Q61847 (MEP1B_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Meprin A subunit beta
EC=3.4.24.63

Alternative name(s):
Endopeptidase-2
Meprin B

Gene names

Name:	Mep1b
Synonyms:	Mep-1b

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	704 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 By similarity.
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.5 Ref.7
Cofactor	Binds 1 zinc ion per subunit By similarity.
Enzyme regulation	Strongly inhibited by fetuin-A/AHSG By similarity. Inhibited by cysteine and by the metal ion chelators EDTA and 1,10-phenanthroline. Not inhibited by 3,4-dichloroisocourmarin, soybean trypsin inhibitor, or the cysteine proteinase inhibitors iodoacetic acid and E-64. Ref.5
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. Interacts with MBL2 through its carbohydrate moiety. This interaction may inhibit its catalytic activity. Ref.6 Ref.8
Subcellular location	Cell membrane; Single-pass type I membrane protein.
Tissue specificity	Isoform 1 is expressed in kidney, intestinal brush borders, and salivary ducts. Isoform 2 has been found in carcinoma cells.
Induction	By retinoic acid. Ref.5
Post-translational modification	Proteolytically activated by trypsin in the intestinal lumen and kallikrein-related peptidases in other tissues By similarity. N-glycosylated; contains high mannose and/or complex biantennary structures. Ref.5
Sequence similarities	Belongs to the peptidase M12A family. Contains 1 EGF-like domain. Contains 1 MAM domain. Contains 1 MATH domain.
Biophysicochemical properties	Temperature dependence: The half-life at 58 degrees Celsius is less than 3 minutes. Ref.5

Ontologies

Keywords
Biological process	Inflammatory response
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative promoter usage Alternative splicing
Domain	EGF-like domain Signal Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW membrane Inferred from direct assay Ref.1. Source: MGI plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metalloendopeptidase activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage and alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q61847-1)

Also known as: Beta;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q61847-2)

Also known as: Beta';

The sequence of this isoform differs from the canonical sequence as follows:
     1-27: MDARHQPWFLVFATFLLVSGLPAPEKF → MNSTAGPASRSRHSFKCRMKLLKAPRDGMYMMTFG

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Propeptide	21 – 64	44	By similarity		PRO_0000028885
	Chain	65 – 704	640	Meprin A subunit beta		PRO_0000028886
Regions
	Topological domain	21 – 654	634	Extracellular Potential
	Transmembrane	655 – 678	24	Helical; Potential
	Topological domain	679 – 704	26	Cytoplasmic Potential
	Domain	261 – 430	170	MAM
	Domain	431 – 586	156	MATH
	Domain	607 – 647	41	EGF-like
	Region	63 – 260	198	Metalloprotease
Sites
	Active site	154	1	By similarity
	Metal binding	54	1	Zinc; catalytic By similarity
	Metal binding	153	1	Zinc; catalytic By similarity
	Metal binding	157	1	Zinc; catalytic By similarity
	Metal binding	163	1	Zinc; catalytic By similarity
	Site	239	1	Mediates preference for acidic residues at subsite P1' By similarity
Amino acid modifications
	Glycosylation	193	1	N-linked (GlcNAc...) Potential
	Glycosylation	219	1	N-linked (GlcNAc...) Potential
	Glycosylation	255	1	N-linked (GlcNAc...) Potential
	Glycosylation	316	1	N-linked (GlcNAc...) Potential
	Glycosylation	422	1	N-linked (GlcNAc...) Potential
	Glycosylation	437	1	N-linked (GlcNAc...) Potential
	Glycosylation	529	1	N-linked (GlcNAc...) Potential
	Glycosylation	548	1	N-linked (GlcNAc...) Potential
	Glycosylation	593	1	N-linked (GlcNAc...) Potential
	Disulfide bond	104 ↔ 256		By similarity
	Disulfide bond	125 ↔ 145		By similarity
	Disulfide bond	266 ↔ 428		By similarity
	Disulfide bond	274		Interchain By similarity
	Disulfide bond	306		Interchain By similarity
	Disulfide bond	493		Interchain By similarity
	Disulfide bond	611 ↔ 622		By similarity
	Disulfide bond	616 ↔ 631		By similarity
	Disulfide bond	633 ↔ 646		By similarity
Natural variations
	Alternative sequence	1 – 27	27	MDARH…APEKF → MNSTAGPASRSRHSFKCRMK LLKAPRDGMYMMTFG in isoform 2.		VSP_005460
Experimental info
	Sequence conflict	18	1	V → A in AAA75234. Ref.1
	Sequence conflict	26	1	K → G AA sequence Ref.5
	Sequence conflict	29	1	K → S AA sequence Ref.5
	Sequence conflict	470	1	S → Y in AAA75234. Ref.1
	Sequence conflict	470	1	S → Y no nucleotide entry Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Beta) [UniParc]. Last modified July 13, 2010. Version 2. Checksum: 04F92C493F701525	FASTA	704	79,501
	10 20 30 40 50 60 MDARHQPWFL VFATFLLVSG LPAPEKFVKD IDGGIDQDIF DINQGLGLDL FEGDIKLEAN 70 80 90 100 110 120 GKNSIIGDHK RWPHTIPYVL EDSLEMNAKG VILNAFERYR LKTCIDFKPW SGEANYISVF 130 140 150 160 170 180 KGSGCWSSVG NIHAGKQELS IGTNCDRIAT VQHEFLHALG FWHEQSRADR DDYVIIVWDR 190 200 210 220 230 240 IQPGKEHNFN IYNDSVSDSL NVPYDYTSVM HYSKTAFQNG TESTIVTRIS EFEDVIGQRM 250 260 270 280 290 300 DFSDYDLLKL NQLYNCTSSL SFMDSCDFEL ENICGMIQSS GDSADWQRVS QVLSGPESDH 310 320 330 340 350 360 SKMGQCKDSG FFMHFNTSIL NEGATAMLES RLLYPKRGFQ CLEFYLYNSG SGNDQLNIYT 370 380 390 400 410 420 REYTTGQQGG VLTLQRQIKE VPIGSWQLHY VTLQVTKKFR VVFEGLRGPG TSSGGLSIDD 430 440 450 460 470 480 INLSETRCPH HIWHIQNFTQ ILGGQDTSVY SPPFYSSKGY AFQIYMDLRS STNVGIYFHL 490 500 510 520 530 540 ISGANDDQLQ WPCPWQQATM TLLDQNPDIR QRMFNQRSIT TDPTMTSDNG SYFWDRPSKV 550 560 570 580 590 600 GVTDVFPNGT QFSRGIGYGT TVFITRERLK SREFIKGDDI YILLTVEDIS HLNSTSAVPD 610 620 630 640 650 660 PVPTLAVHNA CSEVVCQNGG ICVVQDGRAE CKCPAGEDWW YMGKRCEKRG STRDTVIIAV 670 680 690 700 SSTVTVFAVM LIITLVSVYC TRRKYRKKAR ANTAAMTLEN QHAF
	Isoform 2 (Beta') [UniParc]. Checksum: 6A876F36D70B70EC	FASTA	712	80,348
	10 20 30 40 50 60 MNSTAGPASR SRHSFKCRMK LLKAPRDGMY MMTFGVKDID GGIDQDIFDI NQGLGLDLFE 70 80 90 100 110 120 GDIKLEANGK NSIIGDHKRW PHTIPYVLED SLEMNAKGVI LNAFERYRLK TCIDFKPWSG 130 140 150 160 170 180 EANYISVFKG SGCWSSVGNI HAGKQELSIG TNCDRIATVQ HEFLHALGFW HEQSRADRDD 190 200 210 220 230 240 YVIIVWDRIQ PGKEHNFNIY NDSVSDSLNV PYDYTSVMHY SKTAFQNGTE STIVTRISEF 250 260 270 280 290 300 EDVIGQRMDF SDYDLLKLNQ LYNCTSSLSF MDSCDFELEN ICGMIQSSGD SADWQRVSQV 310 320 330 340 350 360 LSGPESDHSK MGQCKDSGFF MHFNTSILNE GATAMLESRL LYPKRGFQCL EFYLYNSGSG 370 380 390 400 410 420 NDQLNIYTRE YTTGQQGGVL TLQRQIKEVP IGSWQLHYVT LQVTKKFRVV FEGLRGPGTS 430 440 450 460 470 480 SGGLSIDDIN LSETRCPHHI WHIQNFTQIL GGQDTSVYSP PFYSSKGYAF QIYMDLRSST 490 500 510 520 530 540 NVGIYFHLIS GANDDQLQWP CPWQQATMTL LDQNPDIRQR MFNQRSITTD PTMTSDNGSY 550 560 570 580 590 600 FWDRPSKVGV TDVFPNGTQF SRGIGYGTTV FITRERLKSR EFIKGDDIYI LLTVEDISHL 610 620 630 640 650 660 NSTSAVPDPV PTLAVHNACS EVVCQNGGIC VVQDGRAECK CPAGEDWWYM GKRCEKRGST 670 680 690 700 710 RDTVIIAVSS TVTVFAVMLI ITLVSVYCTR RKYRKKARAN TAAMTLENQH AF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression, and chromosomal localization of the mouse meprin beta subunit." Gorbea C.M., Marchand P., Jiang W., Copeland N.G., Gilbert D.J., Jenkins N.A., Bond J.S. J. Biol. Chem. 268:21035-21043(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 65-88; 96-109; 329-345 AND 541-549. Tissue: Kidney.
[2]	"A novel meprin beta' mRNA in mouse embryonal and human colon carcinoma cells." Dietrich J.M., Bond J.S., Jiang W. J. Biol. Chem. 271:2271-2278(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Kidney.
[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] (ISOFORM 1).
[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] (ISOFORM 1).
[5]	"Meprin-A and -B. Cell surface endopeptidases of the mouse kidney." Kounnas M.Z., Wolz R.L., Gorbea C.M., Bond J.S. J. Biol. Chem. 266:17350-17357(1991) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-30 (ISOFORM 1), CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, GLYCOSYLATION. Strain: C3H/He. Tissue: Kidney.
[6]	"Homo- and heterotetrameric forms of the membrane-bound metalloendopeptidases meprin A and B." Gorbea C.M., Flannery A.V., Bond J.S. Arch. Biochem. Biophys. 290:549-553(1991) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[7]	"Marked differences between metalloproteases meprin A and B in substrate and peptide bond specificity." Bertenshaw G.P., Turk B.E., Hubbard S.J., Matters G.L., Bylander J.E., Crisman J.M., Cantley L.C., Bond J.S. J. Biol. Chem. 276:13248-13255(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY.
[8]	"Mannan-binding protein blocks the activation of metalloproteases meprin alpha and beta." Hirano M., Ma B.Y., Kawasaki N., Okimura K., Baba M., Nakagawa T., Miwa K., Kawasaki N., Oka S., Kawasaki T. J. Immunol. 175:3177-3185(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH MBL2.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L15193 mRNA. Translation: AAA75234.1. CH466557 Genomic DNA. Translation: EDK96962.1. BC125627 mRNA. Translation: AAI25628.1. BC145979 mRNA. Translation: AAI45980.1.
IPI	IPI00126232. IPI00230071.
PIR	A48040.
RefSeq	NP_032612.2. NM_008586.2.
UniGene	Mm.2682.
3D structure databases
ProteinModelPortal	Q61847.
SMR	Q61847. Positions 30-595, 607-649.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q61847. 1 interaction.
Protein family/group databases
MEROPS	M12.004.
PTM databases
PhosphoSite	Q61847.
Proteomic databases
PaxDb	Q61847.
PRIDE	Q61847.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000082235; ENSMUSP00000080866; ENSMUSG00000024313.
GeneID	17288.
KEGG	mmu:17288.
UCSC	uc008eff.1. mouse.
Organism-specific databases
CTD	4225.
MGI	MGI:96964. Mep1b.
Phylogenomic databases
eggNOG	NOG322115.
GeneTree	ENSGT00550000074269.
HOGENOM	HOG000043106.
HOVERGEN	HBG052457.
KO	K08606.
OMA	MDQQSDI.
OrthoDB	EOG408N7Q.
Gene expression databases
Bgee	Q61847.
CleanEx	MM_MEP1B.
Genevestigator	Q61847.
GermOnline	ENSMUSG00000024313. Mus musculus.
Family and domain databases
Gene3D	3.40.390.10. 1 hit.
InterPro	IPR008985. ConA-like_lec_gl_sf. IPR000742. EG-like_dom. IPR000998. MAM_dom. IPR002083. MATH. IPR024079. MetalloPept_cat_dom. IPR008294. Pept_M12A_Meprin. IPR001506. Peptidase_M12A. IPR006026. Peptidase_Metallo. IPR008974. TRAF-like. [Graphical view]
Pfam	PF01400. Astacin. 1 hit. PF00008. EGF. 1 hit. PF00629. MAM. 1 hit. PF00917. MATH. 1 hit. [Graphical view]
PIRSF	PIRSF001196. Meprin. 1 hit.
PRINTS	PR00480. ASTACIN. PR00020. MAMDOMAIN.
SMART	SM00181. EGF. 1 hit. SM00137. MAM. 1 hit. SM00061. MATH. 1 hit. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF49899. ConA_like_lec_gl. 1 hit. SSF49599. Traf_like. 1 hit.
PROSITE	PS00022. EGF_1. False negative. PS01186. EGF_2. False negative. PS50026. 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]
ProtoNet	Search...
Other
NextBio	291804.
SOURCE	Search...

Entry information

Entry name

MEP1B_MOUSE

Accession

Primary (citable) accession number: Q61847
Secondary accession number(s): Q059K0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 13, 2010
Last modified:	May 1, 2013
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program