Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Matrix metalloproteinase-14

Gene

MMP14

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (By similarity). May be involved in actin cytoskeleton reorganization by cleaving PTK7 (PubMed:20837484). Acts as a positive regulator of cell growth and migration via activation of MMP15. Involved in the formation of the fibrovascular tissues in association with pro-MMP2 (PubMed:12714657). Cleaves ADGRB1 to release vasculostatin-40 which inhibits angiogenesis (PubMed:22330140).By similarity4 Publications

Catalytic activityi

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.

Cofactori

Protein has several cofactor binding sites:
  • Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
  • Ca2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi93Zinc; in inhibited formBy similarity1
Metal bindingi239Zinc; catalytic1
Active sitei240PROSITE-ProRule annotation1
Metal bindingi243Zinc; catalytic1
Metal bindingi249Zinc; catalytic1

GO - Molecular functioni

  • metalloaminopeptidase activity Source: ParkinsonsUK-UCL
  • metalloendopeptidase activity Source: UniProtKB
  • peptidase activator activity Source: Ensembl
  • serine-type endopeptidase activity Source: Reactome
  • zinc ion binding Source: ProtInc

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000157227-MONOMER
BRENDAi3.4.24.80 2681
3.4.24.B5 2681
ReactomeiR-HSA-1442490 Collagen degradation
R-HSA-1474228 Degradation of the extracellular matrix
R-HSA-1592389 Activation of Matrix Metalloproteinases
SIGNORiP50281

Protein family/group databases

MEROPSiM10.014

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix metalloproteinase-14 (EC:3.4.24.80)
Short name:
MMP-14
Alternative name(s):
MMP-X1
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 namesi
Name:MMP14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000157227.12
HGNCiHGNC:7160 MMP14
MIMi600754 gene
neXtProtiNX_P50281

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini112 – 541ExtracellularSequence analysisAdd BLAST430
Transmembranei542 – 562HelicalSequence analysisAdd BLAST21
Topological domaini563 – 582CytoplasmicSequence analysisAdd BLAST20

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Involvement in diseasei

Winchester syndrome (WNCHRS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disease characterized by severe osteolysis in the hands and feet, generalized osteoporosis, bone thinning, and absence of subcutaneous nodules. Various additional features include coarse face, corneal opacities, gum hypertrophy, and EKG changes.
See also OMIM:277950
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07056717T → R in WNCHRS; results in increased MMP14 proteosomal degradation and reduced protein localization to cell membrane. 1 PublicationCorresponds to variant dbSNP:rs587777039EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi4323
MalaCardsiMMP14
MIMi277950 phenotype
OpenTargetsiENSG00000157227
Orphaneti85196 Nodulosis-arthropathy-osteolysis syndrome
3460 Torg-Winchester syndrome
PharmGKBiPA30872

Chemistry databases

ChEMBLiCHEMBL3869
DrugBankiDB00786 Marimastat
GuidetoPHARMACOLOGYi1638

Polymorphism and mutation databases

BioMutaiMMP14
DMDMi317373419

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000002879821 – 111Activation peptide1 PublicationAdd BLAST91
ChainiPRO_0000028799112 – 582Matrix metalloproteinase-14Add BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi319 ↔ 508By similarity
Modified residuei399Phosphotyrosine; by PKDCC1 Publication1

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity
Tyrosine phosphorylated by PKDCC/VLK.1 Publication

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Phosphoprotein, Zymogen

Proteomic databases

EPDiP50281
MaxQBiP50281
PaxDbiP50281
PeptideAtlasiP50281
PRIDEiP50281

PTM databases

iPTMnetiP50281
PhosphoSitePlusiP50281
SwissPalmiP50281

Expressioni

Tissue specificityi

Expressed in stromal cells of colon, breast, and head and neck. Expressed in lung tumors.1 Publication

Inductioni

Up-regulated by NANOS1.1 Publication

Gene expression databases

BgeeiENSG00000157227
CleanExiHS_MMP14
ExpressionAtlasiP50281 baseline and differential
GenevisibleiP50281 HS

Organism-specific databases

HPAiCAB009918
HPA051432

Interactioni

Subunit structurei

Interacts (via C-terminal cytoplasmic tail) with BST2. Interacts with DLL1; inhibits DLL1-induced Notch signaling (PubMed:21572390).3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi110466, 17 interactors
CORUMiP50281
DIPiDIP-35111N
IntActiP50281, 36 interactors
MINTiP50281
STRINGi9606.ENSP00000308208

Chemistry databases

BindingDBiP50281

Structurei

Secondary structure

1582
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi120 – 128Combined sources9
Turni133 – 135Combined sources3
Helixi137 – 154Combined sources18
Beta strandi158 – 161Combined sources4
Helixi164 – 168Combined sources5
Beta strandi171 – 173Combined sources3
Beta strandi176 – 182Combined sources7
Beta strandi187 – 190Combined sources4
Beta strandi194 – 202Combined sources9
Beta strandi205 – 207Combined sources3
Turni208 – 211Combined sources4
Beta strandi213 – 216Combined sources4
Beta strandi221 – 223Combined sources3
Beta strandi230 – 232Combined sources3
Helixi233 – 244Combined sources12
Beta strandi258 – 260Combined sources3
Helixi273 – 283Combined sources11
Helixi318 – 320Combined sources3
Beta strandi324 – 329Combined sources6
Beta strandi332 – 337Combined sources6
Beta strandi340 – 345Combined sources6
Beta strandi354 – 356Combined sources3
Helixi357 – 360Combined sources4
Beta strandi370 – 373Combined sources4
Beta strandi375 – 377Combined sources3
Beta strandi379 – 383Combined sources5
Beta strandi386 – 391Combined sources6
Beta strandi400 – 402Combined sources3
Helixi403 – 405Combined sources3
Beta strandi416 – 420Combined sources5
Turni422 – 424Combined sources3
Beta strandi427 – 431Combined sources5
Beta strandi434 – 439Combined sources6
Turni440 – 443Combined sources4
Beta strandi450 – 452Combined sources3
Helixi453 – 455Combined sources3
Beta strandi464 – 468Combined sources5
Beta strandi472 – 479Combined sources8
Beta strandi482 – 487Combined sources6
Turni488 – 491Combined sources4
Helixi501 – 504Combined sources4
Beta strandi569 – 575Combined sources7

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1BQQX-ray2.75M114-287[»]
1BUVX-ray2.75M114-287[»]
2MQSNMR-A316-511[»]
3C7XX-ray1.70A316-511[»]
3MA2X-ray2.05A/D112-292[»]
3X23X-ray2.40B563-582[»]
4P3CX-ray1.94M215-227[»]
4P3DX-ray1.95C/M215-227[»]
4QXUX-ray2.30K218-228[»]
5H0UX-ray2.24A116-285[»]
ProteinModelPortaliP50281
SMRiP50281
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50281

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati316 – 364Hemopexin 1Add BLAST49
Repeati365 – 410Hemopexin 2Add BLAST46
Repeati412 – 460Hemopexin 3Add BLAST49
Repeati461 – 508Hemopexin 4Add BLAST48

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi91 – 98Cysteine switchBy similarity8

Domaini

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.

Sequence similaritiesi

Belongs to the peptidase M10A family.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1565 Eukaryota
ENOG410XQ5D LUCA
GeneTreeiENSGT00760000118870
HOGENOMiHOG000217928
HOVERGENiHBG052484
InParanoidiP50281
KOiK07763
OMAiYQNNEVD
OrthoDBiEOG091G03DP
PhylomeDBiP50281
TreeFamiTF352396

Family and domain databases

CDDicd00094 HX, 1 hit
cd04278 ZnMc_MMP, 1 hit
Gene3Di1.10.101.10, 1 hit
2.110.10.10, 1 hit
3.40.390.10, 1 hit
InterProiView protein in InterPro
IPR000585 Hemopexin-like_dom
IPR036375 Hemopexin-like_dom_sf
IPR018487 Hemopexin-like_repeat
IPR018486 Hemopexin_CS
IPR033739 M10A_MMP
IPR024079 MetalloPept_cat_dom_sf
IPR028693 MMP14
IPR001818 Pept_M10_metallopeptidase
IPR021190 Pept_M10A
IPR021805 Pept_M10A_metallopeptidase_C
IPR021158 Pept_M10A_Zn_BS
IPR006026 Peptidase_Metallo
IPR002477 Peptidoglycan-bd-like
IPR036365 PGBD-like_sf
IPR036366 PGBDSf
PANTHERiPTHR10201:SF24 PTHR10201:SF24, 1 hit
PfamiView protein in Pfam
PF11857 DUF3377, 1 hit
PF00045 Hemopexin, 4 hits
PF00413 Peptidase_M10, 1 hit
PF01471 PG_binding_1, 1 hit
PIRSFiPIRSF001191 Peptidase_M10A_matrix, 1 hit
PRINTSiPR00138 MATRIXIN
SMARTiView protein in SMART
SM00120 HX, 4 hits
SM00235 ZnMc, 1 hit
SUPFAMiSSF47090 SSF47090, 1 hit
SSF50923 SSF50923, 1 hit
PROSITEiView protein in PROSITE
PS00546 CYSTEINE_SWITCH, 1 hit
PS00024 HEMOPEXIN, 1 hit
PS51642 HEMOPEXIN_2, 4 hits
PS00142 ZINC_PROTEASE, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P50281-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSPAPRPPRC LLLPLLTLGT ALASLGSAQS SSFSPEAWLQ QYGYLPPGDL
60 70 80 90 100
RTHTQRSPQS LSAAIAAMQK FYGLQVTGKA DADTMKAMRR PRCGVPDKFG
110 120 130 140 150
AEIKANVRRK RYAIQGLKWQ HNEITFCIQN YTPKVGEYAT YEAIRKAFRV
160 170 180 190 200
WESATPLRFR EVPYAYIREG HEKQADIMIF FAEGFHGDST PFDGEGGFLA
210 220 230 240 250
HAYFPGPNIG GDTHFDSAEP WTVRNEDLNG NDIFLVAVHE LGHALGLEHS
260 270 280 290 300
SDPSAIMAPF YQWMDTENFV LPDDDRRGIQ QLYGGESGFP TKMPPQPRTT
310 320 330 340 350
SRPSVPDKPK NPTYGPNICD GNFDTVAMLR GEMFVFKERW FWRVRNNQVM
360 370 380 390 400
DGYPMPIGQF WRGLPASINT AYERKDGKFV FFKGDKHWVF DEASLEPGYP
410 420 430 440 450
KHIKELGRGL PTDKIDAALF WMPNGKTYFF RGNKYYRFNE ELRAVDSEYP
460 470 480 490 500
KNIKVWEGIP ESPRGSFMGS DEVFTYFYKG NKYWKFNNQK LKVEPGYPKS
510 520 530 540 550
ALRDWMGCPS GGRPDEGTEE ETEVIIIEVD EEGGGAVSAA AVVLPVLLLL
560 570 580
LVLAVGLAVF FFRRHGTPRR LLYCQRSLLD KV
Length:582
Mass (Da):65,894
Last modified:January 11, 2011 - v3
Checksum:i3722DE286A4BBCDE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti338E → K in BAA05519 (PubMed:8015608).Curated1
Sequence conflicti500S → P in CAA62432 (PubMed:8706726).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0210294A → T1 PublicationCorresponds to variant dbSNP:rs17882219Ensembl.1
Natural variantiVAR_0210306R → K1 PublicationCorresponds to variant dbSNP:rs17884647Ensembl.1
Natural variantiVAR_0210318P → S7 PublicationsCorresponds to variant dbSNP:rs1042703Ensembl.1
Natural variantiVAR_07056717T → R in WNCHRS; results in increased MMP14 proteosomal degradation and reduced protein localization to cell membrane. 1 PublicationCorresponds to variant dbSNP:rs587777039EnsemblClinVar.1
Natural variantiVAR_021032233I → V1 PublicationCorresponds to variant dbSNP:rs17884841Ensembl.1
Natural variantiVAR_021033273D → N1 PublicationCorresponds to variant dbSNP:rs1042704Ensembl.1
Natural variantiVAR_021034302R → W1 PublicationCorresponds to variant dbSNP:rs17884719Ensembl.1
Natural variantiVAR_021035355M → I1 PublicationCorresponds to variant dbSNP:rs17880989Ensembl.1
Natural variantiVAR_031267431R → H. Corresponds to variant dbSNP:rs3751489Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AL135998 Genomic DNA No translation available.
BC064803 mRNA Translation: AAH64803.1
CCDSiCCDS9577.1
PIRiI38028
RefSeqiNP_004986.1, NM_004995.3
UniGeneiHs.2399

Genome annotation databases

EnsembliENST00000311852; ENSP00000308208; ENSG00000157227
GeneIDi4323
KEGGihsa:4323
UCSCiuc001whc.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMMP14_HUMAN
AccessioniPrimary (citable) accession number: P50281
Secondary accession number(s): A8K5L0, Q6GSF3, Q92678
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 11, 2011
Last modified: May 23, 2018
This is version 192 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health