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Protein

Membrane metallo-endopeptidase-like 1

Gene

MMEL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei73 – 742CleavageBy similarity
Binding sitei135 – 1351Substrate carboxylBy similarity
Metal bindingi613 – 6131Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi617 – 6171Zinc; catalyticPROSITE-ProRule annotation
Active sitei620 – 6201PROSITE-ProRule annotation
Metal bindingi676 – 6761Zinc; catalyticPROSITE-ProRule annotation
Active sitei680 – 6801Proton donorPROSITE-ProRule annotation

GO - Molecular functioni

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

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BRENDAi3.4.24.B14. 2681.

Protein family/group databases

MEROPSiM13.008.

Names & Taxonomyi

Protein namesi
Recommended 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:
Alternative name(s):
Neprilysin-2 secreted
Short name:
NEP2(s)
Gene namesi
Name:MMEL1
Synonyms:MELL1, MMEL2, NEP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componentsi: Chromosome 1, Unplaced

Organism-specific databases

HGNCiHGNC:14668. MMEL1.

Subcellular locationi

  1. Membrane; Single-pass type II membrane protein
  2. Secreted

  3. Note: A secreted form produced by proteollytic cleavage also exists.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2727CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei28 – 4821Helical; Signal-anchor for type II membrane proteinSequence AnalysisAdd
BLAST
Topological domaini49 – 779731LumenalSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

Orphaneti186. Primary biliary cirrhosis.
PharmGKBiPA30865.

Polymorphism and mutation databases

BioMutaiMMEL1.
DMDMi114150028.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 779779Membrane metallo-endopeptidase-like 1PRO_0000248415Add
BLAST
Chaini74 – 779706Membrane metallo-endopeptidase-like 1, soluble formBy similarityPRO_0000248416Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi89 ↔ 94By similarity
Disulfide bondi112 ↔ 764By similarity
Disulfide bondi120 ↔ 724By similarity
Disulfide bondi175 ↔ 439By similarity
Glycosylationi177 – 1771N-linked (GlcNAc...)Sequence Analysis
Glycosylationi207 – 2071N-linked (GlcNAc...)Sequence Analysis
Glycosylationi350 – 3501N-linked (GlcNAc...)Sequence Analysis
Glycosylationi530 – 5301N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi650 ↔ 776By similarity
Glycosylationi657 – 6571N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

N-glycosylated.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ495T6.
PRIDEiQ495T6.

PTM databases

PhosphoSiteiQ495T6.

Expressioni

Tissue specificityi

Predominantly expressed in testis. Weakly expressed in brain, kidney and heart.1 Publication

Gene expression databases

BgeeiQ495T6.
CleanExiHS_MMEL1.
ExpressionAtlasiQ495T6. baseline and differential.
GenevestigatoriQ495T6.

Organism-specific databases

HPAiCAB020786.
HPA007876.
HPA008205.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000288709.

Structurei

3D structure databases

ProteinModelPortaliQ495T6.
SMRiQ495T6. Positions 88-779.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili515 – 56046Sequence AnalysisAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase M13 family.Curated

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG3590.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiQ495T6.
KOiK08635.
OMAiKAYLKWM.
OrthoDBiEOG7PZRWQ.
PhylomeDBiQ495T6.
TreeFamiTF315192.

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 (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q495T6-1) [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
MGKSEGPVGM VESAGRAGQK RPGFLEGGLL LLLLLVTAAL VALGVLYADR
60 70 80 90 100
RGKQLPRLAS RLCFLQEERT FVKRKPRGIP EAQEVSEVCT TPGCVIAAAR
110 120 130 140 150
ILQNMDPTTE PCDDFYQFAC GGWLRRHVIP ETNSRYSIFD VLRDELEVIL
160 170 180 190 200
KAVLENSTAK DRPAVEKART LYRSCMNQSV IEKRGSQPLL DILEVVGGWP
210 220 230 240 250
VAMDRWNETV GLEWELERQL ALMNSQFNRR VLIDLFIWND DQNSSRHIIY
260 270 280 290 300
IDQPTLGMPS REYYFNGGSN RKVREAYLQF MVSVATLLRE DANLPRDSCL
310 320 330 340 350
VQEDMVQVLE LETQLAKATV PQEERHDVIA LYHRMGLEEL QSQFGLKGFN
360 370 380 390 400
WTLFIQTVLS SVKIKLLPDE EVVVYGIPYL QNLENIIDTY SARTIQNYLV
410 420 430 440 450
WRLVLDRIGS LSQRFKDTRV NYRKALFGTM VEEVRWRECV GYVNSNMENA
460 470 480 490 500
VGSLYVREAF PGDSKSMVRE LIDKVRTVFV ETLDELGWMD EESKKKAQEK
510 520 530 540 550
AMSIREQIGH PDYILEEMNR RLDEEYSNLN FSEDLYFENS LQNLKVGAQR
560 570 580 590 600
SLRKLREKVD PNLWIIGAAV VNAFYSPNRN QIVFPAGILQ PPFFSKEQPQ
610 620 630 640 650
ALNFGGIGMV IGHEITHGFD DNGRNFDKNG NMMDWWSNFS TQHFREQSEC
660 670 680 690 700
MIYQYGNYSW DLADEQNVNG FNTLGENIAD NGGVRQAYKA YLKWMAEGGK
710 720 730 740 750
DQQLPGLDLT HEQLFFINYA QVWCGSYRPE FAIQSIKTDV HSPLKYRVLG
760 770
SLQNLAAFAD TFHCARGTPM HPKERCRVW
Length:779
Mass (Da):89,367
Last modified:September 5, 2006 - v2
Checksum:i08C41819F4E81CBD
GO
Isoform 2 (identifier: Q495T6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     583-611: VFPAGILQPPFFSKEQPQALNFGGIGMVI → AYSLSRPWGQYSLPGSSSPPSSARSSHRP
     612-779: Missing.

Note: No experimental confirmation available.

Show »
Length:611
Mass (Da):69,930
Checksum:iE3275B5EB05886BE
GO
Isoform 3 (identifier: Q495T6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     159-315: Missing.

Note: No experimental confirmation available.

Show »
Length:622
Mass (Da):71,092
Checksum:i1D6C960EE827051A
GO

Sequence cautioni

The sequence AAI01028.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAI01031.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAL08942.1 differs from that shown. Reason: Frameshift at positions 7 and 8. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti351 – 3511W → R in AAI01029 (PubMed:15489334).Curated
Sequence conflicti489 – 4891M → I in AAI01031 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti518 – 5181M → T.1 Publication
Corresponds to variant rs3748816 [ dbSNP | Ensembl ].
VAR_027348

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei159 – 315157Missing in isoform 3. 1 PublicationVSP_020287Add
BLAST
Alternative sequencei583 – 61129VFPAG…IGMVI → AYSLSRPWGQYSLPGSSSPP SSARSSHRP in isoform 2. 1 PublicationVSP_020288Add
BLAST
Alternative sequencei612 – 779168Missing in isoform 2. 1 PublicationVSP_020289Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS30569.2. [Q495T6-1]
RefSeqiNP_258428.2. NM_033467.3. [Q495T6-1]
UniGeneiHs.591453.

Genome annotation databases

EnsembliENST00000378412; ENSP00000367668; ENSG00000142606. [Q495T6-1]
ENST00000502556; ENSP00000422492; ENSG00000142606. [Q495T6-3]
ENST00000504800; ENSP00000425477; ENSG00000142606. [Q495T6-2]
ENST00000611357; ENSP00000484606; ENSG00000277131. [Q495T6-1]
ENST00000621908; ENSP00000482173; ENSG00000277131. [Q495T6-3]
GeneIDi79258.
KEGGihsa:79258.
UCSCiuc001ajy.2. human. [Q495T6-1]

Polymorphism and mutation databases

BioMutaiMMEL1.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS30569.2. [Q495T6-1]
RefSeqiNP_258428.2. NM_033467.3. [Q495T6-1]
UniGeneiHs.591453.

3D structure databases

ProteinModelPortaliQ495T6.
SMRiQ495T6. Positions 88-779.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000288709.

Protein family/group databases

MEROPSiM13.008.

PTM databases

PhosphoSiteiQ495T6.

Polymorphism and mutation databases

BioMutaiMMEL1.
DMDMi114150028.

Proteomic databases

PaxDbiQ495T6.
PRIDEiQ495T6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000378412; ENSP00000367668; ENSG00000142606. [Q495T6-1]
ENST00000502556; ENSP00000422492; ENSG00000142606. [Q495T6-3]
ENST00000504800; ENSP00000425477; ENSG00000142606. [Q495T6-2]
ENST00000611357; ENSP00000484606; ENSG00000277131. [Q495T6-1]
ENST00000621908; ENSP00000482173; ENSG00000277131. [Q495T6-3]
GeneIDi79258.
KEGGihsa:79258.
UCSCiuc001ajy.2. human. [Q495T6-1]

Organism-specific databases

CTDi79258.
GeneCardsiGC01M002557.
H-InvDBHIX0000061.
HGNCiHGNC:14668. MMEL1.
HPAiCAB020786.
HPA007876.
HPA008205.
neXtProtiNX_Q495T6.
Orphaneti186. Primary biliary cirrhosis.
PharmGKBiPA30865.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG3590.
GeneTreeiENSGT00760000119162.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiQ495T6.
KOiK08635.
OMAiKAYLKWM.
OrthoDBiEOG7PZRWQ.
PhylomeDBiQ495T6.
TreeFamiTF315192.

Enzyme and pathway databases

BRENDAi3.4.24.B14. 2681.

Miscellaneous databases

ChiTaRSiMMEL1. human.
GenomeRNAii79258.
NextBioi68218.
PROiQ495T6.

Gene expression databases

BgeeiQ495T6.
CleanExiHS_MMEL1.
ExpressionAtlasiQ495T6. baseline and differential.
GenevestigatoriQ495T6.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.

Entry informationi

Entry nameiMMEL1_HUMAN
AccessioniPrimary (citable) accession number: Q495T6
Secondary accession number(s): B9DI79
, Q495T7, Q495T8, Q5SZS6, Q96PH9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: April 29, 2015
This is version 96 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.