Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P45452 (MMP13_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 152. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Collagenase 3

EC=3.4.24.-
Alternative name(s):
Matrix metalloproteinase-13
Short name=MMP-13
Gene names
Name:MMP13
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length471 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion. Ref.1 Ref.6 Ref.7 Ref.8 Ref.11 Ref.18 Ref.20 Ref.22 Ref.23 Ref.24 Ref.26 Ref.27

Cofactor

Calcium. Can bind about 5 calcium ions per subunit. Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25

Binds 2 zinc ions per subunit. Ref.16 Ref.17 Ref.18 Ref.20 Ref.21 Ref.22 Ref.23 Ref.24 Ref.25

Enzyme regulation

Inhibited by TIMP1, TIMP2 and TIMP3. Inhibited by acetohydroxamic acid and other zinc chelators. Ref.6 Ref.11 Ref.23

Subunit structure

Monomer. Interacts with TIMP1, TIMP2 and TIMP3. Binds (via the C-terminal region) to collagen. Ref.6 Ref.11 Ref.19 Ref.25

Subcellular location

Secretedextracellular spaceextracellular matrix Probable. Secreted Ref.6.

Tissue specificity

Detected in fetal cartilage and calvaria, in chondrocytes of hypertrophic cartilage in vertebrae and in the dorsal end of ribs undergoing ossification, as well as in osteoblasts and periosteal cells below the inner periosteal region of ossified ribs. Detected in chondrocytes from in joint cartilage that have been treated with TNF and IL1B, but not in untreated chondrocytes. Detected in T lymphocytes. Detected in breast carcinoma tissue. Ref.1 Ref.2 Ref.9 Ref.10

Induction

Up-regulated by TNF and IL1B. Ref.6 Ref.9 Ref.10 Ref.11 Ref.23

Domain

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 By similarity. Ref.11

The C-terminal region binds to collagen. Ref.11

Post-translational modification

The proenzyme is activated by removal of the propeptide; this cleavage can be effected by other matrix metalloproteinases, such as MMP2, MMP3 and MMP14 and may involve several cleavage steps. Cleavage can also be autocatalytic, after partial maturation by another protease or after treatment with 4-aminophenylmercuric acetate (APMA) (in vitro).

N-glycosylated. Ref.6

Involvement in disease

Spondyloepimetaphyseal dysplasia Missouri type (SEMD-MO) [MIM:602111]: A bone disease characterized by moderate to severe metaphyseal changes, mild epiphyseal involvement, rhizomelic shortening of the lower limbs with bowing of the femora and/or tibiae, coxa vara, genu varum and pear-shaped vertebrae in childhood. Epimetaphyseal changes improve with age.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.26

Metaphyseal anadysplasia 1 (MANDP1) [MIM:602111]: A bone development disorder characterized by skeletal anomalies that resolve spontaneously with age. Clinical characteristics are evident from the first months of life and include slight shortness of stature and a mild varus deformity of the legs. Patients attain a normal stature in adolescence and show improvement or complete resolution of varus deformity of the legs and rhizomelic micromelia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.27

Sequence similarities

Belongs to the peptidase M10A family.

Contains 4 hemopexin repeats.

Ontologies

Keywords
   Biological processCollagen degradation
   Cellular componentExtracellular matrix
Secreted
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainRepeat
Signal
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processbone mineralization

Inferred from electronic annotation. Source: Ensembl

bone morphogenesis

Inferred from direct assay Ref.26. Source: UniProtKB

cartilage development

Inferred from electronic annotation. Source: Ensembl

cellular protein metabolic process

Inferred from electronic annotation. Source: Ensembl

collagen catabolic process

Inferred from direct assay Ref.6Ref.11. Source: UniProtKB

extracellular matrix disassembly

Inferred from mutant phenotype Ref.6Ref.11. Source: UniProtKB

extracellular matrix organization

Traceable author statement. Source: Reactome

proteolysis

Traceable author statement Ref.1. Source: ProtInc

   Cellular_componentextracellular region

Traceable author statement. Source: Reactome

extracellular space

Traceable author statement Ref.1. Source: ProtInc

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium ion binding

Inferred from direct assay Ref.25. Source: UniProtKB

collagen binding

Inferred from direct assay Ref.11. Source: UniProtKB

metalloendopeptidase activity

Inferred from direct assay Ref.6Ref.11. Source: UniProtKB

zinc ion binding

Inferred from direct assay Ref.25. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Ref.6
Propeptide20 – 10384Activation peptide
PRO_0000028788
Chain104 – 471368Collagenase 3
PRO_0000028789

Regions

Repeat281 – 33050Hemopexin 1
Repeat331 – 37747Hemopexin 2
Repeat379 – 42749Hemopexin 3
Repeat428 – 47144Hemopexin 4
Region176 – 24671Interaction with TIMP2
Region268 – 471204Interaction with collagen
Motif94 – 1018Cysteine switch By similarity

Sites

Active site2231 Probable
Metal binding961Zinc 2; in inhibited form By similarity
Metal binding1281Calcium 1
Metal binding1621Calcium 2; via carbonyl oxygen
Metal binding1721Zinc 1; via tele nitrogen
Metal binding1741Zinc 1
Metal binding1791Calcium 3
Metal binding1801Calcium 3; via carbonyl oxygen
Metal binding1821Calcium 3; via carbonyl oxygen
Metal binding1841Calcium 3; via carbonyl oxygen
Metal binding1871Zinc 1; via tele nitrogen
Metal binding1941Calcium 2; via carbonyl oxygen
Metal binding1961Calcium 2; via carbonyl oxygen
Metal binding1981Calcium 2
Metal binding2001Zinc 1; via pros nitrogen
Metal binding2021Calcium 3
Metal binding2031Calcium 1
Metal binding2051Calcium 1; via carbonyl oxygen
Metal binding2051Calcium 3
Metal binding2221Zinc 2; via tele nitrogen; catalytic
Metal binding2261Zinc 2; via tele nitrogen; catalytic
Metal binding2321Zinc 2; via tele nitrogen; catalytic
Metal binding2401Zinc 2; via carbonyl oxygen; catalytic
Metal binding2911Calcium 4; via carbonyl oxygen
Metal binding2931Calcium 5; via carbonyl oxygen
Metal binding3351Calcium 4; via carbonyl oxygen
Metal binding3371Calcium 5; via carbonyl oxygen
Metal binding3831Calcium 4; via carbonyl oxygen
Metal binding3851Calcium 5; via carbonyl oxygen
Metal binding4321Calcium 4; via carbonyl oxygen
Metal binding4341Calcium 5; via carbonyl oxygen

Amino acid modifications

Glycosylation1171N-linked (GlcNAc...) Ref.6
Glycosylation1521N-linked (GlcNAc...) Potential
Disulfide bond284 ↔ 471 Ref.12 Ref.25

Natural variations

Natural variant21H → L.
Corresponds to variant rs554797 [ dbSNP | Ensembl ].
VAR_011971
Natural variant741F → S in MANDP1. Ref.27
VAR_063432
Natural variant751F → S in SEMD-MO; abnormal intracellular autoactivation and autodegradation within the ER/Golgi resulting in the secretion of small and inactive fragments. Ref.26
VAR_032753
Natural variant911M → T in MANDP1. Ref.27
VAR_063433
Natural variant2321H → N in MANDP1. Ref.27
VAR_063434
Natural variant3901D → G. Ref.4
Corresponds to variant rs17860568 [ dbSNP | Ensembl ].
VAR_020534

Experimental info

Mutagenesis2231E → A: Abolishes enzyme activity. Ref.25
Sequence conflict1471D → G in BAF84900. Ref.3
Sequence conflict2781P → L in AAH67523. Ref.5
Sequence conflict4381N → D in BAG37740. Ref.3

Secondary structure

..................................................................................... 471
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P45452 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: E110F50628B57B60

FASTA47153,820
        10         20         30         40         50         60 
MHPGVLAAFL FLSWTHCRAL PLPSGGDEDD LSEEDLQFAE RYLRSYYHPT NLAGILKENA 

        70         80         90        100        110        120 
ASSMTERLRE MQSFFGLEVT GKLDDNTLDV MKKPRCGVPD VGEYNVFPRT LKWSKMNLTY 

       130        140        150        160        170        180 
RIVNYTPDMT HSEVEKAFKK AFKVWSDVTP LNFTRLHDGI ADIMISFGIK EHGDFYPFDG 

       190        200        210        220        230        240 
PSGLLAHAFP PGPNYGGDAH FDDDETWTSS SKGYNLFLVA AHEFGHSLGL DHSKDPGALM 

       250        260        270        280        290        300 
FPIYTYTGKS HFMLPDDDVQ GIQSLYGPGD EDPNPKHPKT PDKCDPSLSL DAITSLRGET 

       310        320        330        340        350        360 
MIFKDRFFWR LHPQQVDAEL FLTKSFWPEL PNRIDAAYEH PSHDLIFIFR GRKFWALNGY 

       370        380        390        400        410        420 
DILEGYPKKI SELGLPKEVK KISAAVHFED TGKTLLFSGN QVWRYDDTNH IMDKDYPRLI 

       430        440        450        460        470 
EEDFPGIGDK VDAVYEKNGY IYFFNGPIQF EYSIWSNRIV RVMPANSILW C 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas."
Freije J.M.P., Diez-Itza I., Balbin M., Sanchez L.M., Blasco R., Tolivia J., Lopez-Otin C.
J. Biol. Chem. 269:16766-16773(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, FUNCTION, TISSUE SPECIFICITY.
Tissue: Mammary carcinoma.
[2]"A matrix metalloproteinase gene expressed in human T lymphocytes is identical with collagenase 3 from breast carcinomas."
Willmroth F., Peter H.H., Conca W.
Immunobiology 198:375-384(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Esophagus and Synovium.
[4]NIEHS SNPs program
Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-390.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[6]"Biochemical characterization of human collagenase-3."
Knaeuper V., Lopez-Otin C., Smith B., Knight G., Murphy G.
J. Biol. Chem. 271:1544-1550(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 20-27 AND 104-118, PROPEPTIDE, AUTOCATALYTIC PROCESSING, CATALYTIC ACTIVITY, FUNCTION, GLYCOSYLATION AT ASN-117, SUBCELLULAR LOCATION, ENZYME REGULATION, INTERACTION WITH TIMP1; TIMP2 AND TIMP3.
[7]"Cellular mechanisms for human procollagenase-3 (MMP-13) activation. Evidence that MT1-MMP (MMP-14) and gelatinase a (MMP-2) are able to generate active enzyme."
Knaeuper V., Will H., Lopez-Otin C., Smith B., Atkinson S.J., Stanton H., Hembry R.M., Murphy G.
J. Biol. Chem. 271:17124-17131(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL PROTEIN SEQUENCE, PROPEPTIDE, FUNCTION, CATALYTIC ACTIVITY.
[8]"Degradation of cartilage aggrecan by collagenase-3 (MMP-13)."
Fosang A.J., Last K., Knaeuper V., Murphy G., Neame P.J.
FEBS Lett. 380:17-20(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Cytokine control of interstitial collagenase and collagenase-3 gene expression in human chondrocytes."
Borden P., Solymar D., Sucharczuk A., Lindman B., Cannon P., Heller R.A.
J. Biol. Chem. 271:23577-23581(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, TISSUE SPECIFICITY.
[10]"Collagenase-3 (MMP-13) is expressed by hypertrophic chondrocytes, periosteal cells, and osteoblasts during human fetal bone development."
Johansson N., Saarialho-Kere U., Airola K., Herva R., Nissinen L., Westermarck J., Vuorio E., Heino J., Kaehaeri V.M.
Dev. Dyn. 208:387-397(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, INDUCTION BY TGFB1.
[11]"The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction."
Knaeuper V., Cowell S., Smith B., Lopez-Otin C., O'Shea M., Morris H., Zardi L., Murphy G.
J. Biol. Chem. 272:7608-7616(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, CATALYTIC ACTIVITY, AUTOCATALYTIC PROCESSING, FUNCTION, INTERACTION WITH TIMP1; TIMP2 AND TIMP3, ENZYME REGULATION.
[12]"The helping hand of collagenase-3 (MMP-13): 2.7 A crystal structure of its C-terminal haemopexin-like domain."
Gomis-Rueth F.-X., Gohlke U., Betz M., Knaeuper V., Murphy G., Lopez-Otin C., Bode W.
J. Mol. Biol. 264:556-566(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 265-471 IN COMPLEX WITH CALCIUM, DISULFIDE BOND.
[13]"Crystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors."
Lovejoy B., Welch A.R., Carr S., Luong C., Broka C., Hendricks R.T., Campbell J.A., Walker K.A., Martin R., Van Wart H., Browner M.F.
Nat. Struct. Biol. 6:217-221(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 104-271 IN COMPLEXES WITH SYNTHETIC INHIBITORS; CALCIUM AND ZINC, PROPEPTIDE, AUTOCATALYTIC PROCESSING.
[14]"Solution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1."
Zhang X., Gonnella N.C., Koehn J., Pathak N., Ganu V., Melton R., Parker D., Hu S.I., Nam K.Y.
J. Mol. Biol. 301:513-524(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 104-274 IN COMPLEX WITH CALCIUM AND ZINC.
[15]"High-resolution solution structure of the catalytic fragment of human collagenase-3 (MMP-13) complexed with a hydroxamic acid inhibitor."
Moy F.J., Chanda P.K., Chen J.M., Cosmi S., Edris W., Levin J.I., Powers R.
J. Mol. Biol. 302:671-689(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 104-268 IN COMPLEX WITH CALCIUM AND ZINC, CATALYTIC ACTIVITY.
[16]"Potent pyrimidinetrione-based inhibitors of MMP-13 with enhanced selectivity over MMP-14."
Blagg J.A., Noe M.C., Wolf-Gouveia L.A., Reiter L.A., Laird E.R., Chang S.P., Danley D.E., Downs J.T., Elliott N.C., Eskra J.D., Griffiths R.J., Hardink J.R., Haugeto A.I., Jones C.S., Liras J.L., Lopresti-Morrow L.L., Mitchell P.G., Pandit J. expand/collapse author list , Robinson R.P., Subramanyam C., Vaughn-Bowser M.L., Yocum S.A.
Bioorg. Med. Chem. Lett. 15:1807-1810(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 104-271 IN COMPLEX WITH CALCIUM AND ZINC, COFACTOR, CATALYTIC ACTIVITY.
[17]"Structural basis for the highly selective inhibition of MMP-13."
Engel C.K., Pirard B., Schimanski S., Kirsch R., Habermann J., Klingler O., Schlotte V., Weithmann K.U., Wendt K.U.
Chem. Biol. 12:181-189(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 104-274 IN COMPLEX WITH CALCIUM AND ZINC, COFACTOR, CATALYTIC ACTIVITY.
[18]"Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects."
Johnson A.R., Pavlovsky A.G., Ortwine D.F., Prior F., Man C.F., Bornemeier D.A., Banotai C.A., Mueller W.T., McConnell P., Yan C., Baragi V., Lesch C., Roark W.H., Wilson M., Datta K., Guzman R., Han H.K., Dyer R.D.
J. Biol. Chem. 282:27781-27791(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.74 ANGSTROMS) OF 104-270 IN COMPLEX WITH CALCIUM AND ZINC, COFACTOR, CATALYTIC ACTIVITY, FUNCTION IN CARTILAGE DEGRADATION.
[19]"Flexibility and variability of TIMP binding: X-ray structure of the complex between collagenase-3/MMP-13 and TIMP-2."
Maskos K., Lang R., Tschesche H., Bode W.
J. Mol. Biol. 366:1222-1231(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 104-268 IN COMPLEX WITH TIMP2; CALCIUM AND ZINC, INTERACTION WITH TIMP2.
[20]"Discovery of potent, selective, and orally active carboxylic acid based inhibitors of matrix metalloproteinase-13."
Monovich L.G., Tommasi R.A., Fujimoto R.A., Blancuzzi V., Clark K., Cornell W.D., Doti R., Doughty J., Fang J., Farley D., Fitt J., Ganu V., Goldberg R., Goldstein R., Lavoie S., Kulathila R., Macchia W., Parker D.T. expand/collapse author list , Melton R., O'Byrne E., Pastor G., Pellas T., Quadros E., Reel N., Roland D.M., Sakane Y., Singh H., Skiles J., Somers J., Toscano K., Wigg A., Zhou S., Zhu L., Shieh W.C., Xue S., McQuire L.W.
J. Med. Chem. 52:3523-3538(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 104-274 IN COMPLEX WITH CALCIUM AND ZINC, CATALYTIC ACTIVITY, COFACTOR, FUNCTION.
[21]"Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis."
Schnute M.E., O'Brien P.M., Nahra J., Morris M., Howard Roark W., Hanau C.E., Ruminski P.G., Scholten J.A., Fletcher T.R., Hamper B.C., Carroll J.N., Patt W.C., Shieh H.S., Collins B., Pavlovsky A.G., Palmquist K.E., Aston K.W., Hitchcock J. expand/collapse author list , Rogers M.D., McDonald J., Johnson A.R., Munie G.E., Wittwer A.J., Man C.F., Settle S.L., Nemirovskiy O., Vickery L.E., Agawal A., Dyer R.D., Sunyer T.
Bioorg. Med. Chem. Lett. 20:576-580(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) OF 104-270 IN COMPLEX WITH CALCIUM AND ZINC, CATALYTIC ACTIVITY, COFACTOR.
[22]"Orally active MMP-1 sparing alpha-tetrahydropyranyl and alpha-piperidinyl sulfone matrix metalloproteinase (MMP) inhibitors with efficacy in cancer, arthritis, and cardiovascular disease."
Becker D.P., Barta T.E., Bedell L.J., Boehm T.L., Bond B.R., Carroll J., Carron C.P., Decrescenzo G.A., Easton A.M., Freskos J.N., Funckes-Shippy C.L., Heron M., Hockerman S., Howard C.P., Kiefer J.R., Li M.H., Mathis K.J., McDonald J.J. expand/collapse author list , Mehta P.P., Munie G.E., Sunyer T., Swearingen C.A., Villamil C.I., Welsch D., Williams J.M., Yu Y., Yao J.
J. Med. Chem. 53:6653-6680(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 104-267 IN COMPLEX WITH CALCIUM AND ZINC, CATALYTIC ACTIVITY, COFACTOR, FUNCTION.
[23]"Simple pseudo-dipeptides with a P2' glutamate: a novel inhibitor family of matrix metalloproteases and other metzincins."
Devel L., Beau F., Amoura M., Vera L., Cassar-Lajeunesse E., Garcia S., Czarny B., Stura E.A., Dive V.
J. Biol. Chem. 287:26647-26656(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS) OF 104-272 IN COMPLEX WITH CALCIUM AND ZINC, COFACTOR, CATALYTIC ACTIVITY, ENZYME REGULATION, FUNCTION.
[24]"Hydantoin based inhibitors of MMP13--discovery of AZD6605."
De Savi C., Waterson D., Pape A., Lamont S., Hadley E., Mills M., Page K.M., Bowyer J., Maciewicz R.A.
Bioorg. Med. Chem. Lett. 23:4705-4712(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.43 ANGSTROMS) OF 103-274 IN COMPLEX WITH CALCIUM AND ZINC, COFACTOR, CATALYTIC ACTIVITY, FUNCTION.
[25]"Crystal structure of full-length human collagenase 3 (MMP-13) with peptides in the active site defines exosites in the catalytic domain."
Stura E.A., Visse R., Cuniasse P., Dive V., Nagase H.
FASEB J. 27:4395-4405(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.44 ANGSTROMS) OF 104-471 OF MUTANT ALA-223 IN COMPLEX WITH CALCIUM AND ZINC, COFACTOR, DISULFIDE BOND, MUTAGENESIS OF GLU-223, ACTIVE SITE, SUBUNIT.
[26]"MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO)."
Kennedy A.M., Inada M., Krane S.M., Christie P.T., Harding B., Lopez-Otin C., Sanchez L.M., Pannett A.A.J., Dearlove A., Hartley C., Byrne M.H., Reed A.A.C., Nesbit M.A., Whyte M.P., Thakker R.V.
J. Clin. Invest. 115:2832-2842(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SEMD-MO SER-75, CHARACTERIZATION OF VARIANT SEMD-MO SER-75, FUNCTION IN BONE DEVELOPMENT.
[27]"Mutations in MMP9 and MMP13 determine the mode of inheritance and the clinical spectrum of metaphyseal anadysplasia."
Lausch E., Keppler R., Hilbert K., Cormier-Daire V., Nikkel S., Nishimura G., Unger S., Spranger J., Superti-Furga A., Zabel B.
Am. J. Hum. Genet. 85:168-178(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS MANDP1 SER-74; THR-91 AND ASN-232, FUNCTION IN BONE DEVELOPMENT.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X75308 mRNA. Translation: CAA53056.1.
X81334 mRNA. Translation: CAA57108.1.
AK292211 mRNA. Translation: BAF84900.1.
AK315341 mRNA. Translation: BAG37740.1.
AY741163 Genomic DNA. Translation: AAU13907.1.
BC067522 mRNA. Translation: AAH67522.1.
BC067523 mRNA. Translation: AAH67523.1.
BC074807 mRNA. Translation: AAH74807.1.
BC074808 mRNA. Translation: AAH74808.1.
CCDSCCDS8324.1.
PIRA53711.
RefSeqNP_002418.1. NM_002427.3.
UniGeneHs.2936.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EUBNMR-A104-274[»]
1FLSNMR-A104-268[»]
1FM1NMR-A104-268[»]
1PEXX-ray2.70A265-471[»]
1UC1model-A1-471[»]
1XUCX-ray1.70A/B104-274[»]
1XUDX-ray1.80A/B104-274[»]
1XURX-ray1.85A/B104-274[»]
1YOUX-ray2.30A/B104-271[»]
1ZTQX-ray2.00A/B/C/D104-268[»]
2D1NX-ray2.37A/B104-269[»]
2E2DX-ray2.00A104-268[»]
2OW9X-ray1.74A/B104-270[»]
2OZRX-ray2.30A/B/C/D/E/F/G/H104-270[»]
2PJTX-ray2.80A/B/C/D104-268[»]
2YIGX-ray1.70A/B104-274[»]
3ELMX-ray1.90A/B104-274[»]
3I7GX-ray1.95A/B104-274[»]
3I7IX-ray2.21A/B104-274[»]
3KECX-ray2.05A/B105-267[»]
3KEJX-ray2.30A/B104-270[»]
3KEKX-ray1.97A/B104-270[»]
3KRYX-ray1.90A/B/C/D104-267[»]
3LJZX-ray2.00A/B/C/D104-267[»]
3O2XX-ray1.90A/B/C/D105-267[»]
3TVCX-ray2.43A104-272[»]
3ZXHX-ray1.30A/B104-274[»]
456CX-ray2.40A/B104-271[»]
4A7BX-ray2.20A/B104-272[»]
4FU4X-ray2.85A/B104-471[»]
C/D25-50[»]
4FVLX-ray2.44A/B104-471[»]
C/D31-50[»]
4G0DX-ray2.54A/B/C/D104-471[»]
W/X/Y/Z25-50[»]
4JP4X-ray1.43A/B103-274[»]
4JPAX-ray2.00A/B103-274[»]
830CX-ray1.60A/B104-271[»]
ProteinModelPortalP45452.
SMRP45452. Positions 25-471.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110465. 1 interaction.
STRING9606.ENSP00000260302.

Chemistry

BindingDBP45452.
ChEMBLCHEMBL2111422.
GuidetoPHARMACOLOGY1637.

Protein family/group databases

MEROPSM10.013.

PTM databases

PhosphoSiteP45452.

Polymorphism databases

DMDM1168998.

Proteomic databases

PaxDbP45452.
PRIDEP45452.

Protocols and materials databases

DNASU4322.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260302; ENSP00000260302; ENSG00000137745.
ENST00000571284; ENSP00000461440; ENSG00000262325.
GeneID4322.
KEGGhsa:4322.
UCSCuc001phl.3. human.

Organism-specific databases

CTD4322.
GeneCardsGC11M102847.
HGNCHGNC:7159. MMP13.
MIM600108. gene.
602111. phenotype.
neXtProtNX_P45452.
Orphanet1040. Metaphyseal anadysplasia.
93356. Spondyloepimetaphyseal dysplasia, Missouri type.
PharmGKBPA30871.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG299356.
HOGENOMHOG000217927.
HOVERGENHBG052484.
KOK07994.
OMAELRGEKM.
PhylomeDBP45452.
TreeFamTF315428.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.
REACT_223425. Extracellular matrix organization.

Gene expression databases

ArrayExpressP45452.
BgeeP45452.
CleanExHS_MMP13.
GenevestigatorP45452.

Family and domain databases

Gene3D2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProIPR028711. Collagenase_3.
IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERPTHR10201:SF130. PTHR10201:SF130. 1 hit.
PfamPF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSPR00138. MATRIXIN.
SMARTSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP45452.
GeneWikiMatrix_metallopeptidase_13.
GenomeRNAi4322.
NextBio17005.
PMAP-CutDBP45452.
PROP45452.
SOURCESearch...

Entry information

Entry nameMMP13_HUMAN
AccessionPrimary (citable) accession number: P45452
Secondary accession number(s): A8K846, B2RCZ3, Q6NWN6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: July 9, 2014
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM