MMP28_HUMAN
ID MMP28_HUMAN Reviewed; 520 AA.
AC Q9H239; Q96F04; Q96TE2;
DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2003, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Matrix metalloproteinase-28;
DE Short=MMP-28;
DE EC=3.4.24.-;
DE AltName: Full=Epilysin;
DE Flags: Precursor;
GN Name=MMP28; Synonyms=MMP25; ORFNames=UNQ1893/PRO4339;
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] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=11255011; DOI=10.1016/s0378-1119(01)00360-2;
RA Marchenko G.N., Strongin A.Y.;
RT "MMP-28, a new human matrix metalloproteinase with an unusual cysteine-
RT switch sequence is widely expressed in tumors.";
RL Gene 265:87-93(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND ALTERNATIVE SPLICING.
RC TISSUE=Testis;
RX PubMed=11121398; DOI=10.1074/jbc.m001599200;
RA Lohi J., Wilson C.L., Roby J.D., Parks W.C.;
RT "Epilysin, a novel human matrix metalloproteinase (MMP-28) expressed in
RT testis and keratinocytes and in response to injury.";
RL J. Biol. Chem. 276:10134-10144(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Southan C., Hughes S.A.;
RT "Cloning and genomic localization of a novel matrix metalloprotease.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Can degrade casein. Could play a role in tissues homeostasis
CC and repair.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC -!- INTERACTION:
CC Q9H239; P09958: FURIN; NbExp=3; IntAct=EBI-20858485, EBI-1056807;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9H239-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H239-2; Sequence=VSP_040552, VSP_040553;
CC -!- TISSUE SPECIFICITY: Expressed at high levels in testes and lung. Low
CC levels are detected in kidney, pancreas and skin. Also expressed in
CC fetal lung, brain, skeletal muscle and kidney. Expressed selectively in
CC keratinocytes. Widely expressed in several carcinomas as well. Is up-
CC regulated in response to injury in the skin.
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: The precursor is cleaved by a furin endopeptidase. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; AF315683; AAG41981.1; -; mRNA.
DR EMBL; AF219624; AAK01480.1; -; mRNA.
DR EMBL; AF330002; AAK01706.1; -; mRNA.
DR EMBL; AY358987; AAQ89346.1; -; mRNA.
DR EMBL; AC006237; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC015849; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC011774; AAH11774.1; -; mRNA.
DR CCDS; CCDS45651.1; -. [Q9H239-2]
DR CCDS; CCDS74036.1; -. [Q9H239-1]
DR RefSeq; NP_001027449.1; NM_001032278.2. [Q9H239-2]
DR RefSeq; NP_077278.1; NM_024302.4. [Q9H239-1]
DR RefSeq; NP_116568.1; NM_032950.3.
DR AlphaFoldDB; Q9H239; -.
DR SMR; Q9H239; -.
DR BioGRID; 122566; 12.
DR IntAct; Q9H239; 3.
DR STRING; 9606.ENSP00000473853; -.
DR DrugBank; DB00786; Marimastat.
DR MEROPS; M10.030; -.
DR GlyGen; Q9H239; 2 sites.
DR iPTMnet; Q9H239; -.
DR PhosphoSitePlus; Q9H239; -.
DR BioMuta; MMP28; -.
DR DMDM; 37538314; -.
DR EPD; Q9H239; -.
DR MassIVE; Q9H239; -.
DR PaxDb; Q9H239; -.
DR PeptideAtlas; Q9H239; -.
DR PRIDE; Q9H239; -.
DR ProteomicsDB; 80485; -. [Q9H239-1]
DR ProteomicsDB; 80486; -. [Q9H239-2]
DR Antibodypedia; 73349; 316 antibodies from 33 providers.
DR DNASU; 79148; -.
DR Ensembl; ENST00000605424.6; ENSP00000473853.1; ENSG00000271447.6. [Q9H239-1]
DR Ensembl; ENST00000611911.4; ENSP00000484430.1; ENSG00000278843.4. [Q9H239-1]
DR Ensembl; ENST00000612672.1; ENSP00000483539.1; ENSG00000271447.6. [Q9H239-2]
DR Ensembl; ENST00000632360.1; ENSP00000488096.1; ENSG00000278843.4. [Q9H239-2]
DR GeneID; 79148; -.
DR KEGG; hsa:79148; -.
DR MANE-Select; ENST00000605424.6; ENSP00000473853.1; NM_024302.5; NP_077278.1.
DR UCSC; uc002hka.4; human. [Q9H239-1]
DR CTD; 79148; -.
DR DisGeNET; 79148; -.
DR GeneCards; MMP28; -.
DR HGNC; HGNC:14366; MMP28.
DR HPA; ENSG00000271447; Low tissue specificity.
DR MIM; 608417; gene.
DR neXtProt; NX_Q9H239; -.
DR OpenTargets; ENSG00000271447; -.
DR PharmGKB; PA30885; -.
DR VEuPathDB; HostDB:ENSG00000271447; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000159596; -.
DR HOGENOM; CLU_1937394_0_0_1; -.
DR InParanoid; Q9H239; -.
DR OMA; GSKWYKQ; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q9H239; -.
DR PathwayCommons; Q9H239; -.
DR SignaLink; Q9H239; -.
DR BioGRID-ORCS; 79148; 10 hits in 1066 CRISPR screens.
DR ChiTaRS; MMP28; human.
DR GeneWiki; MMP28; -.
DR GenomeRNAi; 79148; -.
DR Pharos; Q9H239; Tbio.
DR PRO; PR:Q9H239; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9H239; protein.
DR Bgee; ENSG00000271447; Expressed in tibial nerve and 95 other tissues.
DR ExpressionAtlas; Q9H239; baseline and differential.
DR Genevisible; Q9H239; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0031012; C:extracellular matrix; NAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
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:0010760; P:negative regulation of macrophage chemotaxis; IEA:Ensembl.
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; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR Pfam; PF00045; Hemopexin; 2.
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; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Calcium; Cleavage on pair of basic residues;
KW Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..122
FT /evidence="ECO:0000250"
FT /id="PRO_0000028857"
FT CHAIN 123..520
FT /note="Matrix metalloproteinase-28"
FT /id="PRO_0000028858"
FT REPEAT 325..369
FT /note="Hemopexin 1"
FT REPEAT 370..409
FT /note="Hemopexin 2"
FT REPEAT 415..463
FT /note="Hemopexin 3"
FT REPEAT 464..510
FT /note="Hemopexin 4"
FT MOTIF 89..96
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 241
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 91
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /note="in inhibited form"
FT /evidence="ECO:0000250"
FT BINDING 240
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 244
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 250
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 355
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 324..510
FT /evidence="ECO:0000250"
FT VAR_SEQ 128..130
FT /note="NKW -> EHC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040552"
FT VAR_SEQ 131..520
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_040553"
FT CONFLICT 487
FT /note="R -> C (in Ref. 1; AAG41981)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 520 AA; 58939 MW; E85D7ADA3069B063 CRC64;
MVARVGLLLR ALQLLLWGHL DAQPAERGGQ ELRKEAEAFL EKYGYLNEQV PKAPTSTRFS
DAIRAFQWVS QLPVSGVLDR ATLRQMTRPR CGVTDTNSYA AWAERISDLF ARHRTKMRRK
KRFAKQGNKW YKQHLSYRLV NWPEHLPEPA VRGAVRAAFQ LWSNVSALEF WEAPATGPAD
IRLTFFQGDH NDGLGNAFDG PGGALAHAFL PRRGEAHFDQ DERWSLSRRR GRNLFVVLAH
EIGHTLGLTH SPAPRALMAP YYKRLGRDAL LSWDDVLAVQ SLYGKPLGGS VAVQLPGKLF
TDFETWDSYS PQGRRPETQG PKYCHSSFDA ITVDRQQQLY IFKGSHFWEV AADGNVSEPR
PLQERWVGLP PNIEAAAVSL NDGDFYFFKG GRCWRFRGPK PVWGLPQLCR AGGLPRHPDA
ALFFPPLRRL ILFKGARYYV LARGGLQVEP YYPRSLQDWG GIPEEVSGAL PRPDGSIIFF
RDDRYWRLDQ AKLQATTSGR WATELPWMGC WHANSGSALF
