P51511 (MMP15_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	669 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	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-like domains.
Sequence caution	The sequence BAA13071.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein Zymogen
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular protein modification process Traceable author statement PubMed 7559440. Source: ProtInc proteolysis Inferred from electronic annotation. Source: UniProtKB-KW response to estradiol stimulus Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular matrix Inferred from electronic annotation. Source: InterPro integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	calcium 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 zinc ion binding Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PROC	P04070	2	EBI-1383043,EBI-1383018

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 41	41	Or 45 Potential
	Propeptide	42 – 131	90	By similarity		PRO_0000028808
	Chain	132 – 669	538	Matrix metalloproteinase-15		PRO_0000028809
Regions
	Topological domain	132 – 625	494	Extracellular Potential
	Transmembrane	626 – 646	21	Helical; Potential
	Topological domain	647 – 669	23	Cytoplasmic Potential
	Domain	374 – 417	44	Hemopexin-like 1
	Domain	419 – 463	45	Hemopexin-like 2
	Domain	466 – 512	47	Hemopexin-like 3
	Domain	514 – 559	46	Hemopexin-like 4
	Motif	109 – 116	8	Cysteine switch By similarity
	Compositional bias	331 – 340	10	Poly-Pro
Sites
	Active site	260	1	By similarity
	Metal binding	111	1	Zinc; in inhibited form By similarity
	Metal binding	259	1	Zinc; catalytic By similarity
	Metal binding	263	1	Zinc; catalytic By similarity
	Metal binding	269	1	Zinc; catalytic By similarity
Amino acid modifications
	Modified residue	589	1	Phosphoserine Ref.7
	Glycosylation	150	1	N-linked (GlcNAc...) Potential
	Disulfide bond	370 ↔ 559		By similarity
Natural variations
	Natural variant	200	1	L → P. Ref.2 Corresponds to variant rs41340745 [ dbSNP | Ensembl ].		VAR_030523
	Natural variant	350	1	P → L. Ref.2 Corresponds to variant rs41335851 [ dbSNP | Ensembl ].		VAR_030524
	Natural variant	596	1	D → G. Ref.2 Ref.8 Corresponds to variant rs41504346 [ dbSNP | Ensembl ].		VAR_030525
	Natural variant	609	1	G → R. Ref.2 Ref.4 Corresponds to variant rs3743563 [ dbSNP | Ensembl ].		VAR_020055
	Natural variant	622	1	R → W. Ref.2 Corresponds to variant rs41434246 [ dbSNP | Ensembl ].		VAR_030526

Sequences

	Sequence		Length	Mass (Da)
	P51511 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: FE875EC0674B297F	FASTA	669	75,807
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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. , 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.

Web resources

NIEHS-SNPs

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.
IPI	IPI00019242.
PIR	I38029.
RefSeq	NP_002419.1. NM_002428.2.
UniGene	Hs.80343.
3D structure databases
ProteinModelPortal	P51511.
ModBase	Search...
Protein-protein interaction databases
IntAct	P51511. 1 interaction.
STRING	9606.ENSP00000219271.
Protein family/group databases
MEROPS	M10.015.
PTM databases
PhosphoSite	P51511.
Polymorphism databases
DMDM	1705988.
Proteomic databases
PaxDb	P51511.
PRIDE	P51511.
Protocols and materials databases
DNASU	4324.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000219271; ENSP00000219271; ENSG00000102996.
GeneID	4324.
KEGG	hsa:4324.
UCSC	uc002ena.3. human.
Organism-specific databases
CTD	4324.
GeneCards	GC16P058060.
HGNC	HGNC:7161. MMP15.
HPA	CAB002611.
MIM	602261. gene.
neXtProt	NX_P51511.
PharmGKB	PA30873.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG295915.
HOGENOM	HOG000217928.
HOVERGEN	HBG052484.
InParanoid	P51511.
KO	K07995.
OMA	VQMQRKG.
OrthoDB	EOG4W6NVP.
PhylomeDB	P51511.
Enzyme and pathway databases
Reactome	REACT_118779. Extracellular matrix organization.
Gene expression databases
Bgee	P51511.
CleanEx	HS_MMP15.
Genevestigator	P51511.
GermOnline	ENSG00000102996. 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. IPR018486. Hemopexin_CS. IPR024079. MetalloPept_cat_dom. IPR001818. Pept_M10_metallopeptidase. IPR021190. Pept_M10A. IPR021805. Pept_M10A_metallopeptidase_C. IPR016293. Pept_M10A_Metazoans. IPR021158. Pept_M10A_Zn_BS. IPR006026. Peptidase_Metallo. IPR002477. Peptidoglycan-bd-like. [Graphical view]
Pfam	PF11857. DUF3377. 1 hit. 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. 1 hit. PS00024. HEMOPEXIN. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P51511.
ChEMBL	CHEMBL2963.
GenomeRNAi	4324.
NextBio	17013.
SOURCE	Search...

Entry information

Entry name

MMP15_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 135 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.