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Protein

Meprin A subunit beta

Gene

MEP1B

Organism
Homo sapiens (Human)
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.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+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Enzyme regulationi

Strongly inhibited by fetuin-A/AHSG.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi52Zinc; catalyticCombined sources1 Publication1
Metal bindingi152Zinc; via tele nitrogen; catalyticCombined sources1 Publication1
Active sitei153PROSITE-ProRule annotation1
Metal bindingi156Zinc; via tele nitrogen; catalyticCombined sources1 Publication1
Metal bindingi162Zinc; via tele nitrogen; catalyticCombined sources1 Publication1
Sitei238Mediates preference for acidic residues at subsite P1'1

GO - Molecular functioni

  • metalloendopeptidase activity Source: Ensembl
  • zinc ion binding Source: ProtInc

GO - Biological processi

  • digestion Source: ProtInc
  • inflammatory response Source: UniProtKB-KW
  • toxin transport Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Inflammatory response

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141434-MONOMER.
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

HGNCiHGNC:7020. MEP1B.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini23 – 652ExtracellularSequence analysisAdd BLAST630
Transmembranei653 – 673HelicalSequence analysisAdd BLAST21
Topological domaini674 – 701CytoplasmicSequence analysisAdd BLAST28

GO - Cellular componenti

  • extracellular space Source: ProtInc
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: ProtInc
Complete GO annotation...

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...)1 Publication1
Glycosylationi254N-linked (GlcNAc...)1 Publication1
Disulfide bondi265 ↔ 427PROSITE-ProRule annotation1 Publication
Disulfide bondi273InterchainPROSITE-ProRule annotation
Disulfide bondi305InterchainPROSITE-ProRule annotation1 Publication
Glycosylationi370N-linked (GlcNAc...)1 Publication1
Glycosylationi421N-linked (GlcNAc...)Sequence analysis1
Glycosylationi436N-linked (GlcNAc...)1 Publication1
Glycosylationi445N-linked (GlcNAc...)1 Publication1
Disulfide bondi492InterchainPROSITE-ProRule annotation
Glycosylationi547N-linked (GlcNAc...)1 Publication1
Glycosylationi592N-linked (GlcNAc...)1 Publication1
Glycosylationi593O-linked (GalNAc...)Sequence analysis1
Glycosylationi594O-linked (GalNAc...)Sequence analysis1
Glycosylationi599O-linked (GalNAc...)Sequence analysis1
Glycosylationi603O-linked (GalNAc...)Sequence 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.

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.
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

WithEntry#Exp.IntActNotes
MMP9P147802EBI-968418,EBI-1382326

Protein-protein interaction databases

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

Structurei

Secondary structure

1701
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni29 – 32Combined sources4
Helixi37 – 43Combined sources7
Turni50 – 52Combined sources3
Beta strandi63 – 65Combined sources3
Helixi67 – 69Combined sources3
Beta strandi73 – 79Combined sources7
Helixi85 – 101Combined sources17
Beta strandi105 – 108Combined sources4
Beta strandi113 – 119Combined sources7
Beta strandi122 – 126Combined sources5
Beta strandi133 – 140Combined sources8
Helixi147 – 158Combined sources12
Helixi163 – 165Combined sources3
Helixi169 – 171Combined sources3
Beta strandi173 – 175Combined sources3
Helixi177 – 179Combined sources3
Helixi185 – 188Combined sources4
Turni193 – 195Combined sources3
Turni213 – 216Combined sources4
Beta strandi217 – 221Combined sources5
Beta strandi223 – 228Combined sources6
Helixi229 – 231Combined sources3
Turni232 – 236Combined sources5
Helixi243 – 252Combined sources10
Beta strandi259 – 265Combined sources7
Helixi272 – 274Combined sources3
Beta strandi276 – 278Combined sources3
Beta strandi280 – 282Combined sources3
Beta strandi285 – 289Combined sources5
Beta strandi292 – 294Combined sources3
Beta strandi299 – 304Combined sources6
Beta strandi311 – 315Combined sources5
Beta strandi317 – 319Combined sources3
Beta strandi324 – 328Combined sources5
Beta strandi335 – 337Combined sources3
Beta strandi339 – 347Combined sources9
Beta strandi354 – 363Combined sources10
Beta strandi366 – 379Combined sources14
Beta strandi382 – 384Combined sources3
Beta strandi386 – 392Combined sources7
Beta strandi398 – 405Combined sources8
Beta strandi412 – 425Combined sources14
Beta strandi429 – 434Combined sources6
Helixi438 – 440Combined sources3
Beta strandi447 – 449Combined sources3
Beta strandi460 – 466Combined sources7
Beta strandi469 – 480Combined sources12
Helixi485 – 487Combined sources3
Beta strandi494 – 501Combined sources8
Helixi508 – 510Combined sources3
Beta strandi514 – 519Combined sources6
Beta strandi527 – 531Combined sources5
Helixi536 – 539Combined sources4
Beta strandi541 – 544Combined sources4
Beta strandi550 – 564Combined sources15
Helixi565 – 568Combined sources4
Beta strandi573 – 575Combined sources3
Beta strandi578 – 587Combined sources10
Helixi589 – 591Combined sources3

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...

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni64 – 259MetalloproteaseAdd BLAST196
Regioni595 – 607Required for proteolytic processingAdd BLAST13

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.
InParanoidiQ16820.
KOiK08606.
OMAiDYVSIIW.
OrthoDBiEOG091G009U.
PhylomeDBiQ16820.
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.
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.

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

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 → A.1 Publication1
Natural variantiVAR_057064326V → M.Corresponds to variant rs9959396dbSNPEnsembl.1
Natural variantiVAR_057065695P → L.2 PublicationsCorresponds to variant rs616114dbSNPEnsembl.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

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.
DIPiDIP-34900N.
IntActiQ16820. 1 interactor.
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.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4225.
DisGeNETi4225.
GeneCardsiMEP1B.
H-InvDBHIX0039722.
HGNCiHGNC:7020. MEP1B.
HPAiHPA029119.
MIMi600389. gene.
neXtProtiNX_Q16820.
OpenTargetsiENSG00000141434.
PharmGKBiPA30754.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141434-MONOMER.
BRENDAi3.4.24.63. 2681.
SignaLinkiQ16820.

Miscellaneous databases

GeneWikiiMEP1B.
GenomeRNAii4225.
PROiQ16820.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141434.
CleanExiHS_MEP1B.
ExpressionAtlasiQ16820. baseline and differential.
GenevisibleiQ16820. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: Q16820
Secondary accession number(s): B7ZM35, B9EGL6, Q670J1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 18, 2010
Last modified: November 2, 2016
This is version 159 of the entry and version 3 of the sequence. [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 chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.