UniProtKB - Q495T6 (MMEL1_HUMAN)
Protein
Membrane metallo-endopeptidase-like 1
Gene
MMEL1
Organism
Homo sapiens (Human)
Status
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'. EC:3.4.24.11
Cofactori
Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
Activity regulationi
Inhibited by thiorphan and phosphoramidon.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 135 | Substrate carboxylBy similarity | 1 | |
Metal bindingi | 613 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Active sitei | 614 | PROSITE-ProRule annotation | 1 | |
Metal bindingi | 617 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 676 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Active sitei | 680 | Proton donorPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- endopeptidase activity Source: ARUK-UCL
- metal ion binding Source: UniProtKB-KW
- metalloendopeptidase activity Source: UniProtKB-EC
GO - Biological processi
- proteolysis Source: ARUK-UCL
Keywordsi
Molecular function | Hydrolase, Metalloprotease, Protease |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.4.24.B14, 2681 |
PathwayCommonsi | Q495T6 |
Protein family/group databases
MEROPSi | M13.008 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000142606.15 |
HGNCi | HGNC:14668, MMEL1 |
MIMi | 618104, gene |
neXtProti | NX_Q495T6 |
Subcellular locationi
Extracellular region or secreted
Other locations
Note: A secreted form produced by proteolytic cleavage also exists.By similarity
Extracellular region or secreted
- extracellular space Source: ARUK-UCL
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: ARUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 1 – 27 | CytoplasmicSequence analysisAdd BLAST | 27 | |
Transmembranei | 28 – 48 | Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST | 21 | |
Topological domaini | 49 – 779 | LumenalSequence analysisAdd BLAST | 731 |
Keywords - Cellular componenti
Membrane, SecretedPathology & Biotechi
Organism-specific databases
DisGeNETi | 79258 |
MalaCardsi | MMEL1 |
OpenTargetsi | ENSG00000142606 |
Orphaneti | 186, Primary biliary cholangitis |
PharmGKBi | PA30865 |
Miscellaneous databases
Pharosi | Q495T6, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3638356 |
Polymorphism and mutation databases
BioMutai | MMEL1 |
DMDMi | 114150028 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000248415 | 1 – 779 | Membrane metallo-endopeptidase-like 1Add BLAST | 779 | |
ChainiPRO_0000248416 | 74 – 779 | Membrane metallo-endopeptidase-like 1, soluble formBy similarityAdd BLAST | 706 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 89 ↔ 94 | PROSITE-ProRule annotation | ||
Disulfide bondi | 112 ↔ 764 | PROSITE-ProRule annotation | ||
Disulfide bondi | 120 ↔ 724 | PROSITE-ProRule annotation | ||
Disulfide bondi | 175 ↔ 439 | PROSITE-ProRule annotation | ||
Glycosylationi | 177 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 207 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 350 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 530 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 650 ↔ 776 | PROSITE-ProRule annotation | ||
Glycosylationi | 657 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
N-glycosylated.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 73 – 74 | CleavageBy similarity | 2 |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
jPOSTi | Q495T6 |
MassIVEi | Q495T6 |
PaxDbi | Q495T6 |
PeptideAtlasi | Q495T6 |
PRIDEi | Q495T6 |
ProteomicsDBi | 61971 [Q495T6-1] 61972 [Q495T6-2] 61973 [Q495T6-3] |
PTM databases
GlyGeni | Q495T6, 5 sites |
iPTMneti | Q495T6 |
PhosphoSitePlusi | Q495T6 |
Expressioni
Tissue specificityi
Predominantly expressed in testis. Weakly expressed in brain, kidney and heart.1 Publication
Gene expression databases
Bgeei | ENSG00000142606, Expressed in testis and 150 other tissues |
ExpressionAtlasi | Q495T6, baseline and differential |
Genevisiblei | Q495T6, HS |
Organism-specific databases
HPAi | ENSG00000142606, Tissue enhanced (testis) |
Interactioni
Protein-protein interaction databases
IntActi | Q495T6, 1 interactor |
STRINGi | 9606.ENSP00000367668 |
Chemistry databases
BindingDBi | Q495T6 |
Miscellaneous databases
RNActi | Q495T6, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 88 – 779 | Peptidase M13PROSITE-ProRule annotationAdd BLAST | 692 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 515 – 560 | Sequence analysisAdd BLAST | 46 |
Sequence similaritiesi
Keywords - Domaini
Coiled coil, Signal-anchor, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3624, Eukaryota |
GeneTreei | ENSGT00940000157799 |
HOGENOMi | CLU_006187_4_1_1 |
InParanoidi | Q495T6 |
OMAi | WMDAPSK |
OrthoDBi | 282463at2759 |
PhylomeDBi | Q495T6 |
TreeFami | TF315192 |
Family and domain databases
CDDi | cd08662, M13, 1 hit |
Gene3Di | 1.10.1380.10, 1 hit 3.40.390.10, 1 hit |
InterProi | View protein in InterPro IPR024079, MetalloPept_cat_dom_sf IPR029735, MMEL1 IPR000718, Peptidase_M13 IPR018497, Peptidase_M13_C IPR042089, Peptidase_M13_dom_2 IPR008753, Peptidase_M13_N |
PANTHERi | PTHR11733, PTHR11733, 1 hit PTHR11733:SF141, PTHR11733:SF141, 1 hit |
Pfami | View protein in Pfam PF01431, Peptidase_M13, 1 hit PF05649, Peptidase_M13_N, 1 hit |
PRINTSi | PR00786, NEPRILYSIN |
PROSITEi | View protein in PROSITE PS51885, NEPRILYSIN, 1 hit PS00142, ZINC_PROTEASE, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketJ3KRD2 | J3KRD2_HUMAN | Membrane metallo-endopeptidase-like... | MMEL1 | 66 | Annotation score: |
Sequence cautioni
The sequence AAI01028 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAI01031 differs from that shown. Reason: Erroneous initiation. Truncated N-terminus.Curated
The sequence AAL08942 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 351 | W → R in AAI01029 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 489 | M → I in AAI01031 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_027348 | 518 | M → T1 PublicationCorresponds to variant dbSNP:rs3748816Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_020287 | 159 – 315 | Missing in isoform 3. 1 PublicationAdd BLAST | 157 | |
Alternative sequenceiVSP_020288 | 583 – 611 | VFPAG…IGMVI → AYSLSRPWGQYSLPGSSSPP SSARSSHRP in isoform 2. 1 PublicationAdd BLAST | 29 | |
Alternative sequenceiVSP_020289 | 612 – 779 | Missing in isoform 2. 1 PublicationAdd BLAST | 168 |
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. |
CCDSi | CCDS30569.2 [Q495T6-1] |
RefSeqi | NP_258428.2, NM_033467.3 [Q495T6-1] XP_016857799.1, XM_017002310.1 [Q495T6-1] |
Genome annotation databases
Ensembli | ENST00000378412; 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] |
GeneIDi | 79258 |
KEGGi | hsa:79258 |
UCSCi | uc001ajy.3, human [Q495T6-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar 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. |
CCDSi | CCDS30569.2 [Q495T6-1] |
RefSeqi | NP_258428.2, NM_033467.3 [Q495T6-1] XP_016857799.1, XM_017002310.1 [Q495T6-1] |
3D structure databases
SMRi | Q495T6 |
ModBasei | Search... |
Protein-protein interaction databases
IntActi | Q495T6, 1 interactor |
STRINGi | 9606.ENSP00000367668 |
Chemistry databases
BindingDBi | Q495T6 |
ChEMBLi | CHEMBL3638356 |
Protein family/group databases
MEROPSi | M13.008 |
PTM databases
GlyGeni | Q495T6, 5 sites |
iPTMneti | Q495T6 |
PhosphoSitePlusi | Q495T6 |
Polymorphism and mutation databases
BioMutai | MMEL1 |
DMDMi | 114150028 |
Proteomic databases
jPOSTi | Q495T6 |
MassIVEi | Q495T6 |
PaxDbi | Q495T6 |
PeptideAtlasi | Q495T6 |
PRIDEi | Q495T6 |
ProteomicsDBi | 61971 [Q495T6-1] 61972 [Q495T6-2] 61973 [Q495T6-3] |
Protocols and materials databases
Antibodypediai | 1624, 155 antibodies |
Genome annotation databases
Ensembli | ENST00000378412; 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] |
GeneIDi | 79258 |
KEGGi | hsa:79258 |
UCSCi | uc001ajy.3, human [Q495T6-1] |
Organism-specific databases
CTDi | 79258 |
DisGeNETi | 79258 |
EuPathDBi | HostDB:ENSG00000142606.15 |
GeneCardsi | MMEL1 |
HGNCi | HGNC:14668, MMEL1 |
HPAi | ENSG00000142606, Tissue enhanced (testis) |
MalaCardsi | MMEL1 |
MIMi | 618104, gene |
neXtProti | NX_Q495T6 |
OpenTargetsi | ENSG00000142606 |
Orphaneti | 186, Primary biliary cholangitis |
PharmGKBi | PA30865 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3624, Eukaryota |
GeneTreei | ENSGT00940000157799 |
HOGENOMi | CLU_006187_4_1_1 |
InParanoidi | Q495T6 |
OMAi | WMDAPSK |
OrthoDBi | 282463at2759 |
PhylomeDBi | Q495T6 |
TreeFami | TF315192 |
Enzyme and pathway databases
BRENDAi | 3.4.24.B14, 2681 |
PathwayCommonsi | Q495T6 |
Miscellaneous databases
BioGRID-ORCSi | 79258, 6 hits in 842 CRISPR screens |
ChiTaRSi | MMEL1, human |
GenomeRNAii | 79258 |
Pharosi | Q495T6, Tchem |
PROi | PR:Q495T6 |
RNActi | Q495T6, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000142606, Expressed in testis and 150 other tissues |
ExpressionAtlasi | Q495T6, baseline and differential |
Genevisiblei | Q495T6, HS |
Family and domain databases
CDDi | cd08662, M13, 1 hit |
Gene3Di | 1.10.1380.10, 1 hit 3.40.390.10, 1 hit |
InterProi | View protein in InterPro IPR024079, MetalloPept_cat_dom_sf IPR029735, MMEL1 IPR000718, Peptidase_M13 IPR018497, Peptidase_M13_C IPR042089, Peptidase_M13_dom_2 IPR008753, Peptidase_M13_N |
PANTHERi | PTHR11733, PTHR11733, 1 hit PTHR11733:SF141, PTHR11733:SF141, 1 hit |
Pfami | View protein in Pfam PF01431, Peptidase_M13, 1 hit PF05649, Peptidase_M13_N, 1 hit |
PRINTSi | PR00786, NEPRILYSIN |
PROSITEi | View protein in PROSITE PS51885, NEPRILYSIN, 1 hit PS00142, ZINC_PROTEASE, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MMEL1_HUMAN | |
Accessioni | Q495T6Primary (citable) accession number: Q495T6 Secondary accession number(s): B9DI79 Q96PH9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 5, 2006 |
Last sequence update: | September 5, 2006 | |
Last modified: | December 2, 2020 | |
This is version 138 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - 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 - Peptidase families
Classification of peptidase families and list of entries