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Protein

Meprin A subunit beta

Gene

Mep1b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Membrane metallopeptidase that sheds many membrane-bound proteins. Exhibits a strong preference for acidic amino acids at the P1' position (PubMed:11278902). 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).By similarity1 Publication

Catalytic activityi

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.2 Publications

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

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.By similarity1 Publication

Temperature dependencei

The half-life at 58 degrees Celsius is less than 3 minutes.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi54Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi153Zinc; via tele nitrogen; catalyticBy similarity1
Active sitei154PROSITE-ProRule annotation1
Metal bindingi157Zinc; via tele nitrogen; catalyticBy similarity1
Metal bindingi163Zinc; via tele nitrogen; catalyticBy similarity1
Sitei239Mediates preference for acidic residues at subsite P1'By similarity1

GO - Molecular functioni

GO - Biological processi

  • inflammatory response Source: UniProtKB-KW
  • toxin transport Source: MGI

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processInflammatory response
LigandMetal-binding, Zinc

Protein family/group databases

MEROPSiM12.004

Names & Taxonomyi

Protein namesi
Recommended name:
Meprin A subunit beta (EC:3.4.24.63)
Alternative name(s):
Endopeptidase-2
Meprin B
Gene namesi
Name:Mep1b
Synonyms:Mep-1b
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:96964 Mep1b

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 domaini21 – 654ExtracellularSequence analysisAdd BLAST634
Transmembranei655 – 678HelicalSequence analysisAdd BLAST24
Topological domaini679 – 704CytoplasmicSequence analysisAdd BLAST26

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000002888521 – 64By similarityAdd BLAST44
ChainiPRO_000002888665 – 704Meprin A subunit betaAdd BLAST640

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi104 ↔ 256PROSITE-ProRule annotation
Disulfide bondi125 ↔ 145PROSITE-ProRule annotation
Glycosylationi193N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi219N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi255N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi266 ↔ 428PROSITE-ProRule annotation
Disulfide bondi274InterchainPROSITE-ProRule annotation
Disulfide bondi306InterchainPROSITE-ProRule annotation
Glycosylationi316N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi422N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi437N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi493InterchainPROSITE-ProRule annotation
Glycosylationi529N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi548N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi593N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi611 ↔ 622PROSITE-ProRule annotation
Disulfide bondi616 ↔ 631PROSITE-ProRule annotation
Disulfide bondi633 ↔ 646PROSITE-ProRule annotation

Post-translational modificationi

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.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ61847
PeptideAtlasiQ61847
PRIDEiQ61847

PTM databases

PhosphoSitePlusiQ61847

Expressioni

Tissue specificityi

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

Inductioni

By retinoic acid.

Gene expression databases

BgeeiENSMUSG00000024313
CleanExiMM_MEP1B
GenevisibleiQ61847 MM

Interactioni

Subunit structurei

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.2 Publications

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ61847, 4 interactors
MINTiQ61847
STRINGi10090.ENSMUSP00000080866

Structurei

3D structure databases

ProteinModelPortaliQ61847
SMRiQ61847
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini261 – 430MAMPROSITE-ProRule annotationAdd BLAST170
Domaini431 – 586MATHPROSITE-ProRule annotationAdd BLAST156
Domaini607 – 647EGF-likePROSITE-ProRule annotationAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni63 – 260MetalloproteaseAdd BLAST198

Sequence similaritiesi

Belongs to the peptidase M12A family.Curated

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3714 Eukaryota
ENOG410ZPX7 LUCA
GeneTreeiENSGT00760000119227
HOGENOMiHOG000043106
HOVERGENiHBG052457
InParanoidiQ61847
KOiK08606
OMAiCWSSVGN
OrthoDBiEOG091G009U
PhylomeDBiQ61847
TreeFamiTF315280

Family and domain databases

CDDicd06263 MAM, 1 hit
Gene3Di2.60.210.10, 1 hit
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR013320 ConA-like_dom_sf
IPR000742 EGF-like_dom
IPR000998 MAM_dom
IPR002083 MATH/TRAF_dom
IPR008294 Meprin
IPR034302 Meprin_beta
IPR024079 MetalloPept_cat_dom_sf
IPR001506 Peptidase_M12A
IPR006026 Peptidase_Metallo
IPR008974 TRAF-like
PANTHERiPTHR44155 PTHR44155, 1 hit
PTHR44155:SF3 PTHR44155:SF3, 1 hit
PfamiView protein in Pfam
PF01400 Astacin, 1 hit
PF00008 EGF, 1 hit
PF00629 MAM, 1 hit
PIRSFiPIRSF001196 Meprin, 1 hit
PRINTSiPR00480 ASTACIN
PR00020 MAMDOMAIN
SMARTiView protein in SMART
SM00137 MAM, 1 hit
SM00061 MATH, 1 hit
SM00235 ZnMc, 1 hit
SUPFAMiSSF49599 SSF49599, 1 hit
SSF49899 SSF49899, 1 hit
PROSITEiView protein in PROSITE
PS50026 EGF_3, 1 hit
PS00740 MAM_1, 1 hit
PS50060 MAM_2, 1 hit
PS50144 MATH, 1 hit
PS00142 ZINC_PROTEASE, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative promoter usage and alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q61847-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MDARHQPWFL VFATFLLVSG LPAPEKFVKD IDGGIDQDIF DINQGLGLDL
60 70 80 90 100
FEGDIKLEAN GKNSIIGDHK RWPHTIPYVL EDSLEMNAKG VILNAFERYR
110 120 130 140 150
LKTCIDFKPW SGEANYISVF KGSGCWSSVG NIHAGKQELS IGTNCDRIAT
160 170 180 190 200
VQHEFLHALG FWHEQSRADR DDYVIIVWDR IQPGKEHNFN IYNDSVSDSL
210 220 230 240 250
NVPYDYTSVM HYSKTAFQNG TESTIVTRIS EFEDVIGQRM DFSDYDLLKL
260 270 280 290 300
NQLYNCTSSL SFMDSCDFEL ENICGMIQSS GDSADWQRVS QVLSGPESDH
310 320 330 340 350
SKMGQCKDSG FFMHFNTSIL NEGATAMLES RLLYPKRGFQ CLEFYLYNSG
360 370 380 390 400
SGNDQLNIYT REYTTGQQGG VLTLQRQIKE VPIGSWQLHY VTLQVTKKFR
410 420 430 440 450
VVFEGLRGPG TSSGGLSIDD INLSETRCPH HIWHIQNFTQ ILGGQDTSVY
460 470 480 490 500
SPPFYSSKGY AFQIYMDLRS STNVGIYFHL ISGANDDQLQ WPCPWQQATM
510 520 530 540 550
TLLDQNPDIR QRMFNQRSIT TDPTMTSDNG SYFWDRPSKV GVTDVFPNGT
560 570 580 590 600
QFSRGIGYGT TVFITRERLK SREFIKGDDI YILLTVEDIS HLNSTSAVPD
610 620 630 640 650
PVPTLAVHNA CSEVVCQNGG ICVVQDGRAE CKCPAGEDWW YMGKRCEKRG
660 670 680 690 700
STRDTVIIAV SSTVTVFAVM LIITLVSVYC TRRKYRKKAR ANTAAMTLEN

QHAF
Length:704
Mass (Da):79,501
Last modified:July 13, 2010 - v2
Checksum:i04F92C493F701525
GO
Isoform 2 (identifier: Q61847-2) [UniParc]FASTAAdd to basket
Also known as: Beta'

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

Show »
Length:712
Mass (Da):80,348
Checksum:i6A876F36D70B70EC
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti18V → A in AAA75234 (PubMed:8407940).Curated1
Sequence conflicti26K → G AA sequence (PubMed:1894622).Curated1
Sequence conflicti29K → S AA sequence (PubMed:1894622).Curated1
Sequence conflicti470S → Y in AAA75234 (PubMed:8407940).Curated1
Sequence conflicti470S → Y no nucleotide entry (PubMed:8567689).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0054601 – 27MDARH…APEKF → MNSTAGPASRSRHSFKCRMK LLKAPRDGMYMMTFG in isoform 2. 1 PublicationAdd BLAST27

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L15193 mRNA Translation: AAA75234.1
CH466557 Genomic DNA Translation: EDK96962.1
BC125627 mRNA Translation: AAI25628.1
BC145979 mRNA Translation: AAI45980.1
CCDSiCCDS37747.1 [Q61847-1]
PIRiA48040
RefSeqiNP_032612.2, NM_008586.2 [Q61847-1]
UniGeneiMm.2682

Genome annotation databases

EnsembliENSMUST00000082235; ENSMUSP00000080866; ENSMUSG00000024313 [Q61847-1]
GeneIDi17288
KEGGimmu:17288
UCSCiuc008eff.1 mouse [Q61847-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiMEP1B_MOUSE
AccessioniPrimary (citable) accession number: Q61847
Secondary accession number(s): Q059K0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 13, 2010
Last modified: May 23, 2018
This is version 165 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

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