MMP24_MOUSE
ID MMP24_MOUSE Reviewed; 618 AA.
AC Q9R0S2; A2AUV7; Q9Z0J9;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Matrix metalloproteinase-24;
DE Short=MMP-24;
DE EC=3.4.24.-;
DE AltName: Full=Matrix metalloproteinase-21;
DE Short=MMP-21;
DE AltName: Full=Membrane-type matrix metalloproteinase 5;
DE Short=MT-MMP 5;
DE Short=MTMMP5;
DE AltName: Full=Membrane-type-5 matrix metalloproteinase;
DE Short=MT5-MMP;
DE Short=MT5MMP;
DE Contains:
DE RecName: Full=Processed matrix metalloproteinase-24;
DE Flags: Precursor;
GN Name=Mmp24; Synonyms=Mmp21, Mt5mmp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Seiki M.;
RT "Identification of a new membrane-type matrix metalloproteinase, MT5-MMP,
RT that is expressed predominantly in cerebellum.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], MUTAGENESIS OF GLU-256, AND ACTIVE SITE.
RC STRAIN=BALB/cJ; TISSUE=Brain;
RX PubMed=10085137; DOI=10.1074/jbc.274.13.8925;
RA Pei D.Q.;
RT "Identification and characterization of the fifth membrane-type matrix
RT metalloproteinase MT5-MMP.";
RL J. Biol. Chem. 274:8925-8932(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP FUNCTION.
RX PubMed=10622708; DOI=10.1016/s0014-5793(99)01534-3;
RA Wang X., Yi J., Lei J., Pei D.Q.;
RT "Expression, purification and characterization of recombinant mouse MT5-MMP
RT protein products.";
RL FEBS Lett. 462:261-266(1999).
RN [5]
RP SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF GLU-256
RP AND 549-ARG--ARG-555.
RX PubMed=11470782; DOI=10.1074/jbc.m103680200;
RA Wang X., Pei D.;
RT "Shedding of membrane type matrix metalloproteinase 5 by a furin-type
RT convertase: a potential mechanism for down-regulation.";
RL J. Biol. Chem. 276:35953-35960(2001).
RN [6]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=11714638;
RA Hayashita-Kinoh H., Kinoh H., Okada A., Komori K., Itoh Y., Chiba T.,
RA Kajita M., Yana I., Seiki M.;
RT "Membrane-type 5 matrix metalloproteinase is expressed in differentiated
RT neurons and regulates axonal growth.";
RL Cell Growth Differ. 12:573-580(2001).
RN [7]
RP SUBCELLULAR LOCATION, INTERACTION WITH APBA3, AND MUTAGENESIS OF
RP 616-GLU--VAL-618.
RX PubMed=14990567; DOI=10.1074/jbc.m400264200;
RA Wang P., Wang X., Pei D.;
RT "Mint-3 regulates the retrieval of the internalized membrane-type matrix
RT metalloproteinase, MT5-MMP, to the plasma membrane by binding to its
RT carboxyl end motif EWV.";
RL J. Biol. Chem. 279:20461-20470(2004).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=19805319; DOI=10.1073/pnas.0908507106;
RA Folgueras A.R., Valdes-Sanchez T., Llano E., Menendez L., Baamonde A.,
RA Denlinger B.L., Belmonte C., Juarez L., Lastra A., Garcia-Suarez O.,
RA Astudillo A., Kirstein M., Pendas A.M., Farinas I., Lopez-Otin C.;
RT "Metalloproteinase MT5-MMP is an essential modulator of neuro-immune
RT interactions in thermal pain stimulation.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:16451-16456(2009).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=24952463; DOI=10.1038/ncb2993;
RA Porlan E., Marti-Prado B., Morante-Redolat J.M., Consiglio A.,
RA Delgado A.C., Kypta R., Lopez-Otin C., Kirstein M., Farinas I.;
RT "MT5-MMP regulates adult neural stem cell functional quiescence through the
RT cleavage of N-cadherin.";
RL Nat. Cell Biol. 16:629-638(2014).
CC -!- FUNCTION: Metalloprotease that mediates cleavage of N-cadherin (CDH2)
CC and acts as a regulator of neuro-immune interactions and neural stem
CC cell quiescence (PubMed:19805319, PubMed:24952463). Involved in cell-
CC cell interactions between nociceptive neurites and mast cells, possibly
CC by mediating cleavage of CDH2, thereby acting as a mediator of
CC peripheral thermal nociception and inflammatory hyperalgesia
CC (PubMed:19805319). Key regulator of neural stem cells quiescence by
CC mediating cleavage of CDH2, affecting CDH2-mediated anchorage of neural
CC stem cells to ependymocytes in the adult subependymal zone, leading to
CC modulate their quiescence (PubMed:24952463). May play a role in axonal
CC growth (PubMed:11714638). Able to activate progelatinase A. May also be
CC a proteoglycanase involved in degradation of proteoglycans, such as
CC dermatan sulfate and chondroitin sulfate proteoglycans. Cleaves
CC partially fibronectin, but not collagen type I, nor laminin
CC (PubMed:10622708). {ECO:0000269|PubMed:10622708,
CC ECO:0000269|PubMed:11714638, ECO:0000269|PubMed:19805319,
CC ECO:0000269|PubMed:24952463}.
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 -!- SUBUNIT: Interacts with GRIP1 and GRIP2 (By similarity). Interacts (via
CC PDZ-binding motif) with APBA3 (via PDZ domain). {ECO:0000250,
CC ECO:0000269|PubMed:14990567}.
CC -!- SUBCELLULAR LOCATION: [Matrix metalloproteinase-24]: Cell membrane;
CC Single-pass type I membrane protein. Golgi apparatus, trans-Golgi
CC network membrane; Single-pass type I membrane protein. Note=Recycled
CC back to the plasma membrane through the trans-Golgi network via
CC interaction with APBA3. {ECO:0000269|PubMed:14990567}.
CC -!- SUBCELLULAR LOCATION: [Processed matrix metalloproteinase-24]:
CC Secreted, extracellular space, extracellular matrix. Note=Also shed
CC from cell surface as soluble proteinase, by a proteolytic cleavage.
CC {ECO:0000269|PubMed:11470782}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in neuronal cells of both central
CC and peripheral nervous systems. Expressed by CGRP-containing
CC peptidergic nociceptors in dorsal root ganglia (PubMed:19805319).
CC Expressed in adult neural stem cell and ependymocytes
CC (PubMed:24952463). Expressed at low level in testis.
CC {ECO:0000269|PubMed:11714638, ECO:0000269|PubMed:19805319,
CC ECO:0000269|PubMed:24952463}.
CC -!- DEVELOPMENTAL STAGE: Expressed at day 11 until day 15, before dropping
CC around day 17 before birth. Expressed in the cerebrum in embryos, but
CC it declines after birth, while expression in the cerebellum starts to
CC increase postnatally and continues thereafter.
CC {ECO:0000269|PubMed:11714638}.
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 -!- DOMAIN: The PDZ-binding motif (also named EWV motif) is required for
CC interaction with PDZ domains of APBA3 and recycling through the trans-
CC Golgi network. {ECO:0000269|PubMed:14990567}.
CC -!- PTM: Cleaved by a furin endopeptidase in the trans-Golgi network.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are viable, develop
CC normally and are fertile. They however display enhanced sensitivity to
CC noxious thermal stimuli under basal conditions characterized by an
CC absence of thermal inflammatory hyperalgesia (PubMed:19805319). In
CC subependymal zone, more intense signal is observed for extracellular N-
CC cadherin (Cdh2) as well as increased levels of full-length Cdh2 without
CC changes in Cdh2 messenger RNA levels (PubMed:24952463).
CC {ECO:0000269|PubMed:19805319, ECO:0000269|PubMed:24952463}.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR EMBL; AB021226; BAA82966.1; -; mRNA.
DR EMBL; AJ010262; CAA09055.1; -; mRNA.
DR EMBL; AL929233; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS16955.1; -.
DR RefSeq; NP_034938.3; NM_010808.4.
DR AlphaFoldDB; Q9R0S2; -.
DR SMR; Q9R0S2; -.
DR STRING; 10090.ENSMUSP00000029141; -.
DR MEROPS; M10.023; -.
DR iPTMnet; Q9R0S2; -.
DR PhosphoSitePlus; Q9R0S2; -.
DR MaxQB; Q9R0S2; -.
DR PaxDb; Q9R0S2; -.
DR PRIDE; Q9R0S2; -.
DR ProteomicsDB; 291477; -.
DR Antibodypedia; 5282; 217 antibodies from 30 providers.
DR DNASU; 17391; -.
DR Ensembl; ENSMUST00000029141; ENSMUSP00000029141; ENSMUSG00000027612.
DR GeneID; 17391; -.
DR KEGG; mmu:17391; -.
DR UCSC; uc008nlj.1; mouse.
DR CTD; 10893; -.
DR MGI; MGI:1341867; Mmp24.
DR VEuPathDB; HostDB:ENSMUSG00000027612; -.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000158315; -.
DR HOGENOM; CLU_015489_8_1_1; -.
DR InParanoid; Q9R0S2; -.
DR OMA; QSWLKSY; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q9R0S2; -.
DR TreeFam; TF352396; -.
DR Reactome; R-MMU-1592389; Activation of Matrix Metalloproteinases.
DR BioGRID-ORCS; 17391; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Mmp24; mouse.
DR PRO; PR:Q9R0S2; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9R0S2; protein.
DR Bgee; ENSMUSG00000027612; Expressed in embryonic brain and 124 other tissues.
DR Genevisible; Q9R0S2; MM.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0032588; C:trans-Golgi network membrane; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; IPI:UniProtKB.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; IDA:UniProtKB.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IMP:UniProtKB.
DR GO; GO:0030574; P:collagen catabolic process; IBA:GO_Central.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IMP:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0010001; P:glial cell differentiation; IDA:UniProtKB.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IMP:UniProtKB.
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; IPR028723; MMP24.
DR InterPro; IPR001818; Pept_M10_metallopeptidase.
DR InterPro; IPR021190; Pept_M10A.
DR InterPro; IPR021805; Pept_M10A_metallopeptidase_C.
DR InterPro; IPR006026; Peptidase_Metallo.
DR InterPro; IPR002477; Peptidoglycan-bd-like.
DR InterPro; IPR036365; PGBD-like_sf.
DR PANTHER; PTHR10201:SF138; PTHR10201:SF138; 1.
DR Pfam; PF11857; DUF3377; 1.
DR Pfam; PF00045; Hemopexin; 4.
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; PS00024; HEMOPEXIN; 1.
DR PROSITE; PS51642; HEMOPEXIN_2; 4.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Cell membrane; Cleavage on pair of basic residues;
KW Disulfide bond; Extracellular matrix; Golgi apparatus; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Transmembrane; Transmembrane helix; Zinc; Zymogen.
FT SIGNAL 1..41
FT /evidence="ECO:0000255"
FT PROPEP 42..128
FT /evidence="ECO:0000250"
FT /id="PRO_0000028848"
FT CHAIN 129..618
FT /note="Matrix metalloproteinase-24"
FT /id="PRO_0000028849"
FT CHAIN 129..554
FT /note="Processed matrix metalloproteinase-24"
FT /evidence="ECO:0000305"
FT /id="PRO_0000302759"
FT TOPO_DOM 42..575
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 576..596
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 597..618
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 350..398
FT /note="Hemopexin 1"
FT REPEAT 399..444
FT /note="Hemopexin 2"
FT REPEAT 446..494
FT /note="Hemopexin 3"
FT REPEAT 495..542
FT /note="Hemopexin 4"
FT REGION 296..352
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 110..117
FT /note="Cysteine switch"
FT /evidence="ECO:0000250"
FT MOTIF 616..618
FT /note="PDZ-binding"
FT COMPBIAS 320..337
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 256
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:10085137"
FT BINDING 112
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 255
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 259
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 265
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT SITE 554..555
FT /note="Cleavage; by furin"
FT DISULFID 353..542
FT /evidence="ECO:0000250"
FT MUTAGEN 256
FT /note="E->A: Loss of function. Does not prevent proteolytic
FT processing."
FT /evidence="ECO:0000269|PubMed:10085137,
FT ECO:0000269|PubMed:11470782"
FT MUTAGEN 549..554
FT /note="Missing: Abolishes proteolytic processing. Gain of
FT function mutant."
FT MUTAGEN 616..618
FT /note="Missing: Impaired recycling affecting its
FT internalization, leading to decreased activity on the
FT plasma surface."
FT /evidence="ECO:0000269|PubMed:14990567"
FT CONFLICT 7..28
FT /note="GRAAPGQASRWSGWRAPGRLLP -> AALRRARPRAGALAGPGAAA (in
FT Ref. 2; CAA09055)"
FT /evidence="ECO:0000305"
FT CONFLICT 44..50
FT /note="KPAGADA -> SRPGR (in Ref. 2; CAA09055)"
FT /evidence="ECO:0000305"
FT CONFLICT 46
FT /note="A -> T (in Ref. 1; BAA82966)"
FT /evidence="ECO:0000305"
FT CONFLICT 306..308
FT /note="LEP -> SGA (in Ref. 2; CAA09055)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="R -> K (in Ref. 2; CAA09055)"
FT /evidence="ECO:0000305"
FT CONFLICT 337..341
FT /note="PPLGD -> RPWG (in Ref. 2; CAA09055)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="I -> KP (in Ref. 2; CAA09055)"
FT /evidence="ECO:0000305"
FT CONFLICT 502
FT /note="I -> L (in Ref. 2; CAA09055)"
FT /evidence="ECO:0000305"
FT CONFLICT 589
FT /note="L -> R (in Ref. 2; CAA09055)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 618 AA; 70460 MW; 51C8E61B187264F5 CRC64;
MPRSRGGRAA PGQASRWSGW RAPGRLLPLL PALCCLAAAA GAGKPAGADA PFAGQNWLKS
YGYLLPYESR ASALHSGKAL QSAVSTMQQF YGIPVTGVLD QTTIEWMKKP RCGVPDHPHL
SRRRRNKRYA LTGQKWRQKH ITYSIHNYTP KVGELDTRKA IRQAFDVWQK VTPLTFEEVP
YHEIKSDRKE ADIMIFFASG FHGDSSPFDG EGGFLAHAYF PGPGIGGDTH FDSDEPWTLG
NANHDGNDLF LVAVHELGHA LGLEHSNDPS AIMAPFYQYM ETHNFKLPQD DLQGIQKIYG
PPAEPLEPTR PLPTLPVRRI HSPSERKHER HPRPPRPPLG DRPSTPGAKP NICDGNFNTV
ALFRGEMFVF KDRWFWRLRN NRVQEGYPMQ IEQFWKGLPA RIDAAYERAD GRFVFFKGDK
YWVFKEVTVE PGYPHSLGEL GSCLPREGID TALRWEPVGK TYFFKGERYW RYSEERRATD
PGYPKPITVW KGIPQAPQGA FISKEGYYTY FYKGRDYWKF DNQKLSVEPG YPRNILRDWM
GCKQKEVERR KERRLPQDDV DIMVTIDDVP GSVNAVAVVV PCTLSLCLLV LLYTIFQFKN
KAGPQPVTYY KRPVQEWV
