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Q9NPA2

- MMP25_HUMAN

UniProt

Q9NPA2 - MMP25_HUMAN

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Protein

Matrix metalloproteinase-25

Gene

MMP25

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

May activate progelatinase A.

Cofactori

Binds 1 zinc ion per subunit.By similarity
Calcium.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi90 – 901Zinc; in inhibited formBy similarity
Metal bindingi233 – 2331Zinc; catalyticPROSITE-ProRule annotation
Active sitei234 – 2341PROSITE-ProRule annotation
Metal bindingi237 – 2371Zinc; catalyticPROSITE-ProRule annotation
Metal bindingi243 – 2431Zinc; catalyticPROSITE-ProRule annotation

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. metalloendopeptidase activity Source: InterPro
  3. zinc ion binding Source: InterPro

GO - Biological processi

  1. hard palate development Source: Ensembl
  2. inflammatory response Source: UniProtKB
  3. proteolysis Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Calcium, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_118682. Activation of Matrix Metalloproteinases.

Protein family/group databases

MEROPSiM10.024.

Names & Taxonomyi

Protein namesi
Recommended name:
Matrix metalloproteinase-25 (EC:3.4.24.-)
Short name:
MMP-25
Alternative name(s):
Leukolysin
Membrane-type matrix metalloproteinase 6
Short name:
MT-MMP 6
Short name:
MTMMP6
Membrane-type-6 matrix metalloproteinase
Short name:
MT6-MMP
Short name:
MT6MMP
Gene namesi
Name:MMP25
Synonyms:MMP20, MMPL1, MT6MMP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:14246. MMP25.

Subcellular locationi

GO - Cellular componenti

  1. anchored component of membrane Source: UniProtKB-KW
  2. integral component of membrane Source: InterPro
  3. membrane Source: UniProtKB
  4. plasma membrane Source: UniProtKB-KW
  5. proteinaceous extracellular matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Extracellular matrix, Membrane, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA30882.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence AnalysisAdd
BLAST
Propeptidei22 – 10786By similarityPRO_0000028852Add
BLAST
Chaini108 – 539432Matrix metalloproteinase-25PRO_0000028853Add
BLAST
Propeptidei540 – 56223Removed in mature formSequence AnalysisPRO_0000028854Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi317 ↔ 508By similarity
Lipidationi539 – 5391GPI-anchor amidated alanineSequence Analysis

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein, Zymogen

Proteomic databases

PaxDbiQ9NPA2.
PRIDEiQ9NPA2.

PTM databases

PhosphoSiteiQ9NPA2.

Expressioni

Tissue specificityi

Expressed predominantly in leukocytes, lung and spleen. Expressed also in colon carcinoma, astrocytoma and glioblastomas.

Gene expression databases

BgeeiQ9NPA2.
CleanExiHS_MMP20.
HS_MMP25.
ExpressionAtlasiQ9NPA2. baseline and differential.
GenevestigatoriQ9NPA2.

Organism-specific databases

HPAiCAB025177.

Interactioni

Protein-protein interaction databases

BioGridi122149. 2 interactions.
STRINGi9606.ENSP00000337816.

Structurei

3D structure databases

ProteinModelPortaliQ9NPA2.
SMRiQ9NPA2. Positions 58-510.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati314 – 36350Hemopexin 1Add
BLAST
Repeati367 – 41246Hemopexin 2Add
BLAST
Repeati413 – 46149Hemopexin 3Add
BLAST
Repeati462 – 50847Hemopexin 4Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi88 – 958Cysteine switchBy similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi103 – 1075Poly-Arg
Compositional biasi549 – 5557Poly-Leu

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

Phylogenomic databases

eggNOGiNOG295915.
GeneTreeiENSGT00760000118870.
HOGENOMiHOG000217928.
HOVERGENiHBG052484.
InParanoidiQ9NPA2.
KOiK08003.
OMAiHYWRFPK.
OrthoDBiEOG7XPZ57.
PhylomeDBiQ9NPA2.
TreeFamiTF315428.

Family and domain databases

Gene3Di2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProiIPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR024079. MetalloPept_cat_dom.
IPR028733. MMP25.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]
PANTHERiPTHR10201:SF21. PTHR10201:SF21. 1 hit.
PfamiPF00045. 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]
SUPFAMiSSF50923. SSF50923. 1 hit.
PROSITEiPS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9NPA2-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MRLRLRLLAL LLLLLAPPAR APKPSAQDVS LGVDWLTRYG YLPPPHPAQA
60 70 80 90 100
QLQSPEKLRD AIKVMQRFAG LPETGRMDPG TVATMRKPRC SLPDVLGVAG
110 120 130 140 150
LVRRRRRYAL SGSVWKKRTL TWRVRSFPQS SQLSQETVRV LMSYALMAWG
160 170 180 190 200
MESGLTFHEV DSPQGQEPDI LIDFARAFHQ DSYPFDGLGG TLAHAFFPGE
210 220 230 240 250
HPISGDTHFD DEETWTFGSK DGEGTDLFAV AVHEFGHALG LGHSSAPNSI
260 270 280 290 300
MRPFYQGPVG DPDKYRLSQD DRDGLQQLYG KAPQTPYDKP TRKPLAPPPQ
310 320 330 340 350
PPASPTHSPS FPIPDRCEGN FDAIANIRGE TFFFKGPWFW RLQPSGQLVS
360 370 380 390 400
PRPARLHRFW EGLPAQVRVV QAAYARHRDG RILLFSGPQF WVFQDRQLEG
410 420 430 440 450
GARPLTELGL PPGEEVDAVF SWPQNGKTYL VRGRQYWRYD EAAARPDPGY
460 470 480 490 500
PRDLSLWEGA PPSPDDVTVS NAGDTYFFKG AHYWRFPKNS IKTEPDAPQP
510 520 530 540 550
MGPNWLDCPA PSSGPRAPRP PKATPVSETC DCQCELNQAA GRWPAPIPLL
560
LLPLLVGGVA SR
Length:562
Mass (Da):62,554
Last modified:October 1, 2000 - v1
Checksum:iA6A50AE05D969C64
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti47 – 471P → R in BAB20584. (PubMed:11034316)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AJ239053 mRNA. Translation: CAB94713.1.
AF145442 mRNA. Translation: AAF66697.2.
AF185270 mRNA. Translation: AAG17007.1.
AB042328 mRNA. Translation: BAB20584.1.
AJ272137 mRNA. Translation: CAC03490.1.
CH471112 Genomic DNA. Translation: EAW85413.1.
CH471112 Genomic DNA. Translation: EAW85415.1.
CCDSiCCDS10492.1.
RefSeqiNP_071913.1. NM_022468.4.
UniGeneiHs.654979.

Genome annotation databases

EnsembliENST00000336577; ENSP00000337816; ENSG00000008516.
GeneIDi64386.
KEGGihsa:64386.
UCSCiuc002cth.3. human.

Polymorphism databases

DMDMi12585274.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AJ239053 mRNA. Translation: CAB94713.1 .
AF145442 mRNA. Translation: AAF66697.2 .
AF185270 mRNA. Translation: AAG17007.1 .
AB042328 mRNA. Translation: BAB20584.1 .
AJ272137 mRNA. Translation: CAC03490.1 .
CH471112 Genomic DNA. Translation: EAW85413.1 .
CH471112 Genomic DNA. Translation: EAW85415.1 .
CCDSi CCDS10492.1.
RefSeqi NP_071913.1. NM_022468.4.
UniGenei Hs.654979.

3D structure databases

ProteinModelPortali Q9NPA2.
SMRi Q9NPA2. Positions 58-510.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 122149. 2 interactions.
STRINGi 9606.ENSP00000337816.

Chemistry

BindingDBi Q9NPA2.
ChEMBLi CHEMBL1795103.
DrugBanki DB00786. Marimastat.

Protein family/group databases

MEROPSi M10.024.

PTM databases

PhosphoSitei Q9NPA2.

Polymorphism databases

DMDMi 12585274.

Proteomic databases

PaxDbi Q9NPA2.
PRIDEi Q9NPA2.

Protocols and materials databases

DNASUi 64386.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000336577 ; ENSP00000337816 ; ENSG00000008516 .
GeneIDi 64386.
KEGGi hsa:64386.
UCSCi uc002cth.3. human.

Organism-specific databases

CTDi 64386.
GeneCardsi GC16P003151.
HGNCi HGNC:14246. MMP25.
HPAi CAB025177.
MIMi 608482. gene.
neXtProti NX_Q9NPA2.
PharmGKBi PA30882.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG295915.
GeneTreei ENSGT00760000118870.
HOGENOMi HOG000217928.
HOVERGENi HBG052484.
InParanoidi Q9NPA2.
KOi K08003.
OMAi HYWRFPK.
OrthoDBi EOG7XPZ57.
PhylomeDBi Q9NPA2.
TreeFami TF315428.

Enzyme and pathway databases

Reactomei REACT_118682. Activation of Matrix Metalloproteinases.

Miscellaneous databases

GeneWikii MMP25.
GenomeRNAii 64386.
NextBioi 66313.
PROi Q9NPA2.
SOURCEi Search...

Gene expression databases

Bgeei Q9NPA2.
CleanExi HS_MMP20.
HS_MMP25.
ExpressionAtlasi Q9NPA2. baseline and differential.
Genevestigatori Q9NPA2.

Family and domain databases

Gene3Di 2.110.10.10. 1 hit.
3.40.390.10. 1 hit.
InterProi IPR000585. Hemopexin-like_dom.
IPR018487. Hemopexin-like_repeat.
IPR024079. MetalloPept_cat_dom.
IPR028733. MMP25.
IPR001818. Pept_M10_metallopeptidase.
IPR021190. Pept_M10A.
IPR016293. Pept_M10A_stromelysin-type.
IPR006026. Peptidase_Metallo.
IPR002477. Peptidoglycan-bd-like.
[Graphical view ]
PANTHERi PTHR10201:SF21. PTHR10201:SF21. 1 hit.
Pfami PF00045. Hemopexin. 4 hits.
PF00413. Peptidase_M10. 1 hit.
PF01471. PG_binding_1. 1 hit.
[Graphical view ]
PIRSFi PIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTSi PR00138. MATRIXIN.
SMARTi SM00120. HX. 4 hits.
SM00235. ZnMc. 1 hit.
[Graphical view ]
SUPFAMi SSF50923. SSF50923. 1 hit.
PROSITEi PS51642. HEMOPEXIN_2. 4 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Human MT6-matrix metalloproteinase: identification, progelatinase A activation, and expression in brain tumors."
    Velasco G., Cal S., Merlos-Suarez A., Ferrando A.A., Alvarez S., Nakano A., Arribas J., Lopez-Otin C.
    Cancer Res. 60:877-882(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Fetal liver.
  2. "Leukolysin/MMP25/MT6-MMP: a novel matrix metalloproteinase specifically expressed in the leukocyte lineage."
    Pei D.Q.
    Cell Res. 9:291-303(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Membrane-type 6 matrix metalloproteinase (MT6-MMP, MMP-25) is the second glycosyl-phosphatidyl inositol (GPI)-anchored MMP."
    Kojima S., Itoh Y., Matsumoto S., Masuho Y., Seiki M.
    FEBS Lett. 480:142-146(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], GPI-ANCHOR.
  4. "Molecular cloning of a novel human membrane-type matrix metalloproteinase (MT-MMP) predominantly expressed in dendritic cells."
    de Saint-Vis B.M., Clair-Moninot V.A., Lambert C.A., Vanbervliet B., Pin J.J., Chalus L., Ait-Yahia S., Caux C., Richelle-Nusgens B.V., Fossiez F., Lebecque S.
    Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Entry informationi

Entry nameiMMP25_HUMAN
AccessioniPrimary (citable) accession number: Q9NPA2
Secondary accession number(s): D3DUA8, Q9H3Q0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 24, 2001
Last sequence update: October 1, 2000
Last modified: October 29, 2014
This is version 146 of the entry and version 1 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

Complete proteome, Reference proteome

Documents

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

External Data

Dasty 3