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Protein

Meprin A subunit beta

Gene

Mep1b

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Inflammatory response

Keywords - Ligandi

Metal-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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:96964. Mep1b.

Subcellular locationi

  • Cell membrane By similarity; Single-pass type I membrane protein By similarity
  • Secreted By similarity

  • Note: Homodimers are essentially membrane bound but may also be shed from the surface by ADAM-10 and ADAM-17.By similarity

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini21 – 654ExtracellularSequence analysisAdd BLAST634
Transmembranei655 – 678HelicalSequence analysisAdd BLAST24
Topological domaini679 – 704CytoplasmicSequence analysisAdd BLAST26

GO - Cellular componenti

  • extracellular region Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: MGI
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

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...)Sequence analysis1
Glycosylationi219N-linked (GlcNAc...)Sequence analysis1
Glycosylationi255N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi266 ↔ 428PROSITE-ProRule annotation
Disulfide bondi274InterchainPROSITE-ProRule annotation
Disulfide bondi306InterchainPROSITE-ProRule annotation
Glycosylationi316N-linked (GlcNAc...)Sequence analysis1
Glycosylationi422N-linked (GlcNAc...)Sequence analysis1
Glycosylationi437N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi493InterchainPROSITE-ProRule annotation
Glycosylationi529N-linked (GlcNAc...)Sequence analysis1
Glycosylationi548N-linked (GlcNAc...)Sequence analysis1
Glycosylationi593N-linked (GlcNAc...)Sequence 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

Protein-protein interaction databases

IntActiQ61847. 4 interactors.
MINTiMINT-4101747.
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
Contains 1 EGF-like domain.PROSITE-ProRule annotation
Contains 1 MAM domain.PROSITE-ProRule annotation
Contains 1 MATH domain.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

CDDicd06263. MAM. 1 hit.
Gene3Di2.60.210.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR000742. EGF-like_dom.
IPR000998. MAM_dom.
IPR002083. MATH/TRAF_dom.
IPR008294. Meprin.
IPR024079. MetalloPept_cat_dom.
IPR001506. Peptidase_M12A.
IPR006026. Peptidase_Metallo.
IPR008974. TRAF-like.
[Graphical view]
PANTHERiPTHR10127:SF312. PTHR10127:SF312. 1 hit.
PfamiPF01400. Astacin. 1 hit.
PF00008. EGF. 1 hit.
PF00629. MAM. 1 hit.
[Graphical view]
PIRSFiPIRSF001196. Meprin. 1 hit.
PRINTSiPR00480. ASTACIN.
PR00020. MAMDOMAIN.
SMARTiSM00137. MAM. 1 hit.
SM00061. MATH. 1 hit.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEiPS50026. 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]

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

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ61847.
SMRiQ61847.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ61847. 4 interactors.
MINTiMINT-4101747.
STRINGi10090.ENSMUSP00000080866.

Protein family/group databases

MEROPSiM12.004.

PTM databases

PhosphoSitePlusiQ61847.

Proteomic databases

PaxDbiQ61847.
PeptideAtlasiQ61847.
PRIDEiQ61847.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4225.
MGIiMGI:96964. Mep1b.

Phylogenomic databases

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

Miscellaneous databases

PROiQ61847.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024313.
CleanExiMM_MEP1B.
GenevisibleiQ61847. MM.

Family and domain databases

CDDicd06263. MAM. 1 hit.
Gene3Di2.60.210.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR013320. ConA-like_dom.
IPR000742. EGF-like_dom.
IPR000998. MAM_dom.
IPR002083. MATH/TRAF_dom.
IPR008294. Meprin.
IPR024079. MetalloPept_cat_dom.
IPR001506. Peptidase_M12A.
IPR006026. Peptidase_Metallo.
IPR008974. TRAF-like.
[Graphical view]
PANTHERiPTHR10127:SF312. PTHR10127:SF312. 1 hit.
PfamiPF01400. Astacin. 1 hit.
PF00008. EGF. 1 hit.
PF00629. MAM. 1 hit.
[Graphical view]
PIRSFiPIRSF001196. Meprin. 1 hit.
PRINTSiPR00480. ASTACIN.
PR00020. MAMDOMAIN.
SMARTiSM00137. MAM. 1 hit.
SM00061. MATH. 1 hit.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF49599. SSF49599. 1 hit.
SSF49899. SSF49899. 1 hit.
PROSITEiPS50026. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiMEP1B_MOUSE
AccessioniPrimary (citable) accession number: Q61847
Secondary accession number(s): Q059K0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 13, 2010
Last modified: November 2, 2016
This is version 154 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.