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Protein

Meprin A subunit beta

Gene

Mep1b

Organism
Rattus norvegicus (Rat)
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. 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 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.By similarity

Cofactori

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

Enzyme regulationi

Strongly inhibited by fetuin-A/AHSG.By similarity

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

  • metalloendopeptidase activity Source: RGD
  • zinc ion binding Source: InterPro

GO - Biological processi

  • inflammatory response Source: UniProtKB-KW
  • proteolysis Source: RGD
  • toxin transport Source: Ensembl
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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 18

Organism-specific databases

RGDi3081. 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

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi274C → A: Predominantly occurs as a monomer, less than 10% occurs as dimer. 1 Publication1
Mutagenesisi306C → A: Only occurs as a monomer. 1 Publication1
Mutagenesisi492C → A: Only occurs as a monomer. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000002888721 – 64Add BLAST44
ChainiPRO_000002888865 – 704Meprin A subunit betaAdd BLAST640

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi104 ↔ 256PROSITE-ProRule annotation1 Publication
Disulfide bondi125 ↔ 145PROSITE-ProRule annotation1 Publication
Glycosylationi193N-linked (GlcNAc...)Sequence analysis1
Glycosylationi219N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi266 ↔ 428PROSITE-ProRule annotation1 Publication
Disulfide bondi274InterchainPROSITE-ProRule annotation1 Publication
Disulfide bondi306InterchainPROSITE-ProRule annotation1 Publication
Glycosylationi316N-linked (GlcNAc...)Sequence analysis1
Glycosylationi422N-linked (GlcNAc...)Sequence analysis1
Glycosylationi437N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi492InterchainPROSITE-ProRule annotation1 Publication
Glycosylationi528N-linked (GlcNAc...)Sequence analysis1
Glycosylationi547N-linked (GlcNAc...)Sequence analysis1
Glycosylationi592N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi611 ↔ 622PROSITE-ProRule annotation
Disulfide bondi616 ↔ 631PROSITE-ProRule annotation
Disulfide bondi633 ↔ 646PROSITE-ProRule annotation

Post-translational modificationi

N-glycosylated; contains high mannose and/or complex biantennary structures.By similarity
Proteolytically activated by trypsin in the intestinal lumen and kallikrein-related peptidases in other tissues.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiP28826.
PRIDEiP28826.

Expressioni

Tissue specificityi

Kidney, intestinal brush borders and salivary ducts.

Gene expression databases

BgeeiENSRNOG00000049345.
GenevisibleiP28826. RN.

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 (By similarity).By similarity

Protein-protein interaction databases

BioGridi247756. 2 interactors.
STRINGi10116.ENSRNOP00000063916.

Structurei

3D structure databases

ProteinModelPortaliP28826.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini261 – 430MAMPROSITE-ProRule annotationAdd BLAST170
Domaini431 – 585MATHPROSITE-ProRule annotationAdd BLAST155
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.
HOVERGENiHBG052457.
InParanoidiP28826.
KOiK08606.
OMAiDYVSIIW.
OrthoDBiEOG091G009U.
PhylomeDBiP28826.

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.
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]

Sequencei

Sequence statusi: Complete.

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

P28826-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDARHWPWFL VFATFLLVSG LPAPEKFVKD IDGGIDQDIF DINEDLGLDL
60 70 80 90 100
FEGDIKLEAS GRNSIIGDNY RWPHTIPYVL EDSLEMNAKG VILNAFERYR
110 120 130 140 150
LKTCIDFKPW SGEENYISVF KGSGCWSSVG NIHAGKQELS IGTNCDRIAT
160 170 180 190 200
VQHEFLHALG FWHEQSRADR DDYITIVWDR ILSGKEHNFN IYNDSVSDSL
210 220 230 240 250
NVPYDYTSVM HYSKTAFQNG TESTIITKIS DFEDVIGQRM DFSDYDLLKL
260 270 280 290 300
NQLYSCTSSL SFMDSCDFEL ENICGMIQSS QDSADWQRLS QVLSGPENDH
310 320 330 340 350
SNMGQCKDSG FFMHFNTSTG NGGVTAMLES RVLYPKRGFQ CVEFYLYNSG
360 370 380 390 400
SGNGQLNVYT REYTAGHQDG VLTLQREIRD IPTGSWQLYY VTLQVTEKFR
410 420 430 440 450
VVFEGVGGPG ASSGGLSIDD INLSETRCPH HIWHIQNFTQ LLGGQTTVYS
460 470 480 490 500
PPFYSSKGYA FQINLDLTSP TNVGLYFHLI SGANDDQLQW PCPWQQATMT
510 520 530 540 550
LLDQNPDIRQ RMSNQRSITT DPKMTDDNGS YLWDRPSKVG VEAFFPNGTQ
560 570 580 590 600
FSRGRGYGTS VFITQERLKS REFLKGDDVY ILLTVEDISH LNSTAAVPGP
610 620 630 640 650
VPTTSTVHNA CSEVECQNGG ICTLQEGRAE CKCPAGEDWW YMGKRCEKRG
660 670 680 690 700
STKDTIVIAV SSTVTVFAVM LIITLISVYC TRRKYRKKAS AKTAAMNLEN

QHAF
Length:704
Mass (Da):79,236
Last modified:July 13, 2010 - v3
Checksum:i1B40FFDD4D9965E5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti324V → I in AAA41587 (PubMed:1377685).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88601 mRNA. Translation: AAA41587.1.
CH473974 Genomic DNA. Translation: EDL76105.1.
BC081833 mRNA. Translation: AAH81833.1.
PIRiA42908.
RefSeqiNP_037315.1. NM_013183.2.
UniGeneiRn.3520.

Genome annotation databases

EnsembliENSRNOT00000074116; ENSRNOP00000063916; ENSRNOG00000049345.
GeneIDi25727.
KEGGirno:25727.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M88601 mRNA. Translation: AAA41587.1.
CH473974 Genomic DNA. Translation: EDL76105.1.
BC081833 mRNA. Translation: AAH81833.1.
PIRiA42908.
RefSeqiNP_037315.1. NM_013183.2.
UniGeneiRn.3520.

3D structure databases

ProteinModelPortaliP28826.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi247756. 2 interactors.
STRINGi10116.ENSRNOP00000063916.

Protein family/group databases

MEROPSiM12.004.

Proteomic databases

PaxDbiP28826.
PRIDEiP28826.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000074116; ENSRNOP00000063916; ENSRNOG00000049345.
GeneIDi25727.
KEGGirno:25727.

Organism-specific databases

CTDi4225.
RGDi3081. Mep1b.

Phylogenomic databases

eggNOGiKOG3714. Eukaryota.
ENOG410ZPX7. LUCA.
GeneTreeiENSGT00760000119227.
HOVERGENiHBG052457.
InParanoidiP28826.
KOiK08606.
OMAiDYVSIIW.
OrthoDBiEOG091G009U.
PhylomeDBiP28826.

Miscellaneous databases

PROiP28826.

Gene expression databases

BgeeiENSRNOG00000049345.
GenevisibleiP28826. RN.

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.
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_RAT
AccessioniPrimary (citable) accession number: P28826
Secondary accession number(s): Q642D0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: July 13, 2010
Last modified: September 7, 2016
This is version 132 of the entry and version 3 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. Peptidase families
    Classification of peptidase families and list of entries
  2. 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.