Reviewed, UniProtKB/Swiss-Prot P24347 (MMP11_HUMAN)

Names and origin

Protein names

Recommended name:
    Stromelysin-3
      Short name=SL-3
      Short name=ST3
    EC=3.4.24.-
Alternative name(s):
    Matrix metalloproteinase-11
      Short name=MMP-11

Gene names

Name:	MMP11
Synonyms:	STMY3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	488 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 play an important role in the progression of epithelial malignancies.
Cofactor	Binds 1 calcium ion per subunit By similarity. Binds 2 zinc ions per subunit By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix Probable.
Tissue specificity	Specifically expressed in stromal cells of breast carcinomas.
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
Biological process	Collagen degradation
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Calcium Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Zymogen
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Ref.5 Traceable author statement. Source: ProtInc proteolysis Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Inferred from electronic annotation. Source: UniProtKB-SubCell proteinaceous extracellular matrix Ref.1 Traceable author statement. Source: ProtInc
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Ref.5 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 31	31	Potential
	Propeptide	32 – 97	66	Activation peptide By similarity		PRO_0000028770
	Chain	98 – 488	391	Stromelysin-3		PRO_0000028771
Regions
	Domain	298 – 341	44	Hemopexin-like 1
	Domain	343 – 384	42	Hemopexin-like 2
	Domain	387 – 434	48	Hemopexin-like 3
	Domain	436 – 480	45	Hemopexin-like 4
	Motif	78 – 85	8	Cysteine switch By similarity
Sites
	Active site	216	1	By similarity
	Metal binding	80	1	Zinc 2; in inhibited form By similarity
	Metal binding	166	1	Zinc 1 By similarity
	Metal binding	171	1	Calcium By similarity
	Metal binding	172	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	174	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	176	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	179	1	Zinc 1 By similarity
	Metal binding	192	1	Zinc 1 By similarity
	Metal binding	215	1	Zinc 2; catalytic By similarity
	Metal binding	219	1	Zinc 2; catalytic By similarity
	Metal binding	225	1	Zinc 2; catalytic By similarity
Amino acid modifications
	Disulfide bond	294 ↔ 480		By similarity
Natural variations
	Natural variant	38	1	V → A: dbSNP rs738792. Ref.2 Ref.3		VAR_022181
	Natural variant	44	1	E → K: dbSNP rs28363646. Ref.2		VAR_022182
	Natural variant	61	1	P → L: dbSNP rs28363647. Ref.2		VAR_022183
	Natural variant	86	1	S → P: dbSNP rs28363648. Ref.2		VAR_022184
	Natural variant	166	1	D → N in a colorectal cancer sample; somatic mutation. Ref.6		VAR_036140
	Natural variant	182	1	F → S: dbSNP rs17854940. Ref.3		VAR_029659

Sequences

	Sequence		Length	Mass (Da)
	P24347-1 [UniParc]. Last modified April 26, 2005. Version 2. Checksum: 8CEB0F842F34F36E	FASTA	488	54,618
	10 20 30 40 50 60 MAPAAWLRSA AARALLPPML LLLLQPPPLL ARALPPDVHH LHAERRGPQP WHAALPSSPA 70 80 90 100 110 120 PAPATQEAPR PASSLRPPRC GVPDPSDGLS ARNRQKRFVL SGGRWEKTDL TYRILRFPWQ 130 140 150 160 170 180 LVQEQVRQTM AEALKVWSDV TPLTFTEVHE GRADIMIDFA RYWHGDDLPF DGPGGILAHA 190 200 210 220 230 240 FFPKTHREGD VHFDYDETWT IGDDQGTDLL QVAAHEFGHV LGLQHTTAAK ALMSAFYTFR 250 260 270 280 290 300 YPLSLSPDDC RGVQHLYGQP WPTVTSRTPA LGPQAGIDTN EIAPLEPDAP PDACEASFDA 310 320 330 340 350 360 VSTIRGELFF FKAGFVWRLR GGQLQPGYPA LASRHWQGLP SPVDAAFEDA QGHIWFFQGA 370 380 390 400 410 420 QYWVYDGEKP VLGPAPLTEL GLVRFPVHAA LVWGPEKNKI YFFRGRDYWR FHPSTRRVDS 430 440 450 460 470 480 PVPRRATDWR GVPSEIDAAF QDADGYAYFL RGRLYWKFDP VKVKALEGFP RLVGPDFFGC AEPANTFL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel metalloproteinase gene specifically expressed in stromal cells of breast carcinomas." Basset P., Bellocq J.-P., Wolf C., Stoll I., Hutin P., Limacher J.-M., Podhajcer O.L., Chenard M.P., Rio M.C., Chambon P. Nature 348:699-704(1990) [PubMed: 1701851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	NIEHS SNPs program Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ALA-38; LYS-44; LEU-61 AND PRO-86.
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ALA-38 AND SER-182. Tissue: Placenta.
[4]	"Structure and promoter characterization of the human stromelysin-3 gene." Anglard P., Melot T., Guerin E., Thomas G., Basset P. J. Biol. Chem. 270:20337-20344(1995) [PubMed: 7657606] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-36.
[5]	"Furin-dependent intracellular activation of the human stromelysin-3 zymogen." Pei D., Weiss S.J. Nature 375:244-247(1995) [PubMed: 7746327] [Abstract] Cited for: PROTEIN SEQUENCE OF 81-101.
[6]	"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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] ASN-166.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	X57766 mRNA. Translation: CAA40918.1. AY899208 Genomic DNA. Translation: AAW65373.1. BC057788 mRNA. Translation: AAH57788.1. X84664 Genomic DNA. Translation: CAA59150.1.
IPI	IPI00306778.
PIR	S13423.
UniGene	Hs.143751
3D structure databases
HSSP	HSSP built from PDB template 1HV5 based on UniProtKB Q02853.
SMR	P24347. Positions 98-260.
ModBase	Search...
Protein family/group databases
MEROPS	M10.007.
Proteomic databases
PRIDE	P24347.
Genome annotation databases
Ensembl	ENSG00000099953. Homo sapiens. [Contig view]
Organism-specific databases
GeneCards	GC22P022439.
H-InvDB	HIX0027843.
HGNC	HGNC:7157. MMP11.
HPA	CAB002593.
MIM	185261. gene.
PharmGKB	PA30869.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P24347.
HOVERGEN	P24347.
Gene expression databases
ArrayExpress	P24347.
Bgee	P24347.
CleanEx	HS_MMP11.
GermOnline	ENSG00000099953. Homo sapiens.
Family and domain databases
InterPro	IPR000585. Hemopexin/matrixin. IPR018486. Hemopexin/matrixin_CS. IPR018487. Hemopexin/matrixin_repeat. IPR001818. Pept_M10A_M12B. IPR016293. Pept_M10A_matrix. IPR006025. Pept_M_Zn_BS. IPR006026. Peptidase_M. [Graphical view]
Gene3D	G3DSA:2.110.10.10. Hemopexin. 1 hit.
Pfam	PF00045. Hemopexin. 4 hits. PF00413. Peptidase_M10. 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]
PROSITE	PS00546. CYSTEINE_SWITCH. 1 hit. PS00024. HEMOPEXIN. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	16997.
SOURCE	Search...

Entry information

Entry name

MMP11_HUMAN

Accession

Primary (citable) accession number: P24347
Secondary accession number(s): Q5FX24, Q6PEZ6, Q9UC26

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 1, 1992
Last sequence update:	April 26, 2005
Last modified:	June 16, 2009
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)