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P51512 (MMP16_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Matrix metalloproteinase-16

Short name=MMP-16
EC=3.4.24.-
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 names
Name:MMP16
Synonyms:MMPX2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length607 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 shortcleaves 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. Ref.9

Cofactor

Binds 1 zinc ion per subunit By similarity.

Calcium By similarity.

Enzyme regulation

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.

Subunit structure

Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan. Ref.9

Subcellular location

Isoform Long: Cell membrane; Single-pass type I membrane protein; Extracellular side Potential. Note: Localized at the cell surface of melanoma cells. Ref.9

Isoform Short: Secretedextracellular spaceextracellular matrix. Cell surface. Note: Localized at the cell surface of melanoma cells. Ref.9

Tissue specificity

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

Developmental stage

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

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 repeats.

Ontologies

Keywords
   Biological processCollagen degradation
   Cellular componentCell membrane
Extracellular matrix
Membrane
Secreted
   Coding sequence diversityAlternative splicing
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcollagen catabolic process

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

positive regulation of catalytic activity

Traceable author statement Ref.1. Source: GOC

   Cellular_componentGolgi lumen

Traceable author statement. Source: Reactome

cell surface

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

proteinaceous extracellular matrix

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

enzyme activator activity

Traceable author statement Ref.1. Source: ProtInc

metalloendopeptidase activity

Traceable author statement Ref.1. Source: ProtInc

zinc ion binding

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: P51512-1)

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.
Isoform Short (identifier: P51512-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3131 Potential
Propeptide32 – 11988 By similarity
PRO_0000028812
Chain120 – 607488Matrix metalloproteinase-16
PRO_0000028813

Regions

Topological domain120 – 564445Extracellular Potential
Transmembrane565 – 58521Helical; Potential
Topological domain586 – 60722Cytoplasmic Potential
Repeat340 – 38849Hemopexin 1
Repeat389 – 43446Hemopexin 2
Repeat436 – 48449Hemopexin 3
Repeat485 – 53248Hemopexin 4
Motif99 – 1068Cysteine switch By similarity

Sites

Active site2471
Metal binding1011Zinc 1; in inhibited form By similarity
Metal binding1831Calcium 1; via carbonyl oxygen
Metal binding1931Zinc 1
Metal binding1951Zinc 1
Metal binding2001Calcium 2
Metal binding2011Calcium 2; via carbonyl oxygen
Metal binding2031Calcium 2; via carbonyl oxygen
Metal binding2051Calcium 2; via carbonyl oxygen
Metal binding2151Calcium 1; via carbonyl oxygen
Metal binding2171Calcium 1; via carbonyl oxygen
Metal binding2191Calcium 1
Metal binding2231Calcium 2
Metal binding2261Calcium 2
Metal binding2461Zinc 2; catalytic
Metal binding2501Zinc 2; catalytic
Metal binding2561Zinc 2; catalytic

Amino acid modifications

Glycosylation831N-linked (GlcNAc...) Potential
Disulfide bond343 ↔ 532 By similarity

Natural variations

Alternative sequence408 – 45750GNKYW…FFKGD → VKGDTLSVIQDGWLYKYHWK WILEQRQSVPVLSRQTEKHK TYEELSSITY in isoform Short.
VSP_005453
Alternative sequence458 – 607150Missing in isoform Short.
VSP_005454

Experimental info

Sequence conflict5211Y → H in BAA23742. Ref.1

Secondary structure

................................ 607
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified July 15, 1998. Version 2.
Checksum: 30D6247D9CB21663

FASTA60769,521
        10         20         30         40         50         60 
MILLTFSTGR RLDFVHHSGV FFLQTLLWIL CATVCGTEQY FNVEVWLQKY GYLPPTDPRM 

        70         80         90        100        110        120 
SVLRSAETMQ SALAAMQQFY GINMTGKVDR NTIDWMKKPR CGVPDQTRGS SKFHIRRKRY 

       130        140        150        160        170        180 
ALTGQKWQHK HITYSIKNVT PKVGDPETRK AIRRAFDVWQ NVTPLTFEEV PYSELENGKR 

       190        200        210        220        230        240 
DVDITIIFAS GFHGDSSPFD GEGGFLAHAY FPGPGIGGDT HFDSDEPWTL GNPNHDGNDL 

       250        260        270        280        290        300 
FLVAVHELGH ALGLEHSNDP TAIMAPFYQY METDNFKLPN DDLQGIQKIY GPPDKIPPPT 

       310        320        330        340        350        360 
RPLPTVPPHR SIPPADPRKN DRPKPPRPPT GRPSYPGAKP NICDGNFNTL AILRREMFVF 

       370        380        390        400        410        420 
KDQWFWRVRN NRVMDGYPMQ ITYFWRGLPP SIDAVYENSD GNFVFFKGNK YWVFKDTTLQ 

       430        440        450        460        470        480 
PGYPHDLITL GSGIPPHGID SAIWWEDVGK TYFFKGDRYW RYSEEMKTMD PGYPKPITVW 

       490        500        510        520        530        540 
KGIPESPQGA FVHKENGFTY FYKGKEYWKF NNQILKVEPG YPRSILKDFM GCDGPTDRVK 

       550        560        570        580        590        600 
EGHSPPDDVD IVIKLDNTAS TVKAIAIVIP CILALCLLVL VYTVFQFKRK GTPRHILYCK 


RSMQEWV 

« Hide

Isoform Short (SM3) [UniParc].

Checksum: 94184CDA9F76C5EB
Show »

FASTA45752,515

References

« Hide 'large scale' references
[1]"Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a human placenta cDNA library. MT-MMPs form a unique membrane-type subclass in the MMP family."
Takino T., Sato H., Shinagawa A., Seiki M.
J. Biol. Chem. 270:23013-23020(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
Tissue: Placenta.
[2]Seiki M.
Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Identification of soluble type of membrane-type matrix metalloproteinase-3 formed by alternatively spliced mRNA."
Matsumoto S., Katoh M., Saito S., Watanabe T., Masuho Y.
Biochim. Biophys. Acta 1354:159-170(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
Tissue: Ovary.
[4]"Expression of three membrane-type matrix metalloproteinases (MT-MMPs) in rat vascular smooth muscle cells and characterization of MT3-MMPs with and without transmembrane domain."
Shofuda K., Yasumitsu H., Nishihashi A., Miki K., Miyazaki K.
J. Biol. Chem. 272:9749-9754(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
Tissue: Fetal brain.
[5]NIEHS SNPs program
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
Tissue: Brain.
[9]"Melanoma chondroitin sulfate proteoglycan regulates matrix metalloproteinase-dependent human melanoma invasion into type I collagen."
Iida J., Pei D., Kang T., Simpson M.A., Herlyn M., Furcht L.T., McCarthy J.B.
J. Biol. Chem. 276:18786-18794(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CSPG4, SUBCELLULAR LOCATION, FUNCTION.
[10]"Crystal structure of the catalytic domain of MMP-16/MT3-MMP: characterization of MT-MMP specific features."
Lang R., Braun M., Sounni N.E., Noel A., Frankenne F., Foidart J.M., Bode W., Maskos K.
J. Mol. Biol. 336:213-225(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 124-292 IN COMPLEX WITH INHIBITOR, ZINC-BINDING SITES, CALCIUM-BINDING SITES.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS6246.1. [P51512-1]
RefSeqNP_005932.2. NM_005941.4. [P51512-1]
UniGeneHs.492187.
Hs.546267.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1RM8X-ray1.80A124-292[»]
ProteinModelPortalP51512.
SMRP51512. Positions 69-561.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP51512. 1 interaction.
MINTMINT-4722491.
STRING9606.ENSP00000286614.

Chemistry

BindingDBP51512.
ChEMBLCHEMBL2200.

Protein family/group databases

MEROPSM10.016.

PTM databases

PhosphoSiteP51512.

Polymorphism databases

DMDM3041669.

Proteomic databases

PaxDbP51512.
PRIDEP51512.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000286614; ENSP00000286614; ENSG00000156103. [P51512-1]
GeneID4325.
KEGGhsa:4325.
UCSCuc003yeb.4. human. [P51512-1]

Organism-specific databases

CTD4325.
GeneCardsGC08M089044.
HGNCHGNC:7162. MMP16.
HPAHPA023693.
MIM602262. gene.
neXtProtNX_P51512.
PharmGKBPA30874.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295915.
HOGENOMHOG000217928.
HOVERGENHBG052484.
InParanoidP51512.
KOK07996.
OMAVPPHRSV.
OrthoDBEOG7XPZ57.
PhylomeDBP51512.
TreeFamTF352396.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressP51512.
BgeeP51512.
CleanExHS_MMP16.
GenevestigatorP51512.

Family and domain databases

Gene3D2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR018486. Hemopexin_CS.
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]
PANTHERPTHR10201:SF26. PTHR10201:SF26. 1 hit.
PfamPF11857. DUF3377. 1 hit.
PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view]
PIRSFPIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSPR00138. MATRIXIN.
SMARTSM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view]
SUPFAMSSF47090. SSF47090. 1 hit.
SSF50923. SSF50923. 1 hit.
PROSITEPS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP51512.
GeneWikiMMP16.
GenomeRNAi4325.
NextBio17017.
PMAP-CutDBP51512.
PROP51512.
SOURCESearch...

Entry information

Entry nameMMP16_HUMAN
AccessionPrimary (citable) accession number: P51512
Secondary accession number(s): B2RAN7, Q14824, Q52H48
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 15, 1998
Last modified: July 9, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM