MMPA_CAEEL
ID MMPA_CAEEL Reviewed; 521 AA.
AC G5EGM1;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Matrix metalloproteinase-A {ECO:0000305|PubMed:9573338};
DE Short=MMP-A {ECO:0000305|PubMed:9573338};
DE Short=MMP-Y19 {ECO:0000303|PubMed:9573338};
DE EC=3.4.24.- {ECO:0000269|PubMed:9573338};
DE AltName: Full=Zinc metalloprotease 1 {ECO:0000312|WormBase:EGAP1.3};
DE Flags: Precursor;
GN Name=zmp-1 {ECO:0000312|WormBase:EGAP1.3};
GN ORFNames=EGAP1.3 {ECO:0000312|WormBase:EGAP1.3};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|EMBL:BAA28353.1};
RN [1] {ECO:0000312|EMBL:BAA28353.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND CATALYTIC ACTIVITY.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:BAA28353.1};
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 [2] {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 [3] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=11060231; DOI=10.1242/dev.127.23.5047;
RA Wang M., Sternberg P.W.;
RT "Patterning of the C. elegans 1 degrees vulval lineage by RAS and Wnt
RT pathways.";
RL Development 127:5047-5058(2000).
RN [4] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=15960981; DOI=10.1016/j.cell.2005.03.031;
RA Sherwood D.R., Butler J.A., Kramer J.M., Sternberg P.W.;
RT "FOS-1 promotes basement-membrane removal during anchor-cell invasion in C.
RT elegans.";
RL Cell 121:951-962(2005).
RN [5] {ECO:0000305}
RP TISSUE SPECIFICITY.
RX PubMed=19906858; DOI=10.1242/dev.035477;
RA Kato M., Sternberg P.W.;
RT "The C. elegans tailless/Tlx homolog nhr-67 regulates a stage-specific
RT program of linker cell migration in male gonadogenesis.";
RL Development 136:3907-3915(2009).
CC -!- FUNCTION: Metalloprotease which, together with cadherin cdh-3 and
CC hemicentin him-4, plays a role in anchor cell (AC) invasion during
CC postembryonic vulval development probably by promoting the degradation
CC of the basement membrane separating the gonad from the vulva
CC epithelium. {ECO:0000269|PubMed:15960981}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:O60882};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15960981};
CC Single-pass type I membrane protein {ECO:0000305}. Basolateral cell
CC membrane {ECO:0000269|PubMed:15960981}. Note=Localizes to puncta on the
CC cell surface that are often concentrated at the invasive basolateral
CC membrane of the anchor cell. {ECO:0000269|PubMed:15960981}.
CC -!- TISSUE SPECIFICITY: Expressed in the anchor cell (PubMed:11060231,
CC PubMed:15960981). Expressed in the anchor cell throughout the L3 and
CC the early L4 stage, but not in vulva precursor cells P6.p, P6.px, or
CC P6.pxx (PubMed:11060231). Expression in P6.pxxx cells begins in late-L4
CC stage. During L4 lethargus, expressed in all four vulE cells, but not
CC in vulF cells (PubMed:11060231). The expression in vulE cells persists
CC in adulthood (PubMed:11060231). In males, expressed in the linker cell
CC (LC) from the early L4 stage until LC death during the L4-to-adult molt
CC (PubMed:19906858). {ECO:0000269|PubMed:11060231,
CC ECO:0000269|PubMed:15960981, ECO:0000269|PubMed:19906858}.
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: No defect in anchor cell invasion. In 7 percent
CC of cdh-3 and zmp-1 double mutants and in 25 percent of cdh-3, him-4 and
CC zmp-1 triple mutants, anchor cell invasion is delayed.
CC {ECO:0000269|PubMed:15960981}.
CC -!- MISCELLANEOUS: Displays very low catalytic activity compared to zmp-2
CC towards synthetic substrate Mca-Pro-Leu-Gly-Leu-Gly-Leu-Dpa-Ala-Arg-NH2
CC in vitro. {ECO:0000269|PubMed:9573338}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000255}.
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DR EMBL; AB007817; BAA28353.1; -; mRNA.
DR EMBL; BX284603; CCD65979.1; -; Genomic_DNA.
DR PIR; T37252; T37252.
DR RefSeq; NP_741156.1; NM_171138.2.
DR AlphaFoldDB; G5EGM1; -.
DR SMR; G5EGM1; -.
DR STRING; 6239.EGAP1.3; -.
DR MEROPS; M10.067; -.
DR PaxDb; G5EGM1; -.
DR PeptideAtlas; G5EGM1; -.
DR EnsemblMetazoa; EGAP1.3.1; EGAP1.3.1; WBGene00006987.
DR GeneID; 175839; -.
DR KEGG; cel:CELE_EGAP1.3; -.
DR CTD; 175839; -.
DR WormBase; EGAP1.3; CE30930; WBGene00006987; zmp-1.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000166111; -.
DR HOGENOM; CLU_015489_6_0_1; -.
DR InParanoid; G5EGM1; -.
DR OMA; QSWLKSY; -.
DR OrthoDB; 1133360at2759; -.
DR PhylomeDB; G5EGM1; -.
DR Reactome; R-CEL-1592389; Activation of Matrix Metalloproteinases.
DR Reactome; R-CEL-6798695; Neutrophil degranulation.
DR PRO; PR:G5EGM1; -.
DR Proteomes; UP000001940; Chromosome III.
DR Bgee; WBGene00006987; Expressed in embryo and 3 other tissues.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009986; C:cell surface; IDA:WormBase.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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:0034769; P:basement membrane disassembly; IGI:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd00094; HX; 1.
DR CDD; cd04278; ZnMc_MMP; 1.
DR Gene3D; 2.110.10.10; -; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR000585; Hemopexin-like_dom.
DR InterPro; IPR036375; Hemopexin-like_dom_sf.
DR InterPro; IPR018487; Hemopexin-like_repeat.
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; IPR021158; Pept_M10A_Zn_BS.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR InterPro; IPR033595; Zmp-1.
DR PANTHER; PTHR10201:SF280; PTHR10201:SF280; 1.
DR Pfam; PF00413; Peptidase_M10; 1.
DR Pfam; PF01471; PG_binding_1; 1.
DR PIRSF; PIRSF001191; Peptidase_M10A_matrix; 1.
DR PRINTS; PR00138; MATRIXIN.
DR SMART; SM00120; HX; 4.
DR SMART; SM00235; ZnMc; 1.
DR SUPFAM; SSF47090; SSF47090; 1.
DR SUPFAM; SSF50923; SSF50923; 1.
DR PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 3.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cleavage on pair of basic residues; Glycoprotein; Hydrolase;
KW Membrane; Metal-binding; Metalloprotease; Protease; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..95
FT /note="Activation peptide"
FT /evidence="ECO:0000250|UniProtKB:P50281"
FT /id="PRO_0000439231"
FT CHAIN 96..521
FT /note="Matrix metalloproteinase-A"
FT /evidence="ECO:0000305"
FT /id="PRO_5007661160"
FT TOPO_DOM 96..500
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 501..521
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 300..347
FT /note="Hemopexin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01011"
FT REPEAT 391..443
FT /note="Hemopexin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01011"
FT REPEAT 444..492
FT /note="Hemopexin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01011"
FT REGION 259..298
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 78..85
FT /note="Cysteine switch"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT ACT_SITE 216
FT /evidence="ECO:0000250|UniProtKB:P09238"
FT BINDING 80
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 215
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 219
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT BINDING 225
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:P03956"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 469
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 521 AA; 60700 MW; F3936A1C732C6FE2 CRC64;
MFTGLHDILI ILFLLVTLKI AQNVDHTKFL QKYGYLTSGD NQLSSESLSD ALKNMQRMAG
LEETGELDER TIQMMERPRC GHPDVEDHQK SRGKRYAPPQ FKWKEKIITY GCKAVGTSTR
ISLDDLRRTM HQAASQWSEL ADVEIVESSV KNPMMVISAG RENHYPCTVR FDTKTLAHAF
FPTNGQIHIN DRVQFAMTNY TERMGANSLY SVVAHEMGHA LGFSHSPDID SVMFAYDTPR
KWKFTSMDKY NMRSYYGAKA SKKENEEEER KTENEDKRRK TEKDRGRTRE HESDDIRPNE
CRVENPIVVQ YRGEYLIFKS QWVWRVSSDW KRLIIKAVPI NQLFPGLPNP IDAAVTVGHN
LWVFVGEMIY VIYGNHMVHA PLRLSDIGIN EKYVDLAYEW HYFNPPAVYI WKGSRYWKLD
EKMYHRRVDE RYPKDTDLNW ARVPKGVHSA FTYEKEIHLL RGNQVFRMNS SRSVFDIADG
YPQPLQSFFG FCPRNEKLVL NSSSSHFSLI YATITILILI F
