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P51511 (MMP15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Matrix metalloproteinase-15

Short name=MMP-15
EC=3.4.24.-
Alternative name(s):
Membrane-type matrix metalloproteinase 2
Short name=MT-MMP 2
Short name=MTMMP2
Membrane-type-2 matrix metalloproteinase
Short name=MT2-MMP
Short name=MT2MMP
SMCP-2
Gene names
Name:MMP15
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length669 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. May activate progelatinase A. Ref.6

Cofactor

Binds 1 zinc ion per subunit By similarity.

Calcium By similarity.

Subcellular location

Membrane; Single-pass type I membrane protein; Extracellular side Potential.

Tissue specificity

Appeared to be synthesized preferentially in liver, placenta, testis, colon and intestine. Substantial amounts are also detected in pancreas, kidney, lung, heart and skeletal muscle.

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.

Sequence caution

The sequence BAA13071.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
Zinc
   Molecular functionHydrolase
Metalloprotease
Protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Phosphoprotein
Zymogen
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular protein modification process

Traceable author statement PubMed 7559440. Source: ProtInc

collagen catabolic process

Traceable author statement. Source: Reactome

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

positive regulation of catalytic activity

Traceable author statement PubMed 7559440. Source: GOC

response to estradiol

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentextracellular matrix

Inferred from electronic annotation. Source: InterPro

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

enzyme activator activity

Traceable author statement PubMed 7559440. Source: ProtInc

metalloendopeptidase activity

Traceable author statement Ref.1. Source: ProtInc

protein binding

Inferred from physical interaction PubMed 15248212. Source: IntAct

zinc ion binding

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PROCP040702EBI-1383043,EBI-1383018

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4141Or 45 Potential
Propeptide42 – 13190 By similarity
PRO_0000028808
Chain132 – 669538Matrix metalloproteinase-15
PRO_0000028809

Regions

Topological domain132 – 625494Extracellular Potential
Transmembrane626 – 64621Helical; Potential
Topological domain647 – 66923Cytoplasmic Potential
Repeat367 – 41549Hemopexin 1
Repeat416 – 46146Hemopexin 2
Repeat463 – 51149Hemopexin 3
Repeat512 – 55948Hemopexin 4
Motif109 – 1168Cysteine switch By similarity
Compositional bias331 – 34010Poly-Pro

Sites

Active site2601 By similarity
Metal binding1111Zinc; in inhibited form By similarity
Metal binding2591Zinc; catalytic By similarity
Metal binding2631Zinc; catalytic By similarity
Metal binding2691Zinc; catalytic By similarity

Amino acid modifications

Modified residue5891Phosphoserine Ref.7
Glycosylation1501N-linked (GlcNAc...) Potential
Disulfide bond370 ↔ 559 By similarity

Natural variations

Natural variant2001L → P. Ref.2
Corresponds to variant rs41340745 [ dbSNP | Ensembl ].
VAR_030523
Natural variant3501P → L. Ref.2
Corresponds to variant rs41335851 [ dbSNP | Ensembl ].
VAR_030524
Natural variant5961D → G. Ref.2 Ref.8
Corresponds to variant rs41504346 [ dbSNP | Ensembl ].
VAR_030525
Natural variant6091G → R. Ref.2 Ref.4
Corresponds to variant rs3743563 [ dbSNP | Ensembl ].
VAR_020055
Natural variant6221R → W. Ref.2
Corresponds to variant rs41434246 [ dbSNP | Ensembl ].
VAR_030526

Sequences

Sequence LengthMass (Da)Tools
P51511 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: FE875EC0674B297F

FASTA66975,807
        10         20         30         40         50         60 
MGSDPSAPGR PGWTGSLLGD REEAARPRLL PLLLVLLGCL GLGVAAEDAE VHAENWLRLY 

        70         80         90        100        110        120 
GYLPQPSRHM STMRSAQILA SALAEMQRFY GIPVTGVLDE ETKEWMKRPR CGVPDQFGVR 

       130        140        150        160        170        180 
VKANLRRRRK RYALTGRKWN NHHLTFSIQN YTEKLGWYHS MEAVRRAFRV WEQATPLVFQ 

       190        200        210        220        230        240 
EVPYEDIRLR RQKEADIMVL FASGFHGDSS PFDGTGGFLA HAYFPGPGLG GDTHFDADEP 

       250        260        270        280        290        300 
WTFSSTDLHG NNLFLVAVHE LGHALGLEHS SNPNAIMAPF YQWKDVDNFK LPEDDLRGIQ 

       310        320        330        340        350        360 
QLYGTPDGQP QPTQPLPTVT PRRPGRPDHR PPRPPQPPPP GGKPERPPKP GPPVQPRATE 

       370        380        390        400        410        420 
RPDQYGPNIC DGDFDTVAML RGEMFVFKGR WFWRVRHNRV LDNYPMPIGH FWRGLPGDIS 

       430        440        450        460        470        480 
AAYERQDGRF VFFKGDRYWL FREANLEPGY PQPLTSYGLG IPYDRIDTAI WWEPTGHTFF 

       490        500        510        520        530        540 
FQEDRYWRFN EETQRGDPGY PKPISVWQGI PASPKGAFLS NDAAYTYFYK GTKYWKFDNE 

       550        560        570        580        590        600 
RLRMEPGYPK SILRDFMGCQ EHVEPGPRWP DVARPPFNPH GGAEPGADSA EGDVGDGDGD 

       610        620        630        640        650        660 
FGAGVNKDGG SRVVVQMEEV ARTVNVVMVL VPLLLLLCVL GLTYALVQMQ RKGAPRVLLY 


CKRSLQEWV 

« Hide

References

« Hide 'large scale' references
[1]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Lung.
[2]NIEHS SNPs program
Submitted (SEP-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-200; LEU-350; GLY-596; ARG-609 AND TRP-622.
[3]"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].
Tissue: Brain.
[4]"Assignment of the human genes for membrane-type-1, -2, and -3 matrix metalloproteinases (MMP14, MMP15, and MMP16) to 14q12.2, 16q12.2-q21, and 8q21, respectively, by in situ hybridization."
Sato H., Tanaka M., Takino T., Inoue M., Seiki M.
Genomics 39:412-413(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 94-669, VARIANT ARG-609.
[5]Shofuda K., Yasumitsu H., Nishihashi A., Miki K., Miyazaki K.
Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 163-669.
Tissue: Placenta.
[6]"Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases."
d'Ortho M.P., Will H., Atkinson S., Butler G., Messent A., Gavrilovic J., Smith B., Timpl R., Zardi L., Murphy G.
Eur. J. Biochem. 250:751-757(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-589, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLY-596.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z48482 mRNA. Translation: CAA88373.1.
EF032329 Genomic DNA. Translation: ABJ53423.1.
BC036495 mRNA. Translation: AAH36495.1.
BC055428 mRNA. Translation: AAH55428.1.
D86331 mRNA. Translation: BAA13071.1. Different initiation.
D85510 mRNA. Translation: BAA22225.1.
CCDSCCDS10792.1.
PIRI38029.
RefSeqNP_002419.1. NM_002428.2.
UniGeneHs.80343.

3D structure databases

ProteinModelPortalP51511.
SMRP51511. Positions 83-559.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110467. 1 interaction.
IntActP51511. 2 interactions.
MINTMINT-7897770.
STRING9606.ENSP00000219271.

Chemistry

BindingDBP51511.
ChEMBLCHEMBL2963.

Protein family/group databases

MEROPSM10.015.

PTM databases

PhosphoSiteP51511.

Polymorphism databases

DMDM1705988.

Proteomic databases

MaxQBP51511.
PaxDbP51511.
PRIDEP51511.

Protocols and materials databases

DNASU4324.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219271; ENSP00000219271; ENSG00000102996.
GeneID4324.
KEGGhsa:4324.
UCSCuc002ena.3. human.

Organism-specific databases

CTD4324.
GeneCardsGC16P058060.
HGNCHGNC:7161. MMP15.
HPACAB002611.
HPA040390.
MIM602261. gene.
neXtProtNX_P51511.
PharmGKBPA30873.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG295915.
HOGENOMHOG000217928.
HOVERGENHBG052484.
InParanoidP51511.
KOK07995.
OMAVQMQRKG.
OrthoDBEOG7XPZ57.
PhylomeDBP51511.
TreeFamTF352396.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

BgeeP51511.
CleanExHS_MMP15.
GenevestigatorP51511.

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.
IPR028729. MMP15.
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:SF25. PTHR10201:SF25. 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

GeneWikiMMP15.
GenomeRNAi4324.
NextBio17013.
PROP51511.
SOURCESearch...

Entry information

Entry nameMMP15_HUMAN
AccessionPrimary (citable) accession number: P51511
Secondary accession number(s): A0A2U6, Q14111
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 148 of the entry and version 1 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

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM