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P0C1T0

- MMEL1_RAT

UniProt

P0C1T0 - MMEL1_RAT

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Protein

Membrane metallo-endopeptidase-like 1

Gene

Mmel1

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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).By similarity

Catalytic activityi

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

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

Inhibited by thiorphan and phosphoramidon.

Kineticsi

  1. KM=62 µM for Tyrosyl-D-Ala(2)-Leu(5)-enkephalin2 Publications
  2. KM=27 µM for Suc-AA-F-AMC (Membrane metallo-endopeptidase-like 1)2 Publications
  3. KM=50 µM for Suc-AA-F-AMC (Membrane metallo-endopeptidase-like 1, soluble form)2 Publications
  4. KM=40 µM for Suc-AA-V-AMC (Membrane metallo-endopeptidase-like 1)2 Publications
  5. KM=100 µM for Suc-AA-V-AMC (Membrane metallo-endopeptidase-like 1, soluble form)2 Publications
  6. KM=23 µM for Suc-G-LF-AMC (Membrane metallo-endopeptidase-like 1)2 Publications
  7. KM=35 µM for Suc-G-LF-AMC (Membrane metallo-endopeptidase-like 1, soluble form)2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei72 – 732CleavageBy similarity
Binding sitei131 – 1311Substrate carboxylCurated
Metal bindingi608 – 6081Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi612 – 6121Zinc; catalyticPROSITE-ProRule annotation
Active sitei615 – 6151PROSITE-ProRule annotation
Metal bindingi671 – 6711Zinc; catalyticPROSITE-ProRule annotation
Active sitei675 – 6751Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

  1. metalloendopeptidase activity Source: RGD
  2. zinc ion binding Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended 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:
Alternative name(s):
Neprilysin-2 secreted
Short name:
NEP2(s)
Gene namesi
Name:Mmel1
Synonyms:Mell1, Nep2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 5

Organism-specific databases

RGDi1309299. Mmel1.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2626CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei27 – 4721Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini48 – 774727LumenalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: Ensembl
  2. extracellular space Source: RGD
  3. Golgi apparatus Source: Ensembl
  4. integral component of membrane Source: UniProtKB-KW
  5. membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi131 – 1311R → M: Impairs binding of free carboxylate group of substrates. 1 Publication
Mutagenesisi133 – 1331S → G: Impairs both substrate-binding and enzyme activity. 1 Publication
Mutagenesisi567 – 5671N → G: Impairs the enzyme specificity. 1 Publication
Mutagenesisi739 – 7391L → G: Impairs both substrate-binding and enzyme activity. 1 Publication
Mutagenesisi751 – 7511P → A: Loss of function. 1 Publication
Mutagenesisi764 – 7641P → Y: Induces a 3-fold decrease of specific activity. 1 Publication
Mutagenesisi774 – 7741W → F: No effect. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 774774Membrane metallo-endopeptidase-like 1PRO_0000248419Add
BLAST
Chaini73 – 774702Membrane metallo-endopeptidase-like 1, soluble formBy similarityPRO_0000248420Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi85 ↔ 90By similarity
Disulfide bondi108 ↔ 759By similarity
Disulfide bondi116 ↔ 719By similarity
Disulfide bondi171 ↔ 434By similarity
Glycosylationi173 – 1731N-linked (GlcNAc...)Sequence Analysis
Glycosylationi203 – 2031N-linked (GlcNAc...)Sequence Analysis
Glycosylationi239 – 2391N-linked (GlcNAc...)Sequence Analysis
Glycosylationi312 – 3121N-linked (GlcNAc...)Sequence Analysis
Glycosylationi345 – 3451N-linked (GlcNAc...)Sequence Analysis
Glycosylationi633 – 6331N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi645 ↔ 771By similarity
Glycosylationi652 – 6521N-linked (GlcNAc...)Sequence Analysis
Glycosylationi703 – 7031N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP0C1T0.
PRIDEiP0C1T0.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

ExpressionAtlasiP0C1T0. baseline.
GenevestigatoriP0C1T0.

Interactioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000063235.

Structurei

3D structure databases

ProteinModelPortaliP0C1T0.
SMRiP0C1T0. Positions 83-774.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili532 – 55827Sequence AnalysisAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi14 – 218Stop-transfer sequenceSequence Analysis

Sequence similaritiesi

Belongs to the peptidase M13 family.Curated

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG3590.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiP0C1T0.
OMAiDGNMLDW.
OrthoDBiEOG7PZRWQ.

Family and domain databases

Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR029735. MMEL1.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 1 hit.
PTHR11733:SF112. PTHR11733:SF112. 1 hit.
PfamiPF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view]
PRINTSiPR00786. NEPRILYSIN.
PROSITEiPS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P0C1T0-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MGKSESSVGM MERADNCGRR RLGFVECGLL VLLTLLLMGA IVTLGVFYSI
60 70 80 90 100
GKQLPLLNSL LHVSRHERTV VKRVLRDSSQ KSDICTTPSC VIAAARILQN
110 120 130 140 150
MDQSKKPCDN FYQYACGGWL RHHVIPETNS RYSVFDILRD ELEVILKGVL
160 170 180 190 200
EDSSVQHRPA VEKAKTLYRS CMNQSVIEKR DSEPLLNVLD MIGGWPVAMD
210 220 230 240 250
KWNETMGPKW ELERQLAVLN SQFNRRVLID LFIWNDDQNS SRHVIYIDQP
260 270 280 290 300
TLGMPSREYY FKEDSHRVRE AYLQFMTSVA TMLRRDLNLP GETDLVQEEM
310 320 330 340 350
AQVLHLETHL ANATVPQEKR HDVTALYHRM GLEELQERFG LKGFNWTLFI
360 370 380 390 400
QNVLSSVQVE LLPNEEVVVY GIPYLENLEE IIDVFPAQTL QNYLVWRLVL
410 420 430 440 450
DRIGSLSQRF KEARVDYRKA LYGTTMEEVR WRECVSYVNS NMESAVGSLY
460 470 480 490 500
IKRAFSKDSK SIVSELIEKI RSVFVDNLDE LNWMDEESKK KAQEKALNIR
510 520 530 540 550
EQIGYPDYIL EDNNRHLDEE YSSLTFSEDL YFENGLQNLK NNAQRSLKKL
560 570 580 590 600
REKVDQNLWI IGAAVVNAFY SPNRNLIVFP AGILQPPFFS KDQPQALNFG
610 620 630 640 650
GIGMVIGHEI THGFDDNGRN FDKNGNMLDW WSNFSARHFR QQSQCMIYQY
660 670 680 690 700
SNFSWELADN QNVNGFSTLG ENIADNGGVR QAYKAYLQWL AEGGRDQRLP
710 720 730 740 750
GLNLTYAQLF FINYAQVWCG SYRPEFAIQS IKTDVHSPLN AQVLGSLQNL
760 770
PGFSEAFHCP RGSPMHPMNR CRIW
Length:774
Mass (Da):89,197
Last modified:September 5, 2006 - v1
Checksum:iF95E2088CA4B64AD
GO
Isoform 2 (identifier: P0C1T0-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     51-73: Missing.

Show »
Length:751
Mass (Da):86,533
Checksum:i1995504DF1EFCDDF
GO
Isoform 3 (identifier: P0C1T0-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     246-267: Missing.

Show »
Length:752
Mass (Da):86,482
Checksum:iA7E932880187EFFE
GO
Isoform 4 (identifier: P0C1T0-4) [UniParc]FASTAAdd to Basket

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

Show »
Length:763
Mass (Da):87,997
Checksum:i60A7053E8AE2D62A
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei51 – 7323Missing in isoform 2. 1 PublicationVSP_020292Add
BLAST
Alternative sequencei246 – 26722Missing in isoform 3. 1 PublicationVSP_020293Add
BLAST
Alternative sequencei303 – 31311Missing in isoform 4. CuratedVSP_020294Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03040205 Genomic DNA. No translation available.
UniGeneiRn.50873.

Genome annotation databases

EnsembliENSRNOT00000017957; ENSRNOP00000017957; ENSRNOG00000012593. [P0C1T0-1]
ENSRNOT00000064738; ENSRNOP00000063235; ENSRNOG00000012593. [P0C1T0-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03040205 Genomic DNA. No translation available.
UniGenei Rn.50873.

3D structure databases

ProteinModelPortali P0C1T0.
SMRi P0C1T0. Positions 83-774.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10116.ENSRNOP00000063235.

Proteomic databases

PaxDbi P0C1T0.
PRIDEi P0C1T0.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000017957 ; ENSRNOP00000017957 ; ENSRNOG00000012593 . [P0C1T0-1 ]
ENSRNOT00000064738 ; ENSRNOP00000063235 ; ENSRNOG00000012593 . [P0C1T0-2 ]

Organism-specific databases

RGDi 1309299. Mmel1.

Phylogenomic databases

eggNOGi COG3590.
GeneTreei ENSGT00760000119162.
HOGENOMi HOG000245574.
HOVERGENi HBG005554.
InParanoidi P0C1T0.
OMAi DGNMLDW.
OrthoDBi EOG7PZRWQ.

Miscellaneous databases

PROi P0C1T0.

Gene expression databases

ExpressionAtlasi P0C1T0. baseline.
Genevestigatori P0C1T0.

Family and domain databases

Gene3Di 3.40.390.10. 2 hits.
InterProi IPR024079. MetalloPept_cat_dom.
IPR029735. MMEL1.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view ]
PANTHERi PTHR11733. PTHR11733. 1 hit.
PTHR11733:SF112. PTHR11733:SF112. 1 hit.
Pfami PF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view ]
PRINTSi PR00786. NEPRILYSIN.
PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiMMEL1_RAT
AccessioniPrimary (citable) accession number: P0C1T0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: November 26, 2014
This is version 62 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3