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Q495T6

- MMEL1_HUMAN

UniProt

Q495T6 - MMEL1_HUMAN

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Protein

Membrane metallo-endopeptidase-like 1

Gene
MMEL1, MELL1, MMEL2, NEP2
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein 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.

Catalytic activityi

Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.

Cofactori

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 – 742Cleavage By similarity
Binding sitei135 – 1351Substrate carboxyl By similarity
Metal bindingi613 – 6131Zinc; catalytic By similarity
Metal bindingi617 – 6171Zinc; catalytic By similarity
Active sitei620 – 6201 By similarity
Metal bindingi676 – 6761Zinc; catalytic By similarity
Active sitei680 – 6801Proton donor By similarity

GO - Molecular functioni

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

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Metal-binding, Zinc

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: Chromosome 1

Organism-specific databases

HGNCiHGNC:14668. MMEL1.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 2727Cytoplasmic Reviewed predictionAdd
BLAST
Transmembranei28 – 4821Helical; Signal-anchor for type II membrane protein; Reviewed predictionAdd
BLAST
Topological domaini49 – 779731Lumenal Reviewed predictionAdd
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.

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 form By similarityPRO_0000248416Add
BLAST

Amino acid modifications

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

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

ArrayExpressiQ495T6.
BgeeiQ495T6.
CleanExiHS_MMEL1.
GenevestigatoriQ495T6.

Organism-specific databases

HPAiCAB020786.
HPA007876.
HPA008205.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000288709.

Structurei

3D structure databases

ProteinModelPortaliQ495T6.
SMRiQ495T6. Positions 88-779.

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili515 – 56046 Reviewed predictionAdd
BLAST

Sequence similaritiesi

Belongs to the peptidase M13 family.

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG3590.
HOGENOMiHOG000245574.
HOVERGENiHBG005554.
InParanoidiQ495T6.
KOiK08635.
OMAiDGNMLDW.
OrthoDBiEOG7PZRWQ.
PhylomeDBiQ495T6.
TreeFamiTF315192.

Family and domain databases

Gene3Di3.40.390.10. 2 hits.
InterProiIPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view]
PANTHERiPTHR11733. PTHR11733. 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. Align

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

MGKSEGPVGM VESAGRAGQK RPGFLEGGLL LLLLLVTAAL VALGVLYADR    50
RGKQLPRLAS RLCFLQEERT FVKRKPRGIP EAQEVSEVCT TPGCVIAAAR 100
ILQNMDPTTE PCDDFYQFAC GGWLRRHVIP ETNSRYSIFD VLRDELEVIL 150
KAVLENSTAK DRPAVEKART LYRSCMNQSV IEKRGSQPLL DILEVVGGWP 200
VAMDRWNETV GLEWELERQL ALMNSQFNRR VLIDLFIWND DQNSSRHIIY 250
IDQPTLGMPS REYYFNGGSN RKVREAYLQF MVSVATLLRE DANLPRDSCL 300
VQEDMVQVLE LETQLAKATV PQEERHDVIA LYHRMGLEEL QSQFGLKGFN 350
WTLFIQTVLS SVKIKLLPDE EVVVYGIPYL QNLENIIDTY SARTIQNYLV 400
WRLVLDRIGS LSQRFKDTRV NYRKALFGTM VEEVRWRECV GYVNSNMENA 450
VGSLYVREAF PGDSKSMVRE LIDKVRTVFV ETLDELGWMD EESKKKAQEK 500
AMSIREQIGH PDYILEEMNR RLDEEYSNLN FSEDLYFENS LQNLKVGAQR 550
SLRKLREKVD PNLWIIGAAV VNAFYSPNRN QIVFPAGILQ PPFFSKEQPQ 600
ALNFGGIGMV IGHEITHGFD DNGRNFDKNG NMMDWWSNFS TQHFREQSEC 650
MIYQYGNYSW DLADEQNVNG FNTLGENIAD NGGVRQAYKA YLKWMAEGGK 700
DQQLPGLDLT HEQLFFINYA QVWCGSYRPE FAIQSIKTDV HSPLKYRVLG 750
SLQNLAAFAD TFHCARGTPM HPKERCRVW 779
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 AAL08942.1 differs from that shown. Reason: Frameshift at positions 7 and 8.
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.

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. VSP_020287Add
BLAST
Alternative sequencei583 – 61129VFPAG…IGMVI → AYSLSRPWGQYSLPGSSSPP SSARSSHRP in isoform 2. VSP_020288Add
BLAST
Alternative sequencei612 – 779168Missing in isoform 2. VSP_020289Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti351 – 3511W → R in AAI01029. 1 Publication
Sequence conflicti489 – 4891M → I in AAI01031. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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

EnsembliENST00000288709; ENSP00000288709; ENSG00000142606.
ENST00000378412; ENSP00000367668; ENSG00000142606. [Q495T6-1]
ENST00000502556; ENSP00000422492; ENSG00000142606. [Q495T6-3]
ENST00000504800; ENSP00000425477; ENSG00000142606. [Q495T6-2]
GeneIDi79258.
KEGGihsa:79258.
UCSCiuc001ajy.2. human. [Q495T6-1]

Polymorphism databases

DMDMi114150028.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSi CCDS30569.2. [Q495T6-1 ]
RefSeqi NP_258428.2. NM_033467.3. [Q495T6-1 ]
UniGenei Hs.591453.

3D structure databases

ProteinModelPortali Q495T6.
SMRi Q495T6. Positions 88-779.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000288709.

Protein family/group databases

MEROPSi M13.008.

PTM databases

PhosphoSitei Q495T6.

Polymorphism databases

DMDMi 114150028.

Proteomic databases

PaxDbi Q495T6.
PRIDEi Q495T6.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000288709 ; ENSP00000288709 ; ENSG00000142606 .
ENST00000378412 ; ENSP00000367668 ; ENSG00000142606 . [Q495T6-1 ]
ENST00000502556 ; ENSP00000422492 ; ENSG00000142606 . [Q495T6-3 ]
ENST00000504800 ; ENSP00000425477 ; ENSG00000142606 . [Q495T6-2 ]
GeneIDi 79258.
KEGGi hsa:79258.
UCSCi uc001ajy.2. human. [Q495T6-1 ]

Organism-specific databases

CTDi 79258.
GeneCardsi GC01M002557.
H-InvDB HIX0000061.
HGNCi HGNC:14668. MMEL1.
HPAi CAB020786.
HPA007876.
HPA008205.
neXtProti NX_Q495T6.
Orphaneti 186. Primary biliary cirrhosis.
PharmGKBi PA30865.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG3590.
HOGENOMi HOG000245574.
HOVERGENi HBG005554.
InParanoidi Q495T6.
KOi K08635.
OMAi DGNMLDW.
OrthoDBi EOG7PZRWQ.
PhylomeDBi Q495T6.
TreeFami TF315192.

Miscellaneous databases

GenomeRNAii 79258.
NextBioi 68218.
PROi Q495T6.

Gene expression databases

ArrayExpressi Q495T6.
Bgeei Q495T6.
CleanExi HS_MMEL1.
Genevestigatori Q495T6.

Family and domain databases

Gene3Di 3.40.390.10. 2 hits.
InterProi IPR024079. MetalloPept_cat_dom.
IPR000718. Peptidase_M13.
IPR018497. Peptidase_M13_C.
IPR008753. Peptidase_M13_N.
[Graphical view ]
PANTHERi PTHR11733. PTHR11733. 1 hit.
Pfami PF01431. Peptidase_M13. 1 hit.
PF05649. Peptidase_M13_N. 1 hit.
[Graphical view ]
PRINTSi PR00786. NEPRILYSIN.
PROSITEi PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: July 9, 2014
This is version 90 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

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