ID   MMP7_HUMAN              Reviewed;         267 AA.
AC   P09237; Q9BTK9;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1989, sequence version 1.
DT   27-MAR-2024, entry version 223.
DE   RecName: Full=Matrilysin;
DE            EC=3.4.24.23;
DE   AltName: Full=Matrin;
DE   AltName: Full=Matrix metalloproteinase-7;
DE            Short=MMP-7;
DE   AltName: Full=Pump-1 protease;
DE   AltName: Full=Uterine metalloproteinase;
DE   Flags: Precursor;
GN   Name=MMP7; Synonyms=MPSL1, PUMP1;
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].
RX   PubMed=2844164; DOI=10.1042/bj2530187;
RA   Muller D., Quantin B., Gesnel M.-C., Millon-Collard R., Abecassis J.,
RA   Breathnach R.;
RT   "The collagenase gene family in humans consists of at least four members.";
RL   Biochem. J. 253:187-192(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Kidney;
RX   PubMed=1497627; DOI=10.1042/bj2850899;
RA   Marti H.P., McNeil L., Thomas G., Davies M., Lovett D.H.;
RT   "Molecular characterization of a low-molecular-mass matrix
RT   metalloproteinase secreted by glomerular mesangial cells as PUMP-1.";
RL   Biochem. J. 285:899-905(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RX   PubMed=8294454; DOI=10.1016/s0021-9258(17)42131-4;
RA   Gaire M., Magbanua Z., McDonnell S., McNeil L.B., Lovett D.H.,
RA   Matrisian L.M.;
RT   "Structure and expression of the human gene for the matrix
RT   metalloproteinase matrilysin.";
RL   J. Biol. Chem. 269:2032-2040(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS HIS-77; ASP-137 AND
RP   LEU-241.
RG   NIEHS SNPs program;
RL   Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Colon;
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).
RN   [6]
RP   PROTEIN SEQUENCE OF 18-42.
RX   PubMed=2253219;
RA   Miyazaki K., Hattori Y., Umenishi F., Yasumitsu H., Umeda M.;
RT   "Purification and characterization of extracellular matrix-degrading
RT   metalloproteinase, matrin (pump-1), secreted from human rectal carcinoma
RT   cell line.";
RL   Cancer Res. 50:7758-7764(1990).
RN   [7]
RP   FUNCTION.
RX   PubMed=2550050; DOI=10.1021/bi00439a004;
RA   Quantin B., Murphy G., Breathnach R.;
RT   "Pump-1 cDNA codes for a protein with characteristics similar to those of
RT   classical collagenase family members.";
RL   Biochemistry 28:5327-5334(1989).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
RX   PubMed=7756291; DOI=10.1021/bi00020a004;
RA   Browner M.F., Smith W.W., Castelhano A.L.;
RT   "Matrilysin-inhibitor complexes: common themes among metalloproteases.";
RL   Biochemistry 34:6602-6610(1995).
CC   -!- FUNCTION: Degrades casein, gelatins of types I, III, IV, and V, and
CC       fibronectin. Activates procollagenase. {ECO:0000269|PubMed:2550050}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Cleavage of 14-Ala-|-Leu-15 and 16-Tyr-|-Leu-17 in B chain of
CC         insulin. No action on collagen types I, II, IV, V. Cleaves gelatin
CC         chain alpha2(I) > alpha1(I).; EC=3.4.24.23;
CC   -!- COFACTOR:
CC       Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC       Note=Binds 2 calcium ions per subunit.;
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC       Note=Binds 2 Zn(2+) ions per subunit.;
CC   -!- INTERACTION:
CC       P09237; P17931: LGALS3; NbExp=5; IntAct=EBI-6595344, EBI-1170392;
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000305}.
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   -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/mmp7/";
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DR   EMBL; X07819; CAA30678.1; -; mRNA.
DR   EMBL; Z11887; CAA77942.1; -; mRNA.
DR   EMBL; L22524; AAC37543.1; -; Genomic_DNA.
DR   EMBL; L22519; AAC37543.1; JOINED; Genomic_DNA.
DR   EMBL; L22520; AAC37543.1; JOINED; Genomic_DNA.
DR   EMBL; L22521; AAC37543.1; JOINED; Genomic_DNA.
DR   EMBL; L22522; AAC37543.1; JOINED; Genomic_DNA.
DR   EMBL; L22523; AAC37543.1; JOINED; Genomic_DNA.
DR   EMBL; AY795972; AAV40839.1; -; Genomic_DNA.
DR   EMBL; BC003635; AAH03635.1; -; mRNA.
DR   CCDS; CCDS8317.1; -.
DR   PIR; B28816; KCHUM.
DR   RefSeq; NP_002414.1; NM_002423.4.
DR   PDB; 1MMP; X-ray; 2.30 A; A/B=95-264.
DR   PDB; 1MMQ; X-ray; 1.90 A; A=95-264.
DR   PDB; 1MMR; X-ray; 2.40 A; A=95-264.
DR   PDB; 2DDY; NMR; -; A=95-267.
DR   PDB; 2MZE; NMR; -; A=18-267.
DR   PDB; 2MZH; NMR; -; A=20-267.
DR   PDB; 2MZI; NMR; -; A=18-267.
DR   PDB; 2Y6C; X-ray; 1.70 A; A=95-258.
DR   PDB; 2Y6D; X-ray; 1.60 A; A=95-267.
DR   PDB; 5UE2; NMR; -; A=21-267.
DR   PDB; 5UE5; NMR; -; A=21-267.
DR   PDB; 7WXX; X-ray; 1.50 A; A=95-267.
DR   PDB; 8JUD; X-ray; 1.50 A; A=95-267.
DR   PDB; 8JUF; X-ray; 1.39 A; A=95-267.
DR   PDB; 8JUG; X-ray; 1.30 A; A=95-267.
DR   PDBsum; 1MMP; -.
DR   PDBsum; 1MMQ; -.
DR   PDBsum; 1MMR; -.
DR   PDBsum; 2DDY; -.
DR   PDBsum; 2MZE; -.
DR   PDBsum; 2MZH; -.
DR   PDBsum; 2MZI; -.
DR   PDBsum; 2Y6C; -.
DR   PDBsum; 2Y6D; -.
DR   PDBsum; 5UE2; -.
DR   PDBsum; 5UE5; -.
DR   PDBsum; 7WXX; -.
DR   PDBsum; 8JUD; -.
DR   PDBsum; 8JUF; -.
DR   PDBsum; 8JUG; -.
DR   AlphaFoldDB; P09237; -.
DR   BMRB; P09237; -.
DR   SMR; P09237; -.
DR   BioGRID; 110459; 31.
DR   IntAct; P09237; 18.
DR   MINT; P09237; -.
DR   STRING; 9606.ENSP00000260227; -.
DR   BindingDB; P09237; -.
DR   ChEMBL; CHEMBL4073; -.
DR   DrugBank; DB08170; (1R)-N,6-DIHYDROXY-7-METHOXY-2-[(4-METHOXYPHENYL)SULFONYL]-1,2,3,4-TETRAHYDROISOQUINOLINE-1-CARBOXAMIDE.
DR   DrugBank; DB08493; 5-METHYL-3-(9-OXO-1,8-DIAZA-TRICYCLO[10.6.1.013,18]NONADECA-12(19),13,15,17-TETRAEN-10-YLCARBAMOYL)-HEXANOIC ACID.
DR   DrugBank; DB00786; Marimastat.
DR   DrugBank; DB08489; N4-HYDROXY-2-ISOBUTYL-N1-(9-OXO-1,8-DIAZA-TRICYCLO[10.6.1.013,18]NONADECA-12(19),13,15,17-TETRAEN-10-YL)-SUCCINAMIDE.
DR   DrugCentral; P09237; -.
DR   GuidetoPHARMACOLOGY; 1631; -.
DR   MEROPS; M10.008; -.
DR   iPTMnet; P09237; -.
DR   PhosphoSitePlus; P09237; -.
DR   BioMuta; MMP7; -.
DR   DMDM; 116861; -.
DR   jPOST; P09237; -.
DR   MassIVE; P09237; -.
DR   PaxDb; 9606-ENSP00000260227; -.
DR   PeptideAtlas; P09237; -.
DR   ProteomicsDB; 52210; -.
DR   ABCD; P09237; 1 sequenced antibody.
DR   Antibodypedia; 18007; 920 antibodies from 42 providers.
DR   DNASU; 4316; -.
DR   Ensembl; ENST00000260227.5; ENSP00000260227.4; ENSG00000137673.9.
DR   GeneID; 4316; -.
DR   KEGG; hsa:4316; -.
DR   MANE-Select; ENST00000260227.5; ENSP00000260227.4; NM_002423.5; NP_002414.1.
DR   UCSC; uc001phb.4; human.
DR   AGR; HGNC:7174; -.
DR   CTD; 4316; -.
DR   DisGeNET; 4316; -.
DR   GeneCards; MMP7; -.
DR   HGNC; HGNC:7174; MMP7.
DR   HPA; ENSG00000137673; Tissue enhanced (gallbladder, salivary gland, urinary bladder).
DR   MIM; 178990; gene.
DR   neXtProt; NX_P09237; -.
DR   OpenTargets; ENSG00000137673; -.
DR   PharmGKB; PA30887; -.
DR   VEuPathDB; HostDB:ENSG00000137673; -.
DR   eggNOG; KOG1565; Eukaryota.
DR   GeneTree; ENSGT00940000160903; -.
DR   HOGENOM; CLU_015489_4_1_1; -.
DR   InParanoid; P09237; -.
DR   OMA; GINFLYV; -.
DR   OrthoDB; 391167at2759; -.
DR   PhylomeDB; P09237; -.
DR   TreeFam; TF315428; -.
DR   BRENDA; 3.4.24.23; 2681.
DR   PathwayCommons; P09237; -.
DR   Reactome; R-HSA-1442490; Collagen degradation.
DR   Reactome; R-HSA-1474228; Degradation of the extracellular matrix.
DR   Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR   Reactome; R-HSA-2022090; Assembly of collagen fibrils and other multimeric structures.
DR   Reactome; R-HSA-9009391; Extra-nuclear estrogen signaling.
DR   SABIO-RK; P09237; -.
DR   SignaLink; P09237; -.
DR   SIGNOR; P09237; -.
DR   BioGRID-ORCS; 4316; 12 hits in 1159 CRISPR screens.
DR   ChiTaRS; MMP7; human.
DR   EvolutionaryTrace; P09237; -.
DR   GeneWiki; MMP7; -.
DR   GenomeRNAi; 4316; -.
DR   Pharos; P09237; Tchem.
DR   PRO; PR:P09237; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; P09237; Protein.
DR   Bgee; ENSG00000137673; Expressed in gall bladder and 109 other cell types or tissues.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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; IBA:GO_Central.
DR   GO; GO:0004175; F:endopeptidase activity; IDA:UniProtKB.
DR   GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
DR   GO; GO:0008237; F:metallopeptidase activity; IDA:CAFA.
DR   GO; GO:0004252; F:serine-type endopeptidase activity; TAS:Reactome.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR   GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0006509; P:membrane protein ectodomain proteolysis; IMP:ARUK-UCL.
DR   GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IMP:ARUK-UCL.
DR   GO; GO:0030335; P:positive regulation of cell migration; IDA:ARUK-UCL.
DR   GO; GO:0006508; P:proteolysis; IDA:CAFA.
DR   CDD; cd04278; ZnMc_MMP; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 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; 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:SF143; MATRILYSIN; 1.
DR   PANTHER; PTHR10201; MATRIX METALLOPROTEINASE; 1.
DR   Pfam; PF00413; Peptidase_M10; 1.
DR   Pfam; PF01471; PG_binding_1; 1.
DR   PRINTS; PR00138; MATRIXIN.
DR   SMART; SM00235; ZnMc; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF47090; PGBD-like; 1.
DR   PROSITE; PS00546; CYSTEINE_SWITCH; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; P09237; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Calcium; Collagen degradation; Direct protein sequencing;
KW   Extracellular matrix; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW   Reference proteome; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL          1..17
FT                   /evidence="ECO:0000269|PubMed:2253219"
FT   PROPEP          18..94
FT                   /note="Activation peptide"
FT                   /id="PRO_0000028738"
FT   CHAIN           95..267
FT                   /note="Matrilysin"
FT                   /id="PRO_0000028739"
FT   MOTIF           85..92
FT                   /note="Cysteine switch"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        215
FT   BINDING         87
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         153
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT   BINDING         163
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   BINDING         165
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   BINDING         170
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT   BINDING         171
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT   BINDING         173
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT   BINDING         175
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT   BINDING         178
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   BINDING         185
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT   BINDING         187
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT   BINDING         189
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT   BINDING         191
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT   BINDING         193
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT   BINDING         196
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT   BINDING         214
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT   BINDING         218
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT   BINDING         224
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /ligand_note="catalytic"
FT   VARIANT         77
FT                   /note="R -> H (in dbSNP:rs10502001)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_006729"
FT   VARIANT         137
FT                   /note="G -> D (in dbSNP:rs17884789)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_021027"
FT   VARIANT         241
FT                   /note="P -> L (in dbSNP:rs17886506)"
FT                   /evidence="ECO:0000269|Ref.4"
FT                   /id="VAR_021028"
FT   HELIX           24..26
FT                   /evidence="ECO:0007829|PDB:2MZE"
FT   HELIX           29..41
FT                   /evidence="ECO:0007829|PDB:2MZE"
FT   TURN            47..49
FT                   /evidence="ECO:0007829|PDB:2MZH"
FT   HELIX           53..66
FT                   /evidence="ECO:0007829|PDB:2MZE"
FT   STRAND          74..76
FT                   /evidence="ECO:0007829|PDB:5UE5"
FT   HELIX           77..83
FT                   /evidence="ECO:0007829|PDB:2MZE"
FT   STRAND          94..97
FT                   /evidence="ECO:0007829|PDB:5UE2"
FT   STRAND          99..103
FT                   /evidence="ECO:0007829|PDB:2MZE"
FT   STRAND          106..115
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          118..120
FT                   /evidence="ECO:0007829|PDB:1MMP"
FT   HELIX           122..137
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          143..146
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          148..150
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          153..159
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   HELIX           161..163
FT                   /evidence="ECO:0007829|PDB:5UE2"
FT   STRAND          164..166
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          171..174
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          177..180
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          182..184
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   TURN            185..188
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          190..193
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          198..207
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   HELIX           208..219
FT                   /evidence="ECO:0007829|PDB:7WXX"
FT   STRAND          233..236
FT                   /evidence="ECO:0007829|PDB:1MMQ"
FT   STRAND          241..243
FT                   /evidence="ECO:0007829|PDB:2DDY"
FT   HELIX           248..258
FT                   /evidence="ECO:0007829|PDB:7WXX"
SQ   SEQUENCE   267 AA;  29677 MW;  F6BD1FC0ADA23603 CRC64;
     MRLTVLCAVC LLPGSLALPL PQEAGGMSEL QWEQAQDYLK RFYLYDSETK NANSLEAKLK
     EMQKFFGLPI TGMLNSRVIE IMQKPRCGVP DVAEYSLFPN SPKWTSKVVT YRIVSYTRDL
     PHITVDRLVS KALNMWGKEI PLHFRKVVWG TADIMIGFAR GAHGDSYPFD GPGNTLAHAF
     APGTGLGGDA HFDEDERWTD GSSLGINFLY AATHELGHSL GMGHSSDPNA VMYPTYGNGD
     PQNFKLSQDD IKGIQKLYGK RSNSRKK
//