MMPB_CAEEL
ID MMPB_CAEEL Reviewed; 519 AA.
AC O44836; H2L0C2; O61265; Q95X57;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Matrix metalloproteinase-B {ECO:0000305|PubMed:9573338};
DE Short=MMP-B {ECO:0000305|PubMed:9573338};
DE Short=MMP-H19 {ECO:0000303|PubMed:9573338};
DE EC=3.4.24.- {ECO:0000269|PubMed:9573338};
DE AltName: Full=Zinc metalloprotease 2 {ECO:0000312|WormBase:H19M22.3a};
DE Flags: Precursor;
GN Name=zmp-2 {ECO:0000312|WormBase:H19M22.3a};
GN ORFNames=H19M22.3 {ECO:0000312|WormBase:H19M22.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000312|EMBL:BAA28352.1}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 60-519 (ISOFORM A), CATALYTIC ACTIVITY, AND
RP ACTIVITY REGULATION.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:BAA28352.1};
RX PubMed=9573338; DOI=10.1016/s0378-1119(98)00076-6;
RA Wada K., Sato H., Kinoh H., Kajita M., Yamamoto H., Seiki M.;
RT "Cloning of three Caenorhabditis elegans genes potentially encoding novel
RT matrix metalloproteinases.";
RL Gene 211:57-62(1998).
RN [3] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=20600277; DOI=10.1016/j.dci.2010.06.010;
RA Altincicek B., Fischer M., Fischer M., Lueersen K., Boll M., Wenzel U.,
RA Vilcinskas A.;
RT "Role of matrix metalloproteinase ZMP-2 in pathogen resistance and
RT development in Caenorhabditis elegans.";
RL Dev. Comp. Immunol. 34:1160-1169(2010).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=24957743; DOI=10.1007/s12263-014-0414-6;
RA Fischer M., Fitzenberger E., Kull R., Boll M., Wenzel U.;
RT "The zinc matrix metalloproteinase ZMP-2 increases survival of
RT Caenorhabditis elegans through interference with lipoprotein absorption.";
RL Genes Nutr. 9:414-414(2014).
CC -!- FUNCTION: Metalloprotease involved in molting, a process during larval
CC stages in which a new cuticle is formed and the old cuticle is shed
CC (PubMed:24957743). Plays a role in thermotolerance probably by
CC preventing the accumulation of oxidized lipoproteins and cholesterol
CC (PubMed:20600277, PubMed:24957743). {ECO:0000269|PubMed:20600277,
CC ECO:0000269|PubMed:24957743}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P03956};
CC -!- ACTIVITY REGULATION: Inhibited by human TIMP1 and TIMP2 and the broad
CC MMP inhibitors BB94 (Batimastat) and CT543.
CC {ECO:0000269|PubMed:9573338}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000305|PubMed:24957743}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:H19M22.3a};
CC IsoId=O44836-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:H19M22.3b};
CC IsoId=O44836-2; Sequence=VSP_058809, VSP_058810;
CC Name=c {ECO:0000312|WormBase:H19M22.3c};
CC IsoId=O44836-3; Sequence=VSP_058808, VSP_058811;
CC -!- TISSUE SPECIFICITY: Expressed in spermatheca and spermathecal-uterine
CC valve, weakly in vulva and anal muscles and in two cells in the head
CC (probably RMEV and RMED motor neurons). {ECO:0000269|PubMed:20600277}.
CC -!- DEVELOPMENTAL STAGE: Expressed at the comma, 1.5-fold and 3-fold
CC embryonic stages in multiple cells including muscle and somatic gonad
CC cells. In L1 larvae, predominantly expressed in specific muscles and
CC somatic gonad cells, in L2 larvae predominantly expressed in muscles
CC cells and in L4 larvae expressed predominantly in the developing
CC spermatheca and more weakly in vulva muscle cells. Expression increases
CC in the hypodermis in dauer stage larvae prior molting to L4 larval
CC stage. {ECO:0000269|PubMed:20600277}.
CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch motif
CC binds the catalytic zinc ion, thus inhibiting the enzyme. The
CC dissociation of the cysteine from the zinc ion upon the activation-
CC peptide release activates the enzyme. {ECO:0000250|UniProtKB:P03956}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a delay in larval
CC to adult development with reduced motility and feeding
CC (PubMed:20600277). Also reduces fecundity in adults (PubMed:20600277).
CC Larvae have molting defects characterized by incomplete cuticle
CC shedding leaving a constriction ring in the larvae anterior part
CC (PubMed:20600277). Reduces survival upon Gram-negative bacterium
CC P.luminescense infection or heat stress (PubMed:20600277,
CC PubMed:24957743). Production of extra- and intra-cellular reactive
CC oxygen species (ROS) and protein oxidation are increased whereas vit-6
CC transcription and dehydroergosterol (DHE) uptake are reduced
CC (PubMed:24957743). Moreover, causes constitutive daf-16 nuclear
CC localization (PubMed:24957743). Simultaneous RNAi-mediated knockdown of
CC vit-6, rme-2, daf-16 or daf-16 coactivators sir2.1, ftt-2 and par-2
CC restores normal thermotolerance (PubMed:24957743). RNAi-mediated
CC knockdown in a daf-9 or daf-12 mutant background reduces survival
CC further upon heat stress. {ECO:0000269|PubMed:20600277,
CC ECO:0000269|PubMed:24957743}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000255}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA28352.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; BX284603; CCD72394.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD72395.1; -; Genomic_DNA.
DR EMBL; BX284603; CCD72396.1; -; Genomic_DNA.
DR EMBL; AB007816; BAA28352.1; ALT_SEQ; mRNA.
DR PIR; T37250; T37250.
DR RefSeq; NP_497594.1; NM_065193.4. [O44836-1]
DR RefSeq; NP_497595.1; NM_065194.3.
DR RefSeq; NP_497596.2; NM_065195.2. [O44836-3]
DR AlphaFoldDB; O44836; -.
DR SMR; O44836; -.
DR STRING; 6239.H19M22.3a; -.
DR MEROPS; M10.068; -.
DR PaxDb; O44836; -.
DR EnsemblMetazoa; H19M22.3a.1; H19M22.3a.1; WBGene00019212. [O44836-1]
DR EnsemblMetazoa; H19M22.3b.1; H19M22.3b.1; WBGene00019212. [O44836-2]
DR EnsemblMetazoa; H19M22.3c.1; H19M22.3c.1; WBGene00019212. [O44836-3]
DR GeneID; 175383; -.
DR KEGG; cel:CELE_H19M22.3; -.
DR UCSC; H19M22.3a; c. elegans.
DR CTD; 175383; -.
DR WormBase; H19M22.3a; CE26937; WBGene00019212; zmp-2. [O44836-1]
DR WormBase; H19M22.3b; CE29414; WBGene00019212; zmp-2. [O44836-2]
DR WormBase; H19M22.3c; CE34904; WBGene00019212; zmp-2. [O44836-3]
DR eggNOG; KOG1565; Eukaryota.
DR HOGENOM; CLU_656062_0_0_1; -.
DR InParanoid; O44836; -.
DR OMA; ALMHPYY; -.
DR OrthoDB; 899924at2759; -.
DR PhylomeDB; O44836; -.
DR Reactome; R-CEL-1442490; Collagen degradation.
DR Reactome; R-CEL-1474228; Degradation of the extracellular matrix.
DR Reactome; R-CEL-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-CEL-210991; Basigin interactions.
DR Reactome; R-CEL-2179392; EGFR Transactivation by Gastrin.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR PRO; PR:O44836; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00019212; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008237; F:metallopeptidase activity; IMP:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0042395; P:ecdysis, collagen and cuticulin-based cuticle; IMP:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0010286; P:heat acclimation; IMP:UniProtKB.
DR GO; GO:0002164; P:larval development; IMP:UniProtKB.
DR GO; GO:0042308; P:negative regulation of protein import into nucleus; IMP:UniProtKB.
DR GO; GO:1904807; P:negative regulation of protein oxidation; IMP:UniProtKB.
DR GO; GO:1903427; P:negative regulation of reactive oxygen species biosynthetic process; IMP:UniProtKB.
DR GO; GO:1900036; P:positive regulation of cellular response to heat; IMP:UniProtKB.
DR GO; GO:1904109; P:positive regulation of cholesterol import; IMP:UniProtKB.
DR GO; GO:1904000; P:positive regulation of eating behavior; IMP:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0040017; P:positive regulation of locomotion; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR033739; M10A_MMP.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR036365; PGBD-like_sf.
DR Pfam; PF00413; Peptidase_M10; 1.
DR PRINTS; PR00138; MATRIXIN.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cleavage on pair of basic residues;
KW Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Secreted; Signal; Zinc;
KW Zymogen.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT PROPEP 27..126
FT /note="Activation peptide"
FT /evidence="ECO:0000250|UniProtKB:P50281"
FT /id="PRO_0000439232"
FT CHAIN 126..519
FT /note="Matrix metalloproteinase-B"
FT /evidence="ECO:0000305"
FT /id="PRO_5004158457"
FT REGION 29..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 109..116
FT /note="Cysteine switch"
FT /evidence="ECO:0000250|UniProtKB:P03957"
FT ACT_SITE 277
FT /evidence="ECO:0000250|UniProtKB:P09238"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 208
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 210
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 232
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 247
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 276
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 280
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 286
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 408
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT VAR_SEQ 1..87
FT /note="MTKWSPNGNPLSTIYLILSLFTLAHTAPTTQHSRTTTQLRLEDEDGGGGVDE
FT DSIHFVKGQMEKYGYLKGIDHSSPQEFRQALMFFQ -> MARCRRISGGGIRQKVFNTH
FT NCASFSGSNGKVWLSQRHRSLVTARISASSHVLPS (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_058808"
FT VAR_SEQ 88..101
FT /note="EVLEVEQTGNVDEM -> VKFSRWNRLETSMR (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_058809"
FT VAR_SEQ 102..519
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_058810"
FT VAR_SEQ 365..399
FT /note="SEGFFLFQLKFPHSTLTHTDDVVMREKDKRSYRGD -> N (in isoform
FT c)"
FT /id="VSP_058811"
FT CONFLICT 348
FT /note="H -> D (in Ref. 2; BAA28352)"
FT /evidence="ECO:0000305"
FT CONFLICT 365..398
FT /note="Missing (in Ref. 2; BAA28352)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="T -> A (in Ref. 2; BAA28352)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 519 AA; 59254 MW; C02A8C11F6B263F4 CRC64;
MTKWSPNGNP LSTIYLILSL FTLAHTAPTT QHSRTTTQLR LEDEDGGGGV DEDSIHFVKG
QMEKYGYLKG IDHSSPQEFR QALMFFQEVL EVEQTGNVDE MTVEAASKPR CTQTDVRQEQ
TKRTKRFTLS KRAKWAHASG QSVTLKWYIS DYTSDIDRLE TRKVVEKAFK LWSSQSYIKN
EKKVTLTFQE ASSKDEADIN ILWAEGNHGD EHDFDGANGK IEGNKKENVL AHTFFPGYAR
PLNGDIHFDD AEDWEIDVDQ VGHGSNKRFF PYVLAHEIGH ALGLDHSQKA DALMHPYYKN
VPINEIQLDI DDKCGVIWNY GGASDFCLYV WLMSQIVEAH NSSAQNNHGV GSITSSRTNK
KSFKSEGFFL FQLKFPHSTL THTDDVVMRE KDKRSYRGDS KIPKCSSNNS SQRTLAEKKL
TLGLHLSEAD AKRYTEMVCN FLAGLHMWRT NPNHHASESL EKEYKGVSQE MGTFSGKSIA
VRRLIRHAEH QKERSEKGPL DPDYFDDDFF ENFFMEYSK
