MMP24_RAT
ID MMP24_RAT Reviewed; 618 AA.
AC Q99PW6;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 139.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Sekine-Aizawa Y.;
RT "Molecular cloning and characterization of rat MT5-MMP.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10727639; DOI=10.1016/s0006-8993(00)02035-7;
RA Jaworski D.M.;
RT "Developmental regulation of membrane type-5 matrix metalloproteinase (MT5-
RT MMP) expression in the rat nervous system.";
RL Brain Res. 860:174-177(2000).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, INTERACTION WITH
RP GRIP1 AND GRIP2, AND MUTAGENESIS OF 616-GLU--VAL-618.
RX PubMed=16495457; DOI=10.1523/jneurosci.3521-05.2006;
RA Monea S., Jordan B.A., Srivastava S., DeSouza S., Ziff E.B.;
RT "Membrane localization of membrane type 5 matrix metalloproteinase by AMPA
RT receptor binding protein and cleavage of cadherins.";
RL J. Neurosci. 26:2300-2312(2006).
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.
CC {ECO:0000269|PubMed:16495457}.
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 (By similarity). Interacts with GRIP1 and GRIP2. {ECO:0000250,
CC ECO:0000269|PubMed:16495457}.
CC -!- SUBCELLULAR LOCATION: [Matrix metalloproteinase-24]: Cell membrane;
CC Single-pass type I membrane protein. Golgi apparatus, trans-Golgi
CC network membrane {ECO:0000250}; Single-pass type I membrane protein
CC {ECO:0000250}. Note=Recycled back to the plasma membrane through the
CC trans-Golgi network via interaction with APBA3. {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 the nervous system:
CC while enriched in the central nervous system, expression is also
CC detected in the peripheral nervous system, including the trigeminal
CC ganglion. Expression is not restricted to the nervous system: it is
CC also enriched in the thymus, with a lower level of expression present
CC in the aorta. In brain, high expression is present in the brain
CC parenchyma, particularly within the neocortex.
CC {ECO:0000269|PubMed:10727639}.
CC -!- DEVELOPMENTAL STAGE: Expression is first detected in embryonic day 16
CC (E16) brain, strongly increases at E20, and peaks within 24 hours of
CC birth. The postnatal expression declines steadily to reach adult levels
CC at P60. {ECO:0000269|PubMed:10727639}.
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:16495457}.
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: Cleaved by a furin endopeptidase in the trans-Golgi network.
CC -!- SIMILARITY: Belongs to the peptidase M10A family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB023659; BAB32589.1; -; mRNA.
DR RefSeq; NP_113945.1; NM_031757.1.
DR AlphaFoldDB; Q99PW6; -.
DR SMR; Q99PW6; -.
DR STRING; 10116.ENSRNOP00000067398; -.
DR MEROPS; M10.023; -.
DR PhosphoSitePlus; Q99PW6; -.
DR PaxDb; Q99PW6; -.
DR Ensembl; ENSRNOT00000092194; ENSRNOP00000075211; ENSRNOG00000047028.
DR GeneID; 83513; -.
DR KEGG; rno:83513; -.
DR CTD; 10893; -.
DR RGD; 620202; Mmp24.
DR eggNOG; KOG1565; Eukaryota.
DR GeneTree; ENSGT00940000158315; -.
DR InParanoid; Q99PW6; -.
DR OrthoDB; 1075463at2759; -.
DR PhylomeDB; Q99PW6; -.
DR Reactome; R-RNO-1592389; Activation of Matrix Metalloproteinases.
DR PRO; PR:Q99PW6; -.
DR Proteomes; UP000002494; Chromosome 3.
DR GO; GO:0031012; C:extracellular matrix; IEA:InterPro.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0016021; C:integral component of membrane; TAS:RGD.
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; ISO:RGD.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; TAS:RGD.
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 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_0000028850"
FT CHAIN 129..618
FT /note="Matrix metalloproteinase-24"
FT /id="PRO_0000028851"
FT CHAIN 129..554
FT /note="Processed matrix metalloproteinase-24"
FT /evidence="ECO:0000250"
FT /id="PRO_0000302760"
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..336
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 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 /evidence="ECO:0000250"
FT DISULFID 353..542
FT /evidence="ECO:0000250"
FT MUTAGEN 616..618
FT /note="Missing: Impaired interaction with GRIP1 and GRIP2."
FT /evidence="ECO:0000269|PubMed:16495457"
SQ SEQUENCE 618 AA; 70465 MW; 614ED4EEC6B27F5F CRC64;
MPRSRGGRAA PGQAARWSGW 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 QPRPPRPPLG 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
KTGPQPVTYY KRPVQEWV
