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Protein

Matrix metalloproteinase-15

Gene

MMP15

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. May activate progelatinase A.1 Publication

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 bindingi111Zinc; in inhibited formBy similarity1
Metal bindingi259Zinc; catalyticPROSITE-ProRule annotation1
Active sitei260PROSITE-ProRule annotation1
Metal bindingi263Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi269Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

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

GO - Biological processi

  • cellular protein modification process Source: ProtInc
  • collagen catabolic process Source: Reactome
  • endodermal cell differentiation Source: UniProtKB
  • extracellular matrix disassembly Source: Reactome
  • proteolysis Source: ParkinsonsUK-UCL
  • response to estradiol Source: Ensembl

Keywordsi

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

Enzyme and pathway databases

BRENDAi3.4.24.B5. 2681.
ReactomeiR-HSA-1442490. Collagen degradation.
R-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-1592389. Activation of Matrix Metalloproteinases.

Protein family/group databases

MEROPSiM10.015.

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix metalloproteinase-15 (EC:3.4.24.-)
Short name:
MMP-15
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 namesi
Name:MMP15
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

EuPathDBiHostDB:ENSG00000102996.4.
HGNCiHGNC:7161. MMP15.

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 domaini132 – 625ExtracellularSequence analysisAdd BLAST494
Transmembranei626 – 646HelicalSequence analysisAdd BLAST21
Topological domaini647 – 669CytoplasmicSequence analysisAdd BLAST23

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi4324.
OpenTargetsiENSG00000102996.
PharmGKBiPA30873.

Chemistry databases

ChEMBLiCHEMBL2963.
DrugBankiDB00786. Marimastat.
GuidetoPHARMACOLOGYi1639.

Polymorphism and mutation databases

BioMutaiMMP15.
DMDMi1705988.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 41Or 45Sequence analysisAdd BLAST41
PropeptideiPRO_000002880842 – 131By similarityAdd BLAST90
ChainiPRO_0000028809132 – 669Matrix metalloproteinase-15Add BLAST538

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi150N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi370 ↔ 559By similarity
Modified residuei589PhosphoserineCombined sources1

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity

Keywords - PTMi

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

Proteomic databases

EPDiP51511.
MaxQBiP51511.
PaxDbiP51511.
PeptideAtlasiP51511.
PRIDEiP51511.

PTM databases

iPTMnetiP51511.
PhosphoSitePlusiP51511.

Expressioni

Tissue specificityi

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.

Gene expression databases

BgeeiENSG00000102996.
CleanExiHS_MMP15.
ExpressionAtlasiP51511. baseline and differential.
GenevisibleiP51511. HS.

Organism-specific databases

HPAiCAB002611.
HPA040390.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
PROCP040702EBI-1383043,EBI-1383018

Protein-protein interaction databases

BioGridi110467. 2 interactors.
IntActiP51511. 3 interactors.
MINTiMINT-7897770.
STRINGi9606.ENSP00000219271.

Chemistry databases

BindingDBiP51511.

Structurei

3D structure databases

ProteinModelPortaliP51511.
SMRiP51511.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati367 – 415Hemopexin 1Add BLAST49
Repeati416 – 461Hemopexin 2Add BLAST46
Repeati463 – 511Hemopexin 3Add BLAST49
Repeati512 – 559Hemopexin 4Add BLAST48

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi109 – 116Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi331 – 340Poly-Pro10

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.
InParanoidiP51511.
KOiK07995.
OMAiMQRKGAP.
OrthoDBiEOG091G03DP.
PhylomeDBiP51511.
TreeFamiTF352396.

Family and domain databases

CDDicd00094. HX. 1 hit.
cd04278. ZnMc_MMP. 1 hit.
Gene3Di2.110.10.10. 2 hits.
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.
IPR028729. MMP15.
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:SF25. PTHR10201:SF25. 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.

P51511-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSDPSAPGR PGWTGSLLGD REEAARPRLL PLLLVLLGCL GLGVAAEDAE
60 70 80 90 100
VHAENWLRLY GYLPQPSRHM STMRSAQILA SALAEMQRFY GIPVTGVLDE
110 120 130 140 150
ETKEWMKRPR CGVPDQFGVR VKANLRRRRK RYALTGRKWN NHHLTFSIQN
160 170 180 190 200
YTEKLGWYHS MEAVRRAFRV WEQATPLVFQ EVPYEDIRLR RQKEADIMVL
210 220 230 240 250
FASGFHGDSS PFDGTGGFLA HAYFPGPGLG GDTHFDADEP WTFSSTDLHG
260 270 280 290 300
NNLFLVAVHE LGHALGLEHS SNPNAIMAPF YQWKDVDNFK LPEDDLRGIQ
310 320 330 340 350
QLYGTPDGQP QPTQPLPTVT PRRPGRPDHR PPRPPQPPPP GGKPERPPKP
360 370 380 390 400
GPPVQPRATE RPDQYGPNIC DGDFDTVAML RGEMFVFKGR WFWRVRHNRV
410 420 430 440 450
LDNYPMPIGH FWRGLPGDIS AAYERQDGRF VFFKGDRYWL FREANLEPGY
460 470 480 490 500
PQPLTSYGLG IPYDRIDTAI WWEPTGHTFF FQEDRYWRFN EETQRGDPGY
510 520 530 540 550
PKPISVWQGI PASPKGAFLS NDAAYTYFYK GTKYWKFDNE RLRMEPGYPK
560 570 580 590 600
SILRDFMGCQ EHVEPGPRWP DVARPPFNPH GGAEPGADSA EGDVGDGDGD
610 620 630 640 650
FGAGVNKDGG SRVVVQMEEV ARTVNVVMVL VPLLLLLCVL GLTYALVQMQ
660
RKGAPRVLLY CKRSLQEWV
Length:669
Mass (Da):75,807
Last modified:October 1, 1996 - v1
Checksum:iFE875EC0674B297F
GO

Sequence cautioni

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

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030523200L → P1 PublicationCorresponds to variant dbSNP:rs41340745Ensembl.1
Natural variantiVAR_030524350P → L1 PublicationCorresponds to variant dbSNP:rs41335851Ensembl.1
Natural variantiVAR_030525596D → G2 PublicationsCorresponds to variant dbSNP:rs41504346Ensembl.1
Natural variantiVAR_020055609G → R2 PublicationsCorresponds to variant dbSNP:rs3743563Ensembl.1
Natural variantiVAR_030526622R → W1 PublicationCorresponds to variant dbSNP:rs41434246Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS10792.1.
PIRiI38029.
RefSeqiNP_002419.1. NM_002428.3.
UniGeneiHs.80343.

Genome annotation databases

EnsembliENST00000219271; ENSP00000219271; ENSG00000102996.
GeneIDi4324.
KEGGihsa:4324.
UCSCiuc002ena.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMMP15_HUMAN
AccessioniPrimary (citable) accession number: P51511
Secondary accession number(s): A0A2U6, Q14111
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 22, 2017
This is version 179 of the entry and version 1 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families