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Protein

Matrix metalloproteinase-16

Gene

MMP16

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

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

GO - Biological processi

  • chondrocyte proliferation Source: Ensembl
  • collagen catabolic process Source: UniProtKB-KW
  • craniofacial suture morphogenesis Source: Ensembl
  • embryonic cranial skeleton morphogenesis Source: Ensembl
  • endochondral ossification Source: Ensembl
  • extracellular matrix disassembly Source: Reactome
  • protein metabolic process Source: ParkinsonsUK-UCL
  • protein processing Source: ParkinsonsUK-UCL
  • proteolysis Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Collagen degradation

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000156103-MONOMER.
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:MMP16
Synonyms:MMPX2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:7162. MMP16.

Subcellular locationi

Isoform Long :
Isoform Short :

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini120 – 564ExtracellularSequence analysisAdd BLAST445
Transmembranei565 – 585HelicalSequence analysisAdd BLAST21
Topological domaini586 – 607CytoplasmicSequence analysisAdd BLAST22

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Extracellular matrix, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi4325.
OpenTargetsiENSG00000156103.
PharmGKBiPA30874.

Chemistry databases

ChEMBLiCHEMBL2200.
DrugBankiDB00786. 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...)Sequence 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.

PTM databases

iPTMnetiP51512.
PhosphoSitePlusiP51512.

Miscellaneous databases

PMAP-CutDBP51512.

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.
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

IntActiP51512. 1 interactor.
MINTiMINT-4722491.
STRINGi9606.ENSP00000286614.

Chemistry databases

BindingDBiP51512.

Structurei

Secondary structure

1607
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi128 – 136Combined sources9
Turni141 – 143Combined sources3
Helixi145 – 160Combined sources16
Beta strandi166 – 169Combined sources4
Beta strandi177 – 179Combined sources3
Beta strandi183 – 191Combined sources9
Beta strandi194 – 196Combined sources3
Beta strandi201 – 204Combined sources4
Beta strandi207 – 209Combined sources3
Turni215 – 218Combined sources4
Beta strandi220 – 223Combined sources4
Beta strandi228 – 231Combined sources4
Beta strandi234 – 239Combined sources6
Helixi240 – 251Combined sources12
Beta strandi265 – 267Combined sources3
Helixi280 – 290Combined sources11

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...

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
Contains 4 hemopexin repeats.Curated

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1565. Eukaryota.
ENOG410XQ5D. LUCA.
GeneTreeiENSGT00760000118870.
HOGENOMiHOG000217928.
HOVERGENiHBG052484.
InParanoidiP51512.
KOiK07996.
OMAiVPYIELE.
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.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR033739. M10A_MMP.
IPR024079. MetalloPept_cat_dom.
IPR028697. MMP16.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR021805. Pept_M10A_metallopeptidase_C.
IPR016293. Pept_M10A_stromelysin-type.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF26. PTHR10201:SF26. 2 hits.
PfamiPF11857. DUF3377. 1 hit.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

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

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

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

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

IntActiP51512. 1 interactor.
MINTiMINT-4722491.
STRINGi9606.ENSP00000286614.

Chemistry databases

BindingDBiP51512.
ChEMBLiCHEMBL2200.
DrugBankiDB00786. Marimastat.
GuidetoPHARMACOLOGYi1640.

Protein family/group databases

MEROPSiM10.016.

PTM databases

iPTMnetiP51512.
PhosphoSitePlusiP51512.

Polymorphism and mutation databases

BioMutaiMMP16.
DMDMi3041669.

Proteomic databases

EPDiP51512.
PaxDbiP51512.
PeptideAtlasiP51512.
PRIDEiP51512.

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.
GeneCardsiMMP16.
HGNCiHGNC:7162. MMP16.
HPAiHPA023693.
MIMi602262. gene.
neXtProtiNX_P51512.
OpenTargetsiENSG00000156103.
PharmGKBiPA30874.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000156103-MONOMER.
ReactomeiR-HSA-1592389. Activation of Matrix Metalloproteinases.

Miscellaneous databases

EvolutionaryTraceiP51512.
GeneWikiiMMP16.
GenomeRNAii4325.
PMAP-CutDBP51512.
PROiP51512.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156103.
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.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
IPR033739. M10A_MMP.
IPR024079. MetalloPept_cat_dom.
IPR028697. MMP16.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR021805. Pept_M10A_metallopeptidase_C.
IPR016293. Pept_M10A_stromelysin-type.
IPR021158. Pept_M10A_Zn_BS.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF26. PTHR10201:SF26. 2 hits.
PfamiPF11857. DUF3377. 1 hit.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFiPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSiPR00138. MATRIXIN.
SMARTiSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMiSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEiPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiMMP16_HUMAN
AccessioniPrimary (citable) accession number: P51512
Secondary accession number(s): B2RAN7, Q14824, Q52H48
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 15, 1998
Last modified: November 30, 2016
This is version 170 of the entry and version 2 of the sequence. [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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.