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Q9JLI3 (MMEL1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 87. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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
Neprilysin-like 1
Short name=NL-1
Neprilysin-like peptidase
Short name=NEPLP
Soluble secreted endopeptidase

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:Nep2, Nl1, Sep
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length765 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. Ref.1 Ref.3

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. Ref.3

Subcellular location

Membrane; Single-pass type II membrane protein. Secreted. Note: A secreted form produced by proteollytic cleavage also exists. Ref.1

Tissue specificity

Highly expressed in testis. Also expressed in ovary. Weakly or not expressed in brain, lung, heart, liver, kidney, adrenal gland and intestine. Ref.1

Post-translational modification

N-glycosylated. Ref.1 Ref.2

Disruption phenotype

Mice are viable and develop normally. However, males produce smaller litters, indicating specific male fertility problems. Ref.5

Sequence similarities

Belongs to the peptidase M13 family.

Biophysicochemical properties

Kinetic parameters:

KM=18 µM for D-Ala(2)-Leu(5)-enkephalin Ref.2

Sequence caution

The sequence BAE32538.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9JLI3-1)

Also known as: Beta;

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: Q9JLI3-2)

Also known as: Alpha; Delta;

The sequence of this isoform differs from the canonical sequence as follows:
     41-63: Missing.
Isoform 3 (identifier: Q9JLI3-3)

Also known as: Gamma;

The sequence of this isoform differs from the canonical sequence as follows:
     41-63: Missing.
     330-330: F → FGLKDRVSLCSPGCPGTHSVDQAGLELGNPPASDSRVL

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 765765Membrane metallo-endopeptidase-like 1
PRO_0000248417
Chain63 – 765703Membrane metallo-endopeptidase-like 1, soluble form Probable
PRO_0000248418

Regions

Topological domain1 – 1919Cytoplasmic Potential
Transmembrane20 – 4021Helical; Signal-anchor for type II membrane protein; Potential
Topological domain41 – 765725Lumenal Potential
Coiled coil523 – 54927 Potential

Sites

Active site6061 By similarity
Active site6661Proton donor By similarity
Metal binding5991Zinc; catalytic By similarity
Metal binding6031Zinc; catalytic By similarity
Metal binding6621Zinc; catalytic By similarity
Binding site1211Substrate carboxyl By similarity
Site62 – 632Cleavage Probable

Amino acid modifications

Glycosylation1631N-linked (GlcNAc...) Potential
Glycosylation2791N-linked (GlcNAc...) Potential
Glycosylation3031N-linked (GlcNAc...) Potential
Glycosylation3361N-linked (GlcNAc...) Potential
Glycosylation6941N-linked (GlcNAc...) Potential
Disulfide bond75 ↔ 80 By similarity
Disulfide bond98 ↔ 750 By similarity
Disulfide bond106 ↔ 710 By similarity
Disulfide bond161 ↔ 425 By similarity
Disulfide bond636 ↔ 762 By similarity

Natural variations

Alternative sequence41 – 6323Missing in isoform 2 and isoform 3.
VSP_020290
Alternative sequence3301F → FGLKDRVSLCSPGCPGTHSV DQAGLELGNPPASDSRVL in isoform 3.
VSP_020291

Experimental info

Mutagenesis62 – 632KR → NG: Abolishes formation the soluble form. Ref.2
Sequence conflict1891M → L in AAF13152. Ref.1
Sequence conflict1891M → L in AAF13153. Ref.1
Sequence conflict2641L → P in AAF13152. Ref.1
Sequence conflict2641L → P in AAF13153. Ref.1
Sequence conflict6591T → S in AAF13152. Ref.1
Sequence conflict6591T → S in AAF13153. Ref.1

Sequences

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

Last modified October 1, 2000. Version 1.
Checksum: D3662F1CE5B957F7

FASTA76588,700
        10         20         30         40         50         60 
MVERAGWCRK KSPGFVEYGL MVLLLLLLGA IVTLGVFYSI GKQLPLLTSL LHFSWDERTV 

        70         80         90        100        110        120 
VKRALRDSSL KSDICTTPSC VIAAARILEN MDQSRNPCEN FYQYACGGWL RHHVIPETNS 

       130        140        150        160        170        180 
RYSVFDILRD ELEVILKGVL EDSTSQHRPA VEKAKTLYRS CMNQSVIEKR DSEPLLSVLK 

       190        200        210        220        230        240 
MVGGWPVAMD KWNETMGLKW ELERQLAVLN SQFNRRVLID LFIWNDDQNS SRHVIYIDQP 

       250        260        270        280        290        300 
TLGMPSREYY FQEDNNHKVR KAYLEFMTSV ATMLRKDQNL SKESAMVREE MAEVLELETH 

       310        320        330        340        350        360 
LANATVPQEK RHDVTALYHR MDLMELQERF GLKGFNWTLF IQNVLSSVEV ELFPDEEVVV 

