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Reviewed, UniProtKB/Swiss-Prot P45452 (MMP13_HUMAN)

Last modified November 3, 2009. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

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

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General annotation (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.

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.

Involvement in 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. Ref.6

Sequence similarities

Belongs to the peptidase M10A family.

Contains 4 hemopexin-like domains.

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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
Gene Ontology (GO)
   Biological processcollagen catabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

proteolysis Ref.1

Traceable author statement. Source: ProtInc

   Cellular componentextracellular space Ref.1

Traceable author statement. Source: ProtInc

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular functioncalcium ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

metalloendopeptidase activity

Traceable author statement. Source: ProtInc

zinc ion binding Ref.1

Traceable author statement. Source: ProtInc

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Propeptide20 – 10384Activation peptide Potential
PRO_0000028788
Chain104 – 471368Collagenase 3
PRO_0000028789

Regions

Domain290 – 33243Hemopexin-like 1
Domain334 – 37744Hemopexin-like 2
Domain382 – 42948Hemopexin-like 3
Domain431 – 47141Hemopexin-like 4
Motif94 – 1018Cysteine switch By similarity

Sites

Active site2231 By similarity
Metal binding961Zinc 2; in inhibited form By similarity
Metal binding1621Calcium 1 By similarity
Metal binding1721Zinc 1 By similarity
Metal binding1741Zinc 1 By similarity
Metal binding1791Calcium 2 By similarity
Metal binding1801Calcium 2; via carbonyl oxygen By similarity
Metal binding1871Zinc 1 By similarity
Metal binding1941Calcium 1; via carbonyl oxygen By similarity
Metal binding1961Calcium 1; via carbonyl oxygen By similarity
Metal binding1981Calcium 1 By similarity
Metal binding2001Zinc 1 By similarity
Metal binding2051Calcium 2 By similarity
Metal binding2221Zinc 2; catalytic By similarity
Metal binding2261Zinc 2; catalytic By similarity
Metal binding2321Zinc 2; catalytic By similarity
Metal binding2911Calcium 3; via carbonyl oxygen By similarity
Metal binding2931Calcium 4; via carbonyl oxygen By similarity
Metal binding3351Calcium 3; via carbonyl oxygen By similarity
Metal binding3371Calcium 4; via carbonyl oxygen By similarity
Metal binding3831Calcium 3; via carbonyl oxygen By similarity
Metal binding3851Calcium 4; via carbonyl oxygen By similarity
Metal binding4321Calcium 3; via carbonyl oxygen By similarity
Metal binding4341Calcium 4; via carbonyl oxygen By similarity

Amino acid modifications

Glycosylation1171N-linked (GlcNAc...) Potential
Glycosylation1521N-linked (GlcNAc...) Potential
Disulfide bond284 ↔ 471

Natural variations

Natural variant21H → L: dbSNP rs554797.
VAR_011971
Natural variant751F → S in SEMD2; abnormal intracellular autoactivation and autodegradation within the ER/Golgi resulting in the secretion of small and inactive fragments. Ref.6
VAR_032753
Natural variant3901D → G: dbSNP rs17860568. Ref.3
VAR_020534

Secondary structure

1 .......................... 471
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P45452-1 [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

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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: 8207000] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
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: 9562863] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]NIEHS SNPs program
Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLY-390.
[4]"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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[5]"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: 8969305] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 265-471.
[6]"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: 16167086] [Abstract]
Cited for: VARIANT SEMD2 SER-75, CHARACTERIZATION OF VARIANT SEMD2 SER-75.
+Additional computationally mapped references.

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Web resources

NIEHS-SNPs

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Cross-references

Sequence databases

X75308 mRNA. Translation: CAA53056.1.
X81334 mRNA. Translation: CAA57108.1.
AY741163 Genomic DNA. Translation: AAU13907.1.
BC067522 mRNA. Translation: AAH67522.1.
BC074807 mRNA. Translation: AAH74807.1.
BC074808 mRNA. Translation: AAH74808.1.
IPIIPI00021738.
PIRA53711.
RefSeqNP_002418.1.
UniGeneHs.2936

3D structure databases

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[»]
3ELMX-ray1.90A/B104-274[»]
3I7GX-ray1.95A/B104-274[»]
3I7IX-ray2.21A/B104-274[»]
456CX-ray2.40A/B104-271[»]
830CX-ray1.60A/B104-271[»]
ModBaseSearch...

Protein-protein interaction databases

STRINGP45452.

PTM databases

PhosphoSiteP45452.

Proteomic databases

PRIDEP45452.

Genome annotation databases

EnsemblENST00000260302; ENSP00000260302; ENSG00000137745; Homo sapiens. [Genome view]
ENST00000340273; ENSP00000339672; ENSG00000137745; Homo sapiens. [Genome view]
GeneID4322.
KEGGhsa:4322.
UCSCuc001phl.1. human.

Organism-specific databases

CTD4322.
GeneCardsGC11M102318.
H-InvDBHIX0035939.
HGNCHGNC:7159. MMP13.
MIM600108. gene.
602111. phenotype.
Orphanet252. Spondyloepimetaphyseal dysplasia.
93356. Spondyloepimetaphyseal dysplasia, Missouri type.
PharmGKBPA30871.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP45452.

Gene expression databases

ArrayExpressP45452.
BgeeP45452.
CleanExHS_MMP13.
GenevestigatorP45452.
GermOnlineENSG00000137745. Homo sapiens.

Family and domain databases

InterProIPR000585. 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]
Gene3DG3DSA:2.110.10.10. Hemopexin. 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]
PROSITEPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio17005.
PMAP-CutDBP45452.
SOURCESearch...

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Entry information

Entry nameMMP13_HUMAN
AccessionPrimary (citable) accession number: P45452
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 3, 2009
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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

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List of human entries with polymorphisms or disease mutations

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents