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Protein

Matrix metalloproteinase-16

Gene

MMP16

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 type III and fibronectin. Activates progelatinase A. Involved in the matrix remodeling of blood vessels. Isoform short cleaves fibronectin and also collagen type III, but at lower rate. It has no effect on type I, II, IV and V collagen. However, upon interaction with CSPG4, it may be involved in degradation and invasion of type I collagen by melanoma cells.1 Publication

Cofactori

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

Activity regulationi

TIMP-2 shows little inhibitory activity compared to TIMP-1. TIMP-1 seems to have less binding affinity than TIMP-2 for the short isoform.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi101Zinc 1; in inhibited formBy similarity1
Metal bindingi183Calcium 1; via carbonyl oxygen1
Metal bindingi193Zinc 11
Metal bindingi195Zinc 11
Metal bindingi200Calcium 21
Metal bindingi201Calcium 2; via carbonyl oxygen1
Metal bindingi203Calcium 2; via carbonyl oxygen1
Metal bindingi205Calcium 2; via carbonyl oxygen1
Metal bindingi215Calcium 1; via carbonyl oxygen1
Metal bindingi217Calcium 1; via carbonyl oxygen1
Metal bindingi219Calcium 11
Metal bindingi223Calcium 21
Metal bindingi226Calcium 21
Metal bindingi246Zinc 2; catalytic1
Active sitei2471
Metal bindingi250Zinc 2; catalytic1
Metal bindingi256Zinc 2; catalytic1

GO - Molecular functioni

  • enzyme activator activity Source: ProtInc
  • metalloaminopeptidase activity Source: ParkinsonsUK-UCL
  • metalloendopeptidase activity Source: ParkinsonsUK-UCL
  • zinc ion binding Source: ParkinsonsUK-UCL

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Metalloprotease, Protease
Biological processCollagen degradation
LigandCalcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-1592389 Activation of Matrix Metalloproteinases

Protein family/group databases

MEROPSiM10.016

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix metalloproteinase-16 (EC:3.4.24.-)
Short name:
MMP-16
Alternative name(s):
MMP-X2
Membrane-type matrix metalloproteinase 3
Short name:
MT-MMP 3
Short name:
MTMMP3
Membrane-type-3 matrix metalloproteinase
Short name:
MT3-MMP
Short name:
MT3MMP
Gene namesi
Name:MMP16Imported
Synonyms:C8orf57Imported, MMPX2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000156103.15
HGNCiHGNC:7162 MMP16
MIMi602262 gene
neXtProtiNX_P51512

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 domaini120 – 564ExtracellularSequence analysisAdd BLAST445
Transmembranei565 – 585HelicalSequence analysisAdd BLAST21
Topological domaini586 – 607CytoplasmicSequence analysisAdd BLAST22

Keywords - Cellular componenti

Cell membrane, Extracellular matrix, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi4325
OpenTargetsiENSG00000156103
PharmGKBiPA30874

Chemistry databases

ChEMBLiCHEMBL2200
DrugBankiDB03880 Batimastat
DB00786 Marimastat
GuidetoPHARMACOLOGYi1640

Polymorphism and mutation databases

BioMutaiMMP16
DMDMi3041669

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
PropeptideiPRO_000002881232 – 119By similarityAdd BLAST88
ChainiPRO_0000028813120 – 607Matrix metalloproteinase-16Add BLAST488

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi83N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi343 ↔ 532By similarity

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity

Keywords - PTMi

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

Proteomic databases

EPDiP51512
PaxDbiP51512
PeptideAtlasiP51512
PRIDEiP51512
ProteomicsDBi56313
56314 [P51512-2]

PTM databases

iPTMnetiP51512
PhosphoSitePlusiP51512

Miscellaneous databases

PMAP-CutDBiP51512

Expressioni

Tissue specificityi

Expressed in heart, brain, placenta, ovary and small intestine. Isoform Short is found in the ovary.

Developmental stagei

Expressed in tissues undergoing reconstruction. Present in fetal tissues, especially in brain. Expression seems to decline with advanced development.

Gene expression databases

BgeeiENSG00000156103 Expressed in 167 organ(s), highest expression level in forebrain
CleanExiHS_MMP16
ExpressionAtlasiP51512 baseline and differential
GenevisibleiP51512 HS

Organism-specific databases

HPAiHPA023693

Interactioni

Subunit structurei

Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan.2 Publications

Protein-protein interaction databases

BioGridi110468, 1 interactor
IntActiP51512, 1 interactor
MINTiP51512
STRINGi9606.ENSP00000286614

Chemistry databases

BindingDBiP51512

Structurei

Secondary structure

1607
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP51512
SMRiP51512
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP51512

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati340 – 388Hemopexin 1Add BLAST49
Repeati389 – 434Hemopexin 2Add BLAST46
Repeati436 – 484Hemopexin 3Add BLAST49
Repeati485 – 532Hemopexin 4Add BLAST48

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi99 – 106Cysteine 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
InParanoidiP51512
KOiK07996
OMAiKFWVFKD
OrthoDBiEOG091G03DP
PhylomeDBiP51512
TreeFamiTF352396

Family and domain databases

CDDicd00094 HX, 1 hit
cd04278 ZnMc_MMP, 1 hit
Gene3Di2.110.10.10, 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
IPR028697 MMP16
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
PANTHERiPTHR10201:SF26 PTHR10201:SF26, 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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform Long (identifier: P51512-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MILLTFSTGR RLDFVHHSGV FFLQTLLWIL CATVCGTEQY FNVEVWLQKY
60 70 80 90 100
GYLPPTDPRM SVLRSAETMQ SALAAMQQFY GINMTGKVDR NTIDWMKKPR
110 120 130 140 150
CGVPDQTRGS SKFHIRRKRY ALTGQKWQHK HITYSIKNVT PKVGDPETRK
160 170 180 190 200
AIRRAFDVWQ NVTPLTFEEV PYSELENGKR DVDITIIFAS GFHGDSSPFD
210 220 230 240 250
GEGGFLAHAY FPGPGIGGDT HFDSDEPWTL GNPNHDGNDL FLVAVHELGH
260 270 280 290 300
ALGLEHSNDP TAIMAPFYQY METDNFKLPN DDLQGIQKIY GPPDKIPPPT
310 320 330 340 350
RPLPTVPPHR SIPPADPRKN DRPKPPRPPT GRPSYPGAKP NICDGNFNTL
360 370 380 390 400
AILRREMFVF KDQWFWRVRN NRVMDGYPMQ ITYFWRGLPP SIDAVYENSD
410 420 430 440 450
GNFVFFKGNK YWVFKDTTLQ PGYPHDLITL GSGIPPHGID SAIWWEDVGK
460 470 480 490 500
TYFFKGDRYW RYSEEMKTMD PGYPKPITVW KGIPESPQGA FVHKENGFTY
510 520 530 540 550
FYKGKEYWKF NNQILKVEPG YPRSILKDFM GCDGPTDRVK EGHSPPDDVD
560 570 580 590 600
IVIKLDNTAS TVKAIAIVIP CILALCLLVL VYTVFQFKRK GTPRHILYCK

RSMQEWV
Length:607
Mass (Da):69,521
Last modified:July 15, 1998 - v2
Checksum:i30D6247D9CB21663
GO
Isoform Short (identifier: P51512-2) [UniParc]FASTAAdd to basket
Also known as: SM3

The sequence of this isoform differs from the canonical sequence as follows:
     408-457: GNKYWVFKDT...VGKTYFFKGD → VKGDTLSVIQ...TYEELSSITY
     458-607: Missing.

Show »
Length:457
Mass (Da):52,515
Checksum:i94184CDA9F76C5EB
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RJA7E5RJA7_HUMAN
Matrix metalloproteinase
MMP16
168Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti521Y → H in BAA23742 (PubMed:7559440).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005453408 – 457GNKYW…FFKGD → VKGDTLSVIQDGWLYKYHWK WILEQRQSVPVLSRQTEKHK TYEELSSITY in isoform Short. 1 PublicationAdd BLAST50
Alternative sequenceiVSP_005454458 – 607Missing in isoform Short. 1 PublicationAdd BLAST150

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009303 mRNA Translation: BAA23742.1
D83646 mRNA Translation: BAA12022.1
D83647 mRNA Translation: BAA12023.1
D85511 mRNA Translation: BAA22226.1
DQ003082 Genomic DNA Translation: AAX84515.1
AK314274 mRNA Translation: BAG36934.1
CH471060 Genomic DNA Translation: EAW91651.1
BC069500 mRNA Translation: AAH69500.1
BC075004 mRNA Translation: AAH75004.1
BC075005 mRNA Translation: AAH75005.1
CCDSiCCDS6246.1 [P51512-1]
RefSeqiNP_005932.2, NM_005941.4 [P51512-1]
UniGeneiHs.492187
Hs.546267

Genome annotation databases

EnsembliENST00000286614; ENSP00000286614; ENSG00000156103 [P51512-1]
GeneIDi4325
KEGGihsa:4325
UCSCiuc003yeb.5 human [P51512-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB009303 mRNA Translation: BAA23742.1
D83646 mRNA Translation: BAA12022.1
D83647 mRNA Translation: BAA12023.1
D85511 mRNA Translation: BAA22226.1
DQ003082 Genomic DNA Translation: AAX84515.1
AK314274 mRNA Translation: BAG36934.1
CH471060 Genomic DNA Translation: EAW91651.1
BC069500 mRNA Translation: AAH69500.1
BC075004 mRNA Translation: AAH75004.1
BC075005 mRNA Translation: AAH75005.1
CCDSiCCDS6246.1 [P51512-1]
RefSeqiNP_005932.2, NM_005941.4 [P51512-1]
UniGeneiHs.492187
Hs.546267

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1RM8X-ray1.80A124-292[»]
ProteinModelPortaliP51512
SMRiP51512
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110468, 1 interactor
IntActiP51512, 1 interactor
MINTiP51512
STRINGi9606.ENSP00000286614

Chemistry databases

BindingDBiP51512
ChEMBLiCHEMBL2200
DrugBankiDB03880 Batimastat
DB00786 Marimastat
GuidetoPHARMACOLOGYi1640

Protein family/group databases

MEROPSiM10.016

PTM databases

iPTMnetiP51512
PhosphoSitePlusiP51512

Polymorphism and mutation databases

BioMutaiMMP16
DMDMi3041669

Proteomic databases

EPDiP51512
PaxDbiP51512
PeptideAtlasiP51512
PRIDEiP51512
ProteomicsDBi56313
56314 [P51512-2]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286614; ENSP00000286614; ENSG00000156103 [P51512-1]
GeneIDi4325
KEGGihsa:4325
UCSCiuc003yeb.5 human [P51512-1]

Organism-specific databases

CTDi4325
DisGeNETi4325
EuPathDBiHostDB:ENSG00000156103.15
GeneCardsiMMP16
HGNCiHGNC:7162 MMP16
HPAiHPA023693
MIMi602262 gene
neXtProtiNX_P51512
OpenTargetsiENSG00000156103
PharmGKBiPA30874
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1565 Eukaryota
ENOG410XQ5D LUCA
GeneTreeiENSGT00760000118870
HOGENOMiHOG000217928
HOVERGENiHBG052484
InParanoidiP51512
KOiK07996
OMAiKFWVFKD
OrthoDBiEOG091G03DP
PhylomeDBiP51512
TreeFamiTF352396

Enzyme and pathway databases

ReactomeiR-HSA-1592389 Activation of Matrix Metalloproteinases

Miscellaneous databases

ChiTaRSiMMP16 human
EvolutionaryTraceiP51512
GeneWikiiMMP16
GenomeRNAii4325
PMAP-CutDBiP51512
PROiPR:P51512
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156103 Expressed in 167 organ(s), highest expression level in forebrain
CleanExiHS_MMP16
ExpressionAtlasiP51512 baseline and differential
GenevisibleiP51512 HS

Family and domain databases

CDDicd00094 HX, 1 hit
cd04278 ZnMc_MMP, 1 hit
Gene3Di2.110.10.10, 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
IPR028697 MMP16
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
PANTHERiPTHR10201:SF26 PTHR10201:SF26, 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
ProtoNetiSearch...

Entry informationi

Entry nameiMMP16_HUMAN
AccessioniPrimary (citable) accession number: P51512
Secondary accession number(s): B2RAN7, Q14824, Q52H48
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 15, 1998
Last modified: November 7, 2018
This is version 183 of the entry and version 2 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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