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Q61847 (MEP1B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Meprin A subunit beta

EC=3.4.24.63
Alternative name(s):
Endopeptidase-2
Meprin B
Gene names
Name:Mep1b
Synonyms:Mep-1b
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length704 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Membrane metallopeptidase that sheds many membrane-bound proteins. Known substrates include: FGF19, VGFA, IL1B, IL18, procollagen I and III, E-cadherin, KLK7, gastrin, ADAM10, tenascin-C. The presence of several pro-inflammatory cytokine among substrates implicate MEP1B in inflammation. It is also involved in tissue remodeling due to its capability to degrade extracellular matrix components By similarity.

Catalytic activity

Hydrolysis of proteins, including azocasein, and peptides. Hydrolysis of 5-His-|-Leu-6, 6-Leu-|-Cys-7, 14-Ala-|-Leu-15 and 19-Cys-|-Gly-20 bonds in insulin B chain. Exhibits a strong preference for acidic amino acids at the P1' position. Ref.5 Ref.7

Cofactor

Binds 1 zinc ion per subunit By similarity.

Enzyme regulation

Strongly inhibited by fetuin-A/AHSG By similarity. Inhibited by cysteine and by the metal ion chelators EDTA and 1,10-phenanthroline. Not inhibited by 3,4-dichloroisocourmarin, soybean trypsin inhibitor, or the cysteine proteinase inhibitors iodoacetic acid and E-64. Ref.5

Subunit structure

Homotetramer consisting of disulfide-linked beta subunits, or heterotetramer of two alpha and two beta subunits formed by non-covalent association of two disulfide-linked heterodimers. Interacts with MBL2 through its carbohydrate moiety. This interaction may inhibit its catalytic activity. Ref.6 Ref.8

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

Isoform 1 is expressed in kidney, intestinal brush borders, and salivary ducts. Isoform 2 has been found in carcinoma cells.

Induction

By retinoic acid. Ref.5

Post-translational modification

Proteolytically activated by trypsin in the intestinal lumen and kallikrein-related peptidases in other tissues By similarity.

N-glycosylated; contains high mannose and/or complex biantennary structures. Ref.5

Sequence similarities

Belongs to the peptidase M12A family.

Contains 1 EGF-like domain.

Contains 1 MAM domain.

Contains 1 MATH domain.

Biophysicochemical properties

Temperature dependence:

The half-life at 58 degrees Celsius is less than 3 minutes. Ref.5

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q61847-1)

Also known as: Beta;

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: Q61847-2)

Also known as: Beta';

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MDARHQPWFLVFATFLLVSGLPAPEKF → MNSTAGPASRSRHSFKCRMKLLKAPRDGMYMMTFG

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2020 Potential
Propeptide21 – 6444 By similarity
PRO_0000028885
Chain65 – 704640Meprin A subunit beta
PRO_0000028886

Regions

Topological domain21 – 654634Extracellular Potential
Transmembrane655 – 67824Helical; Potential
Topological domain679 – 70426Cytoplasmic Potential
Domain261 – 430170MAM
Domain431 – 586156MATH
Domain607 – 64741EGF-like
Region63 – 260198Metalloprotease

Sites

Active site1541 By similarity
Metal binding541Zinc; catalytic By similarity
Metal binding1531Zinc; via tele nitrogen; catalytic By similarity
Metal binding1571Zinc; via tele nitrogen; catalytic By similarity
Metal binding1631Zinc; via tele nitrogen; catalytic By similarity
Site2391Mediates preference for acidic residues at subsite P1' By similarity

Amino acid modifications

Glycosylation1931N-linked (GlcNAc...) Potential
Glycosylation2191N-linked (GlcNAc...) Potential
Glycosylation2551N-linked (GlcNAc...) Potential
Glycosylation3161N-linked (GlcNAc...) Potential
Glycosylation4221N-linked (GlcNAc...) Potential
Glycosylation4371N-linked (GlcNAc...) Potential
Glycosylation5291N-linked (GlcNAc...) Potential
Glycosylation5481N-linked (GlcNAc...) Potential
Glycosylation5931N-linked (GlcNAc...) Potential
Disulfide bond104 ↔ 256 By similarity
Disulfide bond125 ↔ 145 By similarity
Disulfide bond266 ↔ 428 By similarity
Disulfide bond274Interchain By similarity
Disulfide bond306Interchain By similarity
Disulfide bond493Interchain By similarity
Disulfide bond611 ↔ 622 By similarity
Disulfide bond616 ↔ 631 By similarity
Disulfide bond633 ↔ 646 By similarity

Natural variations

Alternative sequence1 – 2727MDARH…APEKF → MNSTAGPASRSRHSFKCRMK LLKAPRDGMYMMTFG in isoform 2.
VSP_005460

Experimental info

Sequence conflict181V → A in AAA75234. Ref.1
Sequence conflict261K → G AA sequence Ref.5
Sequence conflict291K → S AA sequence Ref.5
Sequence conflict4701S → Y in AAA75234. Ref.1
Sequence conflict4701S → Y no nucleotide entry Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Beta) [UniParc].

Last modified July 13, 2010. Version 2.
Checksum: 04F92C493F701525

FASTA70479,501
        10         20         30         40         50         60 
MDARHQPWFL VFATFLLVSG LPAPEKFVKD IDGGIDQDIF DINQGLGLDL FEGDIKLEAN 

        70         80         90        100        110        120 
GKNSIIGDHK RWPHTIPYVL EDSLEMNAKG VILNAFERYR LKTCIDFKPW SGEANYISVF 

       130        140        150        160        170        180 
KGSGCWSSVG NIHAGKQELS IGTNCDRIAT VQHEFLHALG FWHEQSRADR DDYVIIVWDR 

       190        200        210        220        230        240 
IQPGKEHNFN IYNDSVSDSL NVPYDYTSVM HYSKTAFQNG TESTIVTRIS EFEDVIGQRM 

       250        260        270        280        290        300 
DFSDYDLLKL NQLYNCTSSL SFMDSCDFEL ENICGMIQSS GDSADWQRVS QVLSGPESDH 

       310        320        330        340        350        360 
SKMGQCKDSG FFMHFNTSIL NEGATAMLES RLLYPKRGFQ CLEFYLYNSG SGNDQLNIYT 

       370        380        390        400        410        420 
REYTTGQQGG VLTLQRQIKE VPIGSWQLHY VTLQVTKKFR VVFEGLRGPG TSSGGLSIDD 

       430        440        450        460        470        480 
INLSETRCPH HIWHIQNFTQ ILGGQDTSVY SPPFYSSKGY AFQIYMDLRS STNVGIYFHL 

       490        500        510        520        530        540 
ISGANDDQLQ WPCPWQQATM TLLDQNPDIR QRMFNQRSIT TDPTMTSDNG SYFWDRPSKV 

       550        560        570        580        590        600 
GVTDVFPNGT QFSRGIGYGT TVFITRERLK SREFIKGDDI YILLTVEDIS HLNSTSAVPD 

       610        620        630        640        650        660 
PVPTLAVHNA CSEVVCQNGG ICVVQDGRAE CKCPAGEDWW YMGKRCEKRG STRDTVIIAV 

       670        680        690        700 
SSTVTVFAVM LIITLVSVYC TRRKYRKKAR ANTAAMTLEN QHAF 

« Hide

Isoform 2 (Beta') [UniParc].

Checksum: 6A876F36D70B70EC
Show »

FASTA71280,348

References

« Hide 'large scale' references
[1]"Cloning, expression, and chromosomal localization of the mouse meprin beta subunit."
Gorbea C.M., Marchand P., Jiang W., Copeland N.G., Gilbert D.J., Jenkins N.A., Bond J.S.
J. Biol. Chem. 268:21035-21043(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 65-88; 96-109; 329-345 AND 541-549.
Tissue: Kidney.
[2]"A novel meprin beta' mRNA in mouse embryonal and human colon carcinoma cells."
Dietrich J.M., Bond J.S., Jiang W.
J. Biol. Chem. 271:2271-2278(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Kidney.
[3]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORM 1).
[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] (ISOFORM 1).
[5]"Meprin-A and -B. Cell surface endopeptidases of the mouse kidney."
Kounnas M.Z., Wolz R.L., Gorbea C.M., Bond J.S.
J. Biol. Chem. 266:17350-17357(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 21-30 (ISOFORM 1), CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION.
Strain: C3H/He.
Tissue: Kidney.
[6]"Homo- and heterotetrameric forms of the membrane-bound metalloendopeptidases meprin A and B."
Gorbea C.M., Flannery A.V., Bond J.S.
Arch. Biochem. Biophys. 290:549-553(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[7]"Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity."
Bertenshaw G.P., Turk B.E., Hubbard S.J., Matters G.L., Bylander J.E., Crisman J.M., Cantley L.C., Bond J.S.
J. Biol. Chem. 276:13248-13255(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY.
[8]"Mannan-binding protein blocks the activation of metalloproteases meprin alpha and beta."
Hirano M., Ma B.Y., Kawasaki N., Okimura K., Baba M., Nakagawa T., Miwa K., Kawasaki N., Oka S., Kawasaki T.
J. Immunol. 175:3177-3185(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MBL2.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L15193 mRNA. Translation: AAA75234.1.
CH466557 Genomic DNA. Translation: EDK96962.1.
BC125627 mRNA. Translation: AAI25628.1.
BC145979 mRNA. Translation: AAI45980.1.
CCDSCCDS37747.1. [Q61847-1]
PIRA48040.
RefSeqNP_032612.2. NM_008586.2. [Q61847-1]
UniGeneMm.2682.

3D structure databases

ProteinModelPortalQ61847.
SMRQ61847. Positions 30-595.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ61847. 4 interactions.
MINTMINT-4101747.
STRING10090.ENSMUSP00000111506.

Protein family/group databases

MEROPSM12.004.

PTM databases

PhosphoSiteQ61847.

Proteomic databases

MaxQBQ61847.
PaxDbQ61847.
PRIDEQ61847.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000082235; ENSMUSP00000080866; ENSMUSG00000024313. [Q61847-1]
GeneID17288.
KEGGmmu:17288.
UCSCuc008eff.1. mouse. [Q61847-1]

Organism-specific databases

CTD4225.
MGIMGI:96964. Mep1b.

Phylogenomic databases

eggNOGNOG322115.
GeneTreeENSGT00740000115357.
HOGENOMHOG000043106.
HOVERGENHBG052457.
KOK08606.
OMAFEEENIC.
OrthoDBEOG73V6MT.
PhylomeDBQ61847.
TreeFamTF315280.

Gene expression databases

BgeeQ61847.
CleanExMM_MEP1B.
GenevestigatorQ61847.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR000742. EG-like_dom.
IPR000998. MAM_dom.
IPR002083. MATH.
IPR008294. Meprin.
IPR024079. MetalloPept_cat_dom.
IPR001506. Peptidase_M12A.
IPR006026. Peptidase_Metallo.
IPR008974. TRAF-like.
[Graphical view]
PfamPF01400. Astacin. 1 hit.
PF00008. EGF. 1 hit.
PF00629. MAM. 1 hit.
PF00917. MATH. 1 hit.
[Graphical view]
PIRSFPIRSF001196. Meprin. 1 hit.
PRINTSPR00480. ASTACIN.
PR00020. MAMDOMAIN.
SMARTSM00181. EGF. 1 hit.
SM00137. MAM. 1 hit.
SM00061. MATH. 1 hit.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF49599. SSF49599. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEPS50026. EGF_3. 1 hit.
PS00740. MAM_1. 1 hit.
PS50060. MAM_2. 1 hit.
PS50144. MATH. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio291804.
PROQ61847.
SOURCESearch...

Entry information

Entry nameMEP1B_MOUSE
AccessionPrimary (citable) accession number: Q61847
Secondary accession number(s): Q059K0
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 13, 2010
Last modified: July 9, 2014
This is version 137 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot