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Protein

Meprin A subunit beta

Gene

MEP1B

Organism
Homo sapiens (Human)
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. 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.1 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.1 Publication

Cofactori

Zn2+PROSITE-ProRule annotation1 PublicationNote: Binds 1 zinc ion per subunit.PROSITE-ProRule annotation1 Publication

Activity regulationi

Strongly inhibited by fetuin-A/AHSG.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi152Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1 Publication1
Active sitei153PROSITE-ProRule annotation1
Metal bindingi156Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1 Publication1
Metal bindingi162Zinc; via tele nitrogen; catalyticPROSITE-ProRule annotationCombined sources1 Publication1
Sitei238Mediates preference for acidic residues at subsite P1'1

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • metalloendopeptidase activity Source: GO_Central
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BRENDAi3.4.24.63 2681
SignaLinkiQ16820

Protein family/group databases

MEROPSiM12.004
TCDBi8.A.77.2.1 the sheddase (sheddase) family

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:MEP1B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000141434.11
HGNCiHGNC:7020 MEP1B
MIMi600389 gene
neXtProtiNX_Q16820

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 domaini23 – 652ExtracellularSequence analysisAdd BLAST630
Transmembranei653 – 673HelicalSequence analysisAdd BLAST21
Topological domaini674 – 701CytoplasmicSequence analysisAdd BLAST28

Keywords - Cellular componenti

Cell membrane, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi248K → Y: Decreased activity toward gastrin. 1 Publication1
Mutagenesisi595 – 607Missing : Abolishes secretion. 1 PublicationAdd BLAST13

Organism-specific databases

DisGeNETi4225
OpenTargetsiENSG00000141434
PharmGKBiPA30754

Polymorphism and mutation databases

BioMutaiMEP1B
DMDMi296439304

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 22Sequence analysisAdd BLAST22
PropeptideiPRO_000002888323 – 612 PublicationsAdd BLAST39
ChainiPRO_000002888462 – 701Meprin A subunit betaAdd BLAST640

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi103 ↔ 255PROSITE-ProRule annotation1 Publication
Disulfide bondi124 ↔ 144PROSITE-ProRule annotation1 Publication
Glycosylationi218N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi254N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi265 ↔ 427PROSITE-ProRule annotation1 Publication
Disulfide bondi273InterchainPROSITE-ProRule annotation
Disulfide bondi305InterchainPROSITE-ProRule annotation1 Publication
Glycosylationi370N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi421N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi436N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi445N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi492InterchainPROSITE-ProRule annotation
Glycosylationi547N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi592N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi593O-linked (GalNAc...) serineSequence analysis1
Glycosylationi594O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi599O-linked (GalNAc...) threonineSequence analysis1
Glycosylationi603O-linked (GalNAc...) serineSequence analysis1
Disulfide bondi608 ↔ 619PROSITE-ProRule annotation
Disulfide bondi613 ↔ 628PROSITE-ProRule annotation
Disulfide bondi630 ↔ 643PROSITE-ProRule annotation

Post-translational modificationi

N-glycosylated; contains high mannose and/or complex biantennary structures.
O-glycosylation protect the C-terminal region from proteolytic cleavage and diminish secretion, this seems to be specific to human.7 Publications
Proteolytically activated by trypsin in the intestinal lumen and kallikrein-related peptidases in other tissues.

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiQ16820
PeptideAtlasiQ16820
PRIDEiQ16820
ProteomicsDBi61079

PTM databases

iPTMnetiQ16820
PhosphoSitePlusiQ16820

Expressioni

Tissue specificityi

The major site of expression is the brush border membrane of small intestinal and kidney epithelial cells.1 Publication

Gene expression databases

BgeeiENSG00000141434 Expressed in 93 organ(s), highest expression level in jejunal mucosa
CleanExiHS_MEP1B
ExpressionAtlasiQ16820 baseline and differential
GenevisibleiQ16820 HS

Organism-specific databases

HPAiHPA029119

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

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110388, 4 interactors
CORUMiQ16820
DIPiDIP-34900N
IntActiQ16820, 1 interactor
MINTiQ16820
STRINGi9606.ENSP00000269202

Structurei

Secondary structure

1701
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ16820
SMRiQ16820
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini62 – 256Peptidase M12APROSITE-ProRule annotationAdd BLAST195
Domaini260 – 429MAMPROSITE-ProRule annotationAdd BLAST170
Domaini430 – 585MATHPROSITE-ProRule annotationAdd BLAST156
Domaini604 – 644EGF-likePROSITE-ProRule annotationAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni595 – 607Required for proteolytic processingAdd BLAST13

Keywords - Domaini

EGF-like domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3714 Eukaryota
ENOG410ZPX7 LUCA
GeneTreeiENSGT00760000119227
HOGENOMiHOG000043106
HOVERGENiHBG052457
InParanoidiQ16820
KOiK08606
OMAiWHIRNFT
OrthoDBiEOG091G009U
PhylomeDBiQ16820
TreeFamiTF315280

Family and domain databases

CDDicd06263 MAM, 1 hit
cd04282 ZnMc_meprin, 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
IPR034038 ZnMP_meprin
PANTHERiPTHR44155 PTHR44155, 1 hit
PTHR44155:SF3 PTHR44155:SF3, 1 hit
PfamiView protein in Pfam
PF01400 Astacin, 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
PS51864 ASTACIN, 1 hit
PS50026 EGF_3, 1 hit
PS00740 MAM_1, 1 hit
PS50060 MAM_2, 1 hit
PS50144 MATH, 1 hit
PS00142 ZINC_PROTEASE, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

Q16820-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDLWNLSWFL FLDALLVISG LATPENFDVD GGMDQDIFDI NEGLGLDLFE
60 70 80 90 100
GDIRLDRAQI RNSIIGEKYR WPHTIPYVLE DSLEMNAKGV ILNAFERYRL
110 120 130 140 150
KTCIDFKPWA GETNYISVFK GSGCWSSVGN RRVGKQELSI GANCDRIATV
160 170 180 190 200
QHEFLHALGF WHEQSRSDRD DYVRIMWDRI LSGREHNFNT YSDDISDSLN
210 220 230 240 250
VPYDYTSVMH YSKTAFQNGT EPTIVTRISD FEDVIGQRMD FSDSDLLKLN
260 270 280 290 300
QLYNCSSSLS FMDSCSFELE NVCGMIQSSG DNADWQRVSQ VPRGPESDHS
310 320 330 340 350
NMGQCQGSGF FMHFDSSSVN VGATAVLESR TLYPKRGFQC LQFYLYNSGS
360 370 380 390 400
ESDQLNIYIR EYSADNVDGN LTLVEEIKEI PTGSWQLYHV TLKVTKKFRV
410 420 430 440 450
VFEGRKGSGA SLGGLSIDDI NLSETRCPHH IWHIRNFTQF IGSPNGTLYS
460 470 480 490 500
PPFYSSKGYA FQIYLNLAHV TNAGIYFHLI SGANDDQLQW PCPWQQATMT
510 520 530 540 550
LLDQNPDIRQ RMSNQRSITT DPFMTTDNGN YFWDRPSKVG TVALFSNGTQ
560 570 580 590 600
FRRGGGYGTS AFITHERLKS RDFIKGDDVY ILLTVEDISH LNSTQIQLTP
610 620 630 640 650
APSVQDLCSK TTCKNDGVCT VRDGKAECRC QSGEDWWYMG ERCEKRGSTR
660 670 680 690 700
DTIVIAVSST VAVFALMLII TLVSVYCTRK KYRERMSSNR PNLTPQNQHA

F
Length:701
Mass (Da):79,571
Last modified:May 18, 2010 - v3
Checksum:i4733DBF018A4F3CD
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
J3QKX5J3QKX5_HUMAN
Meprin A subunit
MEP1B hCG_25081
700Annotation score:
J3KRK1J3KRK1_HUMAN
Meprin A subunit beta
MEP1B
114Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti71W → S AA sequence (PubMed:8262185).Curated1
Sequence conflicti74T → P AA sequence (PubMed:8262185).Curated1
Sequence conflicti546S → P in AAU05377 (Ref. 2) Curated1
Sequence conflicti546S → P in AAI36560 (PubMed:15489334).Curated1
Sequence conflicti546S → P in AAI44245 (PubMed:15489334).Curated1
Sequence conflicti698Missing in CAA57107 (PubMed:9288916).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069387324T → A1 Publication1
Natural variantiVAR_057064326V → M. Corresponds to variant dbSNP:rs9959396Ensembl.1
Natural variantiVAR_057065695P → L2 PublicationsCorresponds to variant dbSNP:rs616114Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81333 mRNA Translation: CAA57107.1
AY695931 mRNA Translation: AAU05377.1
BC136559 mRNA Translation: AAI36560.1
BC144244 mRNA Translation: AAI44245.1
CCDSiCCDS45846.1
PIRiS49383 HYHUMB
RefSeqiNP_001295100.1, NM_001308171.1
NP_005916.2, NM_005925.2
UniGeneiHs.194777

Genome annotation databases

EnsembliENST00000269202; ENSP00000269202; ENSG00000141434
GeneIDi4225
KEGGihsa:4225
UCSCiuc002kxj.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X81333 mRNA Translation: CAA57107.1
AY695931 mRNA Translation: AAU05377.1
BC136559 mRNA Translation: AAI36560.1
BC144244 mRNA Translation: AAI44245.1
CCDSiCCDS45846.1
PIRiS49383 HYHUMB
RefSeqiNP_001295100.1, NM_001308171.1
NP_005916.2, NM_005925.2
UniGeneiHs.194777

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4GWMX-ray1.85A/B23-614[»]
4GWNX-ray3.00A62-614[»]
ProteinModelPortaliQ16820
SMRiQ16820
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110388, 4 interactors
CORUMiQ16820
DIPiDIP-34900N
IntActiQ16820, 1 interactor
MINTiQ16820
STRINGi9606.ENSP00000269202

Protein family/group databases

MEROPSiM12.004
TCDBi8.A.77.2.1 the sheddase (sheddase) family

PTM databases

iPTMnetiQ16820
PhosphoSitePlusiQ16820

Polymorphism and mutation databases

BioMutaiMEP1B
DMDMi296439304

Proteomic databases

PaxDbiQ16820
PeptideAtlasiQ16820
PRIDEiQ16820
ProteomicsDBi61079

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269202; ENSP00000269202; ENSG00000141434
GeneIDi4225
KEGGihsa:4225
UCSCiuc002kxj.5 human

Organism-specific databases

CTDi4225
DisGeNETi4225
EuPathDBiHostDB:ENSG00000141434.11
GeneCardsiMEP1B
H-InvDBiHIX0039722
HGNCiHGNC:7020 MEP1B
HPAiHPA029119
MIMi600389 gene
neXtProtiNX_Q16820
OpenTargetsiENSG00000141434
PharmGKBiPA30754
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3714 Eukaryota
ENOG410ZPX7 LUCA
GeneTreeiENSGT00760000119227
HOGENOMiHOG000043106
HOVERGENiHBG052457
InParanoidiQ16820
KOiK08606
OMAiWHIRNFT
OrthoDBiEOG091G009U
PhylomeDBiQ16820
TreeFamiTF315280

Enzyme and pathway databases

BRENDAi3.4.24.63 2681
SignaLinkiQ16820

Miscellaneous databases

GeneWikiiMEP1B
GenomeRNAii4225
PROiPR:Q16820
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141434 Expressed in 93 organ(s), highest expression level in jejunal mucosa
CleanExiHS_MEP1B
ExpressionAtlasiQ16820 baseline and differential
GenevisibleiQ16820 HS

Family and domain databases

CDDicd06263 MAM, 1 hit
cd04282 ZnMc_meprin, 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
IPR034038 ZnMP_meprin
PANTHERiPTHR44155 PTHR44155, 1 hit
PTHR44155:SF3 PTHR44155:SF3, 1 hit
PfamiView protein in Pfam
PF01400 Astacin, 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
PS51864 ASTACIN, 1 hit
PS50026 EGF_3, 1 hit
PS00740 MAM_1, 1 hit
PS50060 MAM_2, 1 hit
PS50144 MATH, 1 hit
PS00142 ZINC_PROTEASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMEP1B_HUMAN
AccessioniPrimary (citable) accession number: Q16820
Secondary accession number(s): B7ZM35, B9EGL6, Q670J1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 174 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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