P53690 (MMP14_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	582 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 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-like domains.

Ontologies

Keywords
Biological process	Collagen degradation
Cellular component	Cytoplasm Membrane
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	angiogenesis Inferred from electronic annotation. Source: Compara astrocyte cell migration Inferred from electronic annotation. Source: Compara branching morphogenesis of an epithelial tube Inferred from mutant phenotype PubMed 15572153. Source: MGI cell migration Inferred from mutant phenotype PubMed 15572153. Source: MGI collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW endothelial cell proliferation Inferred from electronic annotation. Source: Compara lung development Inferred from mutant phenotype PubMed 15572153. Source: MGI negative regulation of focal adhesion assembly Inferred from electronic annotation. Source: Compara ossification Inferred from electronic annotation. Source: Compara ovarian follicle development Inferred from electronic annotation. Source: Compara positive regulation of cell growth Inferred from electronic annotation. Source: Compara positive regulation of cell migration Inferred from electronic annotation. Source: Compara proteolysis Inferred from electronic annotation. Source: UniProtKB-KW response to estrogen stimulus Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to mechanical stimulus Inferred from electronic annotation. Source: Compara response to oxidative stress Inferred from electronic annotation. Source: Compara tissue remodeling Inferred from electronic annotation. Source: Compara zymogen activation Inferred from mutant phenotype PubMed 15572153. Source: MGI
Cellular_component	extracellular matrix Inferred from electronic annotation. Source: InterPro integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro peptidase activator activity Inferred from electronic annotation. Source: Compara 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 20	20	Potential
	Propeptide	21 – 111	91	By similarity		PRO_0000028800
	Chain	112 – 582	471	Matrix metalloproteinase-14		PRO_0000028801
Regions
	Topological domain	112 – 541	430	Extracellular Potential
	Transmembrane	542 – 562	21	Helical; Potential
	Topological domain	563 – 582	20	Cytoplasmic Potential
	Domain	323 – 366	44	Hemopexin-like 1
	Domain	368 – 412	45	Hemopexin-like 2
	Domain	415 – 461	47	Hemopexin-like 3
	Domain	463 – 508	46	Hemopexin-like 4
	Motif	91 – 98	8	Cysteine switch By similarity
Sites
	Active site	240	1	By similarity
	Metal binding	93	1	Zinc; in inhibited form By similarity
	Metal binding	239	1	Zinc; catalytic By similarity
	Metal binding	243	1	Zinc; catalytic By similarity
	Metal binding	249	1	Zinc; catalytic By similarity
Amino acid modifications
	Disulfide bond	319 ↔ 508		By similarity
Experimental info
	Sequence conflict	133	1	P → S in AAB86602. Ref.3
	Sequence conflict	255	1	A → D in CAA58520. Ref.1
	Sequence conflict	258	1	A → S in CAA58520. Ref.1
	Sequence conflict	258	1	A → S in AAB51753. Ref.4
	Sequence conflict	341	1	F → L in CAA58520. Ref.1
	Sequence conflict	346	1	N → P in AAB86602. Ref.3
	Sequence conflict	378	1	K → T in CAA58520. Ref.1
	Sequence conflict	390 – 391	2	FD → CV in CAA58520. Ref.1
	Sequence conflict	400 – 401	2	PK → AN in CAA58520. Ref.1
	Sequence conflict	407	1	G → V in CAA58520. Ref.1
	Sequence conflict	412	1	T → S in CAA58520. Ref.1
	Sequence conflict	417	1	A → T in CAA58520. Ref.1
	Sequence conflict	512	1	G → R in AAB51753. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P53690 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 6CA95CFD5811B093	FASTA	582	65,919
	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

References

	« Hide 'large scale' referencesShow '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. , 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 , 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.
IPI	IPI00133725.
PIR	I48673.
RefSeq	NP_032634.3. NM_008608.3.
UniGene	Mm.280175. Mm.486486.
3D structure databases
ProteinModelPortal	P53690.
SMR	P53690. Positions 65-511.
ModBase	Search...
Protein family/group databases
MEROPS	M10.014.
PTM databases
PhosphoSite	P53690.
Proteomic databases
PRIDE	P53690.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000089688; ENSMUSP00000087119; ENSMUSG00000000957.
GeneID	17387.
KEGG	mmu:17387.
Organism-specific databases
CTD	4323.
MGI	MGI:101900. Mmp14.
Phylogenomic databases
eggNOG	NOG295915.
GeneTree	ENSGT00700000104046.
HOGENOM	HOG000217928.
HOVERGEN	HBG052484.
InParanoid	Q8BTX2.
KO	K07763.
OMA	WMGCPSG.
OrthoDB	EOG4FR0RF.
Gene expression databases
ArrayExpress	P53690.
Bgee	P53690.
CleanEx	MM_MMP14.
Genevestigator	P53690.
GermOnline	ENSMUSG00000000957. Mus musculus.
Family and domain databases
Gene3D	2.110.10.10. 1 hit. 3.40.390.10. 1 hit.
InterPro	IPR000585. Hemopexin-like_dom. IPR018487. Hemopexin-like_repeat. IPR018486. Hemopexin_CS. IPR024079. MetalloPept_cat_dom. IPR001818. Pept_M10_metallopeptidase. IPR021190. Pept_M10A. IPR021805. Pept_M10A_metallopeptidase_C. IPR016293. Pept_M10A_Metazoans. IPR021158. Pept_M10A_Zn_BS. IPR006026. Peptidase_Metallo. IPR002477. Peptidoglycan-bd-like. [Graphical view]
Pfam	PF11857. DUF3377. 1 hit. PF00045. Hemopexin. 4 hits. PF00413. Peptidase_M10. 1 hit. PF01471. PG_binding_1. 1 hit. [Graphical view]
PIRSF	PIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTS	PR00138. MATRIXIN.
SMART	SM00120. HX. 4 hits. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF50923. Hemopexin. 1 hit. SSF47090. PGBD_like. 1 hit.
PROSITE	PS00546. CYSTEINE_SWITCH. 1 hit. PS00024. HEMOPEXIN. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	MMP14. mouse.
NextBio	292000.
SOURCE	Search...

Entry information

Entry name

MMP14_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 124 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program