MMP20_HUMAN
ID MMP20_HUMAN Reviewed; 483 AA.
AC O60882; Q6DKT9;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 3.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=Matrix metalloproteinase-20;
DE Short=MMP-20;
DE EC=3.4.24.-;
DE AltName: Full=Enamel metalloproteinase;
DE AltName: Full=Enamelysin;
DE Flags: Precursor;
GN Name=MMP20;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Odontoblast;
RX PubMed=9398237; DOI=10.1021/bi972120y;
RA Llano E., Pendas A.M., Knaeuper V., Sorsa T., Salo T., Salido E.,
RA Murphy G., Simmer J.P., Bartlett J.D., Lopez-Otin C.;
RT "Identification and structural and functional characterization of human
RT enamelysin (MMP-20).";
RL Biochemistry 36:15101-15108(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS THR-18; ASN-139; LEU-169;
RP ALA-275 AND ASN-281.
RG NIEHS SNPs program;
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP FUNCTION.
RX PubMed=10922468; DOI=10.1016/s0014-5793(00)01819-6;
RA Stracke J.O., Fosang A.J., Last K., Mercuri F.A., Pendas A.M., Llano E.,
RA Perris R., Di Cesare P.E., Murphy G., Knaeuper V.;
RT "Matrix metalloproteinases 19 and 20 cleave aggrecan and cartilage
RT oligomeric matrix protein (COMP).";
RL FEBS Lett. 478:52-56(2000).
RN [5]
RP INVOLVEMENT IN AI2A2.
RX PubMed=15744043; DOI=10.1136/jmg.2004.024505;
RA Kim J.-W., Simmer J.P., Hart T.C., Hart P.S., Ramaswami M.D.,
RA Bartlett J.D., Hu J.C.-C.;
RT "MMP-20 mutation in autosomal recessive pigmented hypomaturation
RT amelogenesis imperfecta.";
RL J. Med. Genet. 42:271-275(2005).
RN [6]
RP STRUCTURE BY NMR OF 113-272 IN COMPLEX WITH INHIBITOR, COFACTOR,
RP ZINC-BINDING SITES, AND CALCIUM-BINDING SITES.
RX PubMed=17869250; DOI=10.1016/j.febslet.2007.08.069;
RA Arendt Y., Banci L., Bertini I., Cantini F., Cozzi R., Del Conte R.,
RA Gonnelli L.;
RT "Catalytic domain of MMP20 (Enamelysin) - the NMR structure of a new matrix
RT metalloproteinase.";
RL FEBS Lett. 581:4723-4726(2007).
CC -!- FUNCTION: Degrades amelogenin, the major protein component of the
CC enamel matrix and two of the macromolecules characterizing the
CC cartilage extracellular matrix: aggrecan and the cartilage oligomeric
CC matrix protein (COMP). May play a central role in tooth enamel
CC formation. Cleaves aggrecan at the '360-Asn-|-Phe-361' site.
CC {ECO:0000269|PubMed:10922468, ECO:0000269|PubMed:9398237}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:17869250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000269|PubMed:17869250};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:17869250};
CC Note=Binds 2 calcium ions per subunit. {ECO:0000269|PubMed:17869250};
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed specifically in the enamel organ.
CC -!- DEVELOPMENTAL STAGE: Expression initiates prior to the onset of dentin
CC mineralization and continues throughout the secretory stage of
CC amelogenesis.
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.
CC -!- PTM: Autoactivates at least at the 107-Asn-|-Tyr-108 site.
CC {ECO:0000250}.
CC -!- DISEASE: Amelogenesis imperfecta, hypomaturation type, 2A2 (AI2A2)
CC [MIM:612529]: A defect of enamel formation. The disorder involves both
CC primary and secondary dentitions. The teeth have a shiny agar jelly
CC appearance and the enamel is softer than normal. Brown pigment is
CC present in middle layers of enamel. {ECO:0000269|PubMed:15744043}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/mmp20/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; Y12779; CAA73317.1; -; mRNA.
DR EMBL; AY673603; AAT70722.1; -; Genomic_DNA.
DR EMBL; AP000851; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS8318.1; -.
DR RefSeq; NP_004762.2; NM_004771.3.
DR PDB; 2JSD; NMR; -; A=113-272.
DR PDBsum; 2JSD; -.
DR AlphaFoldDB; O60882; -.
DR BMRB; O60882; -.
DR SMR; O60882; -.
DR BioGRID; 114725; 3.
DR STRING; 9606.ENSP00000260228; -.
DR BindingDB; O60882; -.
DR ChEMBL; CHEMBL1938226; -.
DR DrugBank; DB00786; Marimastat.
DR DrugBank; DB08271; N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID.
DR MEROPS; M10.019; -.
DR iPTMnet; O60882; -.
DR PhosphoSitePlus; O60882; -.
DR BioMuta; MMP20; -.
DR MassIVE; O60882; -.
DR PaxDb; O60882; -.
DR PeptideAtlas; O60882; -.
DR PRIDE; O60882; -.
DR Antibodypedia; 31760; 281 antibodies from 28 providers.
DR DNASU; 9313; -.
DR Ensembl; ENST00000260228.3; ENSP00000260228.2; ENSG00000137674.4.
DR GeneID; 9313; -.
DR KEGG; hsa:9313; -.
DR MANE-Select; ENST00000260228.3; ENSP00000260228.2; NM_004771.4; NP_004762.2.
DR UCSC; uc001phc.3; human.
DR CTD; 9313; -.
DR DisGeNET; 9313; -.
DR GeneCards; MMP20; -.
DR HGNC; HGNC:7167; MMP20.
DR HPA; ENSG00000137674; Not detected.
DR MalaCards; MMP20; -.
DR MIM; 604629; gene.
DR MIM; 612529; phenotype.
DR neXtProt; NX_O60882; -.
DR OpenTargets; ENSG00000137674; -.
DR Orphanet; 100033; Hypomaturation amelogenesis imperfecta.
DR PharmGKB; PA30878; -.
DR VEuPathDB; HostDB:ENSG00000137674; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000161277; -.
DR HOGENOM; CLU_015489_6_0_1; -.
DR InParanoid; O60882; -.
DR OMA; HYWVTRG; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; O60882; -.
DR TreeFam; TF315428; -.
DR BRENDA; 3.4.24.B6; 2681.
DR PathwayCommons; O60882; -.
DR Reactome; R-HSA-1442490; Collagen degradation.
DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR SignaLink; O60882; -.
DR SIGNOR; O60882; -.
DR BioGRID-ORCS; 9313; 11 hits in 1017 CRISPR screens.
DR EvolutionaryTrace; O60882; -.
DR GeneWiki; MMP20; -.
DR GenomeRNAi; 9313; -.
DR Pharos; O60882; Tbio.
DR PRO; PR:O60882; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O60882; protein.
DR Bgee; ENSG00000137674; Expressed in left testis and 52 other tissues.
DR Genevisible; O60882; HS.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:CACAO.
DR GO; GO:0008270; F:zinc ion binding; TAS:ProtInc.
DR GO; GO:0097186; P:amelogenesis; IBA:GO_Central.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0022617; P:extracellular matrix disassembly; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0030163; P:protein catabolic process; IEA:Ensembl.
DR GO; GO:0006508; P:proteolysis; TAS:ProtInc.
DR GO; GO:0070173; P:regulation of enamel mineralization; TAS:BHF-UCL.
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; IPR028716; MMP20.
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 PANTHER; PTHR10201:SF125; PTHR10201:SF125; 1.
DR Pfam; PF00045; Hemopexin; 3.
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; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amelogenesis imperfecta; Autocatalytic cleavage; Calcium;
KW Disulfide bond; Extracellular matrix; Hydrolase; Metal-binding;
KW Metalloprotease; Protease; Reference proteome; Repeat; Secreted; Signal;
KW Zinc; Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..107
FT /evidence="ECO:0000250"
FT /id="PRO_0000028833"
FT CHAIN 108..483
FT /note="Matrix metalloproteinase-20"
FT /id="PRO_0000028834"
FT REPEAT 293..343
FT /note="Hemopexin 1"
FT REPEAT 344..389
FT /note="Hemopexin 2"
FT REPEAT 391..439
FT /note="Hemopexin 3"
FT REPEAT 440..483
FT /note="Hemopexin 4"
FT MOTIF 98..105
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 227
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 100
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 165
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 166
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 178
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 183
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 184
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 188
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 197
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 198
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 200
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 202
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT BINDING 204
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 206
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 209
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT BINDING 230
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT BINDING 236
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT DISULFID 296..483
FT /evidence="ECO:0000255"
FT VARIANT 18
FT /note="K -> T (in dbSNP:rs2245803)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020511"
FT VARIANT 139
FT /note="D -> N (in dbSNP:rs17099014)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020512"
FT VARIANT 169
FT /note="I -> L (in dbSNP:rs17099008)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020513"
FT VARIANT 275
FT /note="V -> A (in dbSNP:rs1784423)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_020514"
FT VARIANT 281
FT /note="T -> N (in dbSNP:rs1784424)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VAR_057802"
FT CONFLICT 208
FT /note="A -> P (in Ref. 1; CAA73317)"
FT /evidence="ECO:0000305"
FT STRAND 120..126
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:2JSD"
FT HELIX 135..152
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 156..159
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 161..163
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 166..172
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 176..180
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 184..187
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 203..206
FT /evidence="ECO:0007829|PDB:2JSD"
FT STRAND 211..219
FT /evidence="ECO:0007829|PDB:2JSD"
FT HELIX 220..232
FT /evidence="ECO:0007829|PDB:2JSD"
FT TURN 253..255
FT /evidence="ECO:0007829|PDB:2JSD"
FT HELIX 261..270
FT /evidence="ECO:0007829|PDB:2JSD"
SQ SEQUENCE 483 AA; 54387 MW; 561B0A03E0BB0399 CRC64;
MKVLPASGLA VFLIMALKFS TAAPSLVAAS PRTWRNNYRL AQAYLDKYYT NKEGHQIGEM
VARGSNSMIR KIKELQAFFG LQVTGKLDQT TMNVIKKPRC GVPDVANYRL FPGEPKWKKN
TLTYRISKYT PSMSSVEVDK AVEMALQAWS SAVPLSFVRI NSGEADIMIS FENGDHGDSY
PFDGPRGTLA HAFAPGEGLG GDTHFDNAEK WTMGTNGFNL FTVAAHEFGH ALGLAHSTDP
SALMYPTYKY KNPYGFHLPK DDVKGIQALY GPRKVFLGKP TLPHAPHHKP SIPDLCDSSS
SFDAVTMLGK ELLLFKDRIF WRRQVHLRTG IRPSTITSSF PQLMSNVDAA YEVAERGTAY
FFKGPHYWIT RGFQMQGPPR TIYDFGFPRH VQQIDAAVYL REPQKTLFFV GDEYYSYDER
KRKMEKDYPK NTEEEFSGVN GQIDAAVELN GYIYFFSGPK TYKYDTEKED VVSVVKSSSW
IGC
