopeptidase-like 1)

KM=50 µM for Suc-AA-F-AMC (Membrane metallo-endopeptidase-like 1, soluble form)

KM=40 µM for Suc-AA-V-AMC (Membrane metallo-endopeptidase-like 1)

KM=100 µM for Suc-AA-V-AMC (Membrane metallo-endopeptidase-like 1, soluble form)

KM=23 µM for Suc-G-LF-AMC (Membrane metallo-endopeptidase-like 1)

KM=35 µM for Suc-G-LF-AMC (Membrane metallo-endopeptidase-like 1, soluble form)

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P0C1T0-1)

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: P0C1T0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     51-73: Missing.
Isoform 3 (identifier: P0C1T0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     246-267: Missing.
Isoform 4 (identifier: P0C1T0-4)

The sequence of this isoform differs from the canonical sequence as follows:
     303-313: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 774774Membrane metallo-endopeptidase-like 1
PRO_0000248419
Chain73 – 774702Membrane metallo-endopeptidase-like 1, soluble form By similarity
PRO_0000248420

Regions

Topological domain1 – 2626Cytoplasmic Potential
Transmembrane27 – 4721Helical; Signal-anchor for type II membrane protein; Potential
Topological domain48 – 774727Lumenal Potential
Coiled coil532 – 55827 Potential
Motif14 – 218Stop-transfer sequence Potential

Sites

Active site6151 By similarity
Active site6751Proton donor By similarity
Metal binding6081Zinc; catalytic By similarity
Metal binding6121Zinc; catalytic By similarity
Metal binding6711Zinc; catalytic By similarity
Binding site1311Substrate carboxyl Probable
Site72 – 732Cleavage By similarity

Amino acid modifications

Glycosylation1731N-linked (GlcNAc...) Potential
Glycosylation2031N-linked (GlcNAc...) Potential
Glycosylation2391N-linked (GlcNAc...) Potential
Glycosylation3121N-linked (GlcNAc...) Potential
Glycosylation3451N-linked (GlcNAc...) Potential
Glycosylation6331N-linked (GlcNAc...) Potential
Glycosylation6521N-linked (GlcNAc...) Potential
Glycosylation7031N-linked (GlcNAc...) Potential
Disulfide bond85 ↔ 90 By similarity
Disulfide bond108 ↔ 759 By similarity
Disulfide bond116 ↔ 719 By similarity
Disulfide bond171 ↔ 434 By similarity
Disulfide bond645 ↔ 771 By similarity

Natural variations

Alternative sequence51 – 7323Missing in isoform 2.
VSP_020292
Alternative sequence246 – 26722Missing in isoform 3.
VSP_020293
Alternative sequence303 – 31311Missing in isoform 4.
VSP_020294

Experimental info

Mutagenesis1311R → M: Impairs binding of free carboxylate group of substrates. Ref.5
Mutagenesis1331S → G: Impairs both substrate-binding and enzyme activity. Ref.5
Mutagenesis5671N → G: Impairs the enzyme specificity. Ref.5
Mutagenesis7391L → G: Impairs both substrate-binding and enzyme activity. Ref.5
Mutagenesis7511P → A: Loss of function. Ref.7
Mutagenesis7641P → Y: Induces a 3-fold decrease of specific activity. Ref.7
Mutagenesis7741W → F: No effect. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified September 5, 2006. Version 1.
Checksum: F95E2088CA4B64AD

FASTA77489,197
        10         20         30         40         50         60 
MGKSESSVGM MERADNCGRR RLGFVECGLL VLLTLLLMGA IVTLGVFYSI GKQLPLLNSL 

        70         80         90        100        110        120 
LHVSRHERTV VKRVLRDSSQ KSDICTTPSC VIAAARILQN MDQSKKPCDN FYQYACGGWL 

       130        140        150        160        170        180 
RHHVIPETNS RYSVFDILRD ELEVILKGVL EDSSVQHRPA VEKAKTLYRS CMNQSVIEKR 

       190        200        210        220        230        240 
DSEPLLNVLD MIGGWPVAMD KWNETMGPKW ELERQLAVLN SQFNRRVLID LFIWNDDQNS 

       250        260        270        280        290        300 
SRHVIYIDQP TLGMPSREYY FKEDSHRVRE AYLQFMTSVA TMLRRDLNLP GETDLVQEEM 

       310        320        330        340        350        360 
AQVLHLETHL ANATVPQEKR HDVTALYHRM GLEELQERFG LKGFNWTLFI QNVLSSVQVE 

       370        380        390        400        410        420 
LLPNEEVVVY GIPYLENLEE IIDVFPAQTL QNYLVWRLVL DRIGSLSQRF KEARVDYRKA 

       430        440        450        460        470        480 
LYGTTMEEVR WRECVSYVNS NMESAVGSLY IKRAFSKDSK SIVSELIEKI RSVFVDNLDE 

       490        500        510        520        530        540 
LNWMDEESKK KAQEKALNIR EQIGYPDYIL EDNNRHLDEE YSSLTFSEDL YFENGLQNLK 

       550        560        570        580        590        600 
NNAQRSLKKL REKVDQNLWI IGAAVVNAFY SPNRNLIVFP AGILQPPFFS KDQPQALNFG 

       610        620        630        640        650        660 
GIGMVIGHEI THGFDDNGRN FDKNGNMLDW WSNFSARHFR QQSQCMIYQY SNFSWELADN 

       670        680        690        700        710        720 
QNVNGFSTLG ENIADNGGVR QAYKAYLQWL AEGGRDQRLP GLNLTYAQLF FINYAQVWCG 

       730        740        750        760        770 
SYRPEFAIQS IKTDVHSPLN AQVLGSLQNL PGFSEAFHCP RGSPMHPMNR CRIW 

« Hide

Isoform 2 [UniParc].

Checksum: 1995504DF1EFCDDF
Show »

FASTA75186,533
Isoform 3 [UniParc].

Checksum: A7E932880187EFFE
Show »

FASTA75286,482
Isoform 4 [UniParc].

Checksum: 60A7053E8AE2D62A
Show »

FASTA76387,997

References

« Hide 'large scale' references
[1]"Neprilysin II: a putative novel metalloprotease and its isoforms in CNS and testis."
Ouimet T., Facchinetti P., Rose C., Bonhomme M.-C., Gros C., Schwartz J.-C.
Biochem. Biophys. Res. Commun. 271:565-570(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), TISSUE SPECIFICITY.
[2]Erratum
Ouimet T., Facchinetti P., Rose C., Bonhomme M.-C., Gros C., Schwartz J.-C.
Biochem. Biophys. Res. Commun. 275:247-247(2000)
[3]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
[4]"Ontogeny, regional and cellular distribution of the novel metalloprotease neprilysin 2 in the rat: a comparison with neprilysin and endothelin-converting enzyme-1."
Facchinetti P., Rose C., Schwartz J.C., Ouimet T.
Neuroscience 118:627-639(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[5]"A three-dimensional model of the neprilysin 2 active site based on the X-ray structure of neprilysin. Identification of residues involved in substrate hydrolysis and inhibitor binding of neprilysin 2."
Voisin S., Rognan D., Gros C., Ouimet T.
J. Biol. Chem. 279:46172-46181(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF ARG-131; SER-133; ASN-567 AND LEU-739.
[6]"Cell-specific activity of neprilysin 2 isoforms and enzymic specificity compared with neprilysin."
Rose C., Voisin S., Gros C., Schwartz J.-C., Ouimet T.
Biochem. J. 363:697-705(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES.
[7]"The ultimate tryptophan residue of neprilysin 2 is not involved in protein maturation and enzymatic activity."
Voisin S., Ouimet T.
Biochem. Biophys. Res. Commun. 335:356-360(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PRO-751; PRO-764 AND TRP-774.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AABR03040205 Genomic DNA. No translation available.
UniGeneRn.50873.

3D structure databases

ProteinModelPortalP0C1T0.
SMRP0C1T0. Positions 83-774.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000063235.

Proteomic databases

PaxDbP0C1T0.
PRIDEP0C1T0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000017957; ENSRNOP00000017957; ENSRNOG00000012593. [P0C1T0-1]
ENSRNOT00000064738; ENSRNOP00000063235; ENSRNOG00000012593. [P0C1T0-2]

Organism-specific databases

RGD1309299. Mmel1.

Phylogenomic databases

eggNOGCOG3590.
GeneTreeENSGT00650000093248.
HOGENOMHOG000245574.
HOVERGENHBG005554.
OMAPVAMDKW.
OrthoDBEOG7PZRWQ.

Gene expression databases

GenevestigatorP0C1T0.

Family and domain databases

Gene3D3.40.390.10. 2 hits.
InterProIPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERPTHR11733. PTHR11733. 1 hit.
PfamPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSPR00786. NEPRILYSIN.
PROSITEPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROP0C1T0.

Entry information

Entry nameMMEL1_RAT
AccessionPrimary (citable) accession number: P0C1T0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: April 16, 2014
This is version 58 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries