[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Mammary carcinoma; PubMed=8207000 [NCBI, ExPASy, EBI, Israel, Japan] Freije J.M.P., Diez-Itza I., Balbin M., Sanchez L.M., Blasco R., Tolivia J., Lopez-Otin C.; "Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas."; J. Biol. Chem. 269:16766-16773(1994).
[2]	NUCLEOTIDE SEQUENCE [MRNA]. PubMed=9562863 [NCBI, ExPASy, EBI, Israel, Japan] Willmroth F., Peter H.H., Conca W.; "A matrix metalloproteinase gene expressed in human T lymphocytes is identical with collagenase 3 from breast carcinomas."; Immunobiology 198:375-384(1998).
[3]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GLY-390. NIEHS SNPs program; Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
[4]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Lung; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[5]	X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 265-471. DOI=10.1006/jmbi.1996.0661; PubMed=8969305 [NCBI, ExPASy, EBI, Israel, Japan] Gomis-Rueth F.-X., Gohlke U., Betz M., Knaeuper V., Murphy G., Lopez-Otin C., Bode W.; "The helping hand of collagenase-3 (MMP-13): 2.7 A crystal structure of its C-terminal haemopexin-like domain."; J. Mol. Biol. 264:556-566(1996).
[6]	VARIANT SEMD2 SER-75, AND CHARACTERIZATION OF VARIANT SEMD2 SER-75. DOI=10.1172/JCI22900; PubMed=16167086 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "MMP13 mutation causes spondyloepimetaphyseal dysplasia, Missouri type (SEMD(MO)."; J. Clin. Invest. 115:2832-2842(2005).

Comments

FUNCTION: Degrades collagen type I. Does not act on gelatin or casein. Could have a role in tumoral process.
COFACTOR: Binds 4 calcium ions per subunit.
COFACTOR: Binds 2 zinc ions per subunit.
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix (Probable).
TISSUE SPECIFICITY: Seems to be specific to breast carcinomas.
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.
DISEASE: Defects in MMP13 are the cause of spondyloepimetaphyseal dysplasia type 2 (SEMD2) [MIM:602111]; also known as spondyloepimetaphyseal dysplasia type Missouri. SEMDs are a heterogeneous group of skeletal disorders characterized by defective growth and modeling of the spine and long bones. The SEMDs are distinguished from the spondylometaphyseal dysplasias and the spondyloepiphyseal dysplasias by the combined involvement of the epiphyses and metaphyses. The 3 disorders have malformations of the vertebrae in common.
SIMILARITY: Belongs to the peptidase M10A family [view classification].
SIMILARITY: Contains 4 hemopexin-like domains.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mmp13/";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

X75308; CAA53056.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
X81334; CAA57108.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY741163; AAU13907.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC067522; AAH67522.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC074807; AAH74807.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC074808; AAH74808.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00021738; -.

A53711; A53711.

NP_002418.1; -.

3D structure databases

PDB

1EUB; NMR; -; A=104-274.	[ExPASy / RCSB / EBI]
1FLS; NMR; -; A=104-268.	[ExPASy / RCSB / EBI]
1FM1; NMR; -; A=104-268.	[ExPASy / RCSB / EBI]
1PEX; X-ray; 2.70 A; A=265-471.	[ExPASy / RCSB / EBI]
1UC1; Model; -; A=1-471.	[ExPASy / RCSB / EBI]
1XUC; X-ray; 1.70 A; A/B=104-274.	[ExPASy / RCSB / EBI]
1XUD; X-ray; 1.80 A; A/B=104-274.	[ExPASy / RCSB / EBI]
1XUR; X-ray; 1.85 A; A/B=104-274.	[ExPASy / RCSB / EBI]
1YOU; X-ray; 2.30 A; A/B=104-271.	[ExPASy / RCSB / EBI]
1ZTQ; X-ray; 2.00 A; A/B/C/D=104-268.	[ExPASy / RCSB / EBI]
2D1N; X-ray; 2.37 A; A/B=104-269.	[ExPASy / RCSB / EBI]
2E2D; X-ray; 2.00 A; A=104-268.	[ExPASy / RCSB / EBI]
2OW9; X-ray; 1.74 A; A/B=104-270.	[ExPASy / RCSB / EBI]
2OZR; X-ray; 2.30 A; A/B/C/D/E/F/G/H=104-270.	[ExPASy / RCSB / EBI]
2PJT; X-ray; 2.80 A; A/B/C/D=104-268.	[ExPASy / RCSB / EBI]
456C; X-ray; 2.40 A; A/B=104-271.	[ExPASy / RCSB / EBI]
830C; X-ray; 1.60 A; A/B=104-271.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1EUB; -.
1FLS; -.
1FM1; -.
1PEX; -.
1UC1; -.
1XUC; -.
1XUD; -.
1XUR; -.
1YOU; -.
1ZTQ; -.
2D1N; -.
2E2D; -.
2OW9; -.
2OZR; -.
2PJT; -.
456C; -.
830C; -.

ModBase

P45452.

PTM databases

PhosphoSite

P45452; -.

Organism-specific databases

GC11M102318; -.

HIX0035939; -.

HGNC:7159; MMP13.

600108; gene. [NCBI / EBI]
602111; phenotype. [NCBI / EBI]

Orphanet

252; Spondyloepimetaphyseal dysplasia.
93356; Spondyloepimetaphyseal dysplasia, Missouri type.

PharmGKB

PA30871; -.

Gene expression databases

P45452; -.

P45452; -.

HS_MMP13; -.

ENSG00000137745; Homo sapiens.

Ontologies

GO:0005615;	Cellular component: extracellular space (traceable author statement from ProtInc).
GO:0005578;	Cellular component: proteinaceous extracellular matrix (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005509;	Molecular function: calcium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004222;	Molecular function: metalloendopeptidase activity (traceable author statement from ProtInc).
GO:0008270;	Molecular function: zinc ion binding (traceable author statement from ProtInc).
GO:0030574;	Biological process: collagen catabolic process (inferred from electronic annotation from UniProtKB-KW).
GO:0006508;	Biological process: proteolysis (traceable author statement from ProtInc).
QuickGo view.

Family and domain databases

InterPro

IPR000585; Hemopexin/matrixin.
IPR018486; Hemopexin/matrixin_CS.
IPR018487; Hemopexin/matrixin_repeat.
IPR001818; Pept_M10A_M12B.
IPR016293; Pept_M10A_matrix.
IPR006025; Pept_M_Zn_BS.
IPR006026; Peptidase_M.
IPR002477; Peptidoglycan-bd-like.
Graphical view of domain structure.

Gene3D

G3DSA:2.110.10.10; Hemopexin; 1.

Pfam

PF00045; Hemopexin; 4.
PF00413; Peptidase_M10; 1.
PF01471; PG_binding_1; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF001191; Peptidase_M10A_matrix; 1.

PRINTS

PR00138; MATRIXIN.

SMART

SM00120; HX; 4.
SM00235; ZnMc; 1.
SMART graphical view of domain structure.

PROSITE

PS00546; CYSTEINE_SWITCH; 1.
PS00024; HEMOPEXIN; 1.
PS00142; ZINC_PROTEASE; 1.

Proteomic databases

PRIDE

P45452; -.

Genome annotation databases

Ensembl

ENSG00000137745; Homo sapiens. [Contig view]

GeneID

4322; -.

KEGG

hsa:4322; -.

Phylogenomic databases

HOVERGEN

P45452; -.

Other

17005; -.

P45452; -.

MMP13; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Calcium; Collagen degradation; Disease mutation; Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Polymorphism; Protease; Repeat; Secreted; Signal; Zinc; Zymogen.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 19`	`19`	`Potential.`
`PROPEP`	`20 103`	`84`	`Activation peptide (Potential).`	`PRO_0000028788`
`CHAIN`	`104 471`	`368`	`Collagenase 3.`	`PRO_0000028789`
`DOMAIN`	`290 332`	`43`	`Hemopexin-like 1.`
`DOMAIN`	`334 377`	`44`	`Hemopexin-like 2.`
`DOMAIN`	`382 429`	`48`	`Hemopexin-like 3.`
`DOMAIN`	`431 471`	`41`	`Hemopexin-like 4.`
`MOTIF`	`94 101`	`8`	`Cysteine switch (By similarity).`
`ACT_SITE`	`223 223`		`By similarity.`
`METAL`	`96 96`		`Zinc 2; in inhibited form (By similarity).`
`METAL`	`162 162`		`Calcium 1 (By similarity).`
`METAL`	`172 172`		`Zinc 1 (By similarity).`
`METAL`	`174 174`		`Zinc 1 (By similarity).`
`METAL`	`179 179`		`Calcium 2 (By similarity).`
`METAL`	`180 180`		`Calcium 2; via carbonyl oxygen (By similarity).`
`METAL`	`187 187`		`Zinc 1 (By similarity).`
`METAL`	`194 194`		`Calcium 1; via carbonyl oxygen (By similarity).`
`METAL`	`196 196`		`Calcium 1; via carbonyl oxygen (By similarity).`
`METAL`	`198 198`		`Calcium 1 (By similarity).`
`METAL`	`200 200`		`Zinc 1 (By similarity).`
`METAL`	`205 205`		`Calcium 2 (By similarity).`
`METAL`	`222 222`		`Zinc 2; catalytic (By similarity).`
`METAL`	`226 226`		`Zinc 2; catalytic (By similarity).`
`METAL`	`232 232`		`Zinc 2; catalytic (By similarity).`
`METAL`	`291 291`		`Calcium 3; via carbonyl oxygen (By similarity).`
`METAL`	`293 293`		`Calcium 4; via carbonyl oxygen (By similarity).`
`METAL`	`335 335`		`Calcium 3; via carbonyl oxygen (By similarity).`
`METAL`	`337 337`		`Calcium 4; via carbonyl oxygen (By similarity).`
`METAL`	`383 383`		`Calcium 3; via carbonyl oxygen (By similarity).`
`METAL`	`385 385`		`Calcium 4; via carbonyl oxygen (By similarity).`
`METAL`	`432 432`		`Calcium 3; via carbonyl oxygen (By similarity).`
`METAL`	`434 434`		`Calcium 4; via carbonyl oxygen (By similarity).`
`CARBOHYD`	`117 117`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`152 152`		`N-linked (GlcNAc...) (Potential).`
`DISULFID`	`284 471`
`VARIANT`	`2 2`	`1`	`H -> L (in dbSNP:rs554797 [NCBI]).`	`VAR_011971`
`VARIANT`	`75 75`	`1`	`F -> S (in SEMD2; abnormal intracellular autoactivation and autodegradation within the ER/Golgi resulting in the secretion of small and inactive fragments).`	`VAR_032753`
`VARIANT`	`390 390`	`1`	`D -> G (in dbSNP:rs17860568 [NCBI]).`	`VAR_020534`
`STRAND`	`116 122`	`7`
`HELIX`	`131 146`	`16`
`STRAND`	`152 159`	`8`
`STRAND`	`162 168`	`7`
`STRAND`	`173 175`	`3`
`STRAND`	`180 183`	`4`
`STRAND`	`186 188`	`3`
`TURN`	`194 197`	`4`
`STRAND`	`199 202`	`4`
`STRAND`	`207 215`	`9`
`HELIX`	`216 228`	`13`
`STRAND`	`241 243`	`3`
`HELIX`	`256 266`	`11`

Sequence information

Length: 471 AA [This is the length of the unprocessed precursor]

Molecular weight: 53820 Da [This is the MW of the unprocessed precursor]

CRC64: E110F50628B57B60 [This is a checksum on the sequence]

        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

P45452 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools