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Protein

Matrix metalloproteinase-24

Gene

Mmp24

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Metalloprotease that mediates cleavage of N-cadherin (CDH2) and acts as a regulator of neuro-immune interactions and neural stem cell quiescence. Involved in cell-cell interactions between nociceptive neurites and mast cells, possibly by mediating cleavage of CDH2, thereby acting as a mediator of peripheral thermal nociception and inflammatory hyperalgesia. Key regulator of neural stem cells quiescence by mediating cleavage of CDH2, affecting CDH2-mediated anchorage of neural stem cells to ependymocytes in the adult subependymal zone, leading to modulate their quiescence. May play a role in axonal growth. Able to activate progelatinase A. May also be a proteoglycanase involved in degradation of proteoglycans, such as dermatan sulfate and chondroitin sulfate proteoglycans. Cleaves partially fibronectin, but not collagen type I, nor laminin.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
  • Ca2+By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi112 – 1121Zinc; in inhibited formBy similarity
Metal bindingi255 – 2551Zinc; catalyticPROSITE-ProRule annotation
Active sitei256 – 2561PROSITE-ProRule annotation
Metal bindingi259 – 2591Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi265 – 2651Zinc; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

  • calcium ion binding Source: InterPro
  • metalloendopeptidase activity Source: UniProtKB
  • peptidase activity Source: RGD
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Cell adhesion

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Protein family/group databases

MEROPSiM10.023.

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix metalloproteinase-24 (EC:3.4.24.-)
Short name:
MMP-24
Alternative name(s):
Membrane-type matrix metalloproteinase 5
Short name:
MT-MMP 5
Short name:
MTMMP5
Membrane-type-5 matrix metalloproteinase
Short name:
MT5-MMP
Short name:
MT5MMP
Cleaved into the following chain:
Gene namesi
Name:Mmp24
Synonyms:Mt5mmp
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620202. Mmp24.

Subcellular locationi

Matrix metalloproteinase-24 :
Processed matrix metalloproteinase-24 :

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini42 – 575534ExtracellularSequence analysisAdd
BLAST
Transmembranei576 – 59621HelicalSequence analysisAdd
BLAST
Topological domaini597 – 61822CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Extracellular matrix, Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi616 – 6183Missing : Impaired interaction with GRIP1 and GRIP2. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4141Sequence analysisAdd
BLAST
Propeptidei42 – 12887By similarityPRO_0000028850Add
BLAST
Chaini129 – 618490Matrix metalloproteinase-24PRO_0000028851Add
BLAST
Chaini129 – 554426Processed matrix metalloproteinase-24By similarityPRO_0000302760Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi353 ↔ 542By similarity

Post-translational modificationi

Cleaved by a furin endopeptidase in the trans-Golgi network.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei554 – 5552Cleavage; by furinBy similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Zymogen

Proteomic databases

PaxDbiQ99PW6.

PTM databases

PhosphoSiteiQ99PW6.

Expressioni

Tissue specificityi

Predominantly expressed in the nervous system: while enriched in the central nervous system, expression is also detected in the peripheral nervous system, including the trigeminal ganglion. Expression is not restricted to the nervous system: it is also enriched in the thymus, with a lower level of expression present in the aorta. In brain, high expression is present in the brain parenchyma, particularly within the neocortex.1 Publication

Developmental stagei

Expression is first detected in embryonic day 16 (E16) brain, strongly increases at E20, and peaks at postnatal day 0 (P0), within 24 hours of birth. The postnatal expression declines steadily to reach adult levels at P60.1 Publication

Interactioni

Subunit structurei

Interacts (via PDZ-binding motif) with APBA3 (via PDZ domain) (By similarity). Interacts with GRIP1 and GRIP2.By similarity1 Publication

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000067398.

Structurei

3D structure databases

ProteinModelPortaliQ99PW6.
SMRiQ99PW6. Positions 133-301.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati350 – 39849Hemopexin 1Add
BLAST
Repeati399 – 44446Hemopexin 2Add
BLAST
Repeati446 – 49449Hemopexin 3Add
BLAST
Repeati495 – 54248Hemopexin 4Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi110 – 1178Cysteine switchBy similarity
Motifi616 – 6183PDZ-binding

Domaini

The PDZ-binding motif (also named EWV motif) is required for interaction with PDZ domains of APBA3 and recycling through the trans-Golgi network.1 Publication
The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Sequence similaritiesi

Belongs to the peptidase M10A family.Curated
Contains 4 hemopexin repeats.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
HOVERGENiHBG052484.
InParanoidiQ99PW6.
KOiK08002.
PhylomeDBiQ99PW6.

Family and domain databases

Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR028723. MMP24.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR021805. Pept_M10A_metallopeptidase_C.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF138. PTHR10201:SF138. 2 hits.
PfamiPF11857. DUF3377. 1 hit.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99PW6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPRSRGGRAA PGQAARWSGW RAPGRLLPLL PALCCLAAAA GAGKPAGADA
60 70 80 90 100
PFAGQNWLKS YGYLLPYESR ASALHSGKAL QSAVSTMQQF YGIPVTGVLD
110 120 130 140 150
QTTIEWMKKP RCGVPDHPHL SRRRRNKRYA LTGQKWRQKH ITYSIHNYTP
160 170 180 190 200
KVGELDTRKA IRQAFDVWQK VTPLTFEEVP YHEIKSDRKE ADIMIFFASG
210 220 230 240 250
FHGDSSPFDG EGGFLAHAYF PGPGIGGDTH FDSDEPWTLG NANHDGNDLF
260 270 280 290 300
LVAVHELGHA LGLEHSNDPS AIMAPFYQYM ETHNFKLPQD DLQGIQKIYG
310 320 330 340 350
PPAEPLEPTR PLPTLPVRRI HSPSERKHER QPRPPRPPLG DRPSTPGAKP
360 370 380 390 400
NICDGNFNTV ALFRGEMFVF KDRWFWRLRN NRVQEGYPMQ IEQFWKGLPA
410 420 430 440 450
RIDAAYERAD GRFVFFKGDK YWVFKEVTVE PGYPHSLGEL GSCLPREGID
460 470 480 490 500
TALRWEPVGK TYFFKGERYW RYSEERRATD PGYPKPITVW KGIPQAPQGA
510 520 530 540 550
FISKEGYYTY FYKGRDYWKF DNQKLSVEPG YPRNILRDWM GCKQKEVERR
560 570 580 590 600
KERRLPQDDV DIMVTIDDVP GSVNAVAVVV PCTLSLCLLV LLYTIFQFKN
610
KTGPQPVTYY KRPVQEWV
Length:618
Mass (Da):70,465
Last modified:June 1, 2001 - v1
Checksum:i614ED4EEC6B27F5F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB023659 mRNA. Translation: BAB32589.1.
RefSeqiNP_113945.1. NM_031757.1.
UniGeneiRn.3117.

Genome annotation databases

GeneIDi83513.
KEGGirno:83513.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB023659 mRNA. Translation: BAB32589.1.
RefSeqiNP_113945.1. NM_031757.1.
UniGeneiRn.3117.

3D structure databases

ProteinModelPortaliQ99PW6.
SMRiQ99PW6. Positions 133-301.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000067398.

Protein family/group databases

MEROPSiM10.023.

PTM databases

PhosphoSiteiQ99PW6.

Proteomic databases

PaxDbiQ99PW6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi83513.
KEGGirno:83513.

Organism-specific databases

CTDi10893.
RGDi620202. Mmp24.

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
HOVERGENiHBG052484.
InParanoidiQ99PW6.
KOiK08002.
PhylomeDBiQ99PW6.

Miscellaneous databases

NextBioi615966.
PROiQ99PW6.

Family and domain databases

Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR028723. MMP24.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR021805. Pept_M10A_metallopeptidase_C.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF138. PTHR10201:SF138. 2 hits.
PfamiPF11857. DUF3377. 1 hit.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Molecular cloning and characterization of rat MT5-MMP."
    Sekine-Aizawa Y.
    Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  2. "Developmental regulation of membrane type-5 matrix metalloproteinase (MT5-MMP) expression in the rat nervous system."
    Jaworski D.M.
    Brain Res. 860:174-177(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  3. "Membrane localization of membrane type 5 matrix metalloproteinase by AMPA receptor binding protein and cleavage of cadherins."
    Monea S., Jordan B.A., Srivastava S., DeSouza S., Ziff E.B.
    J. Neurosci. 26:2300-2312(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, INTERACTION WITH GRIP1 AND GRIP2, MUTAGENESIS OF 616-GLU--VAL-618.

Entry informationi

Entry nameiMMP24_RAT
AccessioniPrimary (citable) accession number: Q99PW6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: June 1, 2001
Last modified: November 11, 2015
This is version 108 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Peptidase families
    Classification of peptidase families and list of entries
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.