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Protein

Matrix metalloproteinase-24

Gene

MMP24

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at transcript 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 (By similarity).By similarity

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)DescriptionActionsGraphical viewLength
Metal bindingi139Zinc; in inhibited formBy similarity1
Metal bindingi282Zinc; catalyticPROSITE-ProRule annotation1
Active sitei283PROSITE-ProRule annotation1
Metal bindingi286Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi292Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • cadherin binding Source: Ensembl
  • enzyme activator activity Source: ProtInc
  • metalloendopeptidase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processCell adhesion
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1592389 Activation of Matrix Metalloproteinases

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000125966.9
HGNCiHGNC:7172 MMP24
MIMi604871 gene
neXtProtiNX_Q9Y5R2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini53 – 602ExtracellularSequence analysisAdd BLAST550
Transmembranei603 – 623HelicalSequence analysisAdd BLAST21
Topological domaini624 – 645CytoplasmicSequence analysisAdd BLAST22

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi10893
OpenTargetsiENSG00000125966
PharmGKBiPA30881

Chemistry databases

ChEMBLiCHEMBL5050
DrugBankiDB00786 Marimastat

Polymorphism and mutation databases

BioMutaiMMP24
DMDMi12585280

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 52Sequence analysisAdd BLAST52
PropeptideiPRO_000002884653 – 155By similarityAdd BLAST103
ChainiPRO_0000028847156 – 645Matrix metalloproteinase-24Add BLAST490
ChainiPRO_0000302758156 – 581Processed matrix metalloproteinase-24By similarityAdd BLAST426

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi380 ↔ 569By similarity

Post-translational modificationi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei581 – 582Cleavage; by furinBy similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Zymogen

Proteomic databases

EPDiQ9Y5R2
MaxQBiQ9Y5R2
PaxDbiQ9Y5R2
PeptideAtlasiQ9Y5R2
PRIDEiQ9Y5R2
ProteomicsDBi86480

PTM databases

iPTMnetiQ9Y5R2
PhosphoSitePlusiQ9Y5R2

Expressioni

Tissue specificityi

Predominantly expressed in brain, kidney, pancreas and lung. Overexpressed in a series of brain tumors, including astrocytomas and glioblastomas.1 Publication

Gene expression databases

BgeeiENSG00000125966 Expressed in 159 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_MMP24
GenevisibleiQ9Y5R2 HS

Organism-specific databases

HPAiHPA049280

Interactioni

Subunit structurei

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

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9Y5R2, 1 interactor
MINTiQ9Y5R2
STRINGi9606.ENSP00000246186

Chemistry databases

BindingDBiQ9Y5R2

Structurei

3D structure databases

ProteinModelPortaliQ9Y5R2
SMRiQ9Y5R2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati377 – 425Hemopexin 1Add BLAST49
Repeati426 – 471Hemopexin 2Add BLAST46
Repeati473 – 521Hemopexin 3Add BLAST49
Repeati522 – 569Hemopexin 4Add BLAST48

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi137 – 144Cysteine switchBy similarity8
Motifi643 – 645PDZ-binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi149 – 152Poly-Arg4

Domaini

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.
The PDZ-binding motif (also named EWV motif) is required for interaction with PDZ domains of APBA3 and recycling through the trans-Golgi network.By similarity

Sequence similaritiesi

Belongs to the peptidase M10A family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1565 Eukaryota
ENOG410XQ5D LUCA
GeneTreeiENSGT00760000118870
HOGENOMiHOG000217928
HOVERGENiHBG052484
InParanoidiQ9Y5R2
KOiK08002
OMAiGYPHSLV
OrthoDBiEOG091G03DP
PhylomeDBiQ9Y5R2
TreeFamiTF352396

Family and domain databases

CDDicd00094 HX, 1 hit
cd04278 ZnMc_MMP, 1 hit
Gene3Di2.110.10.10, 1 hit
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR000585 Hemopexin-like_dom
IPR036375 Hemopexin-like_dom_sf
IPR018487 Hemopexin-like_repeat
IPR018486 Hemopexin_CS
IPR033739 M10A_MMP
IPR024079 MetalloPept_cat_dom_sf
IPR028723 MMP24
IPR001818 Pept_M10_metallopeptidase
IPR021190 Pept_M10A
IPR021805 Pept_M10A_metallopeptidase_C
IPR006026 Peptidase_Metallo
IPR002477 Peptidoglycan-bd-like
IPR036365 PGBD-like_sf
PANTHERiPTHR10201:SF138 PTHR10201:SF138, 1 hit
PfamiView protein in Pfam
PF11857 DUF3377, 1 hit
PF00045 Hemopexin, 4 hits
PF00413 Peptidase_M10, 1 hit
PF01471 PG_binding_1, 1 hit
PIRSFiPIRSF001191 Peptidase_M10A_matrix, 1 hit
PRINTSiPR00138 MATRIXIN
SMARTiView protein in SMART
SM00120 HX, 4 hits
SM00235 ZnMc, 1 hit
SUPFAMiSSF47090 SSF47090, 1 hit
SSF50923 SSF50923, 1 hit
PROSITEiView protein in PROSITE
PS00024 HEMOPEXIN, 1 hit
PS51642 HEMOPEXIN_2, 4 hits
PS00142 ZINC_PROTEASE, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q9Y5R2-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPRSRGGRAA PGPPPPPPPP GQAPRWSRWR VPGRLLLLLL PALCCLPGAA
60 70 80 90 100
RAAAAAAGAG NRAAVAVAVA RADEAEAPFA GQNWLKSYGY LLPYDSRASA
110 120 130 140 150
LHSAKALQSA VSTMQQFYGI PVTGVLDQTT IEWMKKPRCG VPDHPHLSRR
160 170 180 190 200
RRNKRYALTG QKWRQKHITY SIHNYTPKVG ELDTRKAIRQ AFDVWQKVTP
210 220 230 240 250
LTFEEVPYHE IKSDRKEADI MIFFASGFHG DSSPFDGEGG FLAHAYFPGP
260 270 280 290 300
GIGGDTHFDS DEPWTLGNAN HDGNDLFLVA VHELGHALGL EHSSDPSAIM
310 320 330 340 350
APFYQYMETH NFKLPQDDLQ GIQKIYGPPA EPLEPTRPLP TLPVRRIHSP
360 370 380 390 400
SERKHERQPR PPRPPLGDRP STPGTKPNIC DGNFNTVALF RGEMFVFKDR
410 420 430 440 450
WFWRLRNNRV QEGYPMQIEQ FWKGLPARID AAYERADGRF VFFKGDKYWV
460 470 480 490 500
FKEVTVEPGY PHSLGELGSC LPREGIDTAL RWEPVGKTYF FKGERYWRYS
510 520 530 540 550
EERRATDPGY PKPITVWKGI PQAPQGAFIS KEGYYTYFYK GRDYWKFDNQ
560 570 580 590 600
KLSVEPGYPR NILRDWMGCN QKEVERRKER RLPQDDVDIM VTINDVPGSV
610 620 630 640
NAVAVVIPCI LSLCILVLVY TIFQFKNKTG PQPVTYYKRP VQEWV
Length:645
Mass (Da):73,231
Last modified:November 1, 1999 - v1
Checksum:i06B2B76EA3DABB9D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_060166564R → H. Corresponds to variant dbSNP:rs751887Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF131284 mRNA Translation: AAD42962.1
AB021227 mRNA Translation: BAA82967.1
AL121753 Genomic DNA No translation available.
CCDSiCCDS46593.1
RefSeqiNP_006681.1, NM_006690.3
UniGeneiHs.715494

Genome annotation databases

EnsembliENST00000246186; ENSP00000246186; ENSG00000125966
GeneIDi10893
KEGGihsa:10893
UCSCiuc002xbu.3 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF131284 mRNA Translation: AAD42962.1
AB021227 mRNA Translation: BAA82967.1
AL121753 Genomic DNA No translation available.
CCDSiCCDS46593.1
RefSeqiNP_006681.1, NM_006690.3
UniGeneiHs.715494

3D structure databases

ProteinModelPortaliQ9Y5R2
SMRiQ9Y5R2
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9Y5R2, 1 interactor
MINTiQ9Y5R2
STRINGi9606.ENSP00000246186

Chemistry databases

BindingDBiQ9Y5R2
ChEMBLiCHEMBL5050
DrugBankiDB00786 Marimastat

Protein family/group databases

MEROPSiM10.023

PTM databases

iPTMnetiQ9Y5R2
PhosphoSitePlusiQ9Y5R2

Polymorphism and mutation databases

BioMutaiMMP24
DMDMi12585280

Proteomic databases

EPDiQ9Y5R2
MaxQBiQ9Y5R2
PaxDbiQ9Y5R2
PeptideAtlasiQ9Y5R2
PRIDEiQ9Y5R2
ProteomicsDBi86480

Protocols and materials databases

DNASUi10893
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000246186; ENSP00000246186; ENSG00000125966
GeneIDi10893
KEGGihsa:10893
UCSCiuc002xbu.3 human

Organism-specific databases

CTDi10893
DisGeNETi10893
EuPathDBiHostDB:ENSG00000125966.9
GeneCardsiMMP24
HGNCiHGNC:7172 MMP24
HPAiHPA049280
MIMi604871 gene
neXtProtiNX_Q9Y5R2
OpenTargetsiENSG00000125966
PharmGKBiPA30881
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1565 Eukaryota
ENOG410XQ5D LUCA
GeneTreeiENSGT00760000118870
HOGENOMiHOG000217928
HOVERGENiHBG052484
InParanoidiQ9Y5R2
KOiK08002
OMAiGYPHSLV
OrthoDBiEOG091G03DP
PhylomeDBiQ9Y5R2
TreeFamiTF352396

Enzyme and pathway databases

ReactomeiR-HSA-1592389 Activation of Matrix Metalloproteinases

Miscellaneous databases

ChiTaRSiMMP24 human
GeneWikiiMMP24
GenomeRNAii10893
PROiPR:Q9Y5R2
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125966 Expressed in 159 organ(s), highest expression level in right hemisphere of cerebellum
CleanExiHS_MMP24
GenevisibleiQ9Y5R2 HS

Family and domain databases

CDDicd00094 HX, 1 hit
cd04278 ZnMc_MMP, 1 hit
Gene3Di2.110.10.10, 1 hit
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR000585 Hemopexin-like_dom
IPR036375 Hemopexin-like_dom_sf
IPR018487 Hemopexin-like_repeat
IPR018486 Hemopexin_CS
IPR033739 M10A_MMP
IPR024079 MetalloPept_cat_dom_sf
IPR028723 MMP24
IPR001818 Pept_M10_metallopeptidase
IPR021190 Pept_M10A
IPR021805 Pept_M10A_metallopeptidase_C
IPR006026 Peptidase_Metallo
IPR002477 Peptidoglycan-bd-like
IPR036365 PGBD-like_sf
PANTHERiPTHR10201:SF138 PTHR10201:SF138, 1 hit
PfamiView protein in Pfam
PF11857 DUF3377, 1 hit
PF00045 Hemopexin, 4 hits
PF00413 Peptidase_M10, 1 hit
PF01471 PG_binding_1, 1 hit
PIRSFiPIRSF001191 Peptidase_M10A_matrix, 1 hit
PRINTSiPR00138 MATRIXIN
SMARTiView protein in SMART
SM00120 HX, 4 hits
SM00235 ZnMc, 1 hit
SUPFAMiSSF47090 SSF47090, 1 hit
SSF50923 SSF50923, 1 hit
PROSITEiView protein in PROSITE
PS00024 HEMOPEXIN, 1 hit
PS51642 HEMOPEXIN_2, 4 hits
PS00142 ZINC_PROTEASE, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMMP24_HUMAN
AccessioniPrimary (citable) accession number: Q9Y5R2
Secondary accession number(s): B7ZBG8, Q9H440
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: November 1, 1999
Last modified: November 7, 2018
This is version 172 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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