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UniProtKB - P08254 (MMP3_HUMAN)

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Protein

Stromelysin-1

Gene

MMP3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.

Catalytic activityi

Preferential cleavage where P1', P2' and P3' are hydrophobic residues.

Cofactori

Protein has several cofactor binding sites:
  • Ca2+Note: Binds 4 Ca2+ ions per subunit.
  • Zn2+Note: Binds 2 Zn2+ ions per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi92Zinc 2; in inhibited form1
Metal bindingi124Calcium 11
Metal bindingi158Calcium 21
Metal bindingi168Zinc 11
Metal bindingi170Zinc 11
Metal bindingi175Calcium 31
Metal bindingi176Calcium 3; via carbonyl oxygen1
Metal bindingi178Calcium 3; via carbonyl oxygen1
Metal bindingi180Calcium 3; via carbonyl oxygen1
Metal bindingi183Zinc 11
Metal bindingi190Calcium 2; via carbonyl oxygen1
Metal bindingi192Calcium 2; via carbonyl oxygen1
Metal bindingi194Calcium 21
Metal bindingi196Zinc 11
Metal bindingi198Calcium 31
Metal bindingi199Calcium 11
Metal bindingi201Calcium 11
Metal bindingi201Calcium 31
Metal bindingi218Zinc 2; catalytic1 Publication1
Active sitei2191
Metal bindingi222Zinc 2; catalytic1 Publication1
Metal bindingi228Zinc 2; catalytic1 Publication1
Metal bindingi297Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi389Calcium 4; via carbonyl oxygenBy similarity1
Metal bindingi438Calcium 4; via carbonyl oxygenBy similarity1

GO - Molecular functioni

  • endopeptidase activity Source: ParkinsonsUK-UCL
  • metalloendopeptidase activity Source: Reactome
  • metallopeptidase activity Source: UniProtKB
  • serine-type endopeptidase activity Source: Reactome
  • zinc ion binding Source: InterPro
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cellular response to nitric oxide Source: ParkinsonsUK-UCL
  • collagen catabolic process Source: Reactome
  • cytokine-mediated signaling pathway Source: Reactome
  • extracellular matrix disassembly Source: Reactome
  • negative regulation of hydrogen peroxide metabolic process Source: ParkinsonsUK-UCL
  • positive regulation of oxidative stress-induced cell death Source: ParkinsonsUK-UCL
  • positive regulation of protein oligomerization Source: ParkinsonsUK-UCL
  • proteolysis Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processCollagen degradation
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1442490 Collagen degradation
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-1592389 Activation of Matrix Metalloproteinases
R-HSA-2022090 Assembly of collagen fibrils and other multimeric structures
R-HSA-2179392 EGFR Transactivation by Gastrin
R-HSA-6785807 Interleukin-4 and 13 signaling
SIGNORiP08254

Protein family/group databases

MEROPSiM10.005

Names & Taxonomyi

Protein namesi
Recommended name:
Stromelysin-1 (EC:3.4.24.17)
Short name:
SL-1
Alternative name(s):
Matrix metalloproteinase-3
Short name:
MMP-3
Transin-1
Gene namesi
Name:MMP3
Synonyms:STMY1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000149968.11
HGNCiHGNC:7173 MMP3
MIMi185250 gene
neXtProtiNX_P08254

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

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Coronary heart disease 6 (CHDS6)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry. A polymorphism in the MMP3 promoter region is associated with the risk of coronary heart disease and myocardial infarction, due to lower MMP3 proteolytic activity and higher extracellular matrix deposition in atherosclerotic lesions.
Disease descriptionA multifactorial disease characterized by an imbalance between myocardial functional requirements and the capacity of the coronary vessels to supply sufficient blood flow. Decreased capacity of the coronary vessels is often associated with thickening and loss of elasticity of the coronary arteries.
See also OMIM:614466

Organism-specific databases

DisGeNETi4314
MalaCardsiMMP3
MIMi614466 phenotype
OpenTargetsiENSG00000149968
PharmGKBiPA30886

Chemistry databases

ChEMBLiCHEMBL283
DrugBankiDB02367 (1n)-4-N-Butoxyphenylsulfonyl-(2r)-N-Hydroxycarboxamido-(4s)-Methanesulfonylamino-Pyrrolidine
DB04140 1-Benzyl-3-(4-Methoxy-Benzenesulfonyl)-6-Oxo-Hexahydro-Pyrimidine-4-Carboxylic Acid Hydroxyamide
DB03033 1-Methyloxy-4-Sulfone-Benzene
DB08643 2-(2-{2-[(BIPHENYL-4-YLMETHYL)-AMINO]-3-MERCAPTO-PENTANOYLAMINO}-ACETYLAMINO)-3-METHYL-BUTYRIC ACID METHYL ESTER
DB02449 3-(1h-Indol-3-Yl)-2-[4-(4-Phenyl-Piperidin-1-Yl)-Benzenesulfonylamino]-Propionic Acid
DB08030 3-[(4'-cyanobiphenyl-4-yl)oxy]-N-hydroxypropanamide
DB01996 3-Methylpyridine
DB07986 [4-(4-PHENYL-PIPERIDIN-1-YL)-BENZENESULFONYLAMINO]-ACETIC ACID
DB02090 A Disubstituted Succinyl Caprolactam Hydroxymate Mmp3inhibitor
DB02697 Hydroxyaminovaline
DB00786 Marimastat
DB08507 N-[[2-METHYL-4-HYDROXYCARBAMOYL]BUT-4-YL-N]-BENZYL-P-[PHENYL]-P-[METHYL]PHOSPHINAMID
DB04232 N-Hydroxy-1-(4-Methoxyphenyl)Sulfonyl-4-Benzyloxycarbonyl-Piperazine-2-Carboxamide
DB08271 N-ISOBUTYL-N-[4-METHOXYPHENYLSULFONYL]GLYCYL HYDROXAMIC ACID
DB08029 N~2~-(biphenyl-4-ylsulfonyl)-N-hydroxy-N~2~-(2-hydroxyethyl)glycinamide
GuidetoPHARMACOLOGYi1630

Polymorphism and mutation databases

BioMutaiMMP3
DMDMi116857

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 171 PublicationAdd BLAST17
PropeptideiPRO_000002872818 – 99Activation peptideAdd BLAST82
ChainiPRO_0000028729100 – 477Stromelysin-1Add BLAST378

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi120N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi290 ↔ 477By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiP08254
PaxDbiP08254
PeptideAtlasiP08254
PRIDEiP08254
ProteomicsDBi52102

PTM databases

iPTMnetiP08254
PhosphoSitePlusiP08254

Miscellaneous databases

PMAP-CutDBiP08254

Expressioni

Gene expression databases

BgeeiENSG00000149968
CleanExiHS_MMP3
ExpressionAtlasiP08254 baseline and differential
GenevisibleiP08254 HS

Organism-specific databases

HPAiHPA007875

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
MEOX2P502223EBI-6957351,EBI-748397

Protein-protein interaction databases

BioGridi110458, 16 interactors
IntActiP08254, 1 interactor
MINTiP08254
STRINGi9606.ENSP00000299855

Chemistry databases

BindingDBiP08254

Structurei

Secondary structure

1477
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi34 – 41Combined sources8
Helixi58 – 70Combined sources13
Helixi81 – 86Combined sources6
Beta strandi96 – 98Combined sources3
Beta strandi102 – 104Combined sources3
Beta strandi110 – 118Combined sources9
Beta strandi123 – 125Combined sources3
Helixi127 – 142Combined sources16
Beta strandi144 – 146Combined sources3
Beta strandi148 – 151Combined sources4
Beta strandi153 – 155Combined sources3
Beta strandi158 – 164Combined sources7
Beta strandi169 – 171Combined sources3
Beta strandi176 – 179Combined sources4
Beta strandi182 – 184Combined sources3
Beta strandi187 – 189Combined sources3
Turni190 – 193Combined sources4
Beta strandi195 – 198Combined sources4
Beta strandi199 – 201Combined sources3
Beta strandi203 – 211Combined sources9
Helixi212 – 223Combined sources12
Beta strandi232 – 234Combined sources3
Beta strandi237 – 239Combined sources3
Helixi240 – 243Combined sources4
Helixi246 – 248Combined sources3
Helixi253 – 263Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1B3DX-ray2.30A/B100-272[»]
1B8YX-ray2.00A100-266[»]
1BIWX-ray2.50A/B100-272[»]
1BM6NMR-A100-272[»]
1BQOX-ray2.30A/B100-272[»]
1C3IX-ray1.83A/B100-272[»]
1C8TX-ray2.60A/B103-268[»]
1CAQX-ray1.80A100-267[»]
1CIZX-ray1.64A100-267[»]
1CQRX-ray2.00A/B100-272[»]
1D5JX-ray2.60A/B100-272[»]
1D7XX-ray2.00A/B100-272[»]
1D8FX-ray2.40A/B100-272[»]
1D8MX-ray2.44A/B100-272[»]
1G05X-ray2.45A/B100-272[»]
1G49X-ray1.90A/B100-272[»]
1G4KX-ray2.00A/B/C100-267[»]
1HFSX-ray1.70A105-264[»]
1HY7X-ray1.50A/B100-272[»]
1M1Wmodel-A100-268[»]
1OO9NMR-A100-267[»]
1QIAX-ray2.00A/B/C/D106-267[»]
1QICX-ray2.00A/B/C/D106-266[»]
1SLMX-ray1.90A18-272[»]
1SLNX-ray2.27A100-272[»]
1UEAX-ray2.80A/C100-272[»]
1UMSNMR-A100-273[»]
1UMTNMR-A100-273[»]
1USNX-ray1.80A100-264[»]
2D1OX-ray2.02A/B100-270[»]
2JNPNMR-A105-265[»]
2JT5NMR-A105-265[»]
2JT6NMR-A105-265[»]
2SRTNMR-A100-272[»]
2USNX-ray2.20A100-264[»]
3OHLX-ray2.36A100-266[»]
3OHOX-ray2.50A100-268[»]
3USNNMR-A100-267[»]
4DPEX-ray1.96A/B100-272[»]
4G9LX-ray1.88A/B100-272[»]
4JA1X-ray1.96A/B100-272[»]
ProteinModelPortaliP08254
SMRiP08254
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP08254

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati287 – 336Hemopexin 1Add BLAST50
Repeati337 – 383Hemopexin 2Add BLAST47
Repeati385 – 433Hemopexin 3Add BLAST49
Repeati434 – 477Hemopexin 4Add BLAST44

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi90 – 97Cysteine switchBy similarity8

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.

Sequence similaritiesi

Belongs to the peptidase M10A family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG1565 Eukaryota
ENOG410XQ5D LUCA
GeneTreeiENSGT00760000118870
HOGENOMiHOG000217927
HOVERGENiHBG052484
InParanoidiP08254
KOiK01394
OMAiVAVCSAY
OrthoDBiEOG091G03DP
PhylomeDBiP08254
TreeFamiTF315428

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
IPR001818 Pept_M10_metallopeptidase
IPR021190 Pept_M10A
IPR021158 Pept_M10A_Zn_BS
IPR006026 Peptidase_Metallo
IPR002477 Peptidoglycan-bd-like
IPR036365 PGBD-like_sf
PfamiView protein in Pfam
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
PS00546 CYSTEINE_SWITCH, 1 hit
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.

P08254-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSLPILLLL CVAVCSAYPL DGAARGEDTS MNLVQKYLEN YYDLKKDVKQ 
        60         70         80         90        100
FVRRKDSGPV VKKIREMQKF LGLEVTGKLD SDTLEVMRKP RCGVPDVGHF 
       110        120        130        140        150
RTFPGIPKWR KTHLTYRIVN YTPDLPKDAV DSAVEKALKV WEEVTPLTFS 
       160        170        180        190        200
RLYEGEADIM ISFAVREHGD FYPFDGPGNV LAHAYAPGPG INGDAHFDDD 
       210        220        230        240        250
EQWTKDTTGT NLFLVAAHEI GHSLGLFHSA NTEALMYPLY HSLTDLTRFR 
       260        270        280        290        300
LSQDDINGIQ SLYGPPPDSP ETPLVPTEPV PPEPGTPANC DPALSFDAVS 
       310        320        330        340        350
TLRGEILIFK DRHFWRKSLR KLEPELHLIS SFWPSLPSGV DAAYEVTSKD 
       360        370        380        390        400
LVFIFKGNQF WAIRGNEVRA GYPRGIHTLG FPPTVRKIDA AISDKEKNKT 
       410        420        430        440        450
YFFVEDKYWR FDEKRNSMEP GFPKQIAEDF PGIDSKIDAV FEEFGFFYFF 
       460        470 
TGSSQLEFDP NAKKVTHTLK SNSWLNC
Length:477
Mass (Da):53,977
Last modified:February 1, 1991 - v2
Checksum:i96194833B907668D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti420P → L (PubMed:3477804).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01309045K → E3 PublicationsCorresponds to variant dbSNP:rs679620EnsemblClinVar.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X05232 mRNA Translation: CAA28859.1
J03209 mRNA Translation: AAA36321.1
U78045 Genomic DNA Translation: AAB36942.1
AK223283 mRNA Translation: BAD97003.1
AK223291 mRNA Translation: BAD97011.1
AK313310 mRNA Translation: BAG36115.1
AF405705 Genomic DNA Translation: AAK95247.1
CH471065 Genomic DNA Translation: EAW67032.1
BC069676 mRNA Translation: AAH69676.1
BC069716 mRNA Translation: AAH69716.1
BC074815 mRNA Translation: AAH74815.1
BC074869 mRNA Translation: AAH74869.1
BC105954 mRNA Translation: AAI05955.1
BC107490 mRNA Translation: AAI07491.1
BC107491 mRNA Translation: AAI07492.1
CCDSiCCDS8323.1
PIRiA28156 KCHUS1
RefSeqiNP_002413.1, NM_002422.4
UniGeneiHs.375129

Genome annotation databases

EnsembliENST00000299855; ENSP00000299855; ENSG00000149968
GeneIDi4314
KEGGihsa:4314
UCSCiuc001phj.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMMP3_HUMAN
AccessioniPrimary (citable) accession number: P08254
Secondary accession number(s): B2R8B8, Q3B7S0, Q6GRF8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: February 1, 1991
Last modified: June 20, 2018
This is version 204 of the entry and version 2 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

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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