       370        380        390        400        410        420 
YGIPYLENLE DIIDSYSART MQNYLVWRLV LDRIGSLSQR FKEARVDYRK ALYGTTVEEV 

       430        440        450        460        470        480 
RWRECVSYVN SNMESAVGSL YIKRAFSKDS KSTVRELIEK IRSVFVDNLD ELNWMDEESK 

       490        500        510        520        530        540 
KKAQEKAMNI REQIGYPDYI LEDNNKHLDE EYSSLTFYED LYFENGLQNL KNNAQRSLKK 

       550        560        570        580        590        600 
LREKVDQNLW IIGAAVVNAF YSPNRNQIVF PAGILQPPFF SKDQPQSLNF GGIGMVIGHE 

       610        620        630        640        650        660 
ITHGFDDNGR NFDKNGNMLD WWSNFSARHF QQQSQCMIYQ YGNFSWELAD NQNVNGFSTL 

       670        680        690        700        710        720 
GENIADNGGV RQAYKAYLRW LADGGKDQRL PGLNLTYAQL FFINYAQVWC GSYRPEFAVQ 

       730        740        750        760 
SIKTDVHSPL KYRVLGSLQN LPGFSEAFHC PRGSPMHPMK RCRIW 

« Hide

Isoform 2 (Alpha) (Delta) [UniParc].

Checksum: 4A44EAD211B2499F
Show »

FASTA74285,994
Isoform 3 (Gamma) [UniParc].

Checksum: 5E48CA530828584B
Show »

FASTA77989,710

References

« Hide 'large scale' references
[1]"Molecular identification and characterization of novel membrane-bound metalloprotease, the soluble secreted form of which hydrolyzes a variety of vasoactive peptides."
Ikeda K., Emoto N., Raharjo S.B., Nurhantari Y., Saiki K., Yokoyama M., Matsuo M.
J. Biol. Chem. 274:32469-32477(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, GLYCOSYLATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Testis.
[2]"Molecular cloning and biochemical characterization of a new mouse testis soluble zinc-metallopeptidase of the neprilysin family."
Ghaddar G., Ruchon A.F., Carpentier M., Marcinkiewicz M., Seidah N.G., Crine P., DesGroseillers L., Boileau G.
Biochem. J. 347:419-429(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), GLYCOSYLATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF 62-LYS-ARG-63.
Tissue: Testis.
[3]"Neprilysin degrades both amyloid beta peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases."
Shirotani K., Tsubuki S., Iwata N., Takaki Y., Harigaya W., Maruyama K., Kiryu-Seo S., Kiyama H., Iwata H., Tomita T., Iwatsubo T., Saido T.C.
J. Biol. Chem. 276:21895-21901(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, ENZYME REGULATION.
[4]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 64-765.
Strain: NOD.
[5]"Reduced fertility in male mice deficient in the zinc metallopeptidase NL1."
Carpentier M., Guillemette C., Bailey J.L., Boileau G., Jeannotte L., DesGroseillers L., Charron J.
Mol. Cell. Biol. 24:4428-4437(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF157105 mRNA. Translation: AAF13152.1.
AF157106 mRNA. Translation: AAF13153.1.
AF176569 mRNA. Translation: AAF69247.1.
AF302075 mRNA. Translation: AAG18446.1.
AF302076 mRNA. Translation: AAG18447.1.
AF302077 mRNA. Translation: AAG18448.1.
AK154366 mRNA. Translation: BAE32538.1. Different initiation.
RefSeqNP_038811.2. NM_013783.2.
UniGeneMm.116944.

3D structure databases

ProteinModelPortalQ9JLI3.
SMRQ9JLI3. Positions 74-765.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9JLI3. 2 interactions.
MINTMINT-4129130.

Protein family/group databases

MEROPSM13.008.

PTM databases

PhosphoSiteQ9JLI3.

Proteomic databases

PaxDbQ9JLI3.
PRIDEQ9JLI3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID27390.
KEGGmmu:27390.
UCSCuc008wcg.1. mouse. [Q9JLI3-1]

Organism-specific databases

CTD79258.
MGIMGI:1351603. Mmel1.

Phylogenomic databases

eggNOGCOG3590.
HOGENOMHOG000245574.
HOVERGENHBG005554.
KOK08635.

Gene expression databases

BgeeQ9JLI3.
CleanExMM_MMEL1.
GenevestigatorQ9JLI3.

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

NextBio305354.
PROQ9JLI3.
SOURCESearch...

Entry information

Entry nameMMEL1_MOUSE
AccessionPrimary (citable) accession number: Q9JLI3
Secondary accession number(s): Q3U495 expand/collapse secondary AC list , Q9ERK2, Q9ERK3, Q9QZV6, Q9QZV7
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 87 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

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot