Reviewed, UniProtKB/Swiss-Prot P50281 (MMP14_HUMAN)

Names and origin

Protein names

Recommended name:
    Matrix metalloproteinase-14
      Short name=MMP-14
    EC=3.4.24.80
Alternative name(s):
    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
    MMP-X1

Gene names

Name:

MMP14

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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 protein level.

General annotation (Comments)

Function	Seems to specifically activate progelatinase A. May thus trigger invasion by tumor cells by activating progelatinase A on the tumor cell surface.
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.
Subcellular location	Membrane; Single-pass type I membrane protein Potential. Melanosome. Note: Identified by mass spectrometry in melanosome fractions from stage I to stage IV.
Tissue specificity	In stromal cells of colon, breast, and head and neck.
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
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	proteolysis Ref.1 Traceable author statement. Source: ProtInc
Cellular component	integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc melanosome Inferred from electronic annotation. Source: UniProtKB-SubCell proteinaceous extracellular matrix Inferred from electronic annotation. Source: InterPro
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Ref.1 Traceable author statement. Source: ProtInc protein binding Ref.12 Inferred from physical interaction. Source: UniProtKB zinc ion binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADI1	Q9BV57	2	EBI-992788,EBI-992807
TIMP2	P16368	1	EBI-992788,EBI-1027047	From a different organism.

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

Activation peptide Ref.10

PRO_0000028798

Chain

112 – 582

471

Matrix metalloproteinase-14

PRO_0000028799

Regions

Topological domain

112 – 541

430

Extracellular Potential

Transmembrane

542 – 562

21

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

Metal binding

243

1

Zinc; catalytic

Metal binding

249

1

Zinc; catalytic

Amino acid modifications

Disulfide bond

319 ↔ 508

By similarity

Natural variations

Natural variant

4

1

A → T: dbSNP rs17882219. Ref.8

VAR_021029

Natural variant

6

1

R → K: dbSNP rs17884647. Ref.8

VAR_021030

Natural variant

8

1

S → P: dbSNP rs1042703. Ref.8 Ref.4 Ref.5

VAR_021031

Natural variant

233

1

I → V: dbSNP rs17884841. Ref.8

VAR_021032

Natural variant

273

1

D → N: dbSNP rs1042704. Ref.8

VAR_021033

Natural variant

302

1

R → W: dbSNP rs17884719. Ref.8

VAR_021034

Natural variant

355

1

M → I: dbSNP rs17880989. Ref.8

VAR_021035

Natural variant

431

1

R → H: dbSNP rs3751489.

VAR_031267

Experimental info

Sequence conflict

338

1

E → K in BAA05519. Ref.1

Sequence conflict

500

1

S → P in CAA62432. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

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.

.

.

582

Helix Strand Turn

Details...

Beta strand

122 – 125

4

Turn

133 – 135

3

Helix

137 – 154

18

Beta strand

158 – 160

3

Beta strand

171 – 173

3

Beta strand

176 – 182

7

Beta strand

186 – 189

4

Beta strand

194 – 202

9

Turn

208 – 211

4

Beta strand

213 – 216

4

Helix

233 – 243

11

Turn

244 – 246

3

Beta strand

256 – 260

5

Helix

273 – 276

4

Helix

279 – 282

4

Turn

283 – 285

3

Sequences

	Sequence		Length	Mass (Da)
	P50281-1 [UniParc]. Last modified February 1, 2005. Version 2. Checksum: 09EEDCE6A69BBC53	FASTA	582	65,884
	10 20 30 40 50 60 MSPAPRPSRC LLLPLLTLGT ALASLGSAQS SSFSPEAWLQ QYGYLPPGDL RTHTQRSPQS 70 80 90 100 110 120 LSAAIAAMQK FYGLQVTGKA DADTMKAMRR PRCGVPDKFG AEIKANVRRK RYAIQGLKWQ 130 140 150 160 170 180 HNEITFCIQN YTPKVGEYAT YEAIRKAFRV WESATPLRFR EVPYAYIREG HEKQADIMIF 190 200 210 220 230 240 FAEGFHGDST PFDGEGGFLA HAYFPGPNIG GDTHFDSAEP WTVRNEDLNG NDIFLVAVHE 250 260 270 280 290 300 LGHALGLEHS SDPSAIMAPF YQWMDTENFV LPDDDRRGIQ QLYGGESGFP TKMPPQPRTT 310 320 330 340 350 360 SRPSVPDKPK NPTYGPNICD GNFDTVAMLR GEMFVFKERW FWRVRNNQVM DGYPMPIGQF 370 380 390 400 410 420 WRGLPASINT AYERKDGKFV FFKGDKHWVF DEASLEPGYP KHIKELGRGL PTDKIDAALF 430 440 450 460 470 480 WMPNGKTYFF RGNKYYRFNE ELRAVDSEYP KNIKVWEGIP ESPRGSFMGS DEVFTYFYKG 490 500 510 520 530 540 NKYWKFNNQK LKVEPGYPKS ALRDWMGCPS GGRPDEGTEE ETEVIIIEVD EEGGGAVSAA 550 560 570 580 AVVLPVLLLL LVLAVGLAVF FFRRHGTPRR LLYCQRSLLD KV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A matrix metalloproteinase expressed on the surface of invasive tumour cells." Sato H., Takino T., Okada Y., Cao J., Shinagawa A., Yamamoto E., Seiki M. Nature 370:61-65(1994) [PubMed: 8015608] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[2]	"Cloning of a human gene potentially encoding a novel matrix metalloproteinase having a C-terminal transmembrane domain." Takino T., Sato H., Yamamoto E., Seiki M. Gene 155:293-298(1995) [PubMed: 7721107] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"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: 7708715] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"cDNA sequence and mRNA tissue distribution of a novel human matrix metalloproteinase with a potential transmembrane segment." Will H., Hinzmann B. Eur. J. Biochem. 231:602-608(1995) [PubMed: 7649159] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-8. Tissue: Lung.
[5]	Luo G.-X., Reisfeld R.A., Strongin A.Y. Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-8.
[6]	"Regulation of membrane-type matrix metalloproteinase-1 expression by growth factors and phorbol 12-myristate 13-acetate." Lohi J.L., Westermarck J., Kaehaeri V.M., Keski-Oja J. Eur. J. Biochem. 239:239-247(1996) [PubMed: 8706726] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[7]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Tongue.
[8]	NIEHS SNPs program Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS THR-4; LYS-6; PRO-8; VAL-233; ASN-273; TRP-302 AND ILE-355.
[9]	"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: Skin.
[10]	"Activation of a recombinant membrane type 1-matrix metalloproteinase (MT1-MMP) by furin and its interaction with tissue inhibitor of metalloproteinases (TIMP)-2." Sato H., Kinoshita T., Takino T., Nakayama K., Seiki M. FEBS Lett. 393:101-104(1996) [PubMed: 8804434] [Abstract] Cited for: PROTEIN SEQUENCE OF 112-116.
[11]	"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes." Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F. J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Crystal structure of the complex formed by the membrane type 1-matrix metalloproteinase with the tissue inhibitor of metalloproteinases-2, the soluble progelatinase A receptor." Fernandez-Catalan C., Bode W., Huber R., Turk D., Calvete J.J., Lichte A., Tschesche H., Maskos K. EMBO J. 17:5238-5248(1998) [PubMed: 9724659] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) OF 114-287 IN COMPLEX WITH TIMP2.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

D26512 mRNA. Translation: BAA05519.1.
X83535 mRNA. Translation: CAA58519.1.
Z48481 mRNA. Translation: CAA88372.1.
U41078 mRNA. Translation: AAA83770.1.
X90925 mRNA. Translation: CAA62432.1.
AK291325 mRNA. Translation: BAF84014.1.
AY795074 Genomic DNA. Translation: AAV40837.1.
BC064803 mRNA. Translation: AAH64803.1.

IPI

IPI00218398.

PIR

I38028.

RefSeq

NP_004986.1.

UniGene

Hs.2399

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BQQ	X-ray	2.75	M	114-287	[»]
1BUV	X-ray	2.75	M	114-287	[»]
3C7X	X-ray	1.70	A	316-511	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P50281. 2 interactions.

Protein family/group databases

MEROPS

M10.014.

PTM databases

PhosphoSite

P50281.

Proteomic databases

PRIDE

P50281.

Genome annotation databases

Ensembl

ENSG00000157227. Homo sapiens. [Contig view]

GeneID

4323.

KEGG

hsa:4323.

Organism-specific databases

GeneCards

GC14P022375.

H-InvDB

HIX0037743.

HGNC

HGNC:7160. MMP14.

HPA

CAB009918.

MIM

600754. gene.

PharmGKB

PA30872.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P50281.

HOVERGEN

P50281.

Enzyme and pathway databases

BRENDA

3.4.24.7. 247.
3.4.24.80. 247.

Gene expression databases

ArrayExpress

P50281.

Bgee

P50281.

CleanEx

HS_MMP14.

GermOnline

ENSG00000157227. Homo sapiens.

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]

Gene3D

G3DSA:2.110.10.10. Hemopexin. 1 hit.

Pfam

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]

PROSITE

PS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

P50281.

NextBio

17009.

SOURCE

Search...

Entry information

Entry name

MMP14_HUMAN

Accession

Primary (citable) accession number: P50281
Secondary accession number(s): A8K5L0, Q6GSF3, Q92678

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	February 1, 2005
Last modified:	June 16, 2009
This is version 97 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)