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Reviewed, UniProtKB/Swiss-Prot Q495T6 (MMEL1_HUMAN)

Last modified November 25, 2008. Version 35. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Membrane metallo-endopeptidase-like 1
    EC=3.4.24.11
Alternative name(s):
    Membrane metallo-endopeptidase-like 2
    Neprilysin-2
    Neprilysin II
    NL2
    NEPII
    NEP2(m)
Cleaved into the following chain:
    1- Recommended name:
            Membrane metallo-endopeptidase-like 1, soluble form
        Alternative name(s):
            Neprilysin-2 secreted
              Short name=NEP2(s)
Gene names
Name: MMEL1
Synonyms: MELL1, MMEL2, NEP2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length779 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at transcript 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 specificiy 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 By similarity.

Subcellular location

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

Tissue specificity

Predominantly expressed in testis. Weakly expressed in brain, kidney and heart.

Post-translational modification

N-glycosylated By similarity.

Sequence similarities

Belongs to the peptidase M13 family.

Sequence caution

The sequence AAL08942.1 differs from that shown. Reason: Frameshift at positions 7 and 8.

Ontologies

Keywords

   Cellular componentMembrane
Secreted
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
Signal-anchor
Transmembrane
   LigandMetal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMGlycoprotein

Gene Ontology (GO)

   Biological processproteolysis

Inferred from electronic annotation. Source: InterPro

   Cellular componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-KW

integral to membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular functionmetalloendopeptidase activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q495T6-1)

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: Q495T6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     583-611: VFPAGILQPPFFSKEQPQALNFGGIGMVI → AYSLSRPWGQYSLPGSSSPPSSARSSHRP
     612-779: Missing.
Notes: No experimental confirmation available.
Isoform 3 (identifier: Q495T6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     159-315: Missing.
Notes: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 779779Membrane metallo-endopeptidase-like 1
PRO_0000248415
Chain74 – 779706Membrane metallo-endopeptidase-like 1, soluble form By similarity
PRO_0000248416

Regions

Topological domain1 – 2727Cytoplasmic Potential
Transmembrane28 – 4821Signal-anchor for type II membrane protein Potential
Topological domain49 – 779731Lumenal Potential
Coiled coil515 – 56046 Potential

Sites

Active site6201 By similarity
Active site6801Proton donor By similarity
Metal binding6131Zinc; catalytic By similarity
Metal binding6171Zinc; catalytic By similarity
Metal binding6761Zinc; catalytic By similarity
Binding site1351Substrate carboxyl By similarity
Site73 – 742Cleavage By similarity

Amino acid modifications

Glycosylation1771N-linked (GlcNAc...) Potential
Glycosylation2071N-linked (GlcNAc...) Potential
Glycosylation3501N-linked (GlcNAc...) Potential
Glycosylation5301N-linked (GlcNAc...) Potential
Glycosylation6571N-linked (GlcNAc...) Potential
Disulfide bond89 ↔ 94 By similarity
Disulfide bond112 ↔ 764 By similarity
Disulfide bond120 ↔ 724 By similarity
Disulfide bond175 ↔ 439 By similarity
Disulfide bond650 ↔ 776 By similarity

Natural variations

Alternative sequence159 – 315157Missing in isoform 3.
VSP_020287
Alternative sequence583 – 61129VFPAG…IGMVI → AYSLSRPWGQYSLPGSSSPP SSARSSHRP in isoform 2.
VSP_020288
Alternative sequence612 – 779168Missing in isoform 2.
VSP_020289
Natural variant5181M → T: dbSNP rs3748816.
VAR_027348

Experimental info

Sequence conflict3511W → R in AAI01029. Ref.3
Sequence conflict4891M → I in AAI01031. Ref.3

Sequences

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

Last modified September 5, 2006. Version 2.
Checksum: 08C41819F4E81CBD

FASTA77989,367
        10         20         30         40         50         60 
MGKSEGPVGM VESAGRAGQK RPGFLEGGLL LLLLLVTAAL VALGVLYADR RGKQLPRLAS 

        70         80         90        100        110        120 
RLCFLQEERT FVKRKPRGIP EAQEVSEVCT TPGCVIAAAR ILQNMDPTTE PCDDFYQFAC 

       130        140        150        160        170        180 
GGWLRRHVIP ETNSRYSIFD VLRDELEVIL KAVLENSTAK DRPAVEKART LYRSCMNQSV 

       190        200        210        220        230        240 
IEKRGSQPLL DILEVVGGWP VAMDRWNETV GLEWELERQL ALMNSQFNRR VLIDLFIWND 

       250        260        270        280        290        300 
DQNSSRHIIY IDQPTLGMPS REYYFNGGSN RKVREAYLQF MVSVATLLRE DANLPRDSCL 

       310        320        330        340        350        360 
VQEDMVQVLE LETQLAKATV PQEERHDVIA LYHRMGLEEL QSQFGLKGFN WTLFIQTVLS 

       370        380        390        400        410        420 
SVKIKLLPDE EVVVYGIPYL QNLENIIDTY SARTIQNYLV WRLVLDRIGS LSQRFKDTRV 

       430        440        450        460        470        480 
NYRKALFGTM VEEVRWRECV GYVNSNMENA VGSLYVREAF PGDSKSMVRE LIDKVRTVFV 

       490        500        510        520        530        540 
ETLDELGWMD EESKKKAQEK AMSIREQIGH PDYILEEMNR RLDEEYSNLN FSEDLYFENS 

       550        560        570        580        590        600 
LQNLKVGAQR SLRKLREKVD PNLWIIGAAV VNAFYSPNRN QIVFPAGILQ PPFFSKEQPQ 

       610        620        630        640        650        660 
ALNFGGIGMV IGHEITHGFD DNGRNFDKNG NMMDWWSNFS TQHFREQSEC MIYQYGNYSW 

       670        680        690        700        710        720 
DLADEQNVNG FNTLGENIAD NGGVRQAYKA YLKWMAEGGK DQQLPGLDLT HEQLFFINYA 

       730        740        750        760        770 
QVWCGSYRPE FAIQSIKTDV HSPLKYRVLG SLQNLAAFAD TFHCARGTPM HPKERCRVW 

« Hide

Isoform 2 [UniParc].

Checksum: E3275B5EB05886BE
Show »

61169,930
Isoform 3 [UniParc].

Checksum: 1D6C960EE827051A
Show »

62271,092

References

« Hide 'large scale' references
[1]"Molecular cloning, tissue distribution, and chromosomal localization of MMEL2, a gene coding for a novel human member of the neutral endopeptidase-24.11 family."
Bonvouloir N., Lemieux N., Crine P., Boileau G., DesGroseillers L.
DNA Cell Biol. 20:493-498(2001) [PubMed: 11560781] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed: 16710414] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT THR-518.
+Additional computationally mapped references.

Cross-references

Sequence databases

AF336981 mRNA. Translation: AAL08942.1. Frameshift.
AL139246 Genomic DNA. No translation available.
AL589746, AL831784 Genomic DNA. Translation: CAI22652.1.
AL831784, AL589746 Genomic DNA. Translation: CAI17336.1.
BC101027 mRNA. Translation: AAI01028.2. Different initiation.
BC101028 mRNA. Translation: AAI01029.2.
BC101029 mRNA. Translation: AAI01030.1.
BC101030 mRNA. Translation: AAI01031.2. Different initiation.
UniGeneHs.591453

3D structure databases

ModBaseSearch...

Protein family/group databases

MEROPSM13.008.

PTM databases

PhosphoSiteQ495T6.

Genome annotation databases

EnsemblENSG00000142606. Homo sapiens. [Contig view]
KEGGhsa:79258.

Organism-specific databases

HGNCHGNC:14668. MMEL1.
HPAHPA007876.
HPA008205.
PharmGKBPA30865.
GenAtlasSearch...
GeneCardsSearch...

Phylogenomic databases

HOVERGENQ495T6.

Gene expression databases

CleanExHS_MMEL1.
GermOnlineENSG00000142606. Homo sapiens.

Family and domain databases

InterProIPR006025. Pept_M_Zn_BS.
IPR000718. Peptidase_M13.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERPTHR11733. Peptidase_M13. 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 Resources

NextBio68218.

Entry information

Entry nameMMEL1_HUMAN
AccessionPrimary (citable) accession number: Q495T6
Secondary accession number(s): Q495T7 expand/collapse secondary AC list , Q495T8, Q5SZS6, Q96PH9
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: November 25, 2008
This is version 35 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Peptidase families

Classification of peptidase families and list of entries

UniProtKB secondary accession numbers

Index of UniProtKB secondary accession numbers

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents