ID   MMP24_HUMAN             Reviewed;         645 AA.
AC   Q9Y5R2; B7ZBG8; Q9H440;
DT   24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   27-MAR-2024, entry version 202.
DE   RecName: Full=Matrix metalloproteinase-24;
DE            Short=MMP-24;
DE            EC=3.4.24.-;
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=MT5MMP;
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 TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=10363975;
RA   Llano E., Pendas A.M., Freije J.P., Nakano A., Knaeuper V., Murphy G.,
RA   Lopez-Otin C.;
RT   "Identification and characterization of human MT5-MMP, a new membrane-bound
RT   activator of progelatinase a overexpressed in brain tumors.";
RL   Cancer Res. 59:2570-2576(1999).
RN   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
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. Involved in cell-cell interactions between nociceptive
CC       neurites and mast cells, possibly by mediating cleavage of CDH2,
CC       thereby acting as a mediator of peripheral thermal nociception and
CC       inflammatory hyperalgesia. Key regulator of neural stem cells
CC       quiescence by mediating cleavage of CDH2, affecting CDH2-mediated
CC       anchorage of neural stem cells to ependymocytes in the adult
CC       subependymal zone, leading to modulate their quiescence. May play a
CC       role in axonal growth. Able to activate progelatinase A. May also be a
CC       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 (By
CC       similarity). {ECO:0000250}.
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 (via PDZ-binding motif) with APBA3 (via PDZ domain).
CC       Interacts with GRIP1 and GRIP2 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Matrix metalloproteinase-24]: Cell membrane
CC       {ECO:0000250}; Single-pass type I membrane protein {ECO:0000250}. Golgi
CC       apparatus, trans-Golgi network membrane {ECO:0000250}; Single-pass type
CC       I membrane protein {ECO:0000250}. Note=Recycled back to the plasma
CC       membrane through the trans-Golgi network via interaction with APBA3.
CC       {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: [Processed matrix metalloproteinase-24]:
CC       Secreted, extracellular space, extracellular matrix {ECO:0000250}.
CC       Note=Also shed from cell surface as soluble proteinase, by a
CC       proteolytic cleavage. {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Predominantly expressed in brain, kidney, pancreas
CC       and lung. Overexpressed in a series of brain tumors, including
CC       astrocytomas and glioblastomas. {ECO:0000269|PubMed:10363975}.
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:0000250}.
CC   -!- PTM: Cleaved by a furin endopeptidase in the trans-Golgi network.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
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DR   EMBL; AF131284; AAD42962.1; -; mRNA.
DR   EMBL; AB021227; BAA82967.1; -; mRNA.
DR   EMBL; AL121753; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS46593.1; -.
DR   RefSeq; NP_006681.1; NM_006690.3.
DR   AlphaFoldDB; Q9Y5R2; -.
DR   SMR; Q9Y5R2; -.
DR   BioGRID; 116099; 17.
DR   IntAct; Q9Y5R2; 2.
DR   MINT; Q9Y5R2; -.
DR   STRING; 9606.ENSP00000246186; -.
DR   BindingDB; Q9Y5R2; -.
DR   ChEMBL; CHEMBL5050; -.
DR   DrugBank; DB00786; Marimastat.
DR   MEROPS; M10.023; -.
DR   iPTMnet; Q9Y5R2; -.
DR   PhosphoSitePlus; Q9Y5R2; -.
DR   BioMuta; MMP24; -.
DR   DMDM; 12585280; -.
DR   EPD; Q9Y5R2; -.
DR   jPOST; Q9Y5R2; -.
DR   MassIVE; Q9Y5R2; -.
DR   MaxQB; Q9Y5R2; -.
DR   PaxDb; 9606-ENSP00000246186; -.
DR   PeptideAtlas; Q9Y5R2; -.
DR   ProteomicsDB; 86480; -.
DR   Antibodypedia; 5282; 228 antibodies from 30 providers.
DR   DNASU; 10893; -.
DR   Ensembl; ENST00000246186.8; ENSP00000246186.6; ENSG00000125966.10.
DR   GeneID; 10893; -.
DR   KEGG; hsa:10893; -.
DR   MANE-Select; ENST00000246186.8; ENSP00000246186.6; NM_006690.4; NP_006681.1.
DR   UCSC; uc002xbu.3; human.
DR   AGR; HGNC:7172; -.
DR   CTD; 10893; -.
DR   DisGeNET; 10893; -.
DR   GeneCards; MMP24; -.
DR   HGNC; HGNC:7172; MMP24.
DR   HPA; ENSG00000125966; Tissue enriched (brain).
DR   MIM; 604871; gene.
DR   neXtProt; NX_Q9Y5R2; -.
DR   OpenTargets; ENSG00000125966; -.
DR   PharmGKB; PA30881; -.
DR   VEuPathDB; HostDB:ENSG00000125966; -.
DR   eggNOG; KOG1565; Eukaryota.
DR   GeneTree; ENSGT00940000158315; -.
DR   HOGENOM; CLU_015489_8_1_1; -.
DR   InParanoid; Q9Y5R2; -.
DR   OMA; AMTQHYY; -.
DR   OrthoDB; 2225278at2759; -.
DR   PhylomeDB; Q9Y5R2; -.
DR   TreeFam; TF352396; -.
DR   PathwayCommons; Q9Y5R2; -.
DR   Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR   SignaLink; Q9Y5R2; -.
DR   SIGNOR; Q9Y5R2; -.
DR   BioGRID-ORCS; 10893; 37 hits in 1169 CRISPR screens.
DR   ChiTaRS; MMP24; human.
DR   GeneWiki; MMP24; -.
DR   GenomeRNAi; 10893; -.
DR   Pharos; Q9Y5R2; Tbio.
DR   PRO; PR:Q9Y5R2; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; Q9Y5R2; Protein.
DR   Bgee; ENSG00000125966; Expressed in right hemisphere of cerebellum and 133 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:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR   GO; GO:0032588; C:trans-Golgi network membrane; ISS:UniProtKB.
DR   GO; GO:0045296; F:cadherin binding; IEA:Ensembl.
DR   GO; GO:0008047; F:enzyme activator activity; TAS:ProtInc.
DR   GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0044331; P:cell-cell adhesion mediated by cadherin; ISS:UniProtKB.
DR   GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; ISS: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; ISS:UniProtKB.
DR   GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR   GO; GO:0010001; P:glial cell differentiation; ISS:UniProtKB.
DR   GO; GO:0097150; P:neuronal stem cell population maintenance; ISS:UniProtKB.
DR   GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR   CDD; cd00094; HX; 1.
DR   CDD; cd04278; ZnMc_MMP; 1.
DR   Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1.
DR   Gene3D; 2.110.10.10; Hemopexin-like domain; 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; 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; MATRIX METALLOPROTEINASE; 1.
DR   PANTHER; PTHR10201:SF138; MATRIX METALLOPROTEINASE-24; 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; SSF50923; Hemopexin-like domain; 1.
DR   SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1.
DR   SUPFAM; SSF47090; PGBD-like; 1.
DR   PROSITE; PS00024; HEMOPEXIN; 1.
DR   PROSITE; PS51642; HEMOPEXIN_2; 4.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
DR   Genevisible; Q9Y5R2; HS.
PE   2: Evidence at transcript 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..52
FT                   /evidence="ECO:0000255"
FT   PROPEP          53..155
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000028846"
FT   CHAIN           156..645
FT                   /note="Matrix metalloproteinase-24"
FT                   /id="PRO_0000028847"
FT   CHAIN           156..581
FT                   /note="Processed matrix metalloproteinase-24"
FT                   /evidence="ECO:0000250"
FT                   /id="PRO_0000302758"
FT   TOPO_DOM        53..602
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        603..623
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        624..645
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   REPEAT          377..425
FT                   /note="Hemopexin 1"
FT   REPEAT          426..471
FT                   /note="Hemopexin 2"
FT   REPEAT          473..521
FT                   /note="Hemopexin 3"
FT   REPEAT          522..569
FT                   /note="Hemopexin 4"
FT   REGION          1..26
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          323..380
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           137..144
FT                   /note="Cysteine switch"
FT                   /evidence="ECO:0000250"
FT   MOTIF           643..645
FT                   /note="PDZ-binding"
FT   COMPBIAS        7..25
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        347..363
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        283
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         139
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         282
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         286
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   BINDING         292
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT   SITE            581..582
FT                   /note="Cleavage; by furin"
FT                   /evidence="ECO:0000250"
FT   DISULFID        380..569
FT                   /evidence="ECO:0000250"
FT   VARIANT         564
FT                   /note="R -> H (in dbSNP:rs751887)"
FT                   /id="VAR_060166"
SQ   SEQUENCE   645 AA;  73231 MW;  06B2B76EA3DABB9D CRC64;
     MPRSRGGRAA PGPPPPPPPP GQAPRWSRWR VPGRLLLLLL PALCCLPGAA RAAAAAAGAG
     NRAAVAVAVA RADEAEAPFA GQNWLKSYGY LLPYDSRASA LHSAKALQSA VSTMQQFYGI
     PVTGVLDQTT IEWMKKPRCG VPDHPHLSRR RRNKRYALTG QKWRQKHITY SIHNYTPKVG
     ELDTRKAIRQ AFDVWQKVTP LTFEEVPYHE IKSDRKEADI MIFFASGFHG DSSPFDGEGG
     FLAHAYFPGP GIGGDTHFDS DEPWTLGNAN HDGNDLFLVA VHELGHALGL EHSSDPSAIM
     APFYQYMETH NFKLPQDDLQ GIQKIYGPPA EPLEPTRPLP TLPVRRIHSP SERKHERQPR
     PPRPPLGDRP STPGTKPNIC DGNFNTVALF RGEMFVFKDR WFWRLRNNRV QEGYPMQIEQ
     FWKGLPARID AAYERADGRF VFFKGDKYWV FKEVTVEPGY PHSLGELGSC LPREGIDTAL
     RWEPVGKTYF FKGERYWRYS EERRATDPGY PKPITVWKGI PQAPQGAFIS KEGYYTYFYK
     GRDYWKFDNQ KLSVEPGYPR NILRDWMGCN QKEVERRKER RLPQDDVDIM VTINDVPGSV
     NAVAVVIPCI LSLCILVLVY TIFQFKNKTG PQPVTYYKRP VQEWV
//