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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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi54 – 541Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi153 – 1531Zinc; via tele nitrogen; catalyticBy similarity
Active sitei154 – 1541PROSITE-ProRule annotation
Metal bindingi157 – 1571Zinc; via tele nitrogen; catalyticBy similarity
Metal bindingi163 – 1631Zinc; via tele nitrogen; catalyticBy similarity
Sitei239 – 2391Mediates preference for acidic residues at subsite P1'By similarity

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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini21 – 654634ExtracellularSequence analysisAdd
BLAST
Transmembranei655 – 67824HelicalSequence analysisAdd
BLAST
Topological domaini679 – 70426CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi274 – 2741C → A: Predominantly occurs as a monomer, less than 10% occurs as dimer. 1 Publication
Mutagenesisi306 – 3061C → A: Only occurs as a monomer. 1 Publication
Mutagenesisi492 – 4921C → A: Only occurs as a monomer. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence analysisAdd
BLAST
Propeptidei21 – 6444PRO_0000028887Add
BLAST
Chaini65 – 704640Meprin A subunit betaPRO_0000028888Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi104 ↔ 256PROSITE-ProRule annotation1 Publication
Disulfide bondi125 ↔ 145PROSITE-ProRule annotation1 Publication
Glycosylationi193 – 1931N-linked (GlcNAc...)Sequence analysis
Glycosylationi219 – 2191N-linked (GlcNAc...)Sequence analysis
Disulfide bondi266 ↔ 428PROSITE-ProRule annotation1 Publication
Disulfide bondi274 – 274InterchainPROSITE-ProRule annotation1 Publication
Disulfide bondi306 – 306InterchainPROSITE-ProRule annotation1 Publication
Glycosylationi316 – 3161N-linked (GlcNAc...)Sequence analysis
Glycosylationi422 – 4221N-linked (GlcNAc...)Sequence analysis
Glycosylationi437 – 4371N-linked (GlcNAc...)Sequence analysis
Disulfide bondi492 – 492InterchainPROSITE-ProRule annotation1 Publication
Glycosylationi528 – 5281N-linked (GlcNAc...)Sequence analysis
Glycosylationi547 – 5471N-linked (GlcNAc...)Sequence analysis
Glycosylationi592 – 5921N-linked (GlcNAc...)Sequence analysis
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

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 interactions.
STRINGi10116.ENSRNOP00000063916.

Structurei

3D structure databases

ProteinModelPortaliP28826.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini261 – 430170MAMPROSITE-ProRule annotationAdd
BLAST
Domaini431 – 585155MATHPROSITE-ProRule annotationAdd
BLAST
Domaini607 – 64741EGF-likePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni63 – 260198MetalloproteaseAdd
BLAST

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.
OrthoDBiEOG73V6MT.
PhylomeDBiP28826.

Family and domain databases

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti324 – 3241V → I in AAA41587 (PubMed:1377685).Curated

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 interactions.
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.
OrthoDBiEOG73V6MT.
PhylomeDBiP28826.

Miscellaneous databases

PROiP28826.

Gene expression databases

GenevisibleiP28826. RN.

Family and domain databases

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...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning a rat meprin cDNA reveals the enzyme is a heterodimer."
    Johnson G.D., Hersh L.B.
    J. Biol. Chem. 267:13505-13512(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
    Strain: Sprague-Dawley.
    Tissue: Kidney.
  2. Erratum
    Johnson G.D., Hersh L.B.
    J. Biol. Chem. 268:17647-17647(1993)
    Cited for: RETRACTION.
  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].
  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].
    Strain: Brown Norway.
    Tissue: Kidney.
  5. "Identification of the cysteine residues implicated in the formation of alpha 2 and alpha/beta dimers of rat meprin."
    Chevallier S., Ahn J., Boileau G., Crine P.
    Biochem. J. 317:731-738(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERCHAIN DISULFIDE BOND.
  6. "Intersubunit and domain interactions of the meprin B metalloproteinase. Disulfide bonds and protein-protein interactions in the MAM and TRAF domains."
    Ishmael F.T., Shier V.K., Ishmael S.S., Bond J.S.
    J. Biol. Chem. 280:13895-13901(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISULFIDE BONDS, MUTAGENESIS OF CYS-274; CYS-306 AND CYS-492.

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: June 8, 2016
This is version 131 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.