[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Alveolar macrophage; PubMed=8226919 [NCBI, ExPASy, EBI, Israel, Japan] Shapiro S.D., Kobayashi D.K., Ley T.J.; "Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages."; J. Biol. Chem. 268:23824-23829(1993).
[2]	NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS SER-357 AND ARG-469. NIEHS SNPs program; Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
[3]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[4]	CHARACTERIZATION. DOI=10.1074/jbc.272.18.12189; PubMed=9115292 [NCBI, ExPASy, EBI, Israel, Japan] Gronski T.J. Jr., Martin R.L., Kobayashi D.K., Walsh B.C., Holman M.C., Huber M., Van Wart H.E., Shapiro S.D.; "Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase."; J. Biol. Chem. 272:12189-12194(1997).
[5]	X-RAY CRYSTALLOGRAPHY (1.09 ANGSTROMS) OF 106-263. DOI=10.1006/jmbi.2001.4954; PubMed=11575928 [NCBI, ExPASy, EBI, Israel, Japan] Lang R., Kocourek A., Braun M., Tschesche H., Huber R., Bode W., Maskos K.; "Substrate specificity determinants of human macrophage elastase (MMP-12) based on the 1.1 A crystal structure."; J. Mol. Biol. 312:731-742(2001).
[6]	X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 100-280. DOI=10.1006/jmbi.2001.4953; PubMed=11575929 [NCBI, ExPASy, EBI, Israel, Japan] Nar H., Werle K., Bauer M.M.T., Dollinger H., Jung B.; "Crystal structure of human macrophage elastase (MMP-12) in complex with a hydroxamic acid inhibitor."; J. Mol. Biol. 312:743-751(2001).

Comments

FUNCTION: May be involved in tissue injury and remodeling. Has significant elastolytic activity. Can accept large and small amino acids at the P1' site, but has a preference for leucine. Aromatic or hydrophobic residues are preferred at the P1 site, with small hydrophobic residues (preferably alanine) occupying P3.
CATALYTIC ACTIVITY: Hydrolysis of soluble and insoluble elastin. Specific cleavages are also produced at 14-Ala-|-Leu-15 and 16-Tyr-|-Leu-17 in the B chain of insulin.
COFACTOR: Binds 4 calcium ions per subunit.
COFACTOR: Binds 2 zinc ions per subunit.
SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular matrix (Probable).
TISSUE SPECIFICITY: Found in alveolar macrophages but not in peripheral blood monocytes.
INDUCTION: By exposure to lipopolysaccharide. Inhibited by dexamethasone.
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.
SIMILARITY: Belongs to the peptidase M10A family [view classification].
SIMILARITY: Contains 4 hemopexin-like domains.
WEB RESOURCE: Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/mmp12/";.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

L23808; AAA58658.1; ALT_SEQ; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
AY856072; AAW29944.1; -; Genomic_DNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC112301; AAI12302.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00298246; -.

A49499; A49499.

NP_002417.2; -.

3D structure databases

PDB

1JIZ; X-ray; 2.60 A; A/B=100-264.	[ExPASy / RCSB / EBI]
1JK3; X-ray; 1.09 A; A=106-263.	[ExPASy / RCSB / EBI]
1OS2; X-ray; 2.15 A; A/B/C/D/E/F=106-268.	[ExPASy / RCSB / EBI]
1OS9; X-ray; 1.85 A; A/B/C/D/E/F=106-268.	[ExPASy / RCSB / EBI]
1RMZ; X-ray; 1.34 A; A=106-263.	[ExPASy / RCSB / EBI]
1ROS; X-ray; 2.00 A; A/B=106-268.	[ExPASy / RCSB / EBI]
1UTT; X-ray; 2.20 A; A=106-264.	[ExPASy / RCSB / EBI]
1UTZ; X-ray; 2.50 A; A/B=106-264.	[ExPASy / RCSB / EBI]
1Y93; X-ray; 1.03 A; A=106-263.	[ExPASy / RCSB / EBI]
1YCM; NMR; -; A=106-263.	[ExPASy / RCSB / EBI]
1Z3J; NMR; -; A=106-263.	[ExPASy / RCSB / EBI]
2HU6; X-ray; 1.32 A; A=106-263.	[ExPASy / RCSB / EBI]
2JXY; NMR; -; A=278-470.	[ExPASy / RCSB / EBI]
2K2G; NMR; -; A=100-263.	[ExPASy / RCSB / EBI]
2K9C; NMR; -; A=112-263.	[ExPASy / RCSB / EBI]
2OXU; X-ray; 1.24 A; A=106-263.	[ExPASy / RCSB / EBI]
2OXW; X-ray; 1.15 A; A=106-263.	[ExPASy / RCSB / EBI]
2OXZ; X-ray; 1.90 A; A=106-263.	[ExPASy / RCSB / EBI]
2POJ; NMR; -; A=100-263.	[ExPASy / RCSB / EBI]
2W0D; X-ray; 2.00 A; A/B/C/D=106-263.	[ExPASy / RCSB / EBI]
2Z2D; NMR; -; A=100-263.	[ExPASy / RCSB / EBI]
3BA0; X-ray; 3.00 A; A=106-470.	[ExPASy / RCSB / EBI]
3F15; X-ray; 1.70 A; A=106-263.	[ExPASy / RCSB / EBI]
3F16; X-ray; 1.16 A; A=106-263.	[ExPASy / RCSB / EBI]
3F17; X-ray; 1.10 A; A=106-263.	[ExPASy / RCSB / EBI]
3F18; X-ray; 1.13 A; A=106-263.	[ExPASy / RCSB / EBI]
3F19; X-ray; 1.13 A; A=106-263.	[ExPASy / RCSB / EBI]
3F1A; X-ray; 1.25 A; A=106-263.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

PDBsum

1JIZ; -.
1JK3; -.
1OS2; -.
1OS9; -.
1RMZ; -.
1ROS; -.
1UTT; -.
1UTZ; -.
1Y93; -.
1YCM; -.
1Z3J; -.
2HU6; -.
2JXY; -.
2K2G; -.
2K9C; -.
2OXU; -.
2OXW; -.
2OXZ; -.
2POJ; -.
2W0D; -.
2Z2D; -.
3BA0; -.
3F15; -.
3F16; -.
3F17; -.
3F18; -.
3F19; -.
3F1A; -.

ModBase

P39900.

Protein family/group databases

MEROPS

M10.009; -.

Enzyme and pathway databases

BRENDA

3.4.24.65; 247.

Organism-specific databases

GC11M102238; -.

HIX0036014; -.

HGNC:7158; MMP12.

CAB017481; -.

601046; gene. [NCBI / EBI]

PharmGKB

PA30870; -.

Gene expression databases

P39900; -.

P39900; -.

HS_MMP12; -.

ENSG00000110347; Homo sapiens.

Ontologies

GO:0005615;	Cellular component: extracellular space (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005578;	Cellular component: proteinaceous extracellular matrix (inferred from electronic annotation from UniProtKB-SubCell).
GO:0005509;	Molecular function: calcium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0004222;	Molecular function: metalloendopeptidase activity (traceable author statement from UniProtKB).
GO:0008270;	Molecular function: zinc ion binding (traceable author statement from ProtInc).
GO:0006508;	Biological process: proteolysis (traceable author statement from ProtInc).
QuickGo view.

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 of domain structure.

Gene3D

G3DSA:2.110.10.10; Hemopexin; 1.

Pfam

PF00045; Hemopexin; 4.
PF00413; Peptidase_M10; 1.
PF01471; PG_binding_1; 1.
Pfam graphical view of domain structure.

PIRSF

PIRSF001191; Peptidase_M10A_matrix; 1.

PRINTS

PR00138; MATRIXIN.

SMART

SM00120; HX; 4.
SM00235; ZnMc; 1.
SMART graphical view of domain structure.

PROSITE

PS00546; CYSTEINE_SWITCH; 1.
PS00024; HEMOPEXIN; 1.
PS00142; ZINC_PROTEASE; 1.

Proteomic databases

PRIDE

P39900; -.

Genome annotation databases

Ensembl

ENSG00000110347; Homo sapiens. [Contig view]

GeneID

4321; -.

KEGG

hsa:4321; -.

Phylogenomic databases

HOGENOM

P39900; -.

HOVERGEN

P39900; -.

Other

DrugBank

DB00551; Acetohydroxamic Acid.

17001; -.

