Q9NPA2 (MMP25_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Matrix metalloproteinase-25
Short name=MMP-25
EC=3.4.24.-

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 names

Name:	MMP25
Synonyms:	MMP20, MMPL1, MT6MMP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	562 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May activate progelatinase A.
Cofactor	Binds 1 zinc ion per subunit By similarity. Calcium By similarity.
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor; Extracellular side. Secreted › extracellular space › extracellular matrix Ref.3.
Tissue specificity	Expressed predominantly in leukocytes, lung and spleen. Expressed also in colon carcinoma, astrocytoma and glioblastomas.
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-like domains.

Ontologies

Keywords
Cellular component	Cell membrane Extracellular matrix Membrane Secreted
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond GPI-anchor Glycoprotein Lipoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	hard palate development Inferred from electronic annotation. Source: Compara inflammatory response Non-traceable author statement Ref.2. Source: UniProtKB proteolysis Non-traceable author statement Ref.1. Source: UniProtKB
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cell surface Inferred from direct assay PubMed 12493773. Source: UniProtKB membrane Non-traceable author statement Ref.3. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell proteinaceous extracellular matrix Non-traceable author statement Ref.2. Source: UniProtKB
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 21	21	Potential
	Propeptide	22 – 107	86	By similarity		PRO_0000028852
	Chain	108 – 539	432	Matrix metalloproteinase-25		PRO_0000028853
	Propeptide	540 – 562	23	Removed in mature form Potential		PRO_0000028854
Regions
	Domain	321 – 365	45	Hemopexin-like 1
	Domain	370 – 412	43	Hemopexin-like 2
	Domain	416 – 462	47	Hemopexin-like 3
	Domain	464 – 508	45	Hemopexin-like 4
	Motif	88 – 95	8	Cysteine switch By similarity
	Compositional bias	103 – 107	5	Poly-Arg
	Compositional bias	549 – 555	7	Poly-Leu
Sites
	Active site	234	1	By similarity
	Metal binding	90	1	Zinc; in inhibited form By similarity
	Metal binding	233	1	Zinc; catalytic By similarity
	Metal binding	237	1	Zinc; catalytic By similarity
	Metal binding	243	1	Zinc; catalytic By similarity
Amino acid modifications
	Lipidation	539	1	GPI-anchor amidated alanine Potential
	Disulfide bond	317 ↔ 508		By similarity
Experimental info
	Sequence conflict	47	1	P → R in BAB20584. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9NPA2 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: A6A50AE05D969C64	FASTA	562	62,554
	10 20 30 40 50 60 MRLRLRLLAL LLLLLAPPAR APKPSAQDVS LGVDWLTRYG YLPPPHPAQA QLQSPEKLRD 70 80 90 100 110 120 AIKVMQRFAG LPETGRMDPG TVATMRKPRC SLPDVLGVAG LVRRRRRYAL SGSVWKKRTL 130 140 150 160 170 180 TWRVRSFPQS SQLSQETVRV LMSYALMAWG MESGLTFHEV DSPQGQEPDI LIDFARAFHQ 190 200 210 220 230 240 DSYPFDGLGG TLAHAFFPGE HPISGDTHFD DEETWTFGSK DGEGTDLFAV AVHEFGHALG 250 260 270 280 290 300 LGHSSAPNSI MRPFYQGPVG DPDKYRLSQD DRDGLQQLYG KAPQTPYDKP TRKPLAPPPQ 310 320 330 340 350 360 PPASPTHSPS FPIPDRCEGN FDAIANIRGE TFFFKGPWFW RLQPSGQLVS PRPARLHRFW 370 380 390 400 410 420 EGLPAQVRVV QAAYARHRDG RILLFSGPQF WVFQDRQLEG GARPLTELGL PPGEEVDAVF 430 440 450 460 470 480 SWPQNGKTYL VRGRQYWRYD EAAARPDPGY PRDLSLWEGA PPSPDDVTVS NAGDTYFFKG 490 500 510 520 530 540 AHYWRFPKNS IKTEPDAPQP MGPNWLDCPA PSSGPRAPRP PKATPVSETC DCQCELNQAA 550 560 GRWPAPIPLL LLPLLVGGVA SR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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]	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. , 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00014758.
RefSeq	NP_071913.1. NM_022468.4.
UniGene	Hs.654979.
3D structure databases
ProteinModelPortal	Q9NPA2.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000337816.
Protein family/group databases
MEROPS	M10.024.
PTM databases
PhosphoSite	Q9NPA2.
Polymorphism databases
DMDM	12585274.
Proteomic databases
PaxDb	Q9NPA2.
PRIDE	Q9NPA2.
Protocols and materials databases
DNASU	64386.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000336577; ENSP00000337816; ENSG00000008516.
GeneID	64386.
KEGG	hsa:64386.
UCSC	uc002cth.3. human.
Organism-specific databases
CTD	64386.
GeneCards	GC16P003109.
HGNC	HGNC:14246. MMP25.
HPA	CAB025177.
MIM	608482. gene.
neXtProt	NX_Q9NPA2.
PharmGKB	PA30882.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG295915.
HOGENOM	HOG000217928.
HOVERGEN	HBG052484.
InParanoid	Q9NPA2.
KO	K08003.
OMA	HYWRFPK.
OrthoDB	EOG40VVPC.
PhylomeDB	Q9NPA2.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
Bgee	Q9NPA2.
CleanEx	HS_MMP20. HS_MMP25.
Genevestigator	Q9NPA2.
GermOnline	ENSG00000008516. Homo sapiens.
Family and domain databases
Gene3D	2.110.10.10. 1 hit. 3.40.390.10. 1 hit.
InterPro	IPR000585. Hemopexin-like_dom. IPR018487. Hemopexin-like_repeat. IPR024079. MetalloPept_cat_dom. IPR001818. Pept_M10_metallopeptidase. IPR021190. Pept_M10A. IPR016293. Pept_M10A_Metazoans. IPR006026. Peptidase_Metallo. IPR002477. Peptidoglycan-bd-like. [Graphical view]
Pfam	PF00045. Hemopexin. 4 hits. PF00413. Peptidase_M10. 1 hit. PF01471. PG_binding_1. 1 hit. [Graphical view]
PIRSF	PIRSF001191. Peptidase_M10A_matrix. 1 hit.
PRINTS	PR00138. MATRIXIN.
SMART	SM00120. HX. 4 hits. SM00235. ZnMc. 1 hit. [Graphical view]
SUPFAM	SSF50923. Hemopexin. 1 hit. SSF47090. PGBD_like. 1 hit.
PROSITE	PS00546. CYSTEINE_SWITCH. False negative. PS00024. HEMOPEXIN. False negative. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9NPA2.
ChEMBL	CHEMBL1795103.
GenomeRNAi	64386.
NextBio	66313.
SOURCE	Search...

Entry information

Entry name

MMP25_HUMAN

Accession

Primary (citable) accession number: Q9NPA2
Secondary accession number(s): D3DUA8, Q9H3Q0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 131 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.