Reviewed, UniProtKB/Swiss-Prot P08254 (MMP3_HUMAN)

Names and origin

Protein names

Recommended name:
    Stromelysin-1
      Short name=SL-1
    EC=3.4.24.17
Alternative name(s):
    Matrix metalloproteinase-3
      Short name=MMP-3
    Transin-1

Gene names

Name:	MMP3
Synonyms:	STMY1

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	477 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	Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.
Catalytic activity	Preferential cleavage where P1', P2' and P3' are hydrophobic residues.
Cofactor	Binds 4 calcium ions per subunit. Binds 2 zinc ions per subunit.
Subcellular location	Secreted › extracellular space › extracellular matrix Probable.
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. Ref.9
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	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	collagen catabolic process Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Ref.1 Traceable author statement. Source: ProtInc intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Ref.1 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 – 17

17

Probable

Propeptide

18 – 99

82

Activation peptide

PRO_0000028728

Chain

100 – 477

378

Stromelysin-1

PRO_0000028729

Regions

Domain

296 – 338

43

Hemopexin-like 1

Domain

340 – 383

44

Hemopexin-like 2

Domain

388 – 435

48

Hemopexin-like 3

Domain

437 – 477

41

Hemopexin-like 4

Motif

90 – 97

8

Cysteine switch By similarity

Sites

Active site

219

1

Metal binding

92

1

Zinc 2; in inhibited form

Metal binding

124

1

Calcium 1

Metal binding

158

1

Calcium 2

Metal binding

168

1

Zinc 1

Metal binding

170

1

Zinc 1

Metal binding

175

1

Calcium 3

Metal binding

176

1

Calcium 3; via carbonyl oxygen

Metal binding

178

1

Calcium 3; via carbonyl oxygen

Metal binding

180

1

Calcium 3; via carbonyl oxygen

Metal binding

183

1

Zinc 1

Metal binding

190

1

Calcium 2; via carbonyl oxygen

Metal binding

192

1

Calcium 2; via carbonyl oxygen

Metal binding

194

1

Calcium 2

Metal binding

196

1

Zinc 1

Metal binding

198

1

Calcium 3

Metal binding

199

1

Calcium 1

Metal binding

201

1

Calcium 1

Metal binding

201

1

Calcium 3

Metal binding

218

1

Zinc 2; catalytic Ref.12

Metal binding

222

1

Zinc 2; catalytic Ref.12

Metal binding

228

1

Zinc 2; catalytic Ref.12

Metal binding

297

1

Calcium 4; via carbonyl oxygen By similarity

Metal binding

389

1

Calcium 4; via carbonyl oxygen By similarity

Metal binding

438

1

Calcium 4; via carbonyl oxygen By similarity

Amino acid modifications

Glycosylation

120

1

N-linked (GlcNAc...) Potential

Disulfide bond

290 ↔ 477

By similarity

Natural variations

Natural variant

45

1

K → E: dbSNP rs679620. Ref.5 Ref.6 Ref.7

VAR_013090

Experimental info

Sequence conflict

420

1

P → L Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

477

Helix Strand Turn

Details...

Helix

34 – 41

8

Helix

58 – 70

13

Helix

81 – 86

6

Beta strand

96 – 98

3

Beta strand

110 – 118

9

Helix

127 – 142

16

Beta strand

148 – 151

4

Beta strand

153 – 155

3

Beta strand

158 – 164

7

Beta strand

169 – 171

3

Beta strand

176 – 179

4

Beta strand

182 – 184

3

Beta strand

187 – 189

3

Turn

190 – 193

4

Beta strand

195 – 198

4

Beta strand

203 – 206

4

Beta strand

209 – 211

3

Helix

212 – 224

13

Beta strand

246 – 248

3

Helix

253 – 263

11

Sequences

	Sequence		Length	Mass (Da)
	P08254-1 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: 96194833B907668D	FASTA	477	53,977
	10 20 30 40 50 60 MKSLPILLLL CVAVCSAYPL DGAARGEDTS MNLVQKYLEN YYDLKKDVKQ FVRRKDSGPV 70 80 90 100 110 120 VKKIREMQKF LGLEVTGKLD SDTLEVMRKP RCGVPDVGHF RTFPGIPKWR KTHLTYRIVN 130 140 150 160 170 180 YTPDLPKDAV DSAVEKALKV WEEVTPLTFS RLYEGEADIM ISFAVREHGD FYPFDGPGNV 190 200 210 220 230 240 LAHAYAPGPG INGDAHFDDD EQWTKDTTGT NLFLVAAHEI GHSLGLFHSA NTEALMYPLY 250 260 270 280 290 300 HSLTDLTRFR LSQDDINGIQ SLYGPPPDSP ETPLVPTEPV PPEPGTPANC DPALSFDAVS 310 320 330 340 350 360 TLRGEILIFK DRHFWRKSLR KLEPELHLIS SFWPSLPSGV DAAYEVTSKD LVFIFKGNQF 370 380 390 400 410 420 WAIRGNEVRA GYPRGIHTLG FPPTVRKIDA AISDKEKNKT YFFVEDKYWR FDEKRNSMEP 430 440 450 460 470 GFPKQIAEDF PGIDSKIDAV FEEFGFFYFF TGSSQLEFDP NAKKVTHTLK SNSWLNC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The complete primary structure of human matrix metalloproteinase-3. Identity with stromelysin." Saus J., Quinones S., Otani Y., Nagase H., Harris E.D. Jr., Kurkinen M. J. Biol. Chem. 263:6742-6745(1988) [PubMed: 3360803] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 18-24.
[2]	"Comparison of human stromelysin and collagenase by cloning and sequence analysis." Whitham S.E., Murphy G., Angel P., Rahmsdorf H.J., Smith B., Lyons A., Harris T.J.R., Reynolds J.J., Herrlich P., Docherty A.J.P. Biochem. J. 240:913-916(1986) [PubMed: 3030290] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fibroblast.
[3]	"Human skin fibroblast stromelysin: structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells." Wilhelm S.M., Collier I.E., Kronberger A., Eisen A.Z., Marmer B.L., Grant G.A., Bauer E.A., Goldberg G.I. Proc. Natl. Acad. Sci. U.S.A. 84:6725-6729(1987) [PubMed: 3477804] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Three matrix metalloproteinases on 81kb of P1 insert." Lin D., Duncan M., Allen E., Araujo R., Aparicio A., Chai A., Chung E., Davis K., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lashkari D., Lew H., Namath A., Oefner P., Roberts D., Heller R., Davis R.W. Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-45. Tissue: Synovium.
[6]	SeattleSNPs variation discovery resource Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLU-45.
[7]	"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], VARIANT GLU-45. Tissue: Lung.
[8]	"Stepwise activation mechanisms of the precursor of matrix metalloproteinase 3 (stromelysin) by proteinases and (4-aminophenyl)mercuric acetate." Nagase H., Enghild J.J., Suzuki K., Salvesen G. Biochemistry 29:5783-5789(1990) [PubMed: 2383557] [Abstract] Cited for: ZYMOGEN ACTIVATION.
[9]	"The NMR structure of the inhibited catalytic domain of human stromelysin-1." Gooley P.R., O'Connell J.F., Marcy A.I., Cuca G.C., Salowe S.P., Bush B.L., Hermes J.D., Esser C.K., Hagmann W.K., Springer J.P., Johnson B.A. Nat. Struct. Biol. 1:111-118(1994) [PubMed: 7656014] [Abstract] Cited for: STRUCTURE BY NMR OF CATALYTIC DOMAIN.
[10]	"Solution structures of stromelysin complexed to thiadiazole inhibitors." Stockman B.J., Waldon D.J., Gates J.A., Scahill T.A., Kloosterman D.A., Mizsak S.A., Jacobsen E.J., Belonga K.L., Mitchell M.A., Mao B., Petke J.D., Goodman L., Powers E.A., Ledbetter S.R., Kaytes P.S., Vogeli G., Marshall V.P., Petzold G.L., Poorman R.A. Protein Sci. 7:2281-2286(1998) [PubMed: 9827994] [Abstract] Cited for: STRUCTURE BY NMR OF 100-267.
[11]	"Stromelysin-1: three-dimensional structure of the inhibited catalytic domain and of the C-truncated proenzyme." Becker J.W., Marcy A.I., Rokosz L.L., Axel M.G., Burbaum J.J., Fitzgerald P.M.D., Cameron P.M., Esser C.K., Hagmann W.K., Hermes J.D., Springer J.P. Protein Sci. 4:1966-1976(1995) [PubMed: 8535233] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 18-272.
[12]	"X-ray structure of a hydroxamate inhibitor complex of stromelysin catalytic domain and its comparison with members of the zinc metalloproteinase superfamily." Dhanaraj V., Ye Q.-Z., Johnson L.L., Hupe D.J., Otwine D.F., Dunbar J.B. Jr., Rubin J.R., Pavlovsky A., Humblet C., Blundell T.L. Structure 4:375-386(1996) [PubMed: 8740360] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-266.
[13]	"Inhibition of stromelysin-1 (MMP-3) by P1'-biphenylylethyl carboxyalkyl dipeptides." Esser C.K., Bugianesi R.L., Caldwell C.G., Chapman K.T., Durette P.L., Girotra N.N., Kopka I.E., Lanza T.J., Levorse D.A., Maccoss M., Owens K.A., Ponpipom M.M., Simeone J.P., Harrison R.K., Niedzwiecki L., Becker J.W., Marcy A.I., Axel M.G. , Christen A.J., McDonnell J., Moore V.L., Olszewski J.M., Saphos C., Visco D.M., Shen F., Colletti A., Kriter P.A., Hagmann W.K. J. Med. Chem. 40:1026-1040(1997) [PubMed: 9083493] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 105-264.
[14]	"Mechanism of inhibition of the human matrix metalloproteinase stromelysin-1 by TIMP-1." Gomis-Rueth F.-X., Maskos K., Betz M., Bergner A., Huber R., Suzuki K., Yoshida N., Nagase H., Brew K., Bourenkov G.P., Bartunik H., Bode W. Nature 389:77-81(1997) [PubMed: 9288970] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 100-267 IN COMPLEX WITH TIMP1.
[15]	"Structural characterizations of nonpeptidic thiadiazole inhibitors of matrix metalloproteinases reveal the basis for stromelysin selectivity." Finzel B.C., Baldwin E.T., Bryant G.L. Jr., Hess G.F., Wilks J.W., Trepod C.M., Mott J.E., Marshall V.P., Petzold G.L., Poorman R.A., O'Sullivan T.J., Schostarez H.J., Mitchell M.A. Protein Sci. 7:2118-2126(1998) [PubMed: 9792098] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 100-264.
[16]	"Crystal structure of the stromelysin catalytic domain at 2.0-A resolution: inhibitor-induced conformational changes." Chen L., Rydel T.J., Gu F., Dunaway C.M., Pikul S., Dunham K.M., Barnett B.L. J. Mol. Biol. 293:545-557(1999) [PubMed: 10543949] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 100-272.
[17]	"X-ray structure of human stromelysin catalytic domain complexed with nonpeptide inhibitors: implications for inhibitor selectivity." Pavlovsky A.G., Williams M.G., Ye Q.-Z., Ortwine D.F., Purchase C.F. II, White A.D., Dhanaraj V., Roth B.D., Johnson L.L., Hupe D., Humblet C., Blundell T.L. Protein Sci. 8:1455-1462(1999) [PubMed: 10422833] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 100-267.
[18]	"Solution structure of the catalytic domain of human stromelysin-1 complexed to a potent, nonpeptidic inhibitor." Li Y.C., Zhang X., Melton R., Ganu V., Gonnella N.C. Biochemistry 37:14048-14056(1998) [PubMed: 9760240] [Abstract] Cited for: STRUCTURE BY NMR OF 100-272.
+	Additional computationally mapped references.

Web resources

SeattleSNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

X05232 mRNA. Translation: CAA28859.1.
J03209 mRNA. Translation: AAA36321.1.
U78045 Genomic DNA. Translation: AAB36942.1.
AK223283 mRNA. Translation: BAD97003.1.
AK223291 mRNA. Translation: BAD97011.1.
AF405705 Genomic DNA. Translation: AAK95247.1.
BC069676 mRNA. Translation: AAH69676.1.
BC069716 mRNA. Translation: AAH69716.1.
BC074815 mRNA. Translation: AAH74815.1.
BC074869 mRNA. Translation: AAH74869.1.
BC105954 mRNA. Translation: AAI05955.1.
BC107490 mRNA. Translation: AAI07491.1.
BC107491 mRNA. Translation: AAI07492.1.

IPI

IPI00027782.

PIR

KCHUS1. A28156.

RefSeq

NP_002413.1.

UniGene

Hs.375129

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1B3D	X-ray	2.30	A/B	100-272	[»]
1B8Y	X-ray	2.00	A	100-266	[»]
1BIW	X-ray	2.50	A/B	100-272	[»]
1BM6	NMR	-	A	100-272	[»]
1BQO	X-ray	2.30	A/B	100-272	[»]
1C3I	X-ray	1.83	A/B	100-272	[»]
1C8T	X-ray	2.60	A/B	103-268	[»]
1CAQ	X-ray	1.80	A	100-267	[»]
1CIZ	X-ray	1.64	A	100-267	[»]
1CQR	X-ray	2.00	A/B	100-272	[»]
1D5J	X-ray	2.60	A/B	100-272	[»]
1D7X	X-ray	2.00	A/B	100-272	[»]
1D8F	X-ray	2.40	A/B	100-272	[»]
1D8M	X-ray	2.44	A/B	100-272	[»]
1G05	X-ray	2.45	A/B	100-272	[»]
1G49	X-ray	1.90	A/B	100-272	[»]
1G4K	X-ray	2.00	A/B/C	100-267	[»]
1HFS	X-ray	1.70	A	105-264	[»]
1HY7	X-ray	1.50	A/B	100-272	[»]
1M1W	model	-	A	100-268	[»]
1OO9	NMR	-	A	100-267	[»]
1QIA	X-ray	2.00	A/B/C/D	106-267	[»]
1QIC	X-ray	2.00	A/B/C/D	106-266	[»]
1SLM	X-ray	1.90	A	18-272	[»]
1SLN	X-ray	2.27	A	100-272	[»]
1UEA	X-ray	2.80	A/C	100-272	[»]
1UMS	NMR	-	A	100-273	[»]
1UMT	NMR	-	A	100-273	[»]
1USN	X-ray	1.80	A	100-264	[»]
2D1O	X-ray	2.02	A/B	100-270	[»]
2JNP	NMR	-	A	105-265	[»]
2JT5	NMR	-	A	105-265	[»]
2JT6	NMR	-	A	105-265	[»]
2SRT	NMR	-	A	100-272	[»]
2USN	X-ray	2.20	A	100-264	[»]
3USN	NMR	-	A	100-267	[»]

ModBase

Search...

Protein family/group databases

MEROPS

M10.005.

PTM databases

PhosphoSite

P08254.

Proteomic databases

PRIDE

P08254.

Genome annotation databases

Ensembl

ENSG00000149968. Homo sapiens. [Contig view]

GeneID

4314.

KEGG

hsa:4314.

UCSC

uc001phj.1. human.

Organism-specific databases

GeneCards

GC11M102211.

H-InvDB

HIX0035998.

HGNC

HGNC:7173. MMP3.

HPA

CAB016139.
HPA007875.

MIM

185250. gene+phenotype.

PharmGKB

PA30886.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P08254.

HOVERGEN

P08254.

OMA

P08254. DDEQWTK.

Enzyme and pathway databases

BRENDA

3.4.24.17. 247.

Pathway_Interaction_DB

p75ntrpathway. p75(NTR)-mediated signaling.

Gene expression databases

ArrayExpress

P08254.

Bgee

P08254.

CleanEx

HS_MMP3.

GermOnline

ENSG00000149968. 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.
IPR002477. Peptidoglycan-bd-like.
[Graphical view]

Gene3D

G3DSA:2.110.10.10. Hemopexin. 1 hit.

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]

PROSITE

PS00546. CYSTEINE_SWITCH. 1 hit.
PS00024. HEMOPEXIN. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00786. Marimastat.
DB00641. Simvastatin.

NextBio

16977.

PMAP-CutDB

P08254.

SOURCE

Search...

Entry information

Entry name

MMP3_HUMAN

Accession

Primary (citable) accession number: P08254
Secondary accession number(s): Q3B7S0, Q6GRF8

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	February 1, 1991
Last modified:	July 7, 2009
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)