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Q16820 (MEP1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·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
N-benzoyl-L-tyrosyl-P-amino-benzoic acid hydrolase subunit beta
PABA peptide hydrolase
PPH beta
Gene names
Name:MEP1B
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length701 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. Ref.12

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.12

Cofactor

Binds 1 zinc ion per subunit. Ref.14

Enzyme regulation

Strongly inhibited by fetuin-A/AHSG. Ref.10 Ref.13

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 By similarity. Interacts with MBL2 through its carbohydrate moiety. This interaction may inhibit its catalytic activity By similarity. Ref.14

Subcellular location

Cell membrane; Single-pass type I membrane protein. Secreted. Note: Homodimers are essentially membrane bound but may also be shed from the surface by ADAM-10 and ADAM-17. Ref.5 Ref.14

Tissue specificity

The major site of expression is the brush border membrane of small intestinal and kidney epithelial cells. Ref.6

Post-translational modification

N-glycosylated; contains high mannose and/or complex biantennary structures. Ref.6 Ref.14

O-glycosylation protect the C-terminal region from proteolytic cleavage and diminish secretion, this seems to be specific to human.

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

Sequence similarities

Belongs to the peptidase M12A family.

Contains 1 EGF-like domain.

Contains 1 MAM domain.

Contains 1 MATH domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MMP9P147802EBI-968418,EBI-1382326

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2222 Potential
Propeptide23 – 6139
PRO_0000028883
Chain62 – 701640Meprin A subunit beta
PRO_0000028884

Regions

Topological domain23 – 652630Extracellular Potential
Transmembrane653 – 67321Helical; Potential
Topological domain674 – 70128Cytoplasmic Potential
Domain260 – 429170MAM
Domain430 – 585156MATH
Domain604 – 64441EGF-like
Region64 – 259196Metalloprotease
Region595 – 60713Required for proteolytic processing

Sites

Active site1531 By similarity
Metal binding521Zinc; catalytic
Metal binding1521Zinc; via tele nitrogen; catalytic
Metal binding1561Zinc; via tele nitrogen; catalytic
Metal binding1621Zinc; via tele nitrogen; catalytic
Site2381Mediates preference for acidic residues at subsite P1'

Amino acid modifications

Glycosylation2181N-linked (GlcNAc...) Ref.14
Glycosylation2541N-linked (GlcNAc...) Ref.14
Glycosylation3701N-linked (GlcNAc...) Ref.14
Glycosylation4211N-linked (GlcNAc...) Potential
Glycosylation4361N-linked (GlcNAc...) Ref.14
Glycosylation4451N-linked (GlcNAc...) Ref.14
Glycosylation5471N-linked (GlcNAc...) Ref.14
Glycosylation5921N-linked (GlcNAc...) Ref.14
Glycosylation5931O-linked (GalNAc...) Potential
Glycosylation5941O-linked (GalNAc...) Potential
Glycosylation5991O-linked (GalNAc...) Potential
Glycosylation6031O-linked (GalNAc...) Potential
Disulfide bond103 ↔ 255 Ref.14
Disulfide bond124 ↔ 144 Ref.14
Disulfide bond265 ↔ 427 Ref.14
Disulfide bond273Interchain By similarity
Disulfide bond305Interchain Ref.14
Disulfide bond492Interchain By similarity
Disulfide bond608 ↔ 619 By similarity
Disulfide bond613 ↔ 628 By similarity
Disulfide bond630 ↔ 643 By similarity

Natural variations

Natural variant3241T → A. Ref.15
VAR_069387
Natural variant3261V → M.
Corresponds to variant rs9959396 [ dbSNP | Ensembl ].
VAR_057064
Natural variant6951P → L. Ref.1 Ref.3
Corresponds to variant rs616114 [ dbSNP | Ensembl ].
VAR_057065

Experimental info

Mutagenesis2481K → Y: Decreased activity toward gastrin. Ref.7
Mutagenesis595 – 60713Missing: Abolishes secretion. Ref.6
Sequence conflict711W → S AA sequence Ref.4
Sequence conflict741T → P AA sequence Ref.4
Sequence conflict5461S → P in AAU05377. Ref.2
Sequence conflict5461S → P in AAI36560. Ref.3
Sequence conflict5461S → P in AAI44245. Ref.3
Sequence conflict6981Missing in CAA57107. Ref.1

Secondary structure

................................................................................................................... 701
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16820 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: 4733DBF018A4F3CD

FASTA70179,571
        10         20         30         40         50         60 
MDLWNLSWFL FLDALLVISG LATPENFDVD GGMDQDIFDI NEGLGLDLFE GDIRLDRAQI 

        70         80         90        100        110        120 
RNSIIGEKYR WPHTIPYVLE DSLEMNAKGV ILNAFERYRL KTCIDFKPWA GETNYISVFK 

       130        140        150        160        170        180 
GSGCWSSVGN RRVGKQELSI GANCDRIATV QHEFLHALGF WHEQSRSDRD DYVRIMWDRI 

       190        200        210        220        230        240 
LSGREHNFNT YSDDISDSLN VPYDYTSVMH YSKTAFQNGT EPTIVTRISD FEDVIGQRMD 

       250        260        270        280        290        300 
FSDSDLLKLN QLYNCSSSLS FMDSCSFELE NVCGMIQSSG DNADWQRVSQ VPRGPESDHS 

       310        320        330        340        350        360 
NMGQCQGSGF FMHFDSSSVN VGATAVLESR TLYPKRGFQC LQFYLYNSGS ESDQLNIYIR 

       370        380        390        400        410        420 
EYSADNVDGN LTLVEEIKEI PTGSWQLYHV TLKVTKKFRV VFEGRKGSGA SLGGLSIDDI 

       430        440        450        460        470        480 
NLSETRCPHH IWHIRNFTQF IGSPNGTLYS PPFYSSKGYA FQIYLNLAHV TNAGIYFHLI 

       490        500        510        520        530        540 
SGANDDQLQW PCPWQQATMT LLDQNPDIRQ RMSNQRSITT DPFMTTDNGN YFWDRPSKVG 

       550        560        570        580        590        600 
TVALFSNGTQ FRRGGGYGTS AFITHERLKS RDFIKGDDVY ILLTVEDISH LNSTQIQLTP 

       610        620        630        640        650        660 
APSVQDLCSK TTCKNDGVCT VRDGKAECRC QSGEDWWYMG ERCEKRGSTR DTIVIAVSST 

       670        680        690        700 
VAVFALMLII TLVSVYCTRK KYRERMSSNR PNLTPQNQHA F 

« Hide

References

« Hide 'large scale' references
[1]"Polarised expression of human intestinal N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (human meprin) alpha and beta subunits in Madin-Darby canine kidney cells."
Eldering J.A., Gruenberg J., Hahn D., Croes H.J., Fransen J.A., Sterchi E.E.
Eur. J. Biochem. 247:920-932(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 62-105, VARIANT LEU-695.
Tissue: Intestine.
[2]"Expression of human meprin beta."
Haun R.S.
Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Small intestine.
[3]"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], VARIANT LEU-695.
Tissue: Testis.
[4]"Cloning of the PABA peptide hydrolase alpha subunit (PPH alpha) from human small intestine and its expression in COS-1 cells."
Dumermuth E., Eldering J.A., Gruenberg J., Jiang W., Sterchi E.E.
FEBS Lett. 335:367-375(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 62-79.
Tissue: Small intestine mucosa.
[5]"N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase beta (human meprinbeta). A 13-amino-acid sequence is required for proteolytic processing and subsequent secretion."
Pischitzis A., Hahn D., Leuenberger B., Sterchi E.E.
Eur. J. Biochem. 261:421-429(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING.
[6]"Human meprin beta: O-linked glycans in the intervening region of the type I membrane protein protect the C-terminal region from proteolytic cleavage and diminish its secretion."
Leuenberger B., Hahn D., Pischitzis A., Hansen M.K., Sterchi E.E.
Biochem. J. 369:659-665(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION AT SER-593; THR-594; THR-599 AND SER-603, TISSUE SPECIFICITY, MUTAGENESIS OF 595-GLN--LEU-607.
[7]"Critical amino acids in the active site of meprin metalloproteinases for substrate and peptide bond specificity."
Villa J.P., Bertenshaw G.P., Bond J.S.
J. Biol. Chem. 278:42545-42550(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF GASTRIN, SUBSTRATE SPECIFICITY, MUTAGENESIS OF LYS-248.
[8]"Prointerleukin-18 is activated by meprin beta in vitro and in vivo in intestinal inflammation."
Banerjee S., Bond J.S.
J. Biol. Chem. 283:31371-31377(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF IL18.
[9]"The metalloprotease meprinbeta processes E-cadherin and weakens intercellular adhesion."
Huguenin M., Muller E.J., Trachsel-Rosmann S., Oneda B., Ambort D., Sterchi E.E., Lottaz D.
PLoS ONE 3:E2153-E2153(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF E-CADHERIN.
[10]"Fetuin-A and cystatin C are endogenous inhibitors of human meprin metalloproteases."
Hedrich J., Lottaz D., Meyer K., Yiallouros I., Jahnen-Dechent W., Stocker W., Becker-Pauly C.
Biochemistry 49:8599-8607(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[11]"Specific processing of tenascin-C by the metalloprotease meprinbeta neutralizes its inhibition of cell spreading."
Ambort D., Brellier F., Becker-Pauly C., Stocker W., Andrejevic-Blant S., Chiquet M., Sterchi E.E.
Matrix Biol. 29:31-42(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF TNC.
[12]"Proteomic analyses reveal an acidic prime side specificity for the astacin metalloprotease family reflected by physiological substrates."
Becker-Pauly C., Barre O., Schilling O., Auf dem Keller U., Ohler A., Broder C., Schutte A., Kappelhoff R., Stocker W., Overall C.M.
Mol. Cell. Proteomics 10:M111.009233.01-M111.009233.19(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, CLEAVAGE OF FGF19; KLK7 AND VGFA.
[13]"The substrate degradome of meprin metalloproteases reveals an unexpected proteolytic link between meprin beta and ADAM10."
Jefferson T., Auf dem Keller U., Bellac C., Metz V.V., Broder C., Hedrich J., Ohler A., Maier W., Magdolen V., Sterchi E., Bond J.S., Jayakumar A., Traupe H., Chalaris A., Rose-John S., Pietrzik C.U., Postina R., Overall C.M., Becker-Pauly C.
Cell. Mol. Life Sci. 70:309-333(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: CLEAVAGE OF ADAM10, ENZYME REGULATION.
[14]"Structural basis for the sheddase function of human meprin beta metalloproteinase at the plasma membrane."
Arolas J.L., Broder C., Jefferson T., Guevara T., Sterchi E.E., Bode W., Stocker W., Becker-Pauly C., Gomis-Ruth F.X.
Proc. Natl. Acad. Sci. U.S.A. 109:16131-16136(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 25-614, GLYCOSYLATION AT ASN-218; ASN-254; ASN-370; ASN-436; ASN-445; ASN-547 AND ASN-592, DISULFIDE BONDS, COFACTOR, ZINC-BINDING SITES, SUBUNIT, SUBCELLULAR LOCATION.
[15]"Diagnostic exome sequencing in persons with severe intellectual disability."
de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G., Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C., del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G., Veltman J.A., Vissers L.E.
N. Engl. J. Med. 367:1921-1929(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ALA-324.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X81333 mRNA. Translation: CAA57107.1.
AY695931 mRNA. Translation: AAU05377.1.
BC136559 mRNA. Translation: AAI36560.1.
BC144244 mRNA. Translation: AAI44245.1.
CCDSCCDS45846.1.
PIRHYHUMB. S49383.
RefSeqNP_005916.2. NM_005925.2.
UniGeneHs.194777.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4GWMX-ray1.85A/B23-614[»]
4GWNX-ray3.00A62-614[»]
ProteinModelPortalQ16820.
SMRQ16820. Positions 25-597.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110388. 4 interactions.
DIPDIP-34900N.
IntActQ16820. 1 interaction.
STRING9606.ENSP00000269202.

Protein family/group databases

MEROPSM12.004.

PTM databases

PhosphoSiteQ16820.

Polymorphism databases

DMDM296439304.

Proteomic databases

PaxDbQ16820.
PRIDEQ16820.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000269202; ENSP00000269202; ENSG00000141434.
GeneID4225.
KEGGhsa:4225.
UCSCuc002kxj.4. human.

Organism-specific databases

CTD4225.
GeneCardsGC18P029793.
H-InvDBHIX0039722.
HGNCHGNC:7020. MEP1B.
HPACAB025850.
MIM600389. gene.
neXtProtNX_Q16820.
PharmGKBPA30754.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG322115.
HOGENOMHOG000043106.
HOVERGENHBG052457.
InParanoidQ16820.
KOK08606.
OMADYVSIIW.
OrthoDBEOG73V6MT.
PhylomeDBQ16820.
TreeFamTF315280.

Enzyme and pathway databases

SignaLinkQ16820.

Gene expression databases

BgeeQ16820.
CleanExHS_MEP1B.
GenevestigatorQ16820.

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.
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

GeneWikiMEP1B.
GenomeRNAi4225.
NextBio16675.
PROQ16820.
SOURCESearch...

Entry information

Entry nameMEP1B_HUMAN
AccessionPrimary (citable) accession number: Q16820
Secondary accession number(s): B7ZM35, B9EGL6, Q670J1
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 138 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM