MMP24_HUMAN
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 03-AUG-2022, entry version 193.
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; 4.
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; Q9Y5R2; -.
DR PeptideAtlas; Q9Y5R2; -.
DR PRIDE; Q9Y5R2; -.
DR ProteomicsDB; 86480; -.
DR Antibodypedia; 5282; 217 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 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; QSWLKSY; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q9Y5R2; -.
DR TreeFam; TF352396; -.
DR PathwayCommons; Q9Y5R2; -.
DR Reactome; R-HSA-1592389; Activation of Matrix Metalloproteinases.
DR SignaLink; Q9Y5R2; -.
DR BioGRID-ORCS; 10893; 36 hits in 1085 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 132 other tissues.
DR Genevisible; Q9Y5R2; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005887; C:integral component of 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; 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 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
