MMP27_HUMAN
ID MMP27_HUMAN Reviewed; 513 AA.
AC Q9H306; Q6UWK6;
DT 15-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Matrix metalloproteinase-27;
DE Short=MMP-27;
DE EC=3.4.24.-;
DE Flags: Precursor;
GN Name=MMP27; ORFNames=UNQ2503/PRO5992;
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 VARIANTS MET-24 AND VAL-30.
RA Benoit de Coignac A., Elson G., Magistrelli G., Jeannin P., Delneste Y.,
RA Aubry J.-P., Berthier O., Bonnefoy J.-Y., Gauchat J.-F.;
RT "Cloning of a novel matrix metalloproteinase homologous to stromelysins.";
RL Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS VAL-266 AND ASN-447.
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 [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 TISSUE SPECIFICITY.
RX PubMed=14506071; DOI=10.1093/brain/awg285;
RA Bar-Or A., Nuttall R.K., Duddy M., Alter A., Kim H.J., Ifergan I.,
RA Pennington C.J., Bourgoin P., Edwards D.R., Yong V.W.;
RT "Analyses of all matrix metalloproteinase members in leukocytes emphasize
RT monocytes as major inflammatory mediators in multiple sclerosis.";
RL Brain 126:2738-2749(2003).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=24810263; DOI=10.1093/molehr/gau034;
RA Cominelli A., Gaide Chevronnay H.P., Lemoine P., Courtoy P.J., Marbaix E.,
RA Henriet P.;
RT "Matrix metalloproteinase-27 is expressed in CD163+/CD206+ M2 macrophages
RT in the cycling human endometrium and in superficial endometriotic
RT lesions.";
RL Mol. Hum. Reprod. 20:767-775(2014).
RN [6]
RP SUBCELLULAR LOCATION, GLYCOSYLATION AT ASN-55; ASN-110 AND ASN-452,
RP TOPOLOGY, REGION, AND MUTAGENESIS OF ASN-55; ASN-110 AND ASN-452.
RX PubMed=24548619; DOI=10.1111/tra.12149;
RA Cominelli A., Halbout M., N'Kuli F., Lemoine P., Courtoy P.J., Marbaix E.,
RA Tyteca D., Henriet P.;
RT "A unique C-terminal domain allows retention of matrix metalloproteinase-27
RT in the endoplasmic reticulum.";
RL Traffic 15:401-417(2014).
CC -!- FUNCTION: Matrix metalloproteinases degrade protein components of the
CC extracellular matrix such as fibronectin, laminin, gelatins and/or
CC collagens. {ECO:0000250}.
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250};
CC Note=Binds 4 Ca(2+) ions per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein {ECO:0000269|PubMed:24548619}. Note=Retained in the
CC endoplasmic reticulum. {ECO:0000269|PubMed:24548619}.
CC -!- TISSUE SPECIFICITY: Expressed in B-cells (PubMed:14506071). Expressed
CC in a subset of endometrial macrophages related to menstruation and in
CC ovarian and peritoneal endometriotic lesions (at protein
CC level)(PubMed:24810263). {ECO:0000269|PubMed:14506071,
CC ECO:0000269|PubMed:24810263}.
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: N-glycosylated. {ECO:0000269|PubMed:24548619}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; AF195192; AAG28453.1; -; mRNA.
DR EMBL; AY358752; AAQ89112.1; -; mRNA.
DR EMBL; AP000647; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000851; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS8319.1; -.
DR RefSeq; NP_071405.2; NM_022122.2.
DR AlphaFoldDB; Q9H306; -.
DR SMR; Q9H306; -.
DR BioGRID; 122039; 1.
DR STRING; 9606.ENSP00000260229; -.
DR DrugBank; DB00786; Marimastat.
DR MEROPS; M10.027; -.
DR GlyGen; Q9H306; 3 sites.
DR iPTMnet; Q9H306; -.
DR PhosphoSitePlus; Q9H306; -.
DR BioMuta; MMP27; -.
DR DMDM; 296437372; -.
DR MassIVE; Q9H306; -.
DR PaxDb; Q9H306; -.
DR PeptideAtlas; Q9H306; -.
DR PRIDE; Q9H306; -.
DR ProteomicsDB; 80640; -.
DR Antibodypedia; 31767; 150 antibodies from 27 providers.
DR DNASU; 64066; -.
DR Ensembl; ENST00000260229.5; ENSP00000260229.4; ENSG00000137675.5.
DR GeneID; 64066; -.
DR KEGG; hsa:64066; -.
DR MANE-Select; ENST00000260229.5; ENSP00000260229.4; NM_022122.3; NP_071405.2.
DR UCSC; uc001phd.2; human.
DR CTD; 64066; -.
DR DisGeNET; 64066; -.
DR GeneCards; MMP27; -.
DR HGNC; HGNC:14250; MMP27.
DR HPA; ENSG00000137675; Tissue enhanced (breast, salivary gland, skin).
DR MIM; 618101; gene.
DR neXtProt; NX_Q9H306; -.
DR OpenTargets; ENSG00000137675; -.
DR PharmGKB; PA30884; -.
DR VEuPathDB; HostDB:ENSG00000137675; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000161159; -.
DR HOGENOM; CLU_015489_6_0_1; -.
DR InParanoid; Q9H306; -.
DR OMA; IPHACDP; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q9H306; -.
DR TreeFam; TF315428; -.
DR PathwayCommons; Q9H306; -.
DR BioGRID-ORCS; 64066; 7 hits in 1069 CRISPR screens.
DR GeneWiki; MMP27; -.
DR GenomeRNAi; 64066; -.
DR Pharos; Q9H306; Tbio.
DR PRO; PR:Q9H306; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9H306; protein.
DR Bgee; ENSG00000137675; Expressed in skin of hip and 55 other tissues.
DR Genevisible; Q9H306; HS.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0042406; C:extrinsic component of endoplasmic reticulum membrane; IDA:UniProtKB.
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: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; IPR018486; Hemopexin_CS.
DR InterPro; IPR033739; M10A_MMP.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR028732; MMP27.
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:SF115; PTHR10201:SF115; 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; PS00024; HEMOPEXIN; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Collagen degradation; Disulfide bond; Endoplasmic reticulum;
KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease;
KW Protease; Reference proteome; Repeat; Signal; Zinc; Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT PROPEP 18..98
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000287561"
FT CHAIN 99..513
FT /note="Matrix metalloproteinase-27"
FT /id="PRO_0000287562"
FT REPEAT 276..325
FT /note="Hemopexin 1"
FT REPEAT 326..371
FT /note="Hemopexin 2"
FT REPEAT 373..421
FT /note="Hemopexin 3"
FT REPEAT 422..465
FT /note="Hemopexin 4"
FT REGION 466..513
FT /note="Required for retention in the endoplasmic reticulum"
FT /evidence="ECO:0000269|PubMed:24548619"
FT MOTIF 89..96
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT ACT_SITE 217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 91
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"
FT BINDING 121
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 174
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 188
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 192
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 196
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 199
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT BINDING 216
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 220
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250"
FT BINDING 286
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 377
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT BINDING 426
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="4"
FT /evidence="ECO:0000250"
FT CARBOHYD 55
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24548619"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255, ECO:0000269|PubMed:24548619"
FT CARBOHYD 452
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:24548619"
FT DISULFID 279..465
FT /evidence="ECO:0000250"
FT VARIANT 22
FT /note="R -> W (in dbSNP:rs12099177)"
FT /id="VAR_032326"
FT VARIANT 24
FT /note="T -> M (in dbSNP:rs1939015)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_032327"
FT VARIANT 30
FT /note="M -> V (in dbSNP:rs2846707)"
FT /evidence="ECO:0000269|Ref.1"
FT /id="VAR_032328"
FT VARIANT 266
FT /note="E -> V (in dbSNP:rs1276286)"
FT /evidence="ECO:0000269|PubMed:12975309"
FT /id="VAR_032329"
FT VARIANT 304
FT /note="W -> L (in dbSNP:rs35616217)"
FT /id="VAR_032330"
FT VARIANT 447
FT /note="D -> N (in dbSNP:rs2509010)"
FT /evidence="ECO:0000269|PubMed:12975309"
FT /id="VAR_032331"
FT VARIANT 477
FT /note="I -> V (in dbSNP:rs35822551)"
FT /id="VAR_032332"
FT MUTAGEN 55
FT /note="N->Q: Loss of N-glycosylation; when associated with
FT Q-110 and Q-452."
FT /evidence="ECO:0000269|PubMed:24548619"
FT MUTAGEN 110
FT /note="N->Q: Loss of N-glycosylation; when associated with
FT Q-55 and Q-452."
FT /evidence="ECO:0000269|PubMed:24548619"
FT MUTAGEN 452
FT /note="N->Q: Loss of N-glycosylation; when associated with
FT Q-55 and Q-110."
FT /evidence="ECO:0000269|PubMed:24548619"
SQ SEQUENCE 513 AA; 59026 MW; 941D5B8DA55BD32A CRC64;
MKRLLLLFLF FITFSSAFPL VRMTENEENM QLAQAYLNQF YSLEIEGNHL VQSKNRSLID
DKIREMQAFF GLTVTGKLDS NTLEIMKTPR CGVPDVGQYG YTLPGWRKYN LTYRIINYTP
DMARAAVDEA IQEGLEVWSK VTPLKFTKIS KGIADIMIAF RTRVHGRCPR YFDGPLGVLG
HAFPPGPGLG GDTHFDEDEN WTKDGAGFNL FLVAAHEFGH ALGLSHSNDQ TALMFPNYVS
LDPRKYPLSQ DDINGIQSIY GGLPKEPAKP KEPTIPHACD PDLTFDAITT FRREVMFFKG
RHLWRIYYDI TDVEFELIAS FWPSLPADLQ AAYENPRDKI LVFKDENFWM IRGYAVLPDY
PKSIHTLGFP GRVKKIDAAV CDKTTRKTYF FVGIWCWRFD EMTQTMDKGF PQRVVKHFPG
ISIRVDAAFQ YKGFFFFSRG SKQFEYDIKT KNITRIMRTN TWFQCKEPKN SSFGFDINKE
KAHSGGIKIL YHKSLSLFIF GIVHLLKNTS IYQ
