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Q495T6 (MMEL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 88. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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):
Membrane metallo-endopeptidase-like 2
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, MMEL2, NEP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length779 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 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. Ref.1

Post-translational modification

N-glycosylated By similarity.

Sequence similarities

Belongs to the peptidase M13 family.

Sequence caution

The sequence AAI01028.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

The sequence AAI01031.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

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

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.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q495T6-3)

The sequence of this isoform differs from the canonical sequence as follows:
     159-315: Missing.
Note: 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 – 4821Helical; Signal-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. Ref.4
Corresponds to variant rs3748816 [ dbSNP | Ensembl ].
VAR_027348

Experimental info

Sequence conflict3511W → R in AAI01029. Ref.4
Sequence conflict4891M → I in AAI01031. Ref.4

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 »

FASTA61169,930
Isoform 3 [UniParc].

Checksum: 1D6C960EE827051A
Show »

FASTA62271,092

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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]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 (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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 1; 2 AND 3), VARIANT THR-518.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF336981 mRNA. Translation: AAL08942.1. Frameshift.
AL139246, AL589746, AL831784 Genomic DNA. Translation: CAX30814.1.
AL589746, AL831784 Genomic DNA. Translation: CAI22652.1.
AL831784, AL589746 Genomic DNA. Translation: CAI17336.1.
CH471183 Genomic DNA. Translation: EAW56082.1.
BC101027 mRNA. Translation: AAI01028.2. Different initiation.
BC101028 mRNA. Translation: AAI01029.2.
BC101029 mRNA. Translation: AAI01030.1.
BC101030 mRNA. Translation: AAI01031.2. Different initiation.
RefSeqNP_258428.2. NM_033467.3.
UniGeneHs.591453.

3D structure databases

ProteinModelPortalQ495T6.
SMRQ495T6. Positions 88-779.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000288709.

Protein family/group databases

MEROPSM13.008.

PTM databases

PhosphoSiteQ495T6.

Polymorphism databases

DMDM114150028.

Proteomic databases

PaxDbQ495T6.
PRIDEQ495T6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000288709; ENSP00000288709; ENSG00000142606.
ENST00000378412; ENSP00000367668; ENSG00000142606. [Q495T6-1]
ENST00000502556; ENSP00000422492; ENSG00000142606. [Q495T6-3]
ENST00000504800; ENSP00000425477; ENSG00000142606. [Q495T6-2]
GeneID79258.
KEGGhsa:79258.
UCSCuc001ajy.2. human. [Q495T6-1]

Organism-specific databases

CTD79258.
GeneCardsGC01M002557.
H-InvDBHIX0000061.
HGNCHGNC:14668. MMEL1.
HPACAB020786.
HPA007876.
HPA008205.
neXtProtNX_Q495T6.
Orphanet186. Primary biliary cirrhosis.
PharmGKBPA30865.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3590.
HOGENOMHOG000245574.
HOVERGENHBG005554.
InParanoidQ495T6.
KOK08635.
OMAPVAMDKW.
OrthoDBEOG7PZRWQ.
PhylomeDBQ495T6.
TreeFamTF315192.

Gene expression databases

ArrayExpressQ495T6.
BgeeQ495T6.
CleanExHS_MMEL1.
GenevestigatorQ495T6.

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

GenomeRNAi79258.
NextBio68218.
PROQ495T6.

Entry information

Entry nameMMEL1_HUMAN
AccessionPrimary (citable) accession number: Q495T6
Secondary accession number(s): B9DI79 expand/collapse secondary AC list , Q495T7, Q495T8, Q5SZS6, Q96PH9
Entry history
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: April 16, 2014
This is version 88 of the entry and version 2 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

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 1

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