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P53690 (MMP14_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 137. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Matrix metalloproteinase-14

Short name=MMP-14
EC=3.4.24.80
Alternative name(s):
MMP-X1
MT-MMP
Membrane-type matrix metalloproteinase 1
Short name=MT-MMP 1
Short name=MTMMP1
Membrane-type-1 matrix metalloproteinase
Short name=MT1-MMP
Short name=MT1MMP
Gene names
Name:Mmp14
Synonyms:Mtmmp
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length582 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Endopeptidase that degrades various components of the extracellular matrix, such as collagen. Activates progelatinase A. Essential for pericellular collagenolysis and modeling of skeletal and extraskeletal connective tissues during development. May be involved in actin cytoskeleton reorganization by cleaving PTK7 By similarity. Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues By similarity. Ref.8

Catalytic activity

Endopeptidase activity. Activates progelatinase A by cleavage of the propeptide at 37-Asn-|-Leu-38. Other bonds hydrolyzed include 35-Gly-|-Ile-36 in the propeptide of collagenase 3, and 341-Asn-|-Phe-342, 441-Asp-|-Leu-442 and 354-Gln-|-Thr-355 in the aggrecan interglobular domain.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Calcium By similarity.

Subunit structure

Interacts (via C-terminal cytoplasmic tail) with BST2 By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein; Extracellular side Potential. Melanosome By similarity. Cytoplasm By similarity. Note: Forms a complex with BST2 and localizes to the cytoplasm By similarity.

Tissue specificity

Highly expressed in placenta, kidney, heart, lung, embryonic skeletal and periskeletal tissues.

Developmental stage

Not detected before day 10.5. At day 12.5, prominently expressed in large arteries and the umbilical arteries, expressed at lower levels in the myocardium, craniofacial mesenchyme, nasal epithelium and liver capsule. At days 14.5 and 17.5, expressed in the musculoskeletal system, and ossification areas, with continued expression in the arterial tunica media.

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.

Post-translational modification

The precursor is cleaved by a furin endopeptidase By similarity.

Sequence similarities

Belongs to the peptidase M10A family.

Contains 4 hemopexin repeats.

Ontologies

Keywords
   Biological processCollagen degradation
   Cellular componentCytoplasm
Membrane
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Disulfide bond
Zymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from electronic annotation. Source: Ensembl

astrocyte cell migration

Inferred from electronic annotation. Source: Ensembl

bone development

Inferred from genetic interaction PubMed 18022611. Source: MGI

branching morphogenesis of an epithelial tube

Inferred from mutant phenotype PubMed 15572153. Source: MGI

cell migration

Inferred from mutant phenotype PubMed 15572153. Source: MGI

chondrocyte proliferation

Inferred from genetic interaction PubMed 18022611. Source: MGI

collagen catabolic process

Inferred from genetic interaction PubMed 18022611. Source: MGI

craniofacial suture morphogenesis

Inferred from genetic interaction PubMed 18022611. Source: MGI

embryonic cranial skeleton morphogenesis

Inferred from genetic interaction PubMed 18022611. Source: MGI

endochondral ossification

Inferred from genetic interaction PubMed 18022611. Source: MGI

endothelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

lung development

Inferred from mutant phenotype PubMed 15572153. Source: MGI

male gonad development

Inferred from electronic annotation. Source: Ensembl

negative regulation of focal adhesion assembly

Inferred from electronic annotation. Source: Ensembl

ossification

Inferred from genetic interaction PubMed 18022611. Source: MGI

ovarian follicle development

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell migration

Inferred from electronic annotation. Source: Ensembl

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 14979875. Source: GOC

response to estrogen

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

tissue remodeling

Inferred from electronic annotation. Source: Ensembl

zymogen activation

Inferred from mutant phenotype PubMed 15572153. Source: MGI

   Cellular_componentextracellular matrix

Inferred from electronic annotation. Source: InterPro

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

melanosome

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

peptidase activator activity

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 14979875. Source: UniProtKB

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 – 2020 Potential
Propeptide21 – 11191 By similarity
PRO_0000028800
Chain112 – 582471Matrix metalloproteinase-14
PRO_0000028801

Regions

Topological domain112 – 541430Extracellular Potential
Transmembrane542 – 56221Helical; Potential
Topological domain563 – 58220Cytoplasmic Potential
Repeat316 – 36449Hemopexin 1
Repeat365 – 41046Hemopexin 2
Repeat412 – 46049Hemopexin 3
Repeat461 – 50848Hemopexin 4
Motif91 – 988Cysteine switch By similarity

Sites

Active site2401 By similarity
Metal binding931Zinc; in inhibited form By similarity
Metal binding2391Zinc; catalytic By similarity
Metal binding2431Zinc; catalytic By similarity
Metal binding2491Zinc; catalytic By similarity

Amino acid modifications

Disulfide bond319 ↔ 508 By similarity

Experimental info

Sequence conflict1331P → S in AAB86602. Ref.3
Sequence conflict2551A → D in CAA58520. Ref.1
Sequence conflict2581A → S in CAA58520. Ref.1
Sequence conflict2581A → S in AAB51753. Ref.4
Sequence conflict3411F → L in CAA58520. Ref.1
Sequence conflict3461N → P in AAB86602. Ref.3
Sequence conflict3781K → T in CAA58520. Ref.1
Sequence conflict390 – 3912FD → CV in CAA58520. Ref.1
Sequence conflict400 – 4012PK → AN in CAA58520. Ref.1
Sequence conflict4071G → V in CAA58520. Ref.1
Sequence conflict4121T → S in CAA58520. Ref.1
Sequence conflict4171A → T in CAA58520. Ref.1
Sequence conflict5121G → R in AAB51753. Ref.4

Sequences

Sequence LengthMass (Da)Tools
P53690 [UniParc].

Last modified July 27, 2011. Version 3.
Checksum: 6CA95CFD5811B093

FASTA58265,919
        10         20         30         40         50         60 
MSPAPRPSRS LLLPLLTLGT ALASLGWAQG SNFSPEAWLQ QYGYLPPGDL RTHTQRSPQS 

        70         80         90        100        110        120 
LSAAIAAMQK FYGLQVTGKA DLATMMAMRR PRCGVPDKFG TEIKANVRRK RYAIQGLKWQ 

       130        140        150        160        170        180 
HNEITFCIQN YTPKVGEYAT FEAIRKAFRV WESATPLRFR EVPYAYIREG HEKQADIMIL 

       190        200        210        220        230        240 
FAEGFHGDST PFDGEGGFLA HAYFPGPNIG GDTHFDSAEP WTVQNEDLNG NDIFLVAVHE 

       250        260        270        280        290        300 
LGHALGLEHS NDPSAIMAPF YQWMDTENFV LPDDDRRGIQ QLYGSKSGSP TKMPPQPRTT 

       310        320        330        340        350        360 
SRPSVPDKPK NPAYGPNICD GNFDTVAMLR GEMFVFKERW FWRVRNNQVM DGYPMPIGQF 

       370        380        390        400        410        420 
WRGLPASINT AYERKDGKFV FFKGDKHWVF DEASLEPGYP KHIKELGRGL PTDKIDAALF 

       430        440        450        460        470        480 
WMPNGKTYFF RGNKYYRFNE EFRAVDSEYP KNIKVWEGIP ESPRGSFMGS DEVFTYFYKG 

       490        500        510        520        530        540 
NKYWKFNNQK LKVEPGYPKS ALRDWMGCPS GGRPDEGTEE ETEVIIIEVD EEGSGAVSAA 

       550        560        570        580 
AVVLPVLLLL LVLAVGLAVF FFRRHGTPKR LLYCQRSLLD KV 

« Hide

References

« Hide 'large scale' references
[1]"Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas."
Okada A., Bellocq J.-P., Rouyer N., Chenard M.P., Rio M.C., Chambon P., Basset P.
Proc. Natl. Acad. Sci. U.S.A. 92:2730-2734(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]Odaka A.
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"The matrix metalloproteinase-14 (MMP-14) gene is structurally distinct from other MMP genes and is co-expressed with the TIMP-2 gene during mouse embryogenesis."
Apte S.S., Fukai N., Beier D.R., Olsen B.R.
J. Biol. Chem. 272:25511-25517(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/Sv.
[4]"Cloning of murine membrane-type-1-matrix metalloproteinase (MT-1-MMP) and its metanephric developmental regulation with respect to MMP-2 and its inhibitor."
Ota K., Stetler-Stevenson W.G., Yang Q., Kumar A., Wada J., Kashihara N., Wallner E.I., Kanwar Y.S.
Kidney Int. 54:131-142(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: CD-1.
Tissue: Kidney.
[5]"Interference with the complement system by tumor cell membrane type-1 matrix metalloproteinase plays a significant role in promoting metastasis in mice."
Rozanov D.V., Savinov A.Y., Golubkov V.S., Tomlinson S., Strongin A.Y.
Cancer Res. 66:6258-6263(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: FVB/N.
[6]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J and NOD.
Tissue: Bone marrow, Eye, Spinal cord and Thymus.
[7]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"MT1-MMP-deficient mice develop dwarfism, osteopenia, arthritis, and connective tissue disease due to inadequate collagen turnover."
Holmbeck K., Bianco P., Caterina J., Yamada S., Kromer M., Kuznetsov S.A., Mankani M., Robey P.G., Poole A.R., Pidoux I., Ward J.M., Birkedal-Hansen H.
Cell 99:81-92(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X83536 mRNA. Translation: CAA58520.2.
AF022432 expand/collapse EMBL AC list , AF022424, AF022425, AF022426, AF022427, AF022428, AF022429, AF022430, AF022431 Genomic DNA. Translation: AAB86602.1.
U54984 mRNA. Translation: AAB51753.1.
DQ249870 mRNA. Translation: ABB45784.1.
AK088476 mRNA. Translation: BAC40377.1.
AK138611 mRNA. Translation: BAE23719.1.
AK149907 mRNA. Translation: BAE29158.1.
AK149988 mRNA. Translation: BAE29216.1.
AK165014 mRNA. Translation: BAE38000.1.
CH466535 Genomic DNA. Translation: EDL36348.1.
CCDSCCDS36922.1.
PIRI48673.
RefSeqNP_032634.3. NM_008608.3.
UniGeneMm.280175.
Mm.486486.

3D structure databases

ProteinModelPortalP53690.
SMRP53690. Positions 65-511.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP53690. 1 interaction.

Protein family/group databases

MEROPSM10.014.

PTM databases

PhosphoSiteP53690.

Proteomic databases

MaxQBP53690.
PRIDEP53690.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000089688; ENSMUSP00000087119; ENSMUSG00000000957.
GeneID17387.
KEGGmmu:17387.
UCSCuc007twc.2. mouse.

Organism-specific databases

CTD4323.
MGIMGI:101900. Mmp14.

Phylogenomic databases

eggNOGNOG295915.
GeneTreeENSGT00750000117332.
HOGENOMHOG000217928.
HOVERGENHBG052484.
InParanoidQ8BTX2.
KOK07763.
OMAWMGCPSG.
OrthoDBEOG7XPZ57.
TreeFamTF352396.

Gene expression databases

ArrayExpressP53690.
BgeeP53690.
CleanExMM_MMP14.
GenevestigatorP53690.

Family and domain databases

Gene3D2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR024079. MetalloPept_cat_dom.
IPR028693. MMP14.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR021805. Pept_M10A_metallopeptidase_C.
IPR016293. Pept_M10A_stromelysin-type.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERPTHR10201:SF24. PTHR10201:SF24. 1 hit.
PfamPF11857. DUF3377. 1 hit.
PF00045. 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

ChiTaRSMMP14. mouse.
NextBio292000.
PROP53690.
SOURCESearch...

Entry information

Entry nameMMP14_MOUSE
AccessionPrimary (citable) accession number: P53690
Secondary accession number(s): O08645, O35369, Q8BTX2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 137 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot