Matrix metalloproteinase-14 precursor

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

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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.

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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 proteinPotential. 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.

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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 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.11 Inferred from physical interaction. Source: UniProtKB zinc ion binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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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.

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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

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.

VAR_021029

Natural variant

6

1

R → K: dbSNP rs17884647.

VAR_021030

Natural variant

8

1

S → P: dbSNP rs1042703.

VAR_021031

Natural variant

233

1

I → V: dbSNP rs17884841.

VAR_021032

Natural variant

273

1

D → N: dbSNP rs1042704.

VAR_021033

Natural variant

302

1

R → W: dbSNP rs17884719.

VAR_021034

Natural variant

355

1

M → I: dbSNP rs17880989.

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

.

582

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

P50281-1 [UniParc].

Last modified February 1, 2005. Version 2.
Checksum: 09EEDCE6A69BBC53
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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

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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]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Livingston R.J., Rieder M.J., Chung M.-W., Ritchie T.K., Olson A.N., Nguyen C.P., Nguyen D.A., Poel C.L., Chambers S.W., Schackwitz W.S., Sherwood J.K., Sherwood A.M., Leithauser B.J., Nickerson D.A. 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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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.

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Cross-references

Sequence databases

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.
AY795074 Genomic DNA. Translation: AAV40837.1.
BC064803 mRNA. Translation: AAH64803.1.

PIR

I38028.

RefSeq

NP_004986.1.

UniGene

Hs.2399

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BQQ	X-ray	2.75	M	114-287	[»]
1BUV	X-ray	2.75	M	114-287	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P50281.

Protein family/group databases

MEROPS

M10.014.

PTM databases

PhosphoSite

P50281.

Polymorphism databases

NIEHS-SNPs

Search...

Genome annotation databases

Ensembl

ENSG00000157227. Homo sapiens. [Contig view]

GeneID

4323.

KEGG

hsa:4323.

Organism-specific databases

H-InvDB

HIX0037743.

HGNC

HGNC:7160. MMP14.

HPA

CAB009918.

MIM

600754. gene.

PharmGKB

PA30872.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P50281.

HOVERGEN

P50281.

Gene expression databases

ArrayExpress

P50281.

CleanEx

HS_MMP14.

GermOnline

ENSG00000157227. Homo sapiens.

Family and domain databases

InterPro

IPR000585. Hemopexin.
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

NextBio

17009.

SOURCE

Search...

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Entry information

Entry name

MMP14_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	February 1, 2005
Last modified:	November 25, 2008
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protein family/group databases

PTM databases

Polymorphism databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other Resources

Entry information