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UniProtKB - Q495T6 (MMEL1_HUMAN)

Protein

Membrane metallo-endopeptidase-like 1

Gene

MMEL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Activity regulationi

Inhibited by thiorphan and phosphoramidon.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei135Substrate carboxylBy similarity1
Metal bindingi613Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi617Zinc; catalyticPROSITE-ProRule annotation1
Active sitei620PROSITE-ProRule annotation1
Metal bindingi676Zinc; catalyticPROSITE-ProRule annotation1
Active sitei680Proton donorPROSITE-ProRule annotation1

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandMetal-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:
Membrane metallo-endopeptidase-like 1, soluble form
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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000142606.15
HGNCiHGNC:14668 MMEL1
MIMi618104 gene
neXtProtiNX_Q495T6

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 27CytoplasmicSequence analysisAdd BLAST27
Transmembranei28 – 48Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini49 – 779LumenalSequence analysisAdd BLAST731

Keywords - Cellular componenti

Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi79258
MalaCardsiMMEL1
OpenTargetsiENSG00000142606
Orphaneti186 Primary biliary cholangitis
PharmGKBiPA30865

Chemistry databases

ChEMBLiCHEMBL3638356

Polymorphism and mutation databases

BioMutaiMMEL1
DMDMi114150028

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002484151 – 779Membrane metallo-endopeptidase-like 1Add BLAST779
ChainiPRO_000024841674 – 779Membrane metallo-endopeptidase-like 1, soluble formBy similarityAdd BLAST706

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi89 ↔ 94By similarity
Disulfide bondi112 ↔ 764By similarity
Disulfide bondi120 ↔ 724By similarity
Disulfide bondi175 ↔ 439By similarity
Glycosylationi177N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi207N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi350N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi530N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi650 ↔ 776By similarity
Glycosylationi657N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

N-glycosylated.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei73 – 74CleavageBy similarity2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ495T6
PeptideAtlasiQ495T6
PRIDEiQ495T6
ProteomicsDBi61971
61972 [Q495T6-2]
61973 [Q495T6-3]

PTM databases

iPTMnetiQ495T6
PhosphoSitePlusiQ495T6

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000142606 Expressed in 131 organ(s), highest expression level in testis
CleanExiHS_MMEL1
ExpressionAtlasiQ495T6 baseline and differential
GenevisibleiQ495T6 HS

Organism-specific databases

HPAiCAB020786
HPA007876
HPA008205

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000367668

Chemistry databases

BindingDBiQ495T6

Structurei

3D structure databases

ProteinModelPortaliQ495T6
SMRiQ495T6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili515 – 560Sequence analysisAdd BLAST46

Sequence similaritiesi

Belongs to the peptidase M13 family.Curated

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3624 Eukaryota
COG3590 LUCA
GeneTreeiENSGT00760000119162
HOGENOMiHOG000245574
HOVERGENiHBG005554
InParanoidiQ495T6
KOiK08635
OMAiADAFHCA
OrthoDBiEOG091G025Y
PhylomeDBiQ495T6
TreeFamiTF315192

Family and domain databases

CDDicd08662 M13, 1 hit
Gene3Di3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR024079 MetalloPept_cat_dom_sf
IPR029735 MMEL1
IPR000718 Peptidase_M13
IPR018497 Peptidase_M13_C
IPR008753 Peptidase_M13_N
PANTHERiPTHR11733 PTHR11733, 1 hit
PTHR11733:SF141 PTHR11733:SF141, 1 hit
PfamiView protein in Pfam
PF01431 Peptidase_M13, 1 hit
PF05649 Peptidase_M13_N, 1 hit
PRINTSiPR00786 NEPRILYSIN
PROSITEiView protein in PROSITE
PS00142 ZINC_PROTEASE, 1 hit

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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3KRD2J3KRD2_HUMAN
Membrane metallo-endopeptidase-like...
MMEL1
66Annotation score:

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti351W → R in AAI01029 (PubMed:15489334).Curated1
Sequence conflicti489M → I in AAI01031 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027348518M → T1 PublicationCorresponds to variant dbSNP:rs3748816Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_020287159 – 315Missing in isoform 3. 1 PublicationAdd BLAST157
Alternative sequenceiVSP_020288583 – 611VFPAG…IGMVI → AYSLSRPWGQYSLPGSSSPP SSARSSHRP in isoform 2. 1 PublicationAdd BLAST29
Alternative sequenceiVSP_020289612 – 779Missing in isoform 2. 1 PublicationAdd BLAST168

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF336981 mRNA Translation: AAL08942.1 Frameshift.
AL139246 Genomic DNA No translation available.
AL589746 Genomic DNA No translation available.
AL831784 Genomic DNA No translation available.
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]
XP_016857799.1, XM_017002310.1 [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]
ENST00000628503; ENSP00000486668; ENSG00000277131 [Q495T6-2]
GeneIDi79258
KEGGihsa:79258
UCSCiuc001ajy.3 human [Q495T6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF336981 mRNA Translation: AAL08942.1 Frameshift.
AL139246 Genomic DNA No translation available.
AL589746 Genomic DNA No translation available.
AL831784 Genomic DNA No translation available.
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]
XP_016857799.1, XM_017002310.1 [Q495T6-1]
UniGeneiHs.591453

3D structure databases

ProteinModelPortaliQ495T6
SMRiQ495T6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000367668

Chemistry databases

BindingDBiQ495T6
ChEMBLiCHEMBL3638356

Protein family/group databases

MEROPSiM13.008

PTM databases

iPTMnetiQ495T6
PhosphoSitePlusiQ495T6

Polymorphism and mutation databases

BioMutaiMMEL1
DMDMi114150028

Proteomic databases

PaxDbiQ495T6
PeptideAtlasiQ495T6
PRIDEiQ495T6
ProteomicsDBi61971
61972 [Q495T6-2]
61973 [Q495T6-3]

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]
ENST00000628503; ENSP00000486668; ENSG00000277131 [Q495T6-2]
GeneIDi79258
KEGGihsa:79258
UCSCiuc001ajy.3 human [Q495T6-1]

Organism-specific databases

CTDi79258
DisGeNETi79258
EuPathDBiHostDB:ENSG00000142606.15
GeneCardsiMMEL1
H-InvDBiHIX0000061
HGNCiHGNC:14668 MMEL1
HPAiCAB020786
HPA007876
HPA008205
MalaCardsiMMEL1
MIMi618104 gene
neXtProtiNX_Q495T6
OpenTargetsiENSG00000142606
Orphaneti186 Primary biliary cholangitis
PharmGKBiPA30865
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3624 Eukaryota
COG3590 LUCA
GeneTreeiENSGT00760000119162
HOGENOMiHOG000245574
HOVERGENiHBG005554
InParanoidiQ495T6
KOiK08635
OMAiADAFHCA
OrthoDBiEOG091G025Y
PhylomeDBiQ495T6
TreeFamiTF315192

Enzyme and pathway databases

BRENDAi3.4.24.B14 2681

Miscellaneous databases

ChiTaRSiMMEL1 human
GenomeRNAii79258
PROiPR:Q495T6
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000142606 Expressed in 131 organ(s), highest expression level in testis
CleanExiHS_MMEL1
ExpressionAtlasiQ495T6 baseline and differential
GenevisibleiQ495T6 HS

Family and domain databases

CDDicd08662 M13, 1 hit
Gene3Di3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR024079 MetalloPept_cat_dom_sf
IPR029735 MMEL1
IPR000718 Peptidase_M13
IPR018497 Peptidase_M13_C
IPR008753 Peptidase_M13_N
PANTHERiPTHR11733 PTHR11733, 1 hit
PTHR11733:SF141 PTHR11733:SF141, 1 hit
PfamiView protein in Pfam
PF01431 Peptidase_M13, 1 hit
PF05649 Peptidase_M13_N, 1 hit
PRINTSiPR00786 NEPRILYSIN
PROSITEiView protein in PROSITE
PS00142 ZINC_PROTEASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMMEL1_HUMAN
AccessioniPrimary (citable) accession number: Q495T6
Secondary accession number(s): B9DI79
, Q495T7, Q495T8, Q5SZS6, Q96PH9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: September 5, 2006
Last modified: November 7, 2018
This is version 124 of the entry and version 2 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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