MMP12; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Calcium; Disulfide bond; Extracellular matrix; Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Polymorphism; Protease; Repeat; Secreted; Signal; Zinc; Zymogen.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 16`	`16`	`Probable.`
`PROPEP`	`17 105`	`89`	`Activation peptide (By similarity).`	`PRO_0000028776`
`CHAIN`	`106 470`	`365`	`Macrophage metalloelastase.`	`PRO_0000028777`
`DOMAIN`	`288 330`	`43`	`Hemopexin-like 1.`
`DOMAIN`	`332 375`	`44`	`Hemopexin-like 2.`
`DOMAIN`	`380 427`	`48`	`Hemopexin-like 3.`
`DOMAIN`	`429 470`	`42`	`Hemopexin-like 4.`
`MOTIF`	`90 97`	`8`	`Cysteine switch (By similarity).`
`ACT_SITE`	`219 219`
`METAL`	`92 92`		`Zinc 2; in inhibited form (By similarity).`
`METAL`	`124 124`		`Calcium 1.`
`METAL`	`158 158`		`Calcium 2.`
`METAL`	`168 168`		`Zinc 1.`
`METAL`	`170 170`		`Zinc 1.`
`METAL`	`175 175`		`Calcium 3.`
`METAL`	`176 176`		`Calcium 3; via carbonyl oxygen.`
`METAL`	`178 178`		`Calcium 3; via carbonyl oxygen.`
`METAL`	`180 180`		`Calcium 3; via carbonyl oxygen.`
`METAL`	`183 183`		`Zinc 1.`
`METAL`	`190 190`		`Calcium 2; via carbonyl oxygen.`
`METAL`	`192 192`		`Calcium 2; via carbonyl oxygen.`
`METAL`	`194 194`		`Calcium 2.`
`METAL`	`196 196`		`Zinc 1.`
`METAL`	`198 198`		`Calcium 3.`
`METAL`	`199 199`		`Calcium 1.`
`METAL`	`201 201`		`Calcium 1.`
`METAL`	`201 201`		`Calcium 3.`
`METAL`	`218 218`		`Zinc 2; catalytic.`
`METAL`	`222 222`		`Zinc 2; catalytic.`
`METAL`	`228 228`		`Zinc 2; catalytic.`
`METAL`	`289 289`		`Calcium 4; via carbonyl oxygen (By similarity).`
`METAL`	`333 333`		`Calcium 4; via carbonyl oxygen (By similarity).`
`METAL`	`381 381`		`Calcium 4; via carbonyl oxygen (By similarity).`
`METAL`	`430 430`		`Calcium 4; via carbonyl oxygen (By similarity).`
`CARBOHYD`	`20 20`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`285 285`		`N-linked (GlcNAc...) (Potential).`
`DISULFID`	`282 470`		`By similarity.`
`VARIANT`	`357 357`	`1`	`N -> S (in dbSNP:rs652438 [NCBI]).`	`VAR_021343`
`VARIANT`	`469 469`	`1`	`G -> R.`	`VAR_021344`
`STRAND`	`110 118`	`9`
`HELIX`	`127 142`	`16`
`STRAND`	`148 151`	`4`
`STRAND`	`153 155`	`3`
`STRAND`	`158 164`	`7`
`STRAND`	`169 171`	`3`
`STRAND`	`176 179`	`4`
`STRAND`	`182 184`	`3`
`STRAND`	`187 189`	`3`
`TURN`	`190 193`	`4`
`STRAND`	`195 198`	`4`
`STRAND`	`203 211`	`9`
`HELIX`	`212 224`	`13`
`STRAND`	`237 239`	`3`
`TURN`	`245 247`	`3`
`HELIX`	`252 259`	`8`
`STRAND`	`281 284`	`4`
`STRAND`	`289 294`	`6`
`STRAND`	`297 302`	`6`
`STRAND`	`305 308`	`4`
`STRAND`	`319 321`	`3`
`TURN`	`322 324`	`3`
`STRAND`	`335 338`	`4`
`TURN`	`339 342`	`4`
`STRAND`	`343 348`	`6`
`STRAND`	`351 355`	`5`
`STRAND`	`357 360`	`4`
`HELIX`	`368 370`	`3`
`STRAND`	`383 385`	`3`
`TURN`	`387 389`	`3`
`STRAND`	`391 395`	`5`
`STRAND`	`403 407`	`5`
`HELIX`	`418 421`	`4`
`STRAND`	`430 433`	`4`
`STRAND`	`436 438`	`3`
`STRAND`	`440 446`	`7`
`STRAND`	`448 452`	`5`
`TURN`	`453 456`	`4`
`TURN`	`464 469`	`6`

Sequence information

Length: 470 AA [This is the length of the unprocessed precursor]

Molecular weight: 54002 Da [This is the MW of the unprocessed precursor]

CRC64: 8C745EEA8C0EA216 [This is a checksum on the sequence]

        10         20         30         40         50         60 
MKFLLILLLQ ATASGALPLN SSTSLEKNNV LFGERYLEKF YGLEINKLPV TKMKYSGNLM 

        70         80         90        100        110        120 
KEKIQEMQHF LGLKVTGQLD TSTLEMMHAP RCGVPDVHHF REMPGGPVWR KHYITYRINN 

       130        140        150        160        170        180 
YTPDMNREDV DYAIRKAFQV WSNVTPLKFS KINTGMADIL VVFARGAHGD FHAFDGKGGI 

       190        200        210        220        230        240 
LAHAFGPGSG IGGDAHFDED EFWTTHSGGT NLFLTAVHEI GHSLGLGHSS DPKAVMFPTY 

       250        260        270        280        290        300 
KYVDINTFRL SADDIRGIQS LYGDPKENQR LPNPDNSEPA LCDPNLSFDA VTTVGNKIFF 

       310        320        330        340        350        360 
FKDRFFWLKV SERPKTSVNL ISSLWPTLPS GIEAAYEIEA RNQVFLFKDD KYWLISNLRP 

       370        380        390        400        410        420 
EPNYPKSIHS FGFPNFVKKI DAAVFNPRFY RTYFFVDNQY WRYDERRQMM DPGYPKLITK 

       430        440        450        460        470 
NFQGIGPKID AVFYSKNKYY YFFQGSNQFE YDFLLQRITK TLKSNSWFGC

P39900 in FASTA format

View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools