Q495T6 (MMEL1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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:

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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	779 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.

Ontologies

Keywords
Cellular component	Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil Signal-anchor Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	metalloendopeptidase activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 779	779	Membrane metallo-endopeptidase-like 1		PRO_0000248415
	Chain	74 – 779	706	Membrane metallo-endopeptidase-like 1, soluble form By similarity		PRO_0000248416
Regions
	Topological domain	1 – 27	27	Cytoplasmic Potential
	Transmembrane	28 – 48	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	49 – 779	731	Lumenal Potential
	Coiled coil	515 – 560	46	Potential
Sites
	Active site	620	1	By similarity
	Active site	680	1	Proton donor By similarity
	Metal binding	613	1	Zinc; catalytic By similarity
	Metal binding	617	1	Zinc; catalytic By similarity
	Metal binding	676	1	Zinc; catalytic By similarity
	Binding site	135	1	Substrate carboxyl By similarity
	Site	73 – 74	2	Cleavage By similarity
Amino acid modifications
	Glycosylation	177	1	N-linked (GlcNAc...) Potential
	Glycosylation	207	1	N-linked (GlcNAc...) Potential
	Glycosylation	350	1	N-linked (GlcNAc...) Potential
	Glycosylation	530	1	N-linked (GlcNAc...) Potential
	Glycosylation	657	1	N-linked (GlcNAc...) Potential
	Disulfide bond	89 ↔ 94		By similarity
	Disulfide bond	112 ↔ 764		By similarity
	Disulfide bond	120 ↔ 724		By similarity
	Disulfide bond	175 ↔ 439		By similarity
	Disulfide bond	650 ↔ 776		By similarity
Natural variations
	Alternative sequence	159 – 315	157	Missing in isoform 3.		VSP_020287
	Alternative sequence	583 – 611	29	VFPAG…IGMVI → AYSLSRPWGQYSLPGSSSPP SSARSSHRP in isoform 2.		VSP_020288
	Alternative sequence	612 – 779	168	Missing in isoform 2.		VSP_020289
	Natural variant	518	1	M → T. Ref.4 Corresponds to variant rs3748816 [ dbSNP | Ensembl ].		VAR_027348
Experimental info
	Sequence conflict	351	1	W → R in AAI01029. Ref.4
	Sequence conflict	489	1	M → I in AAI01031. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 5, 2006. Version 2. Checksum: 08C41819F4E81CBD	FASTA	779	89,367
	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
	Isoform 2 [UniParc]. Checksum: E3275B5EB05886BE	FASTA	611	69,930
	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 QIAYSLSRPW GQYSLPGSSS 610 PPSSARSSHR P
	Isoform 3 [UniParc]. Checksum: 1D6C960EE827051A	FASTA	622	71,092
	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 ATVPQEERHD VIALYHRMGL 190 200 210 220 230 240 EELQSQFGLK GFNWTLFIQT VLSSVKIKLL PDEEVVVYGI PYLQNLENII DTYSARTIQN 250 260 270 280 290 300 YLVWRLVLDR IGSLSQRFKD TRVNYRKALF GTMVEEVRWR ECVGYVNSNM ENAVGSLYVR 310 320 330 340 350 360 EAFPGDSKSM VRELIDKVRT VFVETLDELG WMDEESKKKA QEKAMSIREQ IGHPDYILEE 370 380 390 400 410 420 MNRRLDEEYS NLNFSEDLYF ENSLQNLKVG AQRSLRKLRE KVDPNLWIIG AAVVNAFYSP 430 440 450 460 470 480 NRNQIVFPAG ILQPPFFSKE QPQALNFGGI GMVIGHEITH GFDDNGRNFD KNGNMMDWWS 490 500 510 520 530 540 NFSTQHFREQ SECMIYQYGN YSWDLADEQN VNGFNTLGEN IADNGGVRQA YKAYLKWMAE 550 560 570 580 590 600 GGKDQQLPGL DLTHEQLFFI NYAQVWCGSY RPEFAIQSIK TDVHSPLKYR VLGSLQNLAA 610 620 FADTFHCARG TPMHPKERCR VW

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00044461. IPI00647257. IPI00785061.
RefSeq	NP_258428.2. NM_033467.3.
UniGene	Hs.591453.
3D structure databases
ProteinModelPortal	Q495T6.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000288709.
Protein family/group databases
MEROPS	M13.008.
PTM databases
PhosphoSite	Q495T6.
Polymorphism databases
DMDM	114150028.
Proteomic databases
PaxDb	Q495T6.
PRIDE	Q495T6.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000288709; ENSP00000288709; ENSG00000142606. ENST00000378412; ENSP00000367668; ENSG00000142606. ENST00000502556; ENSP00000422492; ENSG00000142606. ENST00000504800; ENSP00000425477; ENSG00000142606.
GeneID	79258.
KEGG	hsa:79258.
UCSC	uc001ajy.2. human.
Organism-specific databases
CTD	79258.
GeneCards	GC01M002557.
H-InvDB	HIX0000061.
HGNC	HGNC:14668. MMEL1.
HPA	CAB020786. HPA007876. HPA008205.
neXtProt	NX_Q495T6.
Orphanet	186. Primary biliary cirrhosis.
PharmGKB	PA30865.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG3590.
HOGENOM	HOG000245574.
HOVERGEN	HBG005554.
InParanoid	Q495T6.
KO	K08635.
OMA	CMNESLI.
OrthoDB	EOG4GXFM5.
Gene expression databases
Bgee	Q495T6.
CleanEx	HS_MMEL1.
Genevestigator	Q495T6.
GermOnline	ENSG00000142606. Homo sapiens.
Family and domain databases
Gene3D	3.40.390.10. 2 hits.
InterPro	IPR024079. MetalloPept_cat_dom. IPR000718. Peptidase_M13. IPR018497. Peptidase_M13_C. IPR008753. Peptidase_M13_N. [Graphical view]
PANTHER	PTHR11733. PTHR11733. 1 hit.
Pfam	PF01431. Peptidase_M13. 1 hit. PF05649. Peptidase_M13_N. 1 hit. [Graphical view]
PRINTS	PR00786. NEPRILYSIN.
PROSITE	PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	79258.
NextBio	68218.

Entry information

Entry name

MMEL1_HUMAN

Accession

Primary (citable) accession number: Q495T6
Secondary accession number(s): B9DI79 , Q495T7, Q495T8, Q5SZS6, Q96PH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 5, 2006
Last sequence update:	September 5, 2006
Last modified:	May 1, 2013
This is version 80 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.