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P45452 (MMP13_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. 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

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

Secretedextracellular spaceextracellular 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

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.7

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.8

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
Reference proteome
Gene Ontology (GO)
   Biological_processbone mineralization

Inferred from electronic annotation. Source: Ensembl

cartilage development

Inferred from electronic annotation. Source: Ensembl

cellular protein metabolic process

Inferred from electronic annotation. Source: Ensembl

collagen catabolic process

Inferred from electronic annotation. Source: InterPro

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

proteolysis

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcollagen

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix

Inferred from electronic annotation. Source: InterPro

extracellular 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 electronic annotation. Source: InterPro

metalloendopeptidase activity

Inferred from electronic annotation. Source: InterPro

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

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

Repeat281 – 33050Hemopexin 1
Repeat331 – 37747Hemopexin 2
Repeat379 – 42749Hemopexin 3
Repeat428 – 47144Hemopexin 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.
Corresponds to variant rs554797 [ dbSNP | Ensembl ].
VAR_011971
Natural variant741F → S in MANDP1. Ref.8
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.7
VAR_032753
Natural variant911M → T in MANDP1. Ref.8
VAR_063433
Natural variant2321H → N in MANDP1. Ref.8
VAR_063434
Natural variant3901D → G. Ref.4
Corresponds to variant rs17860568 [ dbSNP | Ensembl ].
VAR_020534

Experimental info

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].
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].
[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]"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.
[7]"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.
[8]"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.
+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.
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.

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_3/4.
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. PTHR10201. 1 hit.
PTHR10201:SF77. PTHR10201:SF77. 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: April 16, 2014
This is version 149